VERWENDUNG VON ROXITHROMYCIN ZUR HERSTELLUNG EINES MEDIKAMENTS ZUR VERBESSERUNG DER BIOLOGISCHEN UND ANTIVIRALEN AKTIVITÄT VON PROTEASE-INHIBITOREN

Trans-lentivirales Vektor System

FUSION PROTEIN DELIVERY SYSTEM AND USES THEREOF

... ²²²² The present invention provides a composition of matter, comprising: DNA ²encoding a viral Vpx protein fused to DNA encoding a protein. In another ²embodiment ²of the present invention, there is provided a composition of matter, ²comprising: DNA ²encoding a viral Vpr protein fused to DNA encoding a protein. The present ²invention ²further provides DNA, vectors and methods for expressing a lentiviral pol gene ²in ²trans, independent of the lentiviral gag-pol. A gene transduction element is ²optionally ²delivered to a lentiviral vector according to the present invention. Also ²provided are ²various methods of delivering a virus inhibitory molecule to a target in an ²animal. ²Further provided is a pharmaceutical composition.² ...

METHOD OF POTENTIATING AN IMMUNE RESPONSE AND COMPOSITIONS THEREFOR

A method, and compositions for use therein capable, of delivering a bioactive agent to an animal entailing the steps of encapsulating effective amounts of the agent in a biocompatible excipient to form microcapsules having a size less than approximately ten micrometers and administering effective amounts of the microcapsules to the animal. A pulsatile response is obtained, as well as mucosal and systemic immunity.

ENDOTHELIUM MIMICKING NANOMATRIX

Disclosed herein are peptide amphiphiles for use in producing a natural endothelium mimicking nanomatrix. The disclosed natural endothelium mimicking nanomatrix can be used to coat medical devices such as vascular stents to promote endothelializaiton and inhibit restenosis and thrombosis. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

NOVEL METHOD OF DIAGNOSING AND TREATING GLIOMAS

The present invention relates generally to the fields of cell physiology, neurology and neuro-oncology. More specifically, the present invention relates to a novel method of diagnosing and treating gliomas and meningiomas. The present invention describes the expression of a chloride conductance with unique properties that selectively characterizes tumor-derived cells of glial origin. In the present invention, whole-cell patch-clamp techniques were used to characterize the biophysical and pharamacological properties of chloride channels in primary cultures and acutely isolated cells from biopsies of human astrocytomas and established cell lines.

DUAL SHOCK ATRIAL DEFIBRILLATION APPARATUS

An implanted system for the defibrillation of the atria of a patient's heart includes a pair of atrial defibrillation electrodes (60, 65), and a pulse generator (13) operatively associated with the first pair of atrial defibrillation elec-trodes for delivering the first atrial defibrillation pulse. The pulse generator delivers a second atrial defibrillation pulse after the first defibrillation pulse without intervening moni-toring thereof to reduce the voltage necessary for the chock, and the pain associated therewith.

AN ANTIBODY SELECTIVE FOR A TUMOR NECROSIS FACTOR-RELATED APOPTOSIS-INDUCING LIGAND RECEPTOR AND USES THEREOF

Dipeptide analogs as TGF-beta inhibitors

The present disclosure is concerned with dipeptide analogs that are capable of inhibiting TGF-β and methods of treating cancers such as, for example, multiple myeloma and a hematologic malignancy, methods for immunotherapy, and methods of treating fibrotic conditions using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

High frequency large volume resonator

The present invention provides magnetic resonance imaging coils for pursuing large volume images at high magnetic field strengths of 3 Tesla or higher. Also provided are methods of obtaining images by utilizing such magnetic resonance imaging coils. Specifically, the present invention provides a high field large volume resonator comprising a conductive cavity with segments of coaxial cable with exposed center conductors passing through, thereby creating a voltage node corresponding to the center of the conductive cavity. The cavity dimensions of the high frequency large volume resonator are sufficiently large to accommodate a human subject or other appropriate subject of similar size.

Systems and methods for testing protective helmets

In one embodiment, a helmet testing system includes a sled adapted to support a bullet dummy, a track along which the sled can travel, a target dummy support apparatus adapted to support a target dummy at a point near an end of the track, and an impact cushion positioned at the end of the track that is adapted to halt forward motion of the sled along the track to enable the bullet dummy to be launched from the sled and into the target dummy.

VERFAHREN UND VORRICHTUNG ZUR ERFASSUNG VON MEDIZINISCHEN ZUSTÄNDEN DES HERZENS

NEUARTIGE RETINOIDE UND DEREN VERWENDUNG

IMPFUNG DURCH TOPISCHE VERWENDUNG GENETISCHER VEKTOREN

IMMUNOTOXINS AND METHODS OF INDUCING IMMUNE TOLERANCE

Provided are novel DT- and ETA-based immunotoxins and a method of treating a n immune system disorder not involving T cell proliferation, comprising administering to the animal an immunotoxin comprising a mutant diphtheria toxin moiety linked to an antibody moiety which routes by the anti-CD3 pathway, or derivatives thereof under conditions such that the disorder is treated. Thus, the present method can treat graft-versus-host disease. Also provided is a method of inhibiting a rejection response by inducing immune tolerance in a recipient to a foreign mammalian donor tissue or cells, comprising the steps of: a) exposing the recipient to an immunotoxin so as to reduce the recipients' peripheral blood T-cell lymphocyte population by a t least 80%, wherein the immunotoxin is anti-CD3 antibody linked to a diphtheria protein toxin, wherein the protein has a binding site mutation; and b) transplanting the donor cells into the recipient, whereby a rejection response by the recipient to the donor ...

Method of making a catheter

A conformable catheter comprising a catheter handle, an elongated catheter tube, and a distal tip portion of the catheter tube, capable of assuming a desired pre-programmed shape. A wire member is disposed within the core of the catheter's tip portion and is formed of a material, such as, for example, a shape-memory binary nickel-titanium alloy, that will assume a pre-programmed shape after pre-shaping, heat treatment, cooling and subsequent heating. To pre-program the shape of the wire member, prior to assembly of the catheter, the wire member is wound around a shaped, heat resistant fixture, heated until the temperature of the wire member exceeds the temperature at which the shape of the wire member on the fixture becomes programmed into the wire member, and cooled. Upon subsequent heating of the wire member above its activation temperature after inclusion of the wire member into the catheter tubing, such as by controllably connecting the wire member to an electrical power source, the ...

Ligands added to adenovirus fiber

The fiber protein of adenovirus has been genetically altered via attachment at the carboxyl end of a peptide linker, preferably up to 26 amino acids in length which forms a random coil, which can be used to attach a non-adenovirus ligand altering the binding specificity of the fiber protein. Examples of ligands include peptides which are selectively bound by a targeted cell so that the modified fiber protein is internalized by receptor-mediated endocytosis, and peptides which can act as an universal coupling agent, for example, biotin or strepavidin. The linker is designed to not interfere with normal trimerization of fiber protein, to avoid steric hindrance of binding of the fiber protein to a targeted cell, and to serve as a site to introduce new peptide sequence. The modified fiber protein is prepared by genetic engineering of the nucleotide sequence encoding the fiber protein, through the addition of new sequence at the carboxyl tail-encoding region which encodes the linker and the ...

Method and system for the selection of cardiac defibrillation shocks based on discomfort

Methods, systems and computer program products for selecting a shock profile for a defibrillator based on patient discomfort to a plurality of different defibrillating shocks include delivering a first defibrillating shock having an associated first shock profile to a patient, and measuring the associated physical displacement of a selected region in the patient. A second defibrillating shock having an associated second shock profile is delivered to the patient, and the associated physical displacement of the selected region in measured. One of the first or second shock profiles is selected based on which shock profile has the lesser amount of measured physical displacement.

Treatment of tumors with genetically engineered herpes virus

Disclosed are methods for treating cancer by administering an effective amount of a modified Herpes simplex virus.

Pneumococcal serotype 6D

Disclosed is a new and emerging serotype of Streptococcus pneumoniae designated serotype 6D, and assays and monoclonal antibodies useful in identifying same. Also disclosed is a novel pneumococcal polysaccharide with the repeating unit ->2) glucose 1 (1->3) glucose 2 (1->3) rhamnose (1->4) ribitol (5->phosphate. This new serotype may be included in pneumococcal vaccines.

Combinations of antibodies selective for DR5 and other therapeutic agents

An antibody of the invention interacts with human DR5 or with human DR4 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Methods and uses for the antibodies, optionally in combination with various therapeutic agents, are detailed, including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

HERPES SIMPLEX VIRUS EXPRESSING INTERLEUKIN-12 GENE AND AND ITS USE FOR TREATING CANCER

TEMPERATURE CORRELATED FORCE AND STRUCTURE DEVELOPMENT OF ELASTIN POLYTETRAPEPTIDES AND POLYPENTAPEPTIDES

VERFAHREN UND VORRICHTUNG ZUR ERFASSUNG VON MEDIZINISCHEN ZUSTÄNDEN DES HERZENS

METHODS OF TREATMENT USING AN EPITHELIAL SODIUM CHANNEL BLOCKER AND AN INHIBITOR OF THE MINERALOCORTICOID RECEPTOR

Co-administration of a channel blocking epithelial sodium channel (ENaC) blocker in conjunction with a mineralocorticoid receptor inhibitor makes it possible to achieve desired lowering of blood pressure with use in the range of 20% to 75% or less of the presently used dosage of the mineralocorticoid receptor inhibitor (MRI), thus avoiding many of the deleterious side effects usually associated with administration of an MRI. As little as 10% of the usual dosage of MRI may, in some cases, be efficacious. The most commonly used EnaC blocker now in use is amiloride. The most commonly used inhibitors of the mineralocorticoid receptor are precursors of canrenone.

VIRTUAL INTERACTIVE PRESENCE SYSTEMS AND METHODS

Provided herein are methods and systems for virtual interactive presence.

MID-IR MICROCHIP LASER: ZNS:CR2+ LASER WITH SATURABLE ABSORBER MATERIAL

A laser includes a substrate formed of a II-VI semiconductor material, grooves formed at an input end of the substrate and input fibers that engaged to the grooves to receive multiple input optical beams of pump light. The laser further includes optical waveguides formed in the substrate that are respectively coupled to the input fibers, where one waveguide corresponds to one input fiber, and where the optical waveguides extend to an output end of the substrate to form multiple output optical ports. Additionally, the laser includes a laser gain region doped with transitional metal ions in the substrate that overlap with the optical waveguides near the output optical ports, where the laser gain region absorbs the pump light to produce laser gain at multiple laser wavelengths within a broadband luminescence spectral range different from the pump wavelength to generate laser light at the multiple laser wavelengths. The laser further includes a tapered grating formed in the laser gain region ...

Method and apparatus for treating cardiac arrhythmia

An implantable system for the defibrillation or cardioversion of the atria and the ventricles of a patient's heart comprises: a first catheter configured for positioning in the right ventricle of the heart; a second catheter configured for positioning through the coronary sinus ostium and in the coronary sinus of the heart, with the first and second catheters together carrying at least three defibrillation electrodes; a power supply; and a control circuit operatively associated with the power supply and the electrodes. The control circuit is configured for delivering an atrial defibrillation pulse through at least two of the electrodes, or a ventricular defibrillation pulse through at least two of the electrodes.

Transport chairs

In some embodiments, a transport chair includes a base frame, a seat assembly pivotally mounted to the base, and a footrest assembly pivotally mounted to the base frame, the footrest assembly being associated with the seat assembly so as to pivot in unison with the seat assembly until the seat assembly is pivoted forward to an extent at which the footrest assembly contacts the floor or ground, at which point the footrest assembly does not pivot further upon further forward pivoting of the seat assembly.

HIGH TORQUE DENTAL IMPLANT SYSTEM

A dental implant system for securing a dental prosthesis within a prepared site of a jawbone in a subject having an implant configured for insertion within the prepared site of the jawbone and an abutment configured for secure attachment to the implant. The implant can have a shoulder portion having a plurality of circumferential rings and a body portion that can be threaded. The implant can have an internal cavity that is configured or otherwise adapted to receive at least a portion of the abutment. 1. A dental implant system for securing a dental prosthesis therein a prepared site of a jawbone , the dental implant system comprising: a shoulder portion defining a coronal end of the implant and comprising a plurality of spaced circumferential rings;', 'a implant body portion defining an apical end of the implant and having a longitudinal length and an implant thread, the implant thread substantially helically extending along at least a portion of the length of the implant body portion, wherein the implant body portion is tapered in an apical direction; and', 'an internal cavity defined therein the coronal end of the implant and extending along the longitudinal axis of the implant therethrough the shoulder portion and at least a portion of the implant body portion; and, 'an implant having a longitudinal axis, the implant comprising a connector portion configured for selective secure attachment therein the internal cavity of the implant;', 'a transition portion configured to abut the shoulder portion of the implant, the transition portion comprising a plurality of spaced circumferential rings, wherein the connector portion and the transition portion have a common longitudinal axis; and', 'an abutment body portion, wherein the abutment body portion is tapered in a coronal direction,, 'an abutment comprisingwherein, upon attachment of the connector portion of the abutment therein the internal cavity of the implant, the common longitudinal axis of the connector portion ...

Method and device for determining oxygen saturation of hemoglobin, for determining hematocrit of blood, and/or for detecting macular degeneration

A method and device for accurately determining oxygen saturation of hemoglobin by the measurement of the optical density of a sample, such as a blood vessel, in response to illumination by light having at least three wavelengths (1, 2, 3, . . . ) within a range of about 460 nm to about 523 nm. The hematocrit of a sample may be determined from optical density measurements at the three or more wavelengths in conjunction with a known path length. The device may be an intravenous or intra-arterial fiber optic catheter used to deliver the interrogating light signal to the blood and to detect the reflected signal. A method and device of determining the thickness of the retinal well using spectroscopic information are also disclosed.

Adenovirus vector containing a heterologous peptide epitope in the hi loop of the fiber knob

The present invention provides means to modify the tropism of recombinant adenoviral vectors using genetic methods to alter the adenoviral fiber cell-binding protein. The present invention generates an adenovirus with modified fiber gene such that novel tropism is achieved. This recombinant adenovirus has a fiber gene modified in the HI loop domain.

Verfahren zur Potenzierung einer Immunreaktion sowie die dazugehörigen Mittel

NUCLEOSIDES WITH ANTI-HEPATITIS B VIRUS ACTIVITY

A method for the treatment of a host, and in particular, a human, infected with HBV is provided that includes administering an HBV-treatment amount of a nucleoside of formula (I), (II) or (III), wherein R1 is hydrogen, fluoro, bromo, chloro, iodo, methyl or ethyl; and R2 is OH, Cl, NH2, or H; or a pharmaceutically acceptable salt of the compound, optionally in a pharmaceutically acceptable carrier or diluent.

ORALLY ADMINISTERED PEPTIDES TO AMELIORATE ATHEROSCLEROSIS

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis (see Figure 23). The peptides comprises at least one class A amphipathic helix and at least one D-amino acid. The peptides are highly stable and readily administered via an oral route.

NUCLEOSIDES WITH ANTI-HEPATITIS B VIRUS ACTIVITY

A method for the treatment of a host, and in particular, a human, infected with HBV is provided that includes administering an HBV-treatment amount of a nucleoside of formula (I), (II) or (III), wherein R1 is hydrogen, fluoro, bromo, chloro, iodo, methyl or ethyl; and R2 is OH, Cl, NH2, or H; or a pharmaceutically acceptable salt of the compound, optionally in a pharmaceutically acceptable carrier or diluent.

PURINE NUCLEOSIDE PHOSPHORYLASE GENE THERAPY FOR HUMAN MALIGNANCY

Methods and compositions for killing replicating or non-replicating, targete d mammalian cells and bystander cells, comprising: (a) transfecting or transducing mammalian cells with a nucleic acid encoding a purine analog nucleoside cleavage enzyme, or providing the targeted cells directly with the enzyme; and (b) contacting the targeted cel ls with a purine analog nucleoside substrate for the enzyme to produce a toxic purine base analog thereby killing the targeted cells and bystander cells. In the present method of killing cells, the enzyme can be an E. coli purine analog nucleoside phosphorylase.

Human anti-epidermal growth factor receptor single-chain antibodies

Human anti-epidermal growth factor receptor (EGFR) single-chain antibodies (scFvs) were isolated from a human IgM phage display library using purified epidermal growth factor receptor as antigen. Two isolates with different amino acid sequences were identified by ELISA as epidermal growth factor receptor-specific. The scFvs bind to the full length epidermal growth factor receptor and the truncated and/or mutated epidermal growth factor receptor on human cells. These anti-EGFR-scFvs are useful as therapeutic and/or diagnostic agents.

Orally administered peptides synergize statin activity

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. The peptides comprise class A amphiphathic helices, are highly stable and readily administered via an oral route. The peptides are effective to stimulate the formation and cycling of pre-beta high density lipoprotein-like particles and/or to promote lipid transport and detoxification.

SYSTEME UND COMPUTERPROGRAMM-PRODUKTE ZUR HEMMUNG VON KAMMERFLIMMERN BEI DER KARDIOPULMONALEN WIEDERBELEBUNG

SEGMENTIERTE POLYPEPTID-BIOELASTOMERE ZUR MODULIERUNG DES ELASTIZITAETSMODULS.

METHODS OF INDUCING IMMUNE TOLERANCE USING IMMUNOTOXINS

Provided is a method of treating an immune system disorder not involving T-cell proliferation, comprising administering to the animal an immunotoxin comprising a mutant diphtheria toxin moiety linked to an antibody moiety which routes by the anti-CD3 pathway, or derivatives thereof under conditions such that the disorder is treated. Thus, the present method can treat graft-versus-host disease. Also provided is a method of inhibiting a rejection response by inducing immune tolerance in a recipient to a foreign mammalian donor tissue or cells, comprising the steps of: a) exposing the recipient to an immunotoxin so as to reduce the recipients' peripheral blood T-cell lymphocyte population by at least 80 %, wherein the immunotoxin is anti-CD3 antibody linked to a diphtheria protein toxin, wherein the protein has a binding site mutation; and b) transplanting the donor cells into the recipient, whereby a rejection response by the recipient to the donor organ cell is inhibited, and the host is ...

AN ANTIBODY SELECTIVE FOR A TUMOR NECROSIS FACTOR-RELATED APOPTOSIS-INDUCING LIGAND RECEPTOR AND USES THEREOF

... ²²²An antibody of the invention interacts with human DR5 to produce agonistic or ²antagonistic effects downstream of the receptor including inhibition of cell ²proliferation and apoptosis. Nucleic acid sequences and amino acid sequences ²of anti-DR5 antibodies have been elucidated and vectors and cells containing ²and expressing these sequences have been generated. Methods and uses for the ²antibodies are detailed including treatment of apoptosis-related disease and ²treatment of dysregulated cell growth.² ...

USE OF 4-AMINO PYRIDINE FOR TREATMENT OF PERIPHERAL NEUROPATHIES

The present invention provides methods of using aminopyridine compounds to treat peripheral nervous system demyelinating diseases including Guillain- Barre Syndrome, diabetes myelitis, and hereditary sensory-motor neuropathies.

IMPROVED PHOTOBLEACHING METHOD

The present disclosure provides an improved method for photobleaching an eye of a subject. The disclosed method may be used in a number of psychophysical test methods, including, but not limited to, measurement of dark adaptation. The improved method for photobleaching involves at least one of the following improvements: (i) the use of a bleaching light emitting a particular wavelength of light or a tailored spectrum of wavelengths; (ii) restricting or otherwise spatially tailoring the region of the retina that is subject to photobleaching; and (iii) utilizing a bleaching light having an intensity that is at or below the intensity of ambient daylight. The present disclosure additionally provides a combination of a photobleaching light and an apparatus to administer a psychophysical test suitable for use in practicing the disclosed methods.

IMMUNOGENIC PCPA POLYPEPTIDES AND USES THEREOF

Provided herein are compositions and methods for eliciting an immune response against Streptococcus pneumoniae. More particularly, the compositions and methods relate to immunogenic polypeptides, including fragments of PcpA and variants thereof, and nucleic acids, vectors and transfected cells that encode or express the polypeptides. Methods of making and using the immunogenic polypeptides are also described.

Methods and compositions for treating trauma-hemorrhage using estrogen and derivatives thereof

Disclosed are methods and materials for treating or preventing complications due to traumatic injuries using estrogen or derivatives thereof.

Platelet inhibitor eluting ablation catheter

An ablation catheter stores a platelet inhibitor substance within a plurality of pockets or recesses of its shaft. The substance is adapted to elute upon contact with biological fluid. In the pocket configuration, the platelet inhibitor substance is in a capsule positioned within the pocket. In the recess configuration, the platelet inhibitor substance is in a hydrogel or silicone-based porous/semi-porous matrix positioned within the recess. Elution of the platelet inhibitor substance prevents or at least substantially minimizes the adhesion of blood platelets on the catheter surface during ablation. In another configuration, the catheter includes an internal lumen network having apertures terminating at the surface of the shaft. The lumen communicates with a source of platelet inhibitor fluid that is forced through the lumen by a variable pump.

Methods and systems for reducing discomfort from cardiac defibrillation shocks

Methods, systems and computer program products for combining atrial defibrillation treatment techniques include techniques for reducing the discomfort associated with defibrillation and/or reducing the defibrillation threshold. Techniques include timing the defibrillation shock to reduce discomfort based on a sensed signal, giving the shock relatively early during atrial fibrillation, therapeutic drugs, administering more than one shock in succession, pacing the heart before, after, or during the defibrillation shock or shocks, and placing the shock electrodes in locations that may reduce discomfort.

Noninvasive genetic immunization, expression products therefrom, and uses thereof

Disclosed and claimed are methods of non-invasive genetic immunization in an animal and/or methods of inducing a systemic immune or therapeutic response in an animal, products therefrom and uses for the methods and products therefrom. The methods can include contacting skin of the animal with a vector in an amount effective to induce the systemic immune or therapeutic response in the animal. The vector can include and express an exogenous nucleic acid molecule encoding an epitope or gene product of interest. The systemic immune response can be to or from the epitope or gene product. The nucleic acid molecule can encode an epitope of interest and/or an antigen of interest and/or a nucleic acid molecule that stimulates and/or modulates an immunological response and/or stimulates and/or modulates expression, e.g., transcription and/or translation, such as transcription and/or translation of an endogenous and/or exogenous nucleic acid molecule; e.g., one or more of influenza hemagglutinin, ...

Mukosale Verabreichung von Pneumokokken-Antigenen

VERWENDUNG VON IMMUNOTOXINEN ZUR AUSLÖSUNG EINER IMMUNTOLERANZ BEI TRANSPLANTATION DER INSELZELLEN DER BAUCHSPEICHELDRÜSE

Methods of inducing immune tolerance using immunotoxins

Provided is a method of treating an immune system disorder not involving T cell proliferation, comprising administering to the animal an immunotoxin comprising a mutant diphtheria toxin moiety linked to an antibody moiety which routes by the anti-CD3 pathway, or derivatives thereof under conditions such that the disorder is treated. Thus, the present method can treat graft-versus-host disease. Also provided is a method of inhibiting a rejection response by inducing immune tolerance in a recipient to a foreign mammalian donor tissue or cells, comprising the steps of: a) exposing the recipient to an immunotoxin so as to reduce the recipients's peripheral blood T-cell lymphocyte population by at least 80%, wherein the immunotoxin is anti-CD3 antibody linked to a diphtheria protein toxin, wherein the protein has a binding site mutation; and b) transplanting the donor cells into the recipient, whereby a rejection response by the recipient to the donor organ cell is inhibited, and the host is ...

Methods, systems and computer program products to inhibit ventricular fibrillation during cardiopulmonary resuscitation

Methods, systems and computer program products determine and identify a favorable time to deliver cardiac compression to a subject to avoid a vulnerable period of a spontaneous intrinsic cardiac cycle.

Ligands added to adenovirus fiber

The fiber protein of adenovirus has been genetically altered via attachment at the carboxyl end of a peptide linker, preferably up to 26 amino acids in length which forms a random coil, which can be used to attach a non-adenovirus ligand altering the binding specificity of the fiber protein. Examples of ligands include peptides which are selectively bound by a targeted cell so that the modified fiber protein is internalized by receptor-mediated endocytosis, and peptides which can act as an universal coupling agent, for example, biotin or strepavidin. The linker is designed to not interfere with normal trimerization of fiber protein, to avoid steric hindrance of binding of the fiber protein to a targeted cell, and to serve as a site to introduce new peptide sequence.

Methods and apparatus for detecting medical conditions of the heart

An implantable system for detecting electrical activity from a patient's heart comprises a first sensing electrode configured for positioning through the coronary sinus ostium and within a vein on the left surface of the left ventricle of the heart for sensing electrical activity from the heart, and a detector operatively associated with the first sensing electrode for determining (e.g., diagnosing or prognosing) a medical condition of the heart with the sensed electrical activity. Typically the system further comprises a second sensing electrode configured for positioning in the right ventricle of the heart, where the detector is operatively associated with both the first sensing electrode and the second sensing electrode. The second sensing electrode may be positioned in other locations as well, such as also within a vein on the left surface of the left ventricle of the heart (although spaced apart from the first sensing electrode), in the right atrium, in the superior vena cava, etc.

Synthesis of functional human hemoglobin and other proteins in erythroid tissues of transgenic non-human mammals

The present invention relates to the synthesis of functional human hemoglobin and other proteins in erythroid tissues of transgenic non-human animals and erythroid cell lines. It is based on the discovery that two of the five hypersensitivity sites of the beta-globin locus are sufficient to result in high level expression of human alpha- or beta-globin transgenes.

Dual shock atrial defibrillation apparatus

An implantable system for the defibrillation of the atria of a patient's heart includes a pair of atrial defibrillation electrodes configured for delivering a first atrial defibrillation pulse in the heart, and a pulse generator operatively associated with the first pair of atrial defibrillation electrodes for delivering the first atrial defibrillation pulse. The pulse generator delivers a second second atrial defibrillation pulse after the first defibrillation pulse without intervening monitoring thereof to reduce the voltage necessary for the shock, and the pain associated therewith.

Bioelastomeric drug delivery system

A drug delivery composition, comprising a bioelastic polymer, comprising monomeric units selected from the group consisting of bioelastic pentapeptides, tetrapeptides, and nonapeptides, and a drug retained by the polymer, wherein the polymer is selected to be in a first contraction state, selected from the group consisting of contracted and relaxed bioelastomer states, when contacted with a physiological condition present in a human or animal to whom the composition is administered and wherein the polymer contains a reactive functional group that undergoes a reaction, either in the presence of the physiological condition or when the polymer is transported by a natural process in the human or animal to a different location having a different physiological condition, to produce a second functional group, wherein the presence of the second functional group in the polymer causes the polymer to switch to the other of the contraction states, thereby making the drug available for release from ...

Nitrated lipids and methods of making and using thereof

Described herein are nitrated lipids and methods of making and using the nitrated lipids.

Injection device and methods related thereto

Disclosed herein is an injection device with housing that defines a channel and a first injection guide opening. The first injection guide opening enters the channel in a manner that allows a needle to penetrate a vessel in an animal with accuracy and at the same time protect the user from the needle.

METHODE ZUR BEHANDLUNG VON VERLETZUNGEN DES TRAUMATISIERTEN GEHIRNS MIT NICHT-STEROID ENTZÜNDUNGSHEMMENDEN MEDIKAMENTEN

REVERSIBEL MECHANISCH-CHEMISCH ARBEITENDE MASCHINEN, DIE AUS BIOELASTOMEREN BESTEHEN, DIE ZU REGELBAREN INVERSEN TEMPERATURÜBERGÄNGEN FÄHIG SIND, ZUR UMWANDLUNG VON CHEMISCHER IN MECHANISCHE ARBEIT.

Methode und Zusammensetzung zur oralen Verabreichung von bioaktiven Mitteln zur Peyer's Flecken.

RECEPTOR-MEDIATED UPTAKE OF PEPTIDES THAT BIND THE HUMAN TRANSFERRIN RECEPTOR

... ²²²Peptides have been discovered which are capable of binding to and ²internalizing with the human transferrin receptor (hTfR). The sequences ²HAIYPRH (Seq. ID No. 1) and THRPPMWSPVWP (Seq. ID No. 2) are capable of ²binding to and internalizing with the human transferrin receptor. When these ²molecules were fused with other molecules, the fusion product was internalized ²in cells expressing hTfR. The sequences have use for targeting other peptides ²and proteins into cells expressing hTfR.² ...

COMPOSITIONS FOR REDUCING BACTERIAL CARRIAGE AND CNS INVASION AND METHODS OF USING SAME

... ²²²Provided herein are compositions designed to reduce or prevent bacterial ²infections (for example pneuomococcal infections), nasal carriage, nasal ²colonization, and central nervous system invasion. Provided herein is a ²composition comprising a pneumococcal neuraminidase, phosphocholine, ²pneumococcal teichoic acid, pneumococcal lipoteichoic acid, or an antigenic ²portion of either neuraminidase, phosphocholine, pneumococcal teichoic acid, ²pneumococcal lipoteichoic acid. Optionally, the composition can comprise any ²combination of a pneumococcal neuraminidase, a phosphocholine, a pneumococcal ²teichoic acid, a pneumococcal lipoteichoic acid or an antigenic portion of any ²one of these. Optionally the agents are detoxified. Further provided are ²methods of making and using the compositions disclosed herein. Specifically ²provided are methods of generating antibodies in a subject comprising ²administering to the subject an agent or composition taught herein. Also ²provided are methods ...

SYSTEM AND METHOD FOR MANAGING SPATIOTEMPORAL UNCERTAINTY

Provided herein are methods and systems for managing spatiotemporal uncertainty in image processing. A method can comprise determining motion from a first image to a second image, determining a latency value, determining a precision value, generating an uncertainty element based upon the motion, the latency value, and the precision value, and rendering the uncertainty element.

TREATMENT OF TUMORS WITH GENETICALLY ENGINEERED HERPES VIRUS

Disclosed are methods for treating cancer by administering an effective amount of a modified Herpes simplex virus.

Enhancing coagulation or reducing fibrinolysis

Methods for controlling bleeding (e.g., enhancing coagulation and reducing fibrinolysis) in a subject are disclosed. The methods include selecting a subject in need of enhanced coagulation or reduced fibrinolysis, and administering to the subject a carbon monoxide releasing molecule (CORM). Examples of CORMs include tricarbonyldichloro-ruthenium (II) dimer, tricarbonylchloro-(glycinato)ruthenium (II), sodium boranocarbonate, dimanganese decacarbonyl, and iron pentacarbonyl. Further disclosed are compositions and methods for treating a subject in need of a blood product by administering to the subject a composition including a CORM and a blood product (e.g., cryoprecipitate or fresh frozen plasma).

Conjunctival inserts for topical delivery of medication or lubrication

The present invention provides an improved conjunctival insert for topical delivery of medication or lubrication into the conjunctival spaces and upon the ocular surface of human eye. Specifically, three physical designs are provided, differing by size, named "Large", "Medium" and "Small". Also provided are methods of treating ocular maladies and of lubricating or moisturizing a dry eye using the disclosed conjunctival inserts. Such inserts can also be used for veterinary practices in the cases of primates and quadrupeds.

ELASTOMERE POLYPEPTIDE ALS VASKULARE PROTHESEMATERIALIEN.

PROCESS FOR METABOLIC CONTROL AND HIGH SOLUTE CLEARANCE AND SOLUTIONS FOR USE THEREIN

The present disclosure describes novel standardized citrate replacement fluid solutions and a standardized dialysate solution for use with CRRT methods. The standardized citrate replacement fluid solutions and standardized dialysate solutions do not require modification based on the clinical status of the individual patients. The use of the standardized solutions described herein offers significant advantages over the prior art solutions used in CRRT. The present disclosure describes superior metabolic and electrolyte control and significantly increased dialyzer patency in: (a) 24 intensive care unit (ICU) patients with ARF using a 0.67% trisodium citrate replacement fluid solution, and (b) 32 ICU patients with ARF using a 0.5% trisodium citrate replacement fluid solution. Both groups were treated with Bicarbonate-25 dialysate and achieved effluent rates of 35 mL/kg/hr.

SYNTHETIC APOLIPOPROTEIN E MIMICKING POLYPEPTIDES AND METHODS OF USE

The present invention provides methods for using synthetic apolipoprotein E (ApoE)-mimicking peptides. Also disclosed are methods for using synthetic apolipoprotein E (ApoE)-mimicking peptides to reduce plasma glucose levels. Methods of using the disclosed apolipoprotein E (ApoE)-mimicking peptides to treat diabetes and diabetic complications are also disclosed.

NUCLEOSIDES WITH ANTI-HEPATITIS B VIRUS ACTIVITY

A method for the treatment of a host, and in particular, a human, infected with HBV is provided that includes administering an HBV-treatment amount of the stabilized nucleotide of a nucleoside which exhibits anti-hepatitis B activity.

Use of 4-amino pyridine for treatment of peripheral neuropathies

The present invention provides methods of using aminopyridine compounds to treat peripheral nervous system demyelinating diseases including Guillain-Barre Syndrome, diabetes mellitus, and hereditary sensory-motor neuropathies.

Reference clones and sequences for non-subtype B isolates of human immunodeficiency virus type 1

The nucleotide sequences of the genomes of eleven molecular clones for non-subtype B isolates of human immunodeficiency virus type 1 are disclosed. The invention relates to the nucleic acids and peptides encoded by and/or derived from these sequences and their use in diagnostic methods and as immunogens.

HYPDH inhibitors and methods of use for the treatment of kidney stones

Provided herein are compounds of Formula (I), Formula (II), and Formula (III), and compositions comprising the same, as well as methods of use thereof for controlling or inhibiting the formation of calcium oxalate kidney stones, inhibiting the production of glyoxylate and/or oxalate, and/or inhibiting hydroxyproline dehydrogenase (HYPDH).

ADENOVIRUSFASER MIT HINZUGEFÜGTEN LIGANDEN

Methode und Zusammensetzung zur oralen Verabreichung von bioaktiven Mitteln zur Peyer's Flecken.

FÜR EIN DEM TUMOR-NEKROSE-FAKTOR ÄHNLICHEN, APOPTOSE-INDUZIERENDEN LIGANDENREZEPTOR SELEKTIVEN ANTIKÖRPER UND DESSEN ANWENDUNGEN

Biologically active native biomatrix composition

Methods for altering gene expression and methods of treatment utilizing same

ATTENUATION OF NEGATIVE STRANDED RNA VIRUSES BY REARRANGEMENT OF THEIR GENES AND USES THEREOF

Provided is a method of attenuating a virus of the order Mononegavirales, comprising the step of: rearranging said virus' gene order by moving a gene essential for RNA replication away from its wild-type 3' promoter proximal position site, wherein said gene is an essential limiting factor for genome replication and is placed in the next to last position in the gene order. Also provided is a method of making an attenuated virus useful for a vaccine, comprising the steps of: rearranging said virus' gene order by moving a gene essential for RNA replication away from its wild-type 3' promoter proximal position site, wherein a gene which is an essential limiting factor for genome replication is placed in the next to last position in the gene order; and placing a gene coding for an immune response inducing antigen in the position closest to the 3' end of the gene order. Also provided is a method of attenuating a virus of the order Mononegavirales, comprising the step of: rearranging said virus ...

Peptides and peptide mimetics to treat pathologies characterized by an inflammatory response

This invention provides novel active agents (e.g. peptides, small organic molecules, amino acid pairs, etc.) peptides that ameliorate one or more symptoms of atherosclerosis and/or other pathologies characterized by an inflammatory response. In certain embodiment, the peptides resemble a G* amphipathic helix of apolipoprotein J. The agents are highly stable and readily administered via an oral route.

Members of the FC receptor homolog gene family (FcRH1-3,6) related reagents and uses thereof

The invention relates to members of the Fc receptor homolog (FcRH) subfamily, as well as fragments and variants thereof. Each FcRH is a Type I transmembrane receptor, preferably, comprises an extracellular region, a transmembrane region, and a cytoplasmic region. The cytoplasmic region preferably comprises one or more immunoreceptor tyrosine-based inhibitory or activation motifs ("ITIMs" or "ITAMs). The invention provides polypeptides, nucleic acids, vectors, expression systems, and antibodies and antibody fragments related to the FcRHs as well as uses thereof. Such uses include uses in the diagnosis and treatment of a malignancy of hematopoietic cell lineage or an inflammatory or autoimmune disease in a subject and in the modulation of a humoral immune response in a subject.

Compositions and methods for the identification and treatment of immune-mediated inflammatory diseases

Compositions and methods for the therapy and diagnosis of immune-mediated inflammatory diseases, including inflammatory bowel disease (IBD), Crohn's disease and ulcerative colitis, are disclosed. Illustrative compositions comprise one or more bacterial polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention or treatment of immune-mediated inflammatory disease.

Monoclonal antibodies specific for anthrax spores and peptides derived from the antibodies thereof

The present invention provides monoclonal antibodies which are highly specific for Bacillus spores. Also provided are peptides derived from those monoclonal antibodies. Both the antibodies and peptides are highly specific and can discriminate between spores of potentially lethal organisms such as Bacillus anthracis and other harmless but closely related bacilli and provide a very powerful tool in the construction of detection instruments as counter measures.

ERREGUNG DER CHEMOTAXE DURCH CHEMOTAKTISCHE PEPTIDE.

METHOD TO IMPROVE THE BIOLOGICAL AND ANTIVIRAL ACTIVITY OF PROTEASE INHIBITORS

Methods for improving the cellular uptake of protease inhibitors (e.g., HIV protease inhibitor), alone or in the presence of one or more additional therapeutic agents, in protease inhibitor-based therapies, involving administration of one or more AAG-binding compounds, such as macrolide or lincosamide antibiotics, which have sufficient binding affinity for AAG to competitively bind AAG in the presence of the protease inhibitor.

METHOD AND APPARATUS FOR THE DETECTION OF IMPAIRED DARK ADAPTATION

The present method describes a new method for the measurement of dark adaptation. The dark adaptation status of subjects may then be used to identify those subjects who are at risk of developing and/or who are currently suffering from a variety of disease states having their clinical manifestations in impaired dark adaptation. The disease states include, but are not limited to, age related macular degeneration, vitamin A deficiency, Sorsby's Fundus Dystrophy, late autosomal dominant retinal degeneration, retinal impairment related to diabetes and diabetic retinopathy. An apparatus for administering the test method described is also provided.

ORALLY ADMINISTERED PEPTIDES TO AMELIORATE ATHEROSCLEROSIS

This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis (see Figure 23). The peptides comprises at least one class A amphipathic helix and at least one D-amino acid. The peptides are highly stable and readily administered via an oral route.

MID-IR LASER INSTRUMENT FOR ANALYZING A GASEOUS SAMPLE AND METHOD FOR USING THE SAME

An optical nose for detecting the presence of molecular contaminants in gaseous samples utilizes a tunable seed laser output in conjunction with a pulsed reference laser output to generate a mid-range IR laser output in the 2 to 20 micrometer range for use as a discriminating light source in a photo-acoustic gas analyzer.

Fiber receptor-independent system for the propagation of adenoviral vectors

The present invention provides a means for the propagation of adenovirus lacking the native tropism by using genetic methods to modify the fiber protein by addition of a C-terminal tag. The modified virus is then propagated in a cell line transfected with a sequence encoding an artificial receptor for the C-terminal tag on the modified fiber protein.

Osteoclast secreted chemokine and uses thereof

The present invention demonstrates the biological function of a newly identified osteoclast-secreted protein. This protein, mim-1, has sequence homology with but is distinct from a previously identified neutrophil chemokine protein. Mim-1 may be a key signaling protein secreted by osteoclasts that regulates recruitment and/or differentiation of osteoblast and osteoclast precursor cells. This protein may also serve to maintain osteoclasts in a relatively inactive state prior to secretion. This mechanism is essential for regulating the mass and structural integrity of bone. This protein or an analog and/or antagonists of this protein will have potential therapeutic potential in the treatment of a variety of pathological bone diseases including osteoporosis and metastatic bone diseases.

Mutacin I biosynthesis genes and proteins

According to the present invention, an isolated and purified DNA sequence which encodes a lantibiotic, mutacin I, is disclosed. The nucleic acid sequence is set forth in SEQ ID No: 1 and the amino acid sequence is set forth in SEQ ID No: 2.

Antibody selective for a tumor necrosis factor-related apoptosis-inducing ligand receptor and uses thereof

An antibody of the invention interacts with human DR5 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Nucleic acid sequences and amino acid sequences of anti-DR5 antibodies have been elucidated and vectors and cells containing and expressing these sequences have been generated. Methods and uses for the antibodies are detailed including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

System and method for conducting a non-exact matching analysis on a phishing website

A system and method for enhancing spam avoidance efficiency by automatically identifying a phishing website without human intervention. The system receives a stream of suspect Internet urls for potential phishing websites and uses a comparison strategy to determine whether the potential phishing website has already be labeled as a bonefid phishing website. A comparison system is utilized in which similarity data is calculated on various elements of the potential phishing website and then compared to similarity data of known phishing websites. Various types of similarity measure methodologies are potentially incorporated and a similarity threshold value can be varied in order to respond to phishing threats.

Reference clones and sequences for non-subtype B isolates of human immunodeficiency virus type 1

The nucleotide sequences of the genomes of eleven molecular clones for non-subtype B isolates of human immunodeficiency virus type 1 are disclosed. The invention relates to the nucleic acids and peptides encoded by and/or derived from these sequences and their use in diagnostic methods and as immunogens.

DIVALENT ANTI-T CELLS IMMUNOTOXINS AND USE THEREOF

VERWENDUNG VON 4-AMINOPYRIDIN ZUR BEHANDLUNG VON PERIPHEREN NEUROPATHIEN

ENHANCING COAGULATION OR REDUCING FIBRINOLYSIS

Methods for controlling bleeding (e.g., enhancing coagulation and reducing fibrinolysis) in a subject are disclosed. The methods include selecting a subject in need of enhanced coagulation or reduced fibrinolysis, and administering to the subject a carbon monoxide releasing molecule (CORM). Examples of CORMs include tricarbonyldichloro-ruthenium (II) dimer, tricarbonylchloro-(glycinato)ruthenium (II), sodium boranocarbonate, dimanganese decacarbonyl, and iron pentacarbonyl. Further disclosed are compositions and methods for treating a subject in need of a blood product by administering to the subject a composition including a CORM and a blood product (e.g., cryoprecipitate or fresh frozen plasma). 1. A method for enhancing coagulation or reducing fibrinolysis in a subject , comprising:a) selecting a subject in need of enhanced coagulation or reduced fibrinolysis; andb) administering to the subject a carbon monoxide releasing molecule (CORM).2. The method of claim 1 , wherein the CORM is a tricarbonyldichlororuthenium (II) dimer.3. The method of claim 1 , wherein the CORM is selected from the group consisting of tricarbonylchloro(glycinato)ruthenium (II) claim 1 , sodium boranocarbonate claim 1 , dimanganese decacarbonyl claim 1 , and iron pentacarbonyl.4. The method of claim 1 , wherein a single dose of the CORM is administered to the subject.5. (canceled)6. The method of claim 4 , wherein the dose comprises 25 μM to 200 μM of the CORM.7. (canceled)8. (canceled)9. The method of claim 1 , wherein the CORM is administered at or near a site of bleeding.10. The method of claim 1 , wherein the CORM is administered topically claim 1 , by local injection claim 1 , intravenously claim 1 , or intramuscularly.11. The method of claim 1 , wherein the CORM is formulated for administration by an aerosol spray claim 1 , an ointment claim 1 , a bandage claim 1 , a surgical dressing claim 1 , a wound packing claim 1 , a swab claim 1 , a liquid claim 1 , a paste claim 1 , a cream ...

Msp nanopores and related methods

Provided herein are Mycobacterium smegmatis porin nanopores, systems that comprise these nanopores, and methods of using and making these nanopores. Such nanopores may be wild-type MspA porins, mutant MspA porins, wild-type MspA paralog porins, wild-type MspA homolog porins, mutant MspA paralog porins, mutant MspA homolog porins, or single-chain Msp porins. Also provided are bacterial strains capable of inducible Msp porin expression.

ANTIBODY SELECTIVE FOR A TUMOR NECROSIS FACTOR-RELATED APOPTOSIS-INDUCING LIGAND RECEPTOR AND USES THEREOF

An antibody of the invention interacts with human DR5 to produce agonistic or antagonistic effects downstream of o the receptor including inhibition of cell proliferation and apoptosis. Nucleic acid sequences and amino acid sequences of anti-DR5 antibodies have been elucidated and vectors and cells containing and expressing these sequences have been generated. Methods and uses for the antibodies are detailed including treatment of apoptosis-related disease and treatment of dysregulated cell growth. 1. A purified antibody which specifically binds a TRAIL receptor DR5 , wherein the antibody:(a) has apoptosis-inducing activity in vitro in the absence of secondary crosslinking in target cells expressing DR5, wherein the apoptosis-inducing activity in vitro is characterized by less than 80% target cell viability at an antibody concentration of at least 5 μg/ml;(b) has tumoricidal activity in vivo against tumor cells expressing DR5;(c) does not bind TRAIL receptor DR4, DcR1, or DcR2; and(d) is a monoclonal antibody.2. The purified antibody of claim 1 , wherein the antibody blocks TRAIL-induced apoptosis.3. The purified antibody of claim 1 , wherein the antibody is a humanized antibody.4. The purified antibody of claim 1 , wherein the antibody is a human antibody.5. The purified antibody of claim 1 , wherein the DR5 is human DR5.6. The purified antibody of claim 1 , wherein the antibody has the same epitope specificity as an antibody produced by mouse-mouse hybridoma TRA-10 having ATCC Accession Number PTA-1742.7. The purified antibody of claim 1 , wherein the antibody is a monoclonal antibody produced by the mouse-mouse hybridoma TRA-10 having ATCC Accession Number PTA-1742.8. A composition comprising the antibody of and a pharmaceutically acceptable carrier.9. The composition of claim 8 , wherein the antibody is present at a concentration from 0.2 ng to 5000 ng/ml of the carrier.10. A kit comprising the antibody of in a container.11. A method for selectively inducing ...

Agents and Methods Related to Reducing Resistance to Apoptosis-Inducing Death Receptor Agonists

Provided herein is a method of reversing or preventing a target cell's resistance to a death receptor agonist. Also provided are methods of screening for biomarkers resistance of and monitoring resistance to death receptor agonists. Also provided are methods of selectively inducing apoptosis in a target cell, treating a subject with cancer, autoimmune or inflammatory diseases, comprising administering compositions provided herein. Further provided are compositions comprising agents that modulate CARD containing proteins.

DIAGNOSIS AND TREATMENT OF NEUROECTODERMAL TUMORS

The present invention provides fusion proteins for the detection and treatment of neuroectodermal tumors. Previous work demonstrated that chlorotoxin is specific for glial-derived or meningioma-derived tumor cells. The current invention has extended the use of chlorotoxin-cytotoxin fusion proteins to treat the whole class neuroectodermal tumors such as gliomas, meningiomas, ependymonas, medulloblastomas, neuroblastomas, gangliomas, pheochromocytomas, melanomas, PPNET's, small cell carcinoma of the lung, Ewing's sarcoma, and metastatic tumors in the brain. Also, diagnostic methods are provided for screening neoplastic neuroectodermal tumors. 1. A method of treating an individual having a neuroectodermal tumor , comprising the step of:administering a pharmaceutical composition comprising a pharmaceutically effective dose of a neuroectodermal tumor specific ligand fused to a cytotoxic moiety and a pharmaceutically acceptable carrier.2. The method of claim 1 , wherein the neuroectodermal tumor is a tumor type treated is selected from the group consisting of ependymonas claim 1 , medulloblastomas claim 1 , neuroblastomas claim 1 , gangliomas claim 1 , pheochromocytomas claim 1 , melanomas claim 1 , peripheral primitive neuroectodermal tumors claim 1 , small cell carcinoma of the lung claim 1 , Ewing's sarcoma claim 1 , and metastatic tumors in the brain.3. The method of claim 1 , wherein the neuroectodermal tumor specific ligand is chlorotoxin.4. The method of claim 3 , wherein said chlorotoxin is selected from the group consisting of native chlorotoxin claim 3 , synthetic chlorotoxin and recombinant chlorotoxin.5. The method of claim 1 , wherein said cytotoxic moieties is selected from the group consisting of gelonin claim 1 , ricin claim 1 , saponin claim 1 , pseudonomas exotoxin claim 1 , pokeweed antiviral protein claim 1 , diphtheria toxin claim 1 , and complement proteins.6. The method of claim 1 , wherein the neuroectodermal tumor specific ligand is an antibody ...

Methods and Compositions Related to Soluble Monoclonal Variable Lymphocyte Receptors of Defined Antigen Specificity

Disclosed are compositions and methods related to variable lymphocyte receptors (VLRs). More particularly, disclosed are a variety of antigen specific polypeptides, including soluble, monoclonal, and multivalent forms, as well as methods of using the polypeptides, antibodies that bind the antigen specific polypeptides, and nucleic acids, vectors and expression systems that encode the polypeptides. Antigen specific polypeptides that selectively bind pathogens, like anthrax, and carbohydrates, like blood group determinants, are specifically disclosed. 1. A method of making a soluble , monoclonal antigen specific polypeptide comprisinga. isolating a cDNA clone encoding an antigen specific polypeptide, wherein the antigen specific polypeptide comprises an N-terminal leucine rich repeat (LRRNT), one or more leucine rich repeats (LRRs), a C-terminal leucine rich repeat (LRCCT), and a connecting peptide, wherein the connecting peptide comprises an alpha helix;b. transfecting a cell in culture medium with the cDNA clone of step (a); andC. isolating the antigen specific polypeptide from the culture medium.2. The method of claim 1 , wherein the antigen specific polypeptide binds a target protein.3. The method of claim 1 , wherein the antigen specific polypeptide binds a target carbohydrate.4. The method of claim 1 , wherein the antigen specific polypeptide binds a target pathogen.5. The method of claim 1 , further comprising the step of generating a stable cell line comprising the cDNA clone.6. A soluble claim 1 , monoclonal antigen specific polypeptide made by the method of .7. The soluble claim 6 , monoclonal antigen specific polypeptide of claim 6 , wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:5 claim 6 , 47 claim 6 , 49 claim 6 , 51 claim 6 , 53 claim 6 , 55 claim 6 , 57 claim 6 , 59 and 61.8. The soluble claim 6 , monoclonal antigen specific polypeptide of claim 6 , wherein the polypeptide comprises the amino ...

MID-IR MICROCHIP LASER: ZNS:CR2+ LASER WITH SATURABLE ABSORBER MATERIAL

A method of fabrication of laser gain material and utilization of such media includes the steps of introducing a transitional metal, preferably Cr thin film of controllable thickness on the ZnS crystal facets after crystal growth by means of pulse laser deposition or plasma sputtering, thermal annealing of the crystals for effective thermal diffusion of the dopant into the crystal volume with a temperature and exposition time providing the highest concentration of the dopant in the volume without degrading laser performance due to scattering and concentration quenching, and formation of a microchip laser either by means of direct deposition of mirrors on flat and parallel polished facets of a thin Cr:ZnS wafer or by relying on the internal reflectance of such facets. Multiple applications of the laser material are contemplated in the invention. 134.-. (canceled)35. A laser transmitter comprising:a pump radiation source configured to generate radiations in spatially separate channels;an active gain medium having amplification spectra to emit amplified radiations of the spatially separate channels, each channel representing a corresponding wavelength;an intracavity lens to receive the emitted amplified radiations of the spatially separated channel from the active medium and focus the received amplified radiations towards an aperture;the aperture to suppress an off-axis mode of the received amplified radiations of the spatially separate channels;a diffraction grating to diffract the amplified radiations of the spatially separate channels received through the aperture and return a portion of the diffracted radiations back to the aperture; anda collimating system to collimate the diffracted radiations of the spatially separate channel.36. The laser transmitter of claim 35 , further comprising a pump focusing system to focus the radiations generated by the pump radiation source towards the active gain medium.37. The laser transmitter of claim 35 , wherein the active gain ...

Compositions for Improving Bone Mass

The present invention provides a therapeutic composition, and method of use thereof, for improving bone mass, rigidity, or strength, or preventing and treating bone loss via modulation of the RANK signaling pathway. The therapeutic composition of the present invention comprises a RYBP peptide, or fragments thereof, that specifically interact with a motif of RANK to regulate osteoclastogenesis. The present invention further provides a composition, and method of use thereof, comprising a modulator that is capable of modulating the RYBP-RANK interaction, or modulating an effector in the RANK signaling pathway through the RYBP-RANK interaction.

MANIPULATION OF CALCIUM CHANNELS TO REGULATE AFTER-DEPOLARIZATION EVENTS IN CARDIAC MYOCYTES

A novel mechanism by which after-depolarization occurs in cardiac myocytes has been discovered, involving calcium influx through the arachidonate-regulated calcium channel (ARCC) and the store-operated calcium channel (SOCC). Because after-depolarization of the myocyte is a major cause of cardiac arrhythmia, this discovery provides new approaches for treating and preventing heart disease. By down-regulating the activity of the ARCC or the SOCC, after-depolarization can be decreased and cardiac arrhythmia can be prevented, reduced, or eliminated. This can be accomplished using pharmaceuticals containing inhibitors of the ARCC or the SOCC, or by genetically modifying cells to reduce ARCC or SOCC activity. In addition, assays are disclosed using the ARCC or SOCC to discover potential anti-arrhythmic agents. Cellular and animal models of arrhythmia are disclosed in which the activity of the ARCC or SOCC is increased to promote after-depolarization and induce arrhythmia. 17-. (canceled)8. A method of preventing or reversing an after-depolarization in a myocyte comprising contacting the myocyte with an inhibitor of the ARC channel , an inhibitor of a molecule that stimulates ARC channel activity , an inhibitor of the SOCC , or an inhibitor of a molecule that stimulates SOCC activity.9. The method of claim 8 , wherein the inhibitor is selected from the group consisting of an inhibitor of a phospholipase claim 8 , an inhibitor of cellular voltage-independent calcium homeostasis claim 8 , and an inhibitor of a voltage-independent calcium channel.10. The method of claim 9 , wherein the inhibitor is an inhibitor of Stim1.11. The method of claim 9 , wherein the voltage-independent calcium channel is a calcium channel regulated by arachidonic acid claim 9 , regulated by linoleic acid claim 9 , regulated by a metabolite of arachidonic acid claim 9 , regulated a metabolite of linoleic acid claim 9 , or regulated by intracellular calcium stores.12. The method of claim 9 , wherein ...

Polycistronic Vector for Human Induced Pluripotent Stem Cell Production

Methods of producing induced pluripotent stem (iPS) cells are provided. For example, a method of producing an iPS cell from a differentiated cell, which includes transforming the differentiated cell with a first vector comprising a nucleic acid sequence comprising a nucleic acid sequence encoding an Oct4, a nucleic acid sequence encoding a Sox2, and a nucleic acid sequence encoding a Klf4. Each of the nucleic acid sequences are separated from each other by a first and second viral 2A sequence. The method described can further comprise culturing the transformed cell under conditions that allow for the production of an iPS cell and isolating the cultured iPS cell.

Saliva Polymerase Chain Reaction Assay for Cytomegalovirus Infection

Congenital cytomegalovirus (CMV) infection is an important cause of disease in infants and immune-compromised adults. Most infants infected with CMV are not promptly identified because of the absence of symptoms. It has been discovered that an assay based on the polymerase chain reaction (PCR) for testing of saliva specimens for CMV is rapid, accurate, and inexpensive. Some versions of the assay employ primers that are specific for sequences flanking the highly conserved major envelope glycoprotein B or the highly conserved immediate early 2 exon 5 genes. The assay exceeds the standard rapid culture technique in accuracy, speed, and economy. When the assay is performed on dried saliva, it loses no significant amount of accuracy, and is surprisingly much more sensitive than a PCR assay using dried blood. This assay will permit broader testing to detect and intervene in congenital CMV infection, potentially avoiding numerous cases of associated disease. 1. A method of detecting a virus in a saliva sample , the method comprising:(a) contacting the sample with a first forward amplification primer and a first reverse amplification prim r said primers capable of hybridizing to sequences flanking a target sequence;(b) contacting the sample with a second forward amplification primer and a second reverse amplification primer, said second primers capable of hybridizing to sequences flanking a second target sequence, to form a reaction mixture;(b) performing the polymerase chain reaction on the reaction mixture to form an amplicon; and(c) detecting the target sequence in the amplicon.2. The method of claim 1 , wherein the virus is a cytomegalovirus (CMV) claim 1 , wherein at least one target sequence is selected from the group consisting of a consensus sequence among all CMV claim 1 , a consensus sequence of at least one strain of CMV claim 1 , and a sequence unique to CMV.3. The method of claim 2 , wherein the sample is not subject to DNA extraction prior to performing the ...

General Mass Spectrometry Assay Using Continuously Eluting Co-Fractionating Reporters of Mass Spectrometry Detection Efficiency

The invention provides general methods for quantifying any conceivable compound including small organic molecules and biological molecules in mass spectrometric measurements. The methods include the use of chemical or biological reporters such as artificial polypeptides containing proteolytic cleavage sites, which provide proteolytic reporter peptides for standardization of mass spectrometric detection efficiency. In addition to mass spectrometry standardization between different samples, the artificial polypeptides also standardize sample preparation amongst different samples undergoing mass spectrometric analysis when using electrophoresis separation prior to mass spectrometric analysis. Methods of the present invention also include methods for designing artificial polypeptides with peak to peak continuous liquid chromatography elution profiles spanning the complete or partial analyte elution profile for organic and biological molecules. Also included are the artificial polypeptides predigested with protease, which is compatible for use in experiments with native PAGE, in-solution proteolytic digestion of polypeptides, and small organic molecules undergoing fractionation separation followed by mass spectrometric evaluation. 1. A method for characterizing an analyte in a sample , said methods comprising:(a) combining, a plurality of reporters with the sample containing the analyte to create a mixture, wherein each reporter generates a distinct reporter peak, the plurality of reporters provide a continuous set of reporter peaks during at least a fraction of the elution range of the sample and the plurality of reporters are not present in the sample or are not predicted to be created from the sample during processing of the sample;(b) subjecting the mixture to fractionation by liquid chromatography to produce an eluate;(c) subjecting the eluate to detection by a mass spectrometric technique to generate a mass spectrometric signal from the analyte and at least one ...

Latent human immunodeficiency virus reactiviation

Provided herein are methods or reactivating a latent Human Immunodeficiency Virus (HIV) infection in a cell. The methods comprise modulating a level of NF-κB activity in the cell by contacting the cell with an agent that produces a transient first increase in the level of NF-κB activity without a second delayed increase in NF-κB activity. Optionally, a second agent is used to prime the reactivation. Also provided herein is an isolated Massilia bacterium or population thereof capable of producing a HIV-1 reactivating factor (HRF). Also provided are methods of culturing the Massilia bacteria. Further provided are methods of reactivating a latent Human Immunodeficiency Virus-1 (HIV-1) infection in a subject comprising administering to the subject a HIV-1 reactivating factor produced by Massilia bacteria, optionally with a priming agent.

Generation and Consumption of Discrete Segments of Digital Media

Provided are systems and methods of accessing a portion of a media file on a remote server. The method can comprise receiving a first uniform resource identifier associated with the media file; generating a first boundary point and a second boundary point associated with the portion of the media file, each of the first and second boundary points corresponding to a point in time between the beginning and ending points in time of the media file; generating a second uniform resource identifier configured to locate the portion of the media file between the first and the second boundary points; requesting from the remote server at least a part of the media file associated with the first uniform resource identifier; receiving at least the part of the media file from the remote server; and rendering the media file starting at the first boundary point and ending at the second boundary point. 1. A method of accessing a portion of a media file on a remote server , the media file having associated beginning and ending points in time , the method comprising:receiving a first uniform resource identifier associated with the media file;generating a first boundary point and a second boundary point associated with the portion of the media file, each of the first and second boundary points corresponding to a point in time between the beginning and ending points in time of the media file;generating a second uniform resource identifier configured to locate the portion of the media file between the first and the second boundary points;requesting from the remote server at least a part of the media file associated with the first uniform resource identifier;receiving at least the part of the media file from the remote server; andrendering the media file starting at the first boundary point and ending at the second boundary point.2. The method of claim 1 , wherein the first boundary point and the second boundary point generating step comprises receiving the first boundary point and the ...

Prevention and treatment of cast nephropathy

Provided herein are polypeptides comprising or consisting essentially of a QSYDNTLSGSYVF (SEQ ID NO:1) or LSADSSGSYLYVF (SEQ ID NO:2) amino acid sequence. Also provided herein are methods of treating or preventing cast nephropathy in a subject. The methods comprise identifying a subject with or at risk of developing cast nephropathy and administering to the subject any of the polypeptides disclosed herein.

Single and multi-junction light and carrier collection management cells

A material design is provided for a light and carrier collection (LCCM) architecture in single junction and multi-junction photovoltaic and light sensor devices. The LCCM architecture improves performance and, when applied to single or multi-junctions, can lead to solar cells on flexible plastic substrates which can be easily deployed and even draped over various shapes and forms. The device has an array of conducting nano-elements in electrical and physical contact with the planar electrode. A spacer of 0 to 100 nm in thickness may be used to contact the array of conducting nano-elements. One or more volume regions comprised of at least one light absorbing material is present with the first in simultaneous contact with said spacer to form an operating photovoltaic single- or multi-junction device with periodic undulations to enhance trapping of the impinging light and photocarrier collection throughout the absorber volume regions.

Therapeutics and processes for treatment of immune disorders

Processes of diagnosing or treating an autoimmune abnormality are provided whereby the presence of IgA anti-neutrophil cytoplasmic antibodies (ANCA) in a subject are detected correlating with both presence and severity of disease such as Wegener's granulomatosis (WG). The FCAR genotype predicts whether IgA ANCA will be stimulatory or inhibitory of neutrophil activation such that in subjects with an inhibitory genotype, IgA ANCA will act as an inhibitor of disease severity, and in subjects with a proinflammatory genotype, IgA ANCA will increase disease severity as observed by increased prevalence of renal disease in WG. Thus, individualized medical treatment is possible based on determination of the presence of IgA ANCA and FCAR genotype.

MODULATION OF THE INNATE IMMUNE SYSTEM THROUGH THE TREM-LIKE TRANSCRIPT 2 PROTEIN

TREM-like transcript 2 (TLT2), is expressed on neutrophils, macrophages, and B lymphocytes. Expression of TLT2 is up-regulated on neutrophils and macrophages in response to inflammatory stimuli in vivo and synergizes with agonists that bind to G-protein coupled receptors (GPCR) to potentiate the neutrophil antibacterial and chemotactic response. Administration of anti-TLT2 mAb enhances the acute inflammatory response in vivo that is associated with increased neutrophil recruitment to sites of inflammation. TLT2 ligation in vivo also potentiates chemokine and growth factor production indicating that TLT2 can exert both neutrophil intrinsic and extrinsic effects. The administration of anti-TLT2 mAb alone promotes neutrophil recruitment to the lung and peritoneum, as well as the rapid production of G-CSF, CXCL1 (KC) and CXCL2 (MIP-2). Additionally, the administration of an agent to the circulatory system of an animal can reduce the availability of a TLT2 endogenous ligand to reduce the extent of a neutrophil or macrophage-induced inflammatory response. 1. A method for enhancing an innate immune response of an animal or human subject , the method comprising the steps of delivering to a cell or population of cells an effective amount of an agent that specifically interacts with a TREM-like transcript 2 (TLT2) transmembrane receptor of the cell or population of cells and potentiates neutrophil and/or macrophage activation and/or migration.2. The method of claim 1 , wherein the cell or population of cells is a neutrophil or population of neutrophils claim 1 , wherein said cell or population of cells are isolated from an animal or human subject claim 1 , a cultured neutrophil or population of neutrophils; or a neutrophil or population of neutrophils in an animal or human subject.3. The method of claim 1 , wherein the cell or population of cells is a macrophage or population of macrophages claim 1 , wherein said cell or population of cells are isolated from an animal or ...

PNEUMOCOCCAL SEROTYPE 6D

Disclosed is a new and emerging serotype of designated serotype 6D, and assays and monoclonal antibodies useful in identifying same. Also disclosed is a novel pneumococcal polysaccharide with the repeating unit→2) glucose 1 (1→3) glucose 2 (1→3) rhamnose (1→4) ribitol (5→phosphate. This new serotype may be included in pneumococcal vaccines. 1Streptococcus pneumoniae. An isolated bacterial strain designated 6D; said bacterial strain characterized as having a capsular polysaccharide having the repeating unit {→2) glucose 1 (1→3) glucose 2 (1→3) rhamnose (1→4) ribitol (5→phosphate}.2Streptococcus pneumoniae. A vaccine comprising a polysaccharide derived from an isolated bacterial strain designated 6D; said bacterium characterized as having a capsular polysaccharide having the repeating unit {→2) glucose 1 (1→3) glucose 2 (1→3) rhamnose (1→4) ribitol (5→phosphate}.3. A vaccine comprising a purified polysaccharide having the repeating unit {→2) glucose 1 (1→3) glucose 2 (1→3) rhamnose (1→4) ribitol (5→phosphate}.4Streptococcus pneumoniae. An isolated or purified antigen binding molecule that binds to 6D; wherein the antigen comprises a polysaccharide having the repeating unit {→2) glucose 1 (1→3) glucose 2 (1→3) rhamnose (1→4) ribitol (5→phosphate}.5. A composition comprising purified or isolated mono- or polyclonal antibodies that react with a purified or isolated polysaccharide having the repeating unit {→2) glucose 1 (1→3) glucose 2 (1→3) rhamnose (1→4) ribitol (5→phosphate}.6Streptococcus pneumoniae. A chemical , physical , or genetic test that differentiates for the bacterium 6D , wherein said bacterium is differentiated based on a capsular polysaccharide having the repeating unit {→2) glucose 1 (1→3) glucose 2 (1→3) rhamnose (1→4) ribitol (5→phosphate}. This application is a divisional of U.S. patent application Ser. No. 12/601,896, filed May 4, 2010, which is related to and claims the benefit of PCT Application No. U.S.08/064,951, filed May 28, 2008, and U.S. ...

ROD-RECEIVING SPINAL FUSION ATTACHMENT ELEMENTS

In one embodiment, an implantable spinal fusion attachment element includes a rod attachment head having a passage that is adapted to receive a spinal alignment rod and means for securely attaching the attachment element to a vertebra without penetrating the pedicle of the vertebra. 1. An implantable spinal fusion attachment element comprising:a rod attachment head having a passage that is adapted to receive a spinal alignment rod; andmeans for securely attaching the attachment element to a vertebra without penetrating the pedicle of the vertebra.2. The spinal fusion attachment element of claim 1 , wherein the head is a multiaxial tulip head.3. The spinal fusion attachment element of claim 1 , wherein the means for securely attaching comprise first and second arms adapted to grip the vertebral body.4. The spinal fusion attachment element of claim 3 , wherein the first and second arms each comprise a distal end that includes a hook that is adapted to grip the vertebral body.5. The spinal fusion attachment element of claim 3 , wherein the first and second arms each comprise a proximal end that includes an opening adapted to receive a fastener that fastens the arms together.6. The spinal fusion attachment element of claim 5 , wherein the opening of the second arm is an elongated slot.7. The spinal fusion attachment element of claim 1 , wherein the means for securely attaching comprise a shaft that extends from the head and a retainer element associated with the shaft.8. The spinal fusion attachment element of claim 7 , wherein the retainer element comprises a small rod that passes through an opening formed in the distal end of the shaft.9. The spinal fusion attachment element of claim 7 , wherein the retainer element comprises at least one barb or tine that extends out from the shaft.10. The spinal fusion attachment element of claim 9 , wherein the barb or tine can be deployed to extend out from the shaft.11. An implantable spinal fusion system comprising:spinal fusion ...

Antibody Selective for a Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor and Uses Thereof

An antibody of the invention interacts with human DR5 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Nucleic acid sequences and amino acid sequences of anti-DR5 antibodies have been elucidated and vectors and cells containing and expressing these sequences have been generated. Methods and uses for the antibodies are detailed including treatment of apoptosis-related disease and treatment of dysregulated cell growth. 1. A purified antibody comprising a heavy chain and a light chain , the heavy chain comprising SEQ ID NO:25 , SEQ ID NO:26 , and SEQ ID NO:27 , and the light chain comprising SEQ ID NO:28 , SEQ ID NO:29 and SEQ ID NO:30.2. The purified antibody of claim 1 , wherein the antibody is a monoclonal antibody.3. The purified antibody of claim 1 , wherein the antibody claim 1 , in its soluble form claim 1 , has in vitro cell death-inducing activity at concentrations less than 1 μg/ml in target cells expressing DR5.4. The purified antibody of claim 1 , wherein the antibody claim 1 , in its soluble form claim 1 , has in vivo tumoricidal activity in tumor cells expressing DR5.5. The purified antibody of claim 1 , wherein the antibody induces cell death in vitro in the absence of secondary antibody crosslinking6. The purified antibody of claim 1 , wherein the cell-death inducing activity is characterized by less than 40% target cell viability at antibody concentrations of less than 5 μg/ml.7. The antibody of claim 1 , wherein the heavy chain comprises a constant region of a human immunoglobulin G1 heavy chain.8. The antibody of claim 1 , wherein the light chain comprises a constant region of a human immunoglobulin kappa light chain.9. The antibody of claim 1 , wherein the heavy chain comprises SEQ ID NO:56.10. The antibody of claim 1 , wherein the light chain comprises SEQ ID NO:72.11. The antibody of claim 1 , wherein the heavy chain comprises amino acid residues 20-138 of SEQ ID NO: ...

Methods for treatment of nephrotic syndrome and related conditions

The present disclosure provides a method for treating and/or preventing nephrotic syndrome, such as but not limited to MCD and MN, and conditions related to nephrotic syndrome, such as but not limited to, proteinuria and edema, as well as diabetic nephropathy, diabetes mellitus, lupus nephritis or primary glomerular disease. The present disclosure further provides methods for reducing proteinuria and other disease states as discussed herein. Such methods comprise the therapeutic delivery of an Angptl4 polypeptide or Angptl4 polypeptide derivative to a subject.

METHODS FOR MAKING RETINOIDS AND USES THEREOF

Described herein are methods for making retinoids. Also described herein are retinoids and methods of use thereof. 181-. (canceled)84. The compound of claim 83 , wherein n is 1.85. The compound of claim 83 , wherein Ris hydrogen and Ris one or more methyl groups.86. The compound of claim 83 , wherein Ris hydrogen and Ris one or more methyl groups.87. The compound of claim 82 , wherein R claim 82 , R claim 82 , and Rare hydrogen.88. The compound of claim 82 , wherein the compound is (2E claim 82 ,4E claim 82 ,6E claim 82 ,8E)-8-(3′ claim 82 ,4′-dihydro-5′-methyl-1′(2′H-naphthalen-1′-ylidene))-3 claim 82 ,7-dimethyl-2 claim 82 ,4 claim 82 ,6-octatrienoic acid; 4E claim 82 ,6E claim 82 ,8E)-8-(3′ claim 82 ,4′-dihydro-6′-methyl-1′(2′H-naphthalen-1′-ylidene))-3 claim 82 ,7-dimethyl-2 claim 82 ,4 claim 82 ,6-octatrienoic acid; (2E claim 82 ,4E claim 82 ,6E claim 82 ,8E)-8-(3′ claim 82 ,4′-dihydro-7′-methyl-1′(2′H-naphthalen-1′-ylidene))-3 claim 82 ,7-dimethyl-2 claim 82 ,4 claim 82 ,6-octatrienoic acid; (2E claim 82 ,4E claim 82 ,6E claim 82 ,8E)-8-(3′ claim 82 ,4′-dihydro-7′-isopropyl-1′(2′H-naphthalen-1′-ylidene))-3 claim 82 ,7-dimethyl-2 claim 82 ,4 claim 82 ,6-octatrienoic acid; or (2E claim 82 ,4E claim 82 ,6E claim 82 ,8E)-8-(3′ claim 82 ,4′-dihydro-8′-methyl-1′(2′H-naphthalen-1′-ylidene))-3 claim 82 ,7-dimethyl-2 claim 82 ,4 claim 82 ,6-octatrienoic acid.89. The compound of claim 82 , wherein n is 1 claim 82 , and Ris a C-Cbranched or straight chain alkyl group.90. The compound of claim 82 , wherein n is 1 claim 82 , and Ris pentyl claim 82 , isopentyl claim 82 , neopentyl claim 82 , hexyl claim 82 , heptyl claim 82 , octyl claim 82 , nonyl claim 82 , or decyl.91. The compound of claim 82 , wherein Ris an isopentyl group; Ris methyl claim 82 , ethyl claim 82 , propyl claim 82 , isopropyl claim 82 , butyl claim 82 , isobutyl claim 82 , phenyl claim 82 , cyclopropyl claim 82 , cyclobutyl claim 82 , cyclopentyl claim 82 , cyclohexyl claim 82 , or benzyl; and R claim ...

Agents and Methods Related to Reducing Resistance to Apoptosis-Inducing Death Receptor Agonists

Provided herein is a method of reversing or preventing a target cell's resistance to a death receptor agonist. Also provided are methods of screening for biomarkers resistance of and monitoring resistance to death receptor agonists. Also provided are methods of selectively inducing apoptosis in a target cell, treating a subject with cancer, autoimmune or inflammatory diseases, comprising administering compositions provided herein. Further provided are compositions comprising agents that modulate CARD containing proteins. 1. A method of screening a cell for a biomarker of resistance to a death receptor agonist comprising monitoring the association of the death receptor and a CARD containing protein , wherein association signifies resistance to the agonist.2. The method of claim 1 , further comprising pre-contacting the cell with the death receptor agonist.3. The method of claim 1 , wherein the CARD containing protein is selected from the group consisting of DDX3 claim 1 , mda-5 claim 1 , and RIG-1.4. The method of claim 1 , wherein the CARD containing protein is a polypeptide having an amino acid sequence with at least 85% homology to DDX3 claim 1 , mda-5 claim 1 , and RIG-1.5. The method of claim 1 , wherein the death receptor is selected from the group consisting of Fas claim 1 , TNF and a TRAIL receptor.6. The method of claim 5 , wherein the TRAIL receptor is DR5.7. The method of claim 1 , further comprising acquiring the cell from a subject.8. The method of claim 7 , wherein the subject has cancer.9. The method of claim 7 , wherein the subject has been treated with a DR5 antibody.10. The method of claim 1 , wherein the agonist is an antibody. This application is a divisional application of and claims priority to U.S. Ser. No. 13/356,739, filed Jan. 24, 2012, which is a divisional application of U.S. Ser. No. 11/814,551, filed Mar. 19, 2008, which is a §371 of International Application No. PCT/US2006/03503 filed Jan. 31, 2006, now expired. International ...

TREATING MYCOBACTERIAL INFECTION WITH CU+/++ BOOSTING THERAPEUTICS

Provided herein are methods of treating a subject with a mycobacterial infection. The methods comprise administering to the subject a Cu boosting therapeutic. Also provided are compositions comprising a Cu boosting therapeutic. Further provided are methods of screening for a Cu boosting therapeutic. 1. A method of treating a subject with a mycobacterial infection , the method comprising administering to the subject a Cu boosting therapeutic.2. The method of claim 1 , wherein the Cu boosting therapeutic is selected from the group consisting of a therapeutic pre-complexed with Cu; a therapeutic capable of complexing Cu from tissue claim 1 , blood claim 1 , or intracellular compartments; and a therapeutic that interferes with Cu homeostatsis without complexing Cu.3. The method of claim 2 , wherein the Cu boosting therapeutic is a therapeutic pre-complexed with Cu.5. The method of claim 4 , wherein R claim 4 , R claim 4 , R claim 4 , R claim 4 , R claim 4 , and Rare each independently selected from hydrogen and substituted or unsubstituted C-Calkyl.6. The method of claim 4 , wherein Rand Rare hydrogen.7. The method of claim 4 , wherein R claim 4 , R claim 4 , R claim 4 , and Rare each independently selected from hydrogen and methyl.11. The method of claim 3 , wherein the Cu boosting therapeutic is disulfiram pre-complexed with Cu.13. The method of claim 1 , further comprising administering to the subject a supplement capable of increasing Cu availability.14. The method of claim 1 , wherein the mycobacterial infection is the result of an infection by a bacteria from the Mycobacteriaceae family.15. A composition comprising a Cu boosting therapeutic.16. The composition of claim 15 , wherein the Cu+/++ boosting therapeutic is selected from the group consisting of a therapeutic pre-complexed with Cu; a therapeutic capable of complexing Cu from tissue claim 15 , blood claim 15 , or intracellular compartments; and a therapeutic that interferes with Cu homeostatsis without ...

Detoxified pneumococcal neuraminidase and uses thereof

Provided herein are compositions designed to reduce or prevent bacterial infections (for example pneuomococcal infections), nasal carriage, nasal colonization, and central nervous system invasion. Provided herein is a composition comprising a polypeptide comprising the amino acid sequence of SEQ ID NO:19 or a variant thereof that can elicit an anti-neuraminidase immune response. Further provided are methods of making and using the compositions disclosed herein. Specifically provided are methods of generating antibodies in a subject comprising administering to the subject an agent or composition taught herein. Also provided are methods of reducing or preventing nasal carriage or pneumococcal infection in a subject comprising administering to the subject a composition taught herein.

RETINOIDS AND USE THEREOF

The present invention provides new retinoid compounds and uses of the compounds in humans and animals for non-neoplastic dermal or inflammatory conditions or disorders. 4. The method of wherein the skin condition or disorder is selected from dermatological afflictions associated with excessive skin sebum production claim 1 , and/or cell differentiation and/or proliferation disorders claim 1 , and/or keratinization disorders and/or skin pigmentation disorders claim 1 , and/or skin inflammatory disorders.5. The method of wherein the skin condition or disorder is selected from the dermatological afflictions associated photo-induced skin damage or chronological skin aging.6. The method of wherein the skin condition or disorder is selected from the group consisting of acne vulgaris claim 4 , psoriasis claim 4 , actinic keratosis claim 4 , rosacea claim 4 , seborrheic dermatitis claim 4 , actinic lentigines claim 4 , eczema claim 4 , warts claim 4 , keratosis claim 4 , xerosis claim 4 , icthyosis claim 4 , lichen claim 4 , keratoderma claim 4 , folliculitis claim 4 , vitiligo and melasma.7. The method of wherein the skin condition is acne vulgaris.8. The method of wherein the skin condition is psoriasis.9. The method of wherein the skin condition is actinic keratosis.13. The composition of claim 10 , wherein the composition is formulated for topical administration.14. The composition of comprising at least two active ingredients.15. The composition of claim 14 , wherein at least one of the active ingredients is a sunscreen.16. The composition of comprising at least two retinoid compounds.17. The composition of comprising at least one non-retinoid compound.18. The composition of further comprising a non-retinoid compound.19. The composition of wherein said compound is provided at a concentration of about 0.01% to about 10% (w/w).20. The composition of wherein the concentration of the compound is about 0.1% to about 3.0% (w/w).21. The composition of claim 10 , wherein the ...

Methods and Compositions for Pseudoinfectious Alphaviruses

The present invention provides pseudoinfectious alphavirus particles and methods of making them and using them to produce an immune response to an alphavirus in a subject. 1. A pseudoinfectious alphavirus particle comprising a genome encoding:a) alphavirus nonstructural proteins nsP1-4,b) alphavirus structural proteins E2 and E1, andc) an alphavirus capsid protein mutated at one or more positively charged amino acids in the RNA binding domain, whereby binding of RNA to the capsid protein is substantially diminished or eliminated, thereby resulting in production of a noninfectious subviral particle lacking genetic material.2. A noninfectious subviral particle , comprising alphavirus structural proteins E2 and E1 and an alphavirus capsid protein mutated at one or more positively charged amino acids in the RNA binding domain , and lacking genetic material ,5. The pseudoinfectious alphavirus particle of claim 1 , wherein the capsid protein comprises a mutation selected from the group consisting of:1) 8160;2) R23A;3) R24N;4) R29G;5) R53N;6) R54N;7) K64S;8) K65N;9) K67G;10) K68N;11) K73A;12) K75N;13) K81S;14) K82G;15) K83N;16) K84N;17) K88G;18) K89G;19) K9ON;20) K92S;21) K99N;22) K105G;23) K106N;24) K107S;25) K110A;26) K111S; and27) any combination of (1) through (26) above.6. A population of alphavirus particles claim 1 , comprising the pseudoinfectious alphavirus particles of .7. A population of subviral particles claim 2 , comprising the noninfectious subviral particles of .8. The pseudoinfectious alphavirus particle of claim 1 , wherein the capsid protein is from an alphavirus selected from the group consisting of VEEV claim 1 , WEEV claim 1 , EEEV claim 1 , Chikungunya virus claim 1 , o'nyong-nyong virus claim 1 , Ross River virus and Barmah Forest virus.9. A pharmaceutical composition comprising the pseudoinfectious alphavirus particle of in a pharmaceutically acceptable carrier claim 1 ,10. A method of eliciting or enhancing an immune response to an alphavirus in a ...

Methods and Compositions for Alphavirus Replicons

The present invention provides alphavirus replicons and methods of their use in producing heterologous protein.

Polymorphisms in the FCGR2B Promoter and Uses Thereof

The invention relates to the FCGR2B gene and its promoter. In particular, the invention relates to FCGR2B promoters with specific nucleotides at polymorphic sites. Characterization of the nucleotides at polymorphic sites is useful for characterizing the gene and the protein and is useful for determining predisposition or susceptibility to certain diseases and infections in a subject or a population of subjects. Such characterization of the gene or protein is also useful for determining immunoresponsiveness or responsiveness to therapeutic agents in a subject or population of subjects. Thus, disclosed herein are a variety of related nucleic acids, methods and tools. 1. A nucleic acid comprising an FCGR2B promoter comprising SEQ ID NO:1 , wherein SEQ ID NO: 1 comprises one or more polymorphic sites.2. The nucleic acid of claim 1 , wherein one or more polymorphic sites are selected from the group consisting of a polymorphism at position −120 claim 1 , a polymorphism at position −386 claim 1 , a polymorphism at position −893 claim 1 , a polymorphism at position −1153 claim 1 , a polymorphism at position −1223 claim 1 , a polymorphism as position −1443 claim 1 , a polymorphism at position −1614 claim 1 , a polymorphism at position −1700 claim 1 , a polymorphism at position −1867 and a polymorphism at position −1868.3. A method of characterizing a FCGR2B gene comprising the step of identifying nucleotides at one or more polymorphic sites in the promoter nucleic acid claim 1 , the identified nucleotides indicating the character of the polymorphic FCGR2B gene.4. The method of claim 3 , wherein the polymorphic site is at position −386 of the promoter.5. The method of claim 4 , wherein the polymorphic site at position −386 contains a C or a G at this position.6. The method of claim 3 , wherein the polymorphic site is at position −120 of the promoter.7. The method of claim 6 , wherein the polymorphic site at position −120 contains an A or a T at this position.8. The method of ...

Methods and Compositions for Cytomegalovirus IL-10 Protein

The present invention provides methods and compositions for treating and/or preventing a cytomegalovirus infection in a subject, comprising administering to the subject an effective amount of a cytomegalovirus IL-10 protein modified to have reduced functional activity while retaining immunogenicity. The present invention further provides nucleic acid molecules encoding a cytomegalovirus IL-10 protein or fragment thereof of this invention as well as vectors comprising such nucleic acids. Also provided herein are neutralizing antibodies that specifically bind cmvIL-10. 1. A cytomegalovirus IL-10 protein , wherein the protein comprises a mutation in one or more amino acids , wherein the mutation(s) result in a phenotype of reduced binding to an interleukin-10 (IL-10) receptor protein and reduced functional activity as compared to a cytomegalovirus IL-10 protein lacking said mutation(s).2. The cytomegalovirus IL-10 protein of claim 1 , wherein the mutation(s) further result in a phenotype of retained immunogenicity as compared to a cytomegalovirus IL-10 protein lacking said mutation(s).3. The cytomegalovirus IL-10 protein of claim 1 , wherein the mutation is in one or more amino acids located from position 39 through position 78 and/or from position 155 through position 176 in the amino acid sequence of SEQ ID NO:3.4. The cytomegalovirus IL-10 protein of claim 1 , wherein the mutation is in one or more amino acids located from position 42 through position 85 and/or position 169 through position 189 in the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2.5. The cytomegalovirus IL-10 protein of claim 3 , comprising a mutation at K58 claim 3 , Q62 claim 3 , E160 and/or D162 of SEQ ID NO:3 claim 3 , in any combination.6. The cytomegalovirus IL-10 protein of claim 4 , comprising a mutation at R63 claim 4 , Q67 claim 4 , E174 and/or D176 of SEQ ID NO:1 or SEQ ID NO:2 claim 4 , in any combination.7. The cytomegalovirus IL-10 protein of claim 6 , comprising a Q67R mutation ...

Hypdh inhibitors and methods of use for the treatment of kidney stones

Provided herein are compounds of Formula (I), Formula (II), and Formula (III), and compositions comprising the same, as well as methods of use thereof for controlling or inhibiting the formation of calcium oxalate kidney stones, inhibiting the production of glyoxylate and/or oxalate, and/or inhibiting hydroxyproline dehydrogenase (HYPDH).

APOLIPOPROTEIN MIMETICS AND USES THEREOF

The disclosure provides dosing regimens and methods for treating atherosclerosis with an effective amount of Apo E mimetic to provide sustained therapeutic effects even after withdrawal of the treatment. The dosing regimens and methods involve a treatment cycle followed by a rest phase wherein a subject is administered an effective amount of an Apo E mimetic during the treatment cycle and no Apo E mimetic during the rest phase. The treatment cycle and the rest phase can vary. 1. A dosing regimen comprising at least one treatment cycle followed by a rest phase , wherein the treatment cycle comprises administering an effective amount of an Apo E mimetic to allow for a sustained therapeutic effect after withdrawal of the Apo E mimetic , wherein the Apo E mimetic is not administered during the rest phase.2. The dosing regimen of claim 1 , wherein the treatment cycle comprises administration of an effective amount of the Apo E mimetic once a week for three months.3. The dosing regimen of claim 1 , wherein the treatment cycle comprises administration of an effective amount of the Apo E mimetic once every two weeks for up to 12 weeks.4. The dosing regimen of claim 1 , wherein the dosing regimen further comprises a second treatment cycle after the rest phase.5. A method of treating atherosclerosis comprising administering to a subject an effective amount of an Apo E mimetic for at least one treatment cycle claim 1 , wherein the treatment cycle comprises administering an effective amount of an Apo E mimetic to allow for a sustained therapeutic effect after withdrawal of the Apo E mimetic claim 1 , wherein the treatment cycle is followed by a rest phase claim 1 , wherein Apo E mimetic is not administered during the rest phase.6. The method of claim 5 , wherein the rest phase is at least four weeks.7. The method of claim 5 , further comprising a second treatment cycle after the rest phase.8. The method of claim 7 , wherein the second treatment cycle is administered after a ...

Bacterial colicin-immunity protein protein purification system

Provided herein are compositions and methods for protein purification.

Purine nucleoside phosphorylase as enzymatic activator of nucleoside prodrugs

A process for inhibiting a mammalian cancerous cell or virally infected cell includes providing a Trichomonas vaginalis purine nucleoside phosphorylase enzyme or a tail mutant purine nucleoside phosphorylase enzyme in proximity to the mammalian cancerous cell or the virally infected cell and exposing the enzyme to a purine nucleoside phosphorylase enzyme cleavable substrate to yield a cytotoxic purine analog. The process includes introducing to the cell a vector containing the phosphorylase enzyme, or a DNA sequence coding for the same and delivering to the cell an effective amount of the substrate such as 9-(β-D-arabinofuranosyl)-2-fluoroadenine (F-araA).

COLOCALIZED DETECTION OF RETINAL PERFUSION AND OPTIC NERVE HEAD DEFORMATIONS

Relationships between morphological changes to an eye due to intraocular pressure changes and blood perfusion changes in the retina are determined by colocalizing retinal perfusion data and optic nerve head (ONH) mechanical deformation data. Perfusion changes from intraocular pressure (IOP) changes are determined by colocalizing retinal perfusion data with ONH mechanical deformation data. Optical coherence tomography-angiography (OCT-A) can be used to generate both retinal perfusion data and mechanical deformation data for an imaged volume. A three-dimensional model (e.g., connectivity map or connectivity model) of the vasculature can be generated from the OCT-A imaging data and used to predict changes in blood perfusion in various areas of the retina due to IOP-induced mechanical deformations. 1. A method , comprising:capturing imaging data of a retina of an eye, wherein the imaging data includes first topographical data and second topographical data, wherein the second topographical data is captured subsequent the first topographical data, and wherein the imaging data is associated with an imaged volume of the eye;identifying vasculature using the imaging data, wherein identifying vasculature includes comparing the first topographical data to the second topographical data;generating a connectivity model of vasculature of the retina using the identified vasculature; andcalculating deformation data of at least a portion of the imaged volume of the eye, wherein calculating deformation data includes using at least one of the imaging data and additional imaging data associated with the imaged volume of the eye.2. The method of claim 1 , further comprising capturing additional imaging data of the retina of the eye claim 1 , wherein an intraocular pressure of the eye when capturing the additional imaging data is different than when capturing the imaging data claim 1 , and wherein calculating deformation data includes using the imaging data and the additional imaging data ...

Vaccine and drug delivery by topical application of vectors and vector extracts

Disclosed and claimed is a method of non-invasive immunization in an animal and/or a method of inducing a systemic immune response or systemic therapeutic response to a gene product. The skin of the animal is contacted with a non-replicative vector chosen from the group of bacterium, virus, and fungus, wherein the vector comprises and expresses a nucleic acid molecule encoding the gene product, in an amount effective to induce the response. 1B. anthracis. A non-invasive method of inducing a protective immune response to in a mammal , comprising:{'i': B. anthracis', 'B. anthracis, 'administering to the mammal a non-replicating adenoviral vector that contains and expresses one or more protective antigen, one or more lethal factor, or a combination thereof, to a mucosal region of the mammal.'}2. The method of claim 1 , wherein the adenoviral vector is defective in its E1 and/or E3 and/or E4 regions.3. The method of claim 1 , wherein the adenoviral vector is defective in its E1/E3 region.4. The method of claim 1 , wherein the adenoviral vector is defective in all adenoviral genes.5. The method of claim 1 , wherein administering to the mucosal region comprises intranasal or oral administration.6. The method of claim 1 , further comprising administering an adjuvant.7. A non-invasive method of inducing a protective immune response to influenza in an animal claim 1 , comprising:administering, to the animal a non-replicating adenoviral vector that contains and expresses one or more influenza antigens, one or more influenza epitopes, or a combination thereof, to a mucosal region of the animal.8. The method of claim 7 , wherein the adenoviral vector is defective in its E1 and/or E3 and/or E4 regions.9. The method of claim 7 , wherein the adenoviral vector is defective in its E1/E3 region.10. The method of claim 7 , wherein the adenoviral vector is defective in all adenoviral genes.11. The method of claim 7 , wherein administering to the mucosal region comprises intranasal or ...

Method for detecting an open-phase condition of a transformer

A method for detecting an open-phase condition of a transformer having a grounded-wye high voltage side connection including monitoring current flowing in a neutral connection on the high voltage side of the transformer in real time by voltage relaying and current relaying to identify an open phase condition signature in a signal capable of characterizing change of current magnitude. A current signal may be injected onto the neutral terminal and the zero-sequence mode of the transformer monitored to detect an open-phase condition indicated by an increase in network impedance and decrease or elimination of the injection current.

MSP NANOPORES AND USES THEREOF

Provided herein are mutant single-chain porin (Msp) and uses thereof. 1Mycobacterium smegmatis. A nucleic acid sequence encoding a mutant single-chain porin (Msp) , wherein the nucleic acid sequence comprises:(a) a first and second nucleotide sequence, wherein the first nucleotide sequence encodes a first Msp monomer sequence and the second nucleotide sequence encodes a second Msp monomer sequence; and(b) a third nucleotide sequence encoding an amino acid linker sequence,wherein at least one of the first and second Msp monomer sequences is a mutant Msp monomer sequence comprising a P97F mutation.2. The nucleic acid of claim 1 , wherein the mutant Msp monomer sequence further comprises a mutation at one or more amino acid positions D118 claim 1 , D134 or E139.3. The nucleic acid of claim 1 , wherein the mutant Msp monomer sequence further comprises (i) a mutation at position 93 claim 1 , and/or (ii) a mutation at position 90 claim 1 , position 91 or both positions 90 and 91.4. The nucleic acid of claim 3 , wherein the mutant Msp monomer sequence comprises a D90N claim 3 , a D91N and a D93N mutation.5. The nucleic acid of claim 1 , wherein the mutant Msp monomer sequence comprises a D90N mutation claim 1 , a D91N mutation claim 1 , a D93N mutation claim 1 , a P97F mutation claim 1 , a D118 mutation claim 1 , a D134 mutation and a E139 mutation.6. The nucleic acid of claim 1 , wherein the second Msp monomer sequence is selected from the group consisting of a wild-type MspA monomer claim 1 , a mutant MspA monomer claim 1 , a wild-type MspA paralog or homolog monomer and a mutant MspA paralog or homolog monomer.7. A nucleic acid sequence encoding a mutant single-chain Msp claim 1 , wherein the nucleic acid sequence comprises:(a) a first, second, third, fourth, fifth, sixth, seventh, and eighth nucleotide sequence or any subset thereof, wherein the first, second, third, fourth, fifth, sixth, seventh, and eighth nucleotide sequences encode a first, second, third, fourth, ...

ANONYMOUS VERIFICATION PROCESS FOR EXPOSURE NOTIFICATION IN MOBILE APPLICATIONS

The present disclosure relates exposure notification, and in particular to techniques for verification of positive test results from public health authorities where individuals submit notice using public health approved mobile applications for exposure notification and/or contact tracing. When an individual attempts to submit a positive test result notification in a mobile application, the associated device's mobile number will be requested. This mobile number will then be sent a verification code to be entered in the application. At this point, these codes shall be stored digitally in escrow. A regular data feed from a health authority shall be provided that shall include an agreed encryption (irreversibly encrypted or reversibly encrypted) of the mobile numbers associated with any reported test. Any results submitted in the application that have a matching encryption of the mobile numbers shall be released from the escrow for subsequent notification. 1. A method comprising:receiving, by a server computer, a user identifier from a mobile application on a mobile device operated by a user, wherein the user identifier is provided by the user to the mobile application in response to a user receiving a test result for an infectious disease;applying, by the server computer, a first encryption function to the user identifier to generate a first encrypted output of the use identifier;storing, by the server computer, the first encrypted output of the use identifier in a data storage device;transmitting, by the server computer, a user authentication request to a device of the user using the user identifier;receiving, by the server computer, a user authentication response and contact data from the mobile application, wherein the contact data is collected by the mobile application during contact interactions between the mobile device and one or more other mobile devices;validating, by the server computer, the user authentication response based on the user authentication ...

NATURAL SAPONIN-BASED SYNTHETIC IMMUNOADJUVANTS

The present disclosure encompasses QS-21-based structurally-defined adjuvants to address the need for stronger, safer, and easier-to-access adjuvants. The new compositions can provide tools for addressing long-standing mechanistic questions concerning saponin immune-potentiation through structure-activity-relationship (SAR) studies. Most advantageously, the compounds of the disclosure may be formulated into pharmaceutically acceptable compositions, including vaccines that may be delivered to a subject human or animal subject. The compounds can then act as, for example, an adjuvant to augment an immunological response to a vaccine immunogen. 2. The QS-21 derivative according to claim 1 , wherein Ris H claim 1 , apiose or xylose.3. The QS-21 derivative according to claim 1 , wherein Ris H or glucose.7. A pharmaceutically acceptable composition comprising at least one of the compounds according to .8. The pharmaceutically composition according to claim 7 , wherein the composition is formulated as a vaccine. This application claims priority to U.S. Provisional Patent Application Ser. No. 61/614,744 entitled “NATURAL SAPONIN-BASED SYNTHETIC IMMUNOADJUVANTS” and filed Mar. 23 2012, the entirety of which is hereby incorporated by reference.This invention was made with government support under NIH Grant No. R03AI099407 awarded by the U.S. National Institutes of Health of the United States government. The government has certain rights in the invention.The present disclosure is generally related to novel synthetic saponin-based immunoadjuvants.Vaccination is one of the most successful medical practices since its invention 200 years ago, and has been successful in eradicating many severe infectious diseases (Plotkin S A (2005) 11, S5-S11; Mortellaro & Ricciardi-Castagnoli (2011) 89, 332-339). However, the current state of vaccine development is not adequate to meet some emerging, re-emerging or persistent challenges. Infectious diseases are still responsible for one-fifth of ...

Inhaled respiratory probiotics for lung diseases of infancy, childhood and adulthood

The respiratory microbiomes of neonates and those with bronchopulmonary disease have been characterized. Provided are probiotic compositions, which can include at least one living bacterial strain and at least one killed bacterial strain, that can comprise a combination of Lactobacilli species, 5 that when delivered to the bronchi or lungs of a patient can provide a reduction in the symptoms of a bronchopulmonary disease.

Chimeric chlorotoxin receptors

The invention provides chimeric antigen receptor(s) (CAR(s)) that comprise a fusion protein of CTX or any functional variant thereof or a CTX-like peptide or any functional variant thereof as the extracellular antigen recognition moiety of the CAR. CAR(s) comprising CTX, a CTX-like peptide or functional variants of the foregoing are collectively referred to herein as “CTX-CAR(s).” Such CTX-CAR(s) may further comprise additional moieties or domains in the extracellular domain, a transmembrane domain and at least one intracellular! signaling domain. Such CTX-CAR(s) may be expressed in a host cell, such as, but not limited to, an immune effector cell. The present invention also provides methods of treatment (such as, for example, methods for treating cancer) by providing to the patient in need thereof immune effector cells that are engineered to express a CTX-CAR described herein.

IMMUNOTHERAPY FOR THE TREATMENT AND PREVENTION OF INFLAMMATORY BOWEL DISEASE

Provided herein are methods and compositions for treating and preventing inflammatory bowel disease. 1. A method for treating or preventing inflammatory bowel disease comprising administering to a subject having inflammatory bowel disease or at risk of developing inflammatory bowel diseasea) an effective amount of a polypeptide comprising one or more flagellin T-cell receptor (TCR) epitopes; andb) an effective amount of an agent that reduces flagellin antigen-specific memory T cells and/or increases regulatory T cells in the subject.2. A method for delaying or reducing the intensity of a relapse or flare of an inflammatory bowel disease in a subject comprising administering to a subjecta) an effective amount of a polypeptide comprising one or more flagellin T-cell receptor (TCR) epitopes; andb) an effective amount of an agent that increases regulatory T cells in the subject.3. The method of claim 1 , wherein the agent that reduces flagellin antigen-specific memory T cells and/or increases regulatory T cells in the subject is selected from the group consisting of a mutant IL-2 polypeptide claim 1 , a metabolic inhibitor and a combination thereof.4. The method of claim 1 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.5. (canceled)6. (canceled)7. The method of claim 1 , wherein the one or more TCR epitopes activate flagellin-specific CD4 T cells.8. The method of claim 3 , wherein the metabolic inhibitor inactivates flagellin-specific activated T cells.9. The method of claim 3 , wherein the metabolic inhibitor is an FK506-binding protein 12-rapamycin-associated protein 1 (mTOR) inhibitor.10. The method of claim 9 , wherein the mTOR inhibitor is rapamycin.11. The method of claim 1 , further comprising administering a protein kinase AMP-activated catalytic subunit alpha 1 (AMPK) activator to the subject.12. The method of claim 11 , wherein the AMPK activator is metformin.13. The method of claim 1 , wherein an increase in Treg cells and/ ...

BIS-AROMATIC ANTICANCER AGENTS

Treatment of cancer includes administering a compound of formula (I) to a subject. In particular, treatment of colorectal cancer is described. 124-. (canceled)28. The method of claim 25 , wherein the subject is a human.29. The method of claim 25 , wherein the cancer is selected from: bladder cancer claim 25 , brain cancer claim 25 , breast cancer claim 25 , colorectal cancer claim 25 , cervical cancer claim 25 , gastrointestinal cancer claim 25 , genitourinary cancer claim 25 , head and neck cancer claim 25 , lung cancer claim 25 , ovarian cancer claim 25 , pancreatic cancer claim 25 , prostate cancer claim 25 , renal cancer claim 25 , skin cancer claim 25 , and testicular cancer.30. The method of claim 29 , wherein the cancer is colorectal cancer.31. The method of claim 29 , wherein the cancer is pancreatic cancer.32. The method of claim 29 , wherein the cancer is prostate cancer.35. The composition of claim 34 , wherein the carrier claim 34 , excipient claim 34 , or diluent is a physiologically acceptable saline solution.36. The composition of claim 34 , wherein the composition further comprises a pain relief agent claim 34 , an antinausea agent claim 34 , or an additional anticancer agent. This application claims priority to U.S. Provisional Application No. 61/043,845, filed Apr. 10, 2008, incorporated by reference in its entirety herein.This disclosure relates to the treatment of cancers, for example, colorectal cancer, by methods that include administration of a bis-aromatic compound. In particular, methods of treating colorectal, pancreatic, and prostate cancers are described.Cancer is now the second leading cause of death in the United States. In 1995, cancer accounted for 23.3% of all deaths in the United States. See, e.g., U.S. Dept. of Health and Human Services, National Center for Health Statistics, Health United States 1996-97 and 117 (1997).Cancer is now primarily treated with one or a combination of three types of therapies: surgery; radiation; and ...

Mycobacterial Disease Detection, Treatment, and Drug Discovery

Methods for detecting and treating -related diseases including reducing Mycobacterial virulence, reducing RV3133c dimerization, and treating a subject with a Mycobacterial infection using identified compounds are disclosed. Examples of compounds useful in the treatment of -related diseases include N-(4-[(acetylamino)sulfonyl]phenyl)-3-phenylpropanamide; 1-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-(2-imino-3-methyl-2,3-dihydro-1H-benzimidazol-1yl)ethanone hydrochloride; and 1-(1,3-benzoxazol-2-yl)-3-({4-[(2-hydroxyethyl)sulfonyl]phenyl}amino)acrylaldehyde. Further disclosed are methods for identifying agents that interact with a polypeptide in a cell. 166.-. (canceled)68MycobacteriumMycobacterium. The method of claim 67 , wherein contacting the with the compound comprises administering the compound to a subject with a infection.69. The method of claim 67 , wherein X is substituted with a moiety selected from the group consisting of phenyl claim 67 , carboxyl claim 67 , benzooxazole claim 67 , and 1-methyl-1 claim 67 ,3-dihydro-benzoimidazol-2-ylideneamine.70. The method of claim 67 , wherein Y is substituted with a hydroxyl moiety.71. The method of claim 67 , wherein Z is substituted with a carbonyl moiety.74. The method of claim 67 , wherein the compound is selected from the group consisting of N-(4-[(acetylamino)sulfonyl]phenyl)-3-phenylpropanamide; 1-(3 claim 67 ,5-di-tert-butyl-4-hydroxyphenyl)-2-(2-imino-3-methyl-2 claim 67 ,3-dihydro-1H-benzimidazol-1 yl)ethanone hydrochloride; and 1-(1 claim 67 ,3-benzoxazol-2-yl)-3-({4-[(2-hydroxyethyl)sulfonyl]phenyl}amino)acrylaldehyde; and pharmaceutically acceptable salts and derivatives thereof.76Mycobacterium. A method for detecting biomolecular interactions in comprising:(a) combining a first fusion protein and a second fusion protein, wherein the first fusion protein comprises a first fragment of an enzyme reporter molecule and a first Mycobacterial polypeptide, wherein the second fusion protein comprises a second ...

METHODS AND COMPOSITIONS FOR DIAGNOSIS AND TREATMENT OF MENINGITIS

The present invention provides a method of identifying meningitis as either bacterial meningitis or aseptic meningitis in a subject, comprising: a) measuring the amount of complement C3, complement factor B, complement membrane attack complex (MAC) protein, complement C5b, complement C6, complement C7, complement C8, and/or complement C9 in a cerebrospinal fluid (CSF) sample obtained from the subject; and b) comparing the amount of complement C3, complement factor B, complement MAC protein, complement C5b, complement C6, complement C7, complement C8, and/or complement C9 measured in (a) with the amount of complement C3, complement factor B, complement MAC protein, complement C5b, complement C6, complement C7, complement C8, and/or complement C9 measured in a control sample, wherein an amount of complement C3, complement factor B, complement MAC protein, complement C5b, complement C6, complement C7, complement C8, and/or complement C9 measured in (a) that is greater than the amount of complement C3, complement factor B, complement MAC protein, complement C5b, complement C6, complement C7, complement C8, and/or complement C9 measured in the control sample identifies the meningitis in the subject as bacterial meningitis. 28-. (canceled)9. A method of guiding a treatment for bacterial meningitis in a subject in need thereof , comprising:a) measuring the amount of complement C3, complement factor B, complement MAC, complement C5b, complement C6, complement C7, complement C8, and/or complement C9 in a cerebrospinal fluid (CSF) sample obtained from the subject prior to administration of the treatment for bacterial meningitis;b) administering the treatment to the subject;c) measuring the amount of complement C3, complement factor B, complement MAC, complement C5b, complement C6, complement C7, complement C8, and/or complement C9 in a cerebrospinal fluid (CSF) sample obtained from the subject at one or more time points after (b);d) guiding the treatment of the subject for ...

Methods and compositions for il10 signaling antagonism

This invention relates to fusion proteins, nucleic acid molecules, DNA constructs, and pharmaceutical compositions comprising the same, and methods of their use in IL10 antagonism.

SUMOylation Assay and Related Reagents

Provided herein and methods and kits for identifying inhibitors of SUMOylation. The provided methods include contacting a candidate agent with (i) a SUMO-conjugating peptide comprising an N-terminal linker and a detectable tag, and (ii) a SUMO comprising a metal complex, under conditions that allow binding between the SUMO-conjugating peptide and the SUMO, and detecting the detectable tag thereby determining the level of binding between the SUMO-conjugating peptide and SUMO. A reduced level of binding as compared to the level of binding in the absence of the candidate agent indicating the agent inhibits SUMOylation. 1. A method of identifying an inhibitor of SUMOylation comprising:(a) contacting a candidate agent with (i) a SUMO-conjugating peptide comprising an N-terminal linker and a detectable tag, and (ii) a SUMO comprising a metal complex, under conditions that allow binding between the SUMO-conjugating peptide and the SUMO; and(b) detecting the detectable tag thereby determining the level of binding between the SUMO-conjugating peptide and SUMO;a reduced level of binding as compared to the level of binding in the absence of the candidate agent indicating the agent inhibits SUMOylation.2. The method of claim 1 , wherein the detectable tag is a fluorescent molecule.3. The method of claim 1 , wherein the detectable tag is biotin.4. The method of claim 3 , wherein the detecting comprises adding streptavidin labeled with a fluorescent molecule.5. The method of claim 1 , wherein the contacting further comprises a SUMO-conjugating enzyme.6. The method of claim 1 , wherein the SUMO-conjugating enzyme is selected from the group consisting of an E1 enzyme claim 1 , an E2 enzyme claim 1 , an E3 enzyme or a combination thereof.7. The method of claim 1 , wherein the metal complex is a metal chelate or a metal cryptate.8. The method of claim 7 , wherein the metal is a lanthanide metal.9. The method of claim 8 , wherein the lanthanide metal is europium or terbium.10. The ...

Latent human immunodeficiency virus reactivation

Provided herein are methods or reactivating a latent Human Immunodeficiency Virus (HIV) infection in a cell. The methods comprise modulating a level of NF-κB activity in the cell by contacting the cell with an agent that produces a transient first increase in the level of NF-κB activity without a second delayed increase in NF-κB activity. Optionally, a second agent is used to prime the reactivation. Also provided herein is an isolated Massilia bacterium or population thereof capable of producing a HIV-1 reactivating factor (HRF). Also provided are methods of culturing the Massilia bacteria. Further provided are methods of reactivating a latent Human Immunodeficiency Virus-1 (HIV-1) infection in a subject comprising administering to the subject a HIV-1 reactivating factor produced by Massilia bacteria, optionally with a priming agent.

NOVEL REXINOID COMPOUNDS AND METHODS OF USING REXINOID COMPOUNDS FOR TREATING METABOLIC DISORDERS AND CANCER

Novel rexinoid compounds are provided herein. Also provided herein are methods of using the compounds to treat disorders, such as metabolic disorders, diabetes, insulin resistance, glucose intolerance, obesity, steatosis, inflammation, and/or cancer. 10. (canceled)1218-. (canceled)19. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.20. A method of treating or preventing a metabolic disorder in a subject claim 1 , comprising administering to a subject an effective amount of a compound of .21. The method of claim 20 , wherein administering the compound provides a glucose-lowering effect claim 20 , an insulin-sensitizing effect claim 20 , or a plasma triglyceride lowering effect.22. (canceled)23. (canceled)24. A method of treating or preventing insulin resistance claim 1 , glucose intolerance claim 1 , obesity claim 1 , steatosis or inflammation in a subject claim 1 , comprising administrating to a subject in thereof an effective amount of a compound of .25. The method of claim 20 , wherein the subject is a rodent or human claim 20 , obese claim 20 , morbidly obese claim 20 , pre-diabetic claim 20 , or diabetic.2629-. (canceled)30. The method of claim 20 , wherein the compound is administered orally claim 20 , topically claim 20 , intranasally claim 20 , intravenously claim 20 , subcutaneously claim 20 , intradermally claim 20 , transdermally intramucosally intramuscularly claim 20 , by inhalation spray claim 20 , rectally claim 20 , nasally claim 20 , sublingually claim 20 , buccally claim 20 , vaginally or via an implanted reservoir.31. (canceled)32. A method of treating or preventing cancer in a subject claim 1 , comprising administering to a subject an effective amount of a compound of .3336-. (canceled)37. A kit for treating a metabolic disorder claim 1 , insulin resistance claim 1 , glucose intolerance claim 1 , obesity claim 1 , steatosis claim 1 , inflammation claim 1 , or cancer claim 1 , wherein the ...

METHODS FOR MAKING RETINOIDS AND USES THEREOF

Described herein are methods for making retinoids. Also described herein are retinoids and methods of use thereof. 181-. (canceled)83. The pharmaceutical composition according to claim 82 , wherein the compound and the carrier are admixed.84. The pharmaceutical composition according to claim 82 , wherein the carrier is a solution.85. The pharmaceutical composition according to claim 84 , wherein the carrier is sterile water claim 84 , saline claim 84 , or a buffered solution at physiological pH.86. The pharmaceutical composition according to claim 82 , wherein the carrier is a thickener claim 82 , a diluent claim 82 , a buffer claim 82 , a preservative claim 82 , or a surface active agent.87. The pharmaceutical composition according to claim 82 , further comprising an additional active agent.88. The pharmaceutical composition according to claim 87 , wherein the additional active agent is an antimicrobial agent claim 87 , an anti-inflammatory agent claim 87 , or an anesthetic.89. The pharmaceutical composition according to claim 82 , wherein the composition is formulated for topical administration.90. The pharmaceutical composition according to claim 89 , wherein the topical administration is ophthalmically claim 89 , vaginally claim 89 , rectally claim 89 , intranasally claim 89 , or applied to the skin.91. The pharmaceutical composition according to claim 90 , wherein the topical administration is applied to the skin.92. The pharmaceutical composition according to claim 82 , wherein the composition is an aqueous or non-aqueous solution claim 82 , suspension claim 82 , or emulsion.93. The pharmaceutical composition according to claim 89 , wherein the formulation is an ointment claim 89 , a lotion claim 89 , a cream claim 89 , a gel claim 89 , a drop claim 89 , a suppository claim 89 , a spray claim 89 , a liquid claim 89 , or a powder. This application claims priority to U.S. Provisional Application No. 60/604,089, filed Aug. 24, 2004, the entire disclosure of which ...

MSP NANOPORES AND USES THEREOF

Provided herein are mutant single-chain porin (Msp) and uses thereof. 1Mycobacterium smegmatis. A nucleic acid encoding a mutant porin (Msp) monomer , wherein the Msp monomer comprises a mutation at one or more of the following positions: I68 , S73 , S116 , P123 or V128 , and wherein the mutant Msp monomer does not comprise a S73C mutation.2Mycobacterium smegmatis. A nucleic acid sequence encoding a mutant single-chain porin (Msp) , wherein the nucleic acid sequence comprises:(a) a first and second nucleotide sequence, wherein the first nucleotide sequence encodes a first Msp monomer sequence and the second nucleotide sequence encodes a second Msp monomer sequence; and(b) a third, fourth, fifth, sixth, seventh, and eighth nucleotide sequence or any subset thereof, wherein the third, fourth, fifth, sixth, seventh, and eighth nucleotide sequences encode a third, fourth, fifth, sixth, seventh, and eighth Msp monomer sequence, respectively, wherein the first, second, third, fourth, fifth, sixth, seventh and eighth nucleotide sequence or any subset thereof are arranged consecutively in the nucleic acid; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(c) at least one ninth nucleotide sequence encoding an amino acid linker sequence, wherein the ninth nucleotide sequence is positioned between any two consecutive nucleotide sequences encoding Msp monomer sequences, wherein at least one of the first and second Msp monomer sequences is the mutant Msp monomer sequence of .'}3. The nucleic acid sequence of claim 2 , wherein at least one of the first and second Msp monomer sequence further comprises:(i) a mutation at one or more amino acid positions D118, D134 or E139;(ii) a mutation at position 93;(iii) and/or (iii) a mutation at position 90, position 91 or both positions 90 and 91.4. The nucleic acid sequence of claim 3 , wherein the amino acid at position 91 or the amino acid at position 90 is substituted with arginine claim 3 , lysine claim 3 , histidine claim 3 , ...

Systems and methods for facilitating opportunistic screening for cardiomegaly

A computer-implemented method for facilitating opportunistic screening for cardiomegaly includes obtaining a set of computed tomography (CT) images. The set of CT images captures at least a portion of a heart of a patient, and the set of CT images is captured for a purpose independent of assessing cardiomegaly. The method further includes using the set of CT images as an input to an artificial intelligence (AI) module configured to determine a heart measurement based on CT image set input. The method also includes obtaining heart measurement output generated by the AI module and, based on the heart measurement output, classifying the patient into one of a plurality of risk levels for cardiomegaly. The classification is operable to trigger additional action based on the corresponding risk level for the patient.

Dipeptide analogs as tgf-beta inhibitors

The present disclosure is concerned with dipeptide analogs that are capable of inhibiting TGF-β and methods of treating cancers such as, for example, multiple myeloma and a hematologic malignancy, methods for immunotherapy, and methods of treating fibrotic conditions using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Pneumococcal serotypes

Disclosed is a new and emerging serotype of Streptococcus pneumoniae designated serotype 6C, and assays and monoclonal antibodies useful in identifying same. Also disclosed is a novel pneumococcal polysaccharide with the repeating unit {→2) glucose 1 (1→3) glucose 2 (1→3) rhamnose (1→3) ribitol (5→phosphate}. This new serotype may be included in pneumococcal vaccines.

Method, Systems and Computer Program Products for Medical Brian Imaging Analysis

A method for analyzing brain images includes receiving a plurality of three-dimensional image datasets comprising a plurality of voxels for a corresponding plurality of subjects; dividing the plurality of three-dimensional image datasets into at least a first and a second group; dividing the first group into A 1 to A n subgroups; dividing the second group into B 1 to B n subgroups; determining statistical individual variability between datasets selected from the A 1 to A n subgroups and the B 1 to B n subgroups; determining statistical individual variability between datasets in the first and second groups responsive to the statistical individual variability between datasets selected from the plurality of three-dimensional image datasets in the A 1 to A n subgroups and the B 1 to B n subgroups; and for each of the first and second groups, generating a reliability map comprising a map of probabilities that a voxel in an image dataset of the respective first and second groups satisfies a predetermined statistical threshold.

Infectivity-enhanced conditionally-replicative adenovirus and uses thereof

A modified adenovirus capable of overcoming the problem of low level of coxsackie-adenovirus receptor (CAR) expression on tumor cells and methods of using such adenovirus are provided. The fiber protein of the adenovirus is modified by insertion or replacement so as to target the adenovirus to tumor cells, and the replication of the modified adenovirus is limited to tumor cells due to specific promoter control or mutations in E1a or E1b genes.

Enhancing coagulation or reducing fibrinolysis

Methods for controlling bleeding (e.g., enhancing coagulation and reducing fibrinolysis) in a subject are disclosed. The methods include selecting a subject in need of enhanced coagulation or reduced fibrinolysis, and administering to the subject a carbon monoxide releasing molecule (CORM). Examples of CORMs include tricarbonyldichlororuthenium (II) dimer, tricarbonylchloro-(glycinato)ruthenium (II), sodium boranocarbonate, dimanganese decacarbonyl, and iron pentacarbonyl. Further disclosed are compositions and methods for treating a subject in need of a blood product by administering to the subject a composition including a CORM and a blood product (e.g., cryoprecipitate or fresh frozen plasma).

Modulation of Cellular Migration

Methods, kits, and compositions are provided for addressing cancer through the interaction of bradykinin (BK) and the bradykinin-2-receptor (B2R). This interaction controls cellular invasion, as has been unexpectedly observed in glioma cells, A composition is provided for the treatment of cancer by disrupting this interaction using an inhibitor or BK or B2R that can. be administered to the subject. Diagnostic processes are provided, involving measuring levels of BK or B2R to determine the potential for cancer (or to determine the invasive potential of a given cancer). Modulators of BK. and B2R may be used to modulate cellular migration, both in vivo and in vitro. Potential modulators of cellular migration can be screened by measuring the effect of the potential modulator on BK or B2R, 1. A composition comprising a therapeutically effective amount of an inhibitor selected from the group consisting of inhibitor of bradykinin (BK) and an inhibitor of the bradykinin-2-receptor (B2R).2. (canceled)3. A method of modulating migration of a glial cell , said method comprising contacting the cell with a modulator selected from the group consisting of: a modulator of BK and a modulator of B2R.4. The method of claim 3 , wherein the modulator is an activator.5. The method of claim 3 , wherein the modulator is an inhibitor.6. The method of claim 5 , wherein the inhibitor is an inhibitor of BK.7. The method of claim 5 , wherein the inhibitor is an inhibitor of B2R.8. The method of claim 5 , wherein the inhibitor is a nucleic acid inhibitor claim 5 , an antibody claim 5 , or an antibody fragment.9. The method of wherein the inhibitor is not an inhibitor of the bradykinin-1-receptor.10. The method of wherein the inhibitor is selected from the group consisting of: bradyzide claim 7 , HOE-140 claim 7 , icatibant claim 7 , FR173657 claim 7 , FR193517 claim 7 , a tautomer of any of the foregoing claim 7 , and a pharmaceutically acceptable salt of any of the foregoing.11. The method of ...

METHOD OF ENHANCING SOMATIC CELL REPROGRAMMING WITH THE ACETYLLYSINE READER BRD3R

A method of generating an induced pluripotent stem cell (iPSC) comprises introducing to an animal somatic cell at least one nuclear reprogramming inducing factor and a BRD3R polypeptide or at least one nucleic acid expressing the at least one nuclear reprogramming factor and the BRD3R-related polypeptide in the recipient somatic cell, and culturing said cell to generate an induced pluripotent stem cell (iPSC). The introduction of the BRD3R-related polypeptide into the recipient somatic cell can increase the efficiency of inducing the generation of an iPSC by the at least one nuclear reprogramming inducing factor. 1. A method of generating an induced pluripotent stem cell (iPSC) , said method comprising the steps of:introducing to an animal somatic cell at least one nuclear reprogramming inducing factor and (ii) a BRD3R polypeptide having an amino acid sequence having at least 90% sequence similarity to the amino acid sequence according to SEQ ID NO: 47, or at least one nucleic acid expressing said at least one nuclear reprogramming factor and said BRD3R-related polypeptide in the recipient somatic cell; andgenerating a population of induced pluripotent stem cells (iPSCs) by culturing the recipient somatic cell under conditions that promote the proliferation of said cell.2. The method of claim 1 , wherein the amino acid sequence having at least 90% sequence similarity to the amino acid sequence according to SEQ ID NO: 47 is expressed from a recombinant expression vector comprising a nucleotide sequence encoding said amino acid sequence operably linked to a gene expression promoter.3. The method of claim 2 , wherein the expression vector is a lentivirus expression vector.4. The method of claim 1 , wherein the at least one nucleic acid encoding said at least one nuclear reprogramming factor is inserted in a recombinant expression vector and operably linked to a gene expression promoter.5. The method of claim 4 , wherein the expression vector is a lentivirus expression ...

MITOCHONDRIAL-NUCLEAR EXCHANGED CELLS, TISSUES, ORGANS AND ANIMALS

Provided herein are mitochondrial-nuclear exchanged cells and animals comprising mitochondrial DNA (mtDNA) from one subject and nuclear DNA (nDNA) from a different subject. Methods for producing a mitochondrial-nuclear exchanged animal and animals made by the methods are provided. Also provided are methods of screening for agents useful for treating a disease or disorder using mitochondrial-nuclear exchanged animals or cells, tissues or organs thereof. 1. A cell comprising mitochondrial DNA (mtDNA) from a subject susceptible to a disease or disorder and nuclear DNA (nDNA) from a subject that is not susceptible to the disease or disorder.2. The cell of claim 1 , wherein the nDNA is from a wild-type subject.3. The cell of claim 1 , wherein the nDNA is from a subject resistant to the disease or disorder.4. The cell of claim 1 , wherein the disease or disorder is selected from the group consisting of cancer claim 1 , cardiovascular disease claim 1 , diabetes claim 1 , neurological disorder claim 1 , aging claim 1 , metabolic disorder claim 1 , immune disorder claim 1 , obesity claim 1 , and musculoskeletal disorder.5. The cell of claim 1 , wherein the cell is an oocyte.6. The cell of claim 1 , wherein the cell is an embryonic cell.7. A zygote or an embryo comprising the cell of .8. The embryo of claim 7 , wherein the embryo is a pro-nuclear embryo.9. A chimeric animal comprising a plurality of cells of .10. The chimeric animal of claim 9 , wherein the animal further comprises a mutation in a gene associated with the disease or disorder.11. The chimeric animal of claim 10 , wherein the gene is not expressed or the protein expressed by the gene is non-functional.12. The chimeric animal of claim 9 , wherein the animal is a mouse comprising mtDNA from C57BL/6J mice and nDNA from C3H/HeN mice.13. The chimeric animal of claim 9 , wherein the animal is a female.14. A progeny animal of the animal of .15. A progeny animal resulting from a cross between the chimeric animal of and ...

General Mass Spectrometry Assay Using Continuously Eluting Co-Fractionating Reporters of Mass Spectrometry Detection Efficiency

The invention provides general methods for quantifying any conceivable compound including small organic molecules and biological molecules in mass spectrometric measurements. The methods include the use of chemical or biological reporters such as artificial polypeptides containing proteolytic cleavage sites, which provide proteolytic reporter peptides for standardization of mass spectrometric detection efficiency. In addition to mass spectrometry standardization between different samples, the artificial polypeptides also standardize sample preparation amongst different samples undergoing mass spectrometric analysis when using electrophoresis separation prior to mass spectrometric analysis. Methods of the present invention also include methods for designing artificial polypeptides with peak to peak continuous liquid chromatography elution profiles spanning the complete or partial analyte elution profile for organic and biological molecules. Also included are the artificial polypeptides predigested with protease, which is compatible for use in experiments with native PAGE, in-solution proteolytic digestion of polypeptides, and small organic molecules undergoing fractionation separation followed by mass spectrometric evaluation.

Coiled containment guardrail system and terminal

Various embodiments for a coiled containment guardrail system and terminal are described. A guardrail system can include a terminal head configured for placement at a distal end of a guardrail beam, where the terminal head includes a canister having a hollow interior and an impact surface. A chute can be coupled to the terminal head, where the chute is configured to guide a guardrail beam into the terminal head in response to an impact being experienced at the impact surface. The terminal head may further include a flattening device coupled to the chute configured to flatten the guardrail beam in response to the impact being experienced at the terminal head. The canister can be configured to coil and store the guardrail beam as flattened by the flattening device in the hollow interior of the canister.

RECLINING TRANSPORT CHAIRS

A transport chair is provided that includes a base frame, a seat assembly pivotally mounted to the base, and a footrest assembly pivotally mounted to the base frame, the footrest assembly being associated with the seat assembly so as to pivot in unison with the seat assembly until the seat assembly is pivoted forward to an extent at which the footrest assembly contacts the floor or ground, at which point the footrest assembly does not pivot further upon further forward pivoting of the seat assembly. Further embodiments of the transport chair allow the seat assembly to recline, alone or in unison with a leg rest assembly, while the footrest remains in position. 1. A wheelchair configured to recline and incline forward , said wheelchair comprising:(a) a base frame having a first pivot axis;(b) at least two wheels rotationally mounted to said base frame;(c) a seat assembly and a footrest assembly configured to pivot about said first pivot axis from a first seated position to an inclined seated position; and(d) a leg rest assembly pivotally coupled to said base frame and configured to pivot about a second pivot axis to elevate in unison with the seat assembly when said seat assembly reclines but independent of said footrest assembly.2. The wheelchair of claim 1 , wherein the second pivot axis is proximate to or congruent with the first pivot axis.3. The wheelchair of claim 1 , comprising:a pivot shaft defining said first pivot axis, wherein the seat assembly is fixedly mounted to the pivot shaft such that the seat assembly pivots about the pivot shaft to incline forward, and such that the seat assembly pivots about the pivot shaft to recline;wherein the frame member extends from the pivot shaft to the at least two wheels, such that the pivot shaft is free to pivot independent of the frame member; andwherein the footrest assembly is pivotally mounted to the pivot shaft such that the footrest assembly is free to pivot independent of the pivot shaft, the footrest assembly ...

Method and system for mutliline mir-ir laser

A method of performing spatial separation of different wavelengths in a single laser cavity includes generating, from a pump radiation source, pump radiations in spatially separate channels and focusing the generated pump radiations in the spatially separate channels towards an active gain medium having amplification spectra. The method also includes emitting from the active gain medium, amplified radiations of the spatially separate channels, each channel of the spatially separate channels representing a corresponding wavelength and focusing the emitted amplified radiations of the spatially separated channels towards an aperture. The method further includes suppressing, at the aperture, an off-axis mode of the amplified radiations of the spatially separate channels, diffracting the amplified radiations of the spatially separate channels received through the aperture to provide diffracted radiations and returning a portion of the diffracted radiations back to the aperture, and collimating the diffracted radiations of the spatially separate channel.

Novel antiviral compounds from marine extracts

The subject invention pertains to novel biologically active extracts from marine algae and to biologically active fractions and components of these extracts. These extracts have been shown to possess antiviral properties. Pharmaceutical compositions comprising these extracts, or comprising biologically active fractions or components of these extracts, could be used in the treatment of viral diseases including influenza.

SYSTEMS AND METHODS FOR SUPPORTING BOLLARDS

In one embodiment, a bollard system includes multiple support beams adapted to be embedded in concrete, multiple bollards, each bollard being attached to a support beam a point near a center of the beam, and a reinforcing bar that is woven between the support beams to provide reinforcement to the system. 1. A bollard system comprising:multiple support beams adapted to be embedded in concrete;multiple bollards, each bollard being attached to a support beam a point near a center of the beam; anda reinforcing bar that is woven between the support beams to provide reinforcement to the system.2. The system of claim 1 , wherein the support beams are elongated hollow beams.3. The system of claim 1 , wherein the bollards are elongated pipes or tubes.4. The system of claim 1 , wherein each bollard is attached to a support beam near a halfway point along a length of the beam.5. The system of claim 1 , wherein the reinforcing bar is made of steel.6. The system of claim 1 , wherein the reinforcing bar alternately passes over and under adjacent support beams in a first direction that is generally perpendicular to the beams.7. The system of claim 6 , wherein the reinforcing bar also alternately passes under and over adjacent support beams in a second direction that is opposite to the first direction8. The system of claim 6 , wherein the reinforcing bar alternately passes over and under more than two support beams.9. The system of claim 6 , wherein the reinforcing bar forms a crossover point at which the bar crosses over itself and lobes in which support beams can be received.10. The system of claim 6 , wherein the reinforcing bar is an endless bar having no free ends.11. The system of claim 6 , wherein the reinforcing bar has free ends that form hooks that wrap around the same support beam.12. The system of claim 6 , wherein the system comprises two reinforcing bars having similar shapes that are used as a pair claim 6 , the reinforcing bars alternately passing over and under ...

Mri-detectable multilayer microcapsules for ultrasound-triggered delivery of pharmacologically active agents

The theranostic biocompatible microcapsules provided are efficient contrast enhanced imaging agents that combine Magnetic Resonance Imaging (MRI) with ultrasound-triggered drug release for real-time tracking and targeted delivery in vivo. The capsules are assembled via layer-by-layer deposition of the natural polyphenol tannic acid and poly(N-vinylpyrrolidone) with iron oxide nanoparticles incorporated in the capsule wall. The nanoparticle-modified capsules exhibit enhanced T1 and T2 MRI contrast in a clinical MRI scanner. Loaded with the an anticancer drug such as doxorubicin the capsules circulate in the blood stream for at least 48 hours, an improvement compared to non-encapsulated nanoparticles. High-intensity focused ultrasound results in targeted drug release with a 16-fold increase in the pharmacologically active agent localization in tumors compared to off-target organs. Owing to the active contrast, long circulation, customizable size, shape, composition, and precise delivery of high payload concentrations, these materials present an improved platform for imaging-guided precision drug delivery.

NOVEL REXINOID COMPOUNDS AND METHODS OF USING REXINOID COMPOUNDS FOR TREATING METABOLIC DISORDERS AND CANCER

Novel rexinoid compounds are provided herein. Also provided herein are methods of using the compounds to treat disorders, such as metabolic disorders, diabetes, insulin resistance, glucose intolerance, obesity, steatosis, inflammation, and/or cancer. 3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)14. (canceled)17. The compound of claim 16 , wherein Rand Rare not simultaneously methyl.19. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.20. A method of treating or preventing a metabolic disorder in a subject claim 1 , comprising administering to a subject an effective amount of a compound of .21. The method of claim 20 , wherein administering the compound provides a glucose-lowering effect claim 20 , an insulin-sensitizing effect claim 20 , or a plasma triglyceride lowering effect.22. (canceled)23. (canceled)24. A method of treating or preventing insulin resistance claim 1 , glucose intolerance claim 1 , obesity claim 1 , steatosis or inflammation in a subject claim 1 , comprising administrating to a subject in need thereof an effective amount of a compound of .25. The method of claim 20 , wherein the subject is a rodent or human claim 20 , obese claim 20 , morbidly obese claim 20 , pre-diabetic claim 20 , or diabetic.26. (canceled)27. (canceled)28. (canceled)29. (canceled)30. The method of claim 20 , wherein the compound is administered orally claim 20 , topically claim 20 , intranasally claim 20 , intravenously claim 20 , subcutaneously claim 20 , intradermally claim 20 , transdermally intramucosally intramuscularly claim 20 , by inhalation spray claim 20 , rectally claim 20 , nasally claim 20 , sublingually claim 20 , buccally claim 20 , vaginally or via an implanted reservoir.32. A method of treating or preventing cancer in a subject claim 1 , comprising administering to a subject an effective amount of a compound of .33. The method of claim 32 , ...

MYCOBACTERIUM TUBERCULOSIS PORINS AND TOXINS AND RELATED METHODS

Provided herein are isolated polypeptides comprising the amino-terminal domain of porin A (MtpA), wherein the polypeptide is a porin monomer. Also provided are isolated polypeptides comprising the carboxy-terminal domain of porin A, wherein the polypeptide is a toxin. Also provided are methods of treating or preventing a (Mtb) infection in a subject with or at risk of developing a Mtb infection. Further provided are chimeric porin polypeptides comprising a first polypeptide comprising an amino-terminal domain of porin and a second polypeptide comprising an antigen and the use the chimeric porin polypeptides in methods of eliciting an immune response in a subject. 1Mycobacterium tuberculosis. An isolated polypeptide comprising the amino-terminal domain of porin A (MtpA) , wherein the polypeptide is a porin monomer.2. The isolated polypeptide of claim 1 , wherein the amino-terminal domain comprises amino acids 1-443 of SEQ ID NO:1.3. The isolated polypeptide of claim 1 , wherein the polypeptide comprises SEQ ID NO:1.4Mycobacterium tuberculosis. An isolated polypeptide comprising the carboxy-terminal domain of porin A (MtpA) claim 1 , wherein the polypeptide is a toxin.5. The isolated polypeptide of claim 4 , wherein the carboxy-terminal domain of MtpA comprises amino acids 650-846 of SEQ ID NO:1.6. The isolated polypeptide of claim 1 , wherein the amino-terminal domain of MtpA comprises a mutation claim 1 , the carboxy-terminal domain of MtpA comprises a mutation claim 1 , or both.7. A nucleic acid encoding the isolated polypeptide of .8. A vector comprising the nucleic acid of .9Mycobacterium tuberculosisMycobacterium tuberculosis. A method of treating or preventing a (Mtb) infection in a subject with or at risk of developing a Mtb infection claim 7 , the method comprising administering to the subject a first agent that modulates the activity of a porin (Mtp) and a second agent that treats or prevents the Mtb infection.10. (canceled)11. (canceled)12. (canceled)13. ( ...

Msp nanopores and related methods

Provided herein are Mycobacterium smegmatis porin nanopores, systems that comprise these nanopores, and methods of using and making these nanopores. Such nanopores may be wild-type MspA porins, mutant MspA porins, wild-type MspA paralog porins, wild-type MspA homolog porins, mutant MspA paralog porins, mutant MspA homolog porins, or single-chain Msp porins. Also provided are bacterial strains capable of inducible Msp porin expression.

METHODS AND COMPOSITIONS RELATED TO SOLUBLE MONOCLONAL VARIABLE LYMPHOCYTE RECEPTORS OF DEFINED ANTIGEN SPECIFICITY

Disclosed are compositions and methods related to variable lymphocyte receptors (VLRs). More particularly, disclosed are a variety of antigen specific polypeptides, including soluble, monoclonal, and multivalent forms, as well as methods of using the polypeptides, antibodies that bind the antigen specific polypeptides, and nucleic acids, vectors and expression systems that encode the polypeptides. Antigen specific polypeptides that selectively bind pathogens, like anthrax, and carbohydrates, like blood group determinants, are specifically disclosed. 149-. (canceled)50. A cell culture , wherein the culture medium comprises a plurality of multimers comprising a plurality of soluble , monoclonal antigen specific polypeptides , wherein each antigen specific polypeptide comprises an N-terminal leucine rich repeat (LRRNT) , one or more leucine rich repeats (LRRs) , a C-terminal leucine rich repeat (LRRCT) , and a connecting peptide , wherein the connecting peptide comprises an alpha helix.51. The cell culture of claim 50 , wherein the cells comprise a cDNA encoding an antigen specific polypeptide claim 50 , wherein the antigen specific polypeptide comprises an N-terminal leucine rich repeat (LRRNT) claim 50 , one or more leucine rich repeats (LRRs) claim 50 , a C-terminal leucine rich repeat (LRRCT) claim 50 , and a connecting peptide claim 50 , wherein the connecting peptide comprises an alpha helix.52. The cell culture of claim 51 , wherein the cDNA is stably integrated into the genome of the cells.53. The cell culture of claim 51 , wherein the antigen specific polypeptide binds a target protein claim 51 , a target carbohydrate or a target pathogen.54. The cell culture of claim 50 , wherein each multimer comprises up to ten antigen specific polypeptides.55. The cell culture of claim 50 , wherein each multimer is a multivalent multimer that binds to more than one target.56. The cell culture of claim 50 , wherein the antigen specific polypeptide is an affinity matured ...

Middle-infrared volumetric bragg grating based on alkali halide or alkili-earth flouride color center crystals

Volumetric Bragg grating devices that operate in middle-infrared region of the spectrum and methods for producing such devices are described. Such a Volumetric Bragg grating device can be produced by forming a plurality of color centers within an alkali-halide or an alkali-earth fluoride crystal and selectively removing a subset of the plurality of color centers to produce variations in refractive index of the alkali-halide or alkali-earth fluoride crystal in the middle-infrared spectral region and to thereby produce a volumetric Bragg grating that operates in middle-infrared spectral range.

Amyotrophic lateral sclerosis (als) biomarkers and uses thereof

Provided herein are Amyotrophic lateral sclerosis (ALS) biomarkers and methods of using these ALS biomarkers to diagnose and treat ALS.

Polyvalent vaccine

The present invention relates, in general, to an immunogenic composition (e.g., a vaccine) and, in particular, to a polyvalent immunogenic composition, such as a polyvalent HIV vaccine, and to methods of using same. The invention further relates to methods that use a genetic algorithm to create sets of polyvalent antigens suitable for use, for example, in vaccination strategies.

IMAGING RETINAL INTRINSIC OPTICAL SIGNALS

Disclosed are various embodiments for imaging retinal intrinsic optical signals (IOS) in vivo. According to various embodiments, imaging retinal intrinsic optical signals (IOS) may comprise illuminating a host retina with near infrared light (NIR) during a test period, wherein the host retina is continuously illuminated by the NIR light during the test period. Sequentially a host retina may be stimulated with a timed bursts of visible light during the test period. A series of images of the retina may be recorded with a line-scan CCD camera and the images may be processed to produce images of intrinsic optical signals (IOS) from retinal photoreceptor cells identified in the images. 1. A method of imaging retinal intrinsic optical signals (IOS) in vivo comprising:illuminating a host retina with a near infrared light during a test period, wherein the host retina is continuously illuminated by the near infrared light during the test period;sequentially stimulating a host retina with a timed burst of visible light during the test period;recording a series of images of the retina with a camera, wherein images are recorded both before, after, and during stimulus of the retina with the visible light; andprocessing the images to produce images of intrinsic optical signals (IOS) from retinal photoreceptor cells identified in the images.2. The method of claim 1 , wherein the retina is illuminated with the near infrared light at about 600 μW.3. The method of claim 1 , wherein the visible light is a visible green light.4. The method of claim 1 , wherein the camera further comprises a line-scan CCD camera.5. The method of claim 4 , further comprising filtering the visible light from the line-scan CCD camera with a NIR filter.67.-. (canceled)8. The method of claim 1 , wherein the images are recorded at a speed of about 100 frames/s.9. (canceled)10. The method of claim 8 , wherein the images are recorded for a period of time beginning about 400 ms before the stimulus and continuing ...

Stearate Compounds

Preparation and methods of treating and preventing visceral adiposity and cancer are provided involving the administration of stearate to a subject. It has been unexpectedly discovered that the fatty acid stearate, when introduced in the diet, reduces the amount of visceral fat in the body without decreasing overall body weight or causing measurable negative side effects. It has also been unexpectedly discovered that dietary stearate prevents cancer in healthy subjects and reduces both tumor size and metastasis in subjects already afflicted with cancer. 1. A pharmaceutical preparation comprising a therapeutically effective amount of a stearate compound , wherein said stearate compound is neither a naturally occurring triglyceride compound nor a naturally occurring phospholipid compound.2. The pharmaceutical preparation of comprising an antineoplastic agent.3. The pharmaceutical preparation of comprising an antineoplastic agent selected from the group consisting of: taxane claim 1 , a taxane derivative claim 1 , paclitaxel claim 1 , and docetaxel.5. The pharmaceutical preparation of wherein the amount of antineoplastic agent is about 20 mg of antineoplastic agent per kilogram of subject mass.6. The pharmaceutical preparation of claim 1 , wherein the stearate compound is stearic acid or a pharmaceutically acceptable salt thereof.7. The pharmaceutical preparation of claim 1 , wherein the stearate compound is not a stearate ester.8. The pharmaceutical preparation of claim 1 , comprising at least about 2% by weight of the stearate compound or at least about 17% by weight of the stearate compound.9. (canceled)10. The pharmaceutical preparation of claim 1 , wherein the therapeutically effective amount is an amount effective to reduce the likelihood or severity of tumors in a subject claim 1 , is an amount effective to reduce the visceral fat content of a subject claim 1 , is an amount effective to reduce the serum glucose concentration of a subject claim 1 , reduce the ...

SATURABLE ABSORBERS FOR Q-SWITCHING OF MIDDLE INFRARED LASER CAVATIES

This disclosure demonstrates successfully using single, polycrystalline, hot pressed ceramic, and thin film Fe doped binary chalcogenides (such as ZnSe and ZnS) as saturable absorbing passive Q-switches. The method of producing polycrystalline ZnSe(S) yields fairly uniform distribution of dopant, large coefficients of absorption (5-50 cm) and low passive losses while being highly cost effective and easy to reproduce. Using these Fe:ZnSe crystals, stable Q-switched output was achieved with a low threshold and the best cavity configuration yielded 13 mJ/pulse single mode Q-switched output and 85 mJ in a multipulse regime. 1. A method performed by an Erbium or transition metal doped laser for producing laser pulses at a laser wavelength around 3 μm based on passive Q-switching at room temperature , comprising:providing a laser cavity in the Erbium or transition metal doped laser to include a doped laser gain material to produce laser light at a laser wavelength around 3 μm under optical pumping; and{'sup': 2+', '2+, 'using a saturable absorber inside the laser cavity to effectuate passive Q-switching in the laser light that generates laser pulses at the laser wavelength around 3 μm, where the saturable absorber is a single crystalline or polycrystalline material of Fe:ZnSe or Fe:ZnS structured to exhibit a saturable absorption at the laser wavelength around 3 μm that effectuates the passive Q-switching at room temperature.'}2. The method of claim 1 , wherein the laser wavelength is in the range 2.5 μm to 3.4 μm.3. The method of claim 1 , wherein the laser wavelength is in the range 2.5 μm to 4 μm.4. The method of claim 1 , wherein:{'sup': 2+', '2+', '−18', '2, 'the single crystalline or polycrystalline material of Fe:ZnSe or Fe:ZnS is structured to exhibit an absorption cross section of about 10cmfor saturable absorption at the laser wavelength around 3 μm and at the room temperature.'}5. The method of claim 1 , wherein the saturable absorber is formed by:forming a ...

Diagnosing and treating iga nephropathy

Provided are methods of diagnosing IgA nephropathy in a subject. Optionally, the methods comprise isolating an IgG from the subject and determining whether the IgG binds to a galactose-deficient IgA1. Optionally, the methods comprise providing a biological sample from the subject and detecting in the sample a mutation in a IGH gene, wherein the mutation is in a nucleotide sequence encoding a complementarity determining region 3 (CDR3) of a IGH variable region. Optionally, the methods comprise determining a level of IgG specific for a galactose-deficient IgA1 in the subject. Also provided are methods of treating or reducing the risk of developing IgA nephropathy in a subject.

Systems and methods for testing protective helmets

In one embodiment, a helmet testing system includes a sled adapted to support a bullet dummy, a track along which the sled can travel, a target dummy support apparatus adapted to support a target dummy at a point near an end of the track, and an impact cushion positioned at the end of the track that is adapted to halt forward motion of the sled along the track to enable the bullet dummy to be launched from the sled and into the target dummy.

Methods and compositions for increasing mucus clearance

Provided herein are methods of increasing mucus clearance in a subject having decreased mucus clearance. Also provided are methods of treating or preventing a respiratory disorder.

SATURABLE ABSORBERS FOR Q-SWITCHING OF MIDDLE INFRARED LASER CAVITIES

A Q-switched laser includes a laser cavity including a cavity mirror and an output coupler mirror. The Q-switched laser also includes a doped laser gain material disposed in the laser cavity and a Q-switch including a saturable absorber comprising Fe:ZnSe or Fe:ZnS. 1. A Q-switched laser comprising:a laser cavity including a cavity mirror and an output coupler mirror;a doped laser gain material disposed in the laser cavity; and{'sup': 2+', '2+, 'a Q-switch including a saturable absorber comprising Fe:ZnSe or Fe:ZnS.'}2. The Q-switched laser of wherein the Q-switched laser is operable to lase at a wavelength ranging from 2.5 μm to 3.4 μm.3. The Q-switched laser of wherein the doped laser gain material is doped with erbium or a transition metal.4. The Q-switched laser of wherein the doped laser gain material comprises Er:Cr:YSGG.5. The Q-switched laser of wherein the Fe:ZnSe or Fe:ZnS is single crystalline.6. The Q-switched laser of wherein the Fe:ZnSe or Fe:ZnS is polycrystalline.7. The Q-switched laser of wherein the saturable absorber is placed at Brewster's angle.8. The Q-switched laser of wherein the Q-switch is disposed between the cavity mirror and the doped laser gain material.9. The Q-switched laser of wherein the saturable absorber comprises a passive solid state saturable absorber.10. The Q-switched laser of wherein the passive solid state saturable absorber comprises a microchip.11. A Q-switched laser comprising:a laser cavity defined by a first cavity mirror and a second cavity mirror;an output coupler disposed in the laser cavity;a doped laser gain material disposed between the first cavity mirror and the output coupler; and{'sup': 2+', '2+, 'a Q-switch including a saturable absorber comprising Fe:ZnSe or Fe:ZnS.'}12. The Q-switched laser of wherein the Q-switched laser is operable to lase at a wavelength ranging from 2.5 μm to 3.4 μm.13. The Q-switched laser of wherein the doped laser gain material is doped with erbium or a transition metal.14. The Q- ...

Biomarkers and methods for assessing myocardial infarction and serious infection risk in rheumatoid arthritis patients

Provided herein are methods for assessing risk of infection or cardiovascular disease (CVD) in a subject with an inflammatory disease, e.g., rheumatoid arthritis. The methods include performing immunoassays to generate scores based on quantitative data for expression of biomarkers relating to inflammatory biomarkers with or without additional clinical variables to assess infection and CVD risk. Also provided are uses of inflammatory biomarkers for guiding treatment decisions.

Treating Basal-Like Genotype Cancers

Provided herein are methods of treating a subject with cancer comprising administering to the subject a death receptor agonist. Also provided herein are methods of screening a breast cancer cell for responsiveness to a DR5 agonist. Further provided herein are antibodies that selectively bind an N-terminal CARD of DDX3, a DDX3 lacking an N-terminal CARD, and an 80 kDa baculovirus TAP repeat (BIR). 1. A method of treating a subject with cancer , comprising:(a) selecting a subject with a breast cancer, wherein the breast cancer has one or more characteristics selected from the group consisting of a luminal cell, HER2 amplified, or basal-like genotype;(b) administering to the subject an TAP inhibitor; and(c) administering to the subject a death receptor agonist, wherein the death receptor agonist is a DR5 agonist.2. The method of claim 1 , wherein the TAP inhibitor is N-benzhydryl-5-(2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo[1 claim 1 ,2-a][1 claim 1 ,5]diazocine-8-carboxaminde (AT-406).3. The method of claim 1 , further comprising administering to the subject a chemotherapeutic agent.4. The method of claim 2 , wherein the chemotherapeutic agent is selected from the group consisting of adriamycin claim 2 , paclitaxel claim 2 , abraxane claim 2 , cisplatin claim 2 , and carboplatin.5. The method of claim 1 , wherein the death receptor agonist is administered at three week claim 1 , two week claim 1 , or one week intervals.6. The method of claim 3 , wherein the chemotherapeutic agent is administered intravenously every three weeks. This application is a continuation of U.S. patent application Ser. No. 12/940,746, filed Nov. 5, 2010, which claims the benefit of U.S. Provisional Application No. 61/258,274, filed on Nov. 5, 2009, each of which is incorporated by reference herein in its entirety.Triple negative breast cancer (TNBC) represents a significant proportion (about 20-25%) of breast cancer patients. TNBC is characterized by the absence of ...

Systems And Methods For Encouraging Hand Washing Compliance

In some embodiments, a hand washing compliance system includes a primary soap dispenser adapted to be located near an entrance to a room, the primary soap dispenser comprising a motion sensor configured to detect passage of an individual through the room entrance, a soap dispensation sensor configured to detect dispensation of soap from the primary soap dispenser, and a communication device configured to enable communication with other soap dispensers, and a secondary soap dispenser adapted to be located inside of the room, the secondary soap dispenser comprising a soap dispensation sensor configured to detect dispensation of soap from the secondary soap dispenser, a communication device configured to enable communication with other soap dispensers, and a warning indicator configured to generate an alert that encourages individuals entering the room to wash their hands.

MID-IR MICROCHIP LASER: ZNS:CR2+ LASER WITH SATURABLE ABSORBER MATERIAL

A method of fabrication of laser gain material and utilization of such media includes the steps of introducing a transitional metal, preferably Crthin film of controllable thickness on the ZnS crystal facets after crystal growth by means of pulse laser deposition or plasma sputtering, thermal annealing of the crystals for effective thermal diffusion of the dopant into the crystal volume with a temperature and exposition time providing the highest concentration of the dopant in the volume without degrading laser performance due to scattering and concentration quenching, and formation of a microchip laser either by means of direct deposition of mirrors on flat and parallel polished facets of a thin Cr:ZnS wafer or by relying on the internal reflectance of such facets.

Compositions that Inhibit and Prevent the Formation of Dental Caries and Methods of Using the Same

The present invention is related to the inhibition of binding of oral streptococci to the tooth surface. Compositions and methods for preventing, inhibiting and/or treating the formation of dental caries, and methods of identifying compounds that prevent, inhibit and/or treat the formation of dental caries are provided. 1. A composition comprising an inhibitor of the interaction of AgI/II , or a homolog thereof , with salivary agglutinin (SAG).2. The composition of claim 1 , wherein the homolog of AgI/II is selected from the group consisting of SspB claim 1 , Pas claim 1 , GBPC and rcnM claim 1 , or a combination of any thereof.3. The composition of claim 1 , wherein the inhibitor interacts with glycoprotein 340 (Gp340) found within an SAG glycoprotein complex.4. The composition of claim 1 , wherein the inhibitor interacts with a scavenger receptor cysteine rich (SRCR) domain present on Gp340.5. The composition of claim 1 , wherein the inhibitor interacts with AgI/II claim 1 , or homolog thereof.6. The composition of claim 1 , wherein the inhibitor comprises a glycan.7. The composition of claim 6 , wherein the glycan is Galβ1-3-GalNac.8. The composition of claim 1 , wherein the inhibitor comprises a peptide.9. The composition of claim 8 , wherein the peptide interacts with AgI/II claim 8 , or homolog thereof.10. The composition of claim 8 , wherein the peptide is ETNDANVVARQL (SEQ ID NO:10).11. A formulation comprising the composition of .12. The formulation of claim 11 , wherein the formulation is in a form suitable for oral or buccal (sublingual) administration.13. The formulation of claim 11 , wherein the formulation is in a form of a tooth paste claim 11 , oral rinse claim 11 , gel claim 11 , an additive to a digestible product or a strip comprising the formulation to be applied to the teeth of a subject.14. A method of preventing claim 11 , inhibiting or treating the formation of dental caries in a subject comprising the administration of a composition or ...

Compositions and methods for inhibiting fibrosis

Provided herein are compositions and methods for treating or preventing fibrosis.

Urine biomarkers for detecting graft rejection

Provided herein are compositions, systems, kits, and methods for detecting rejection, or an elevated risk of rejection, of an organ or tissue graft (e.g., kidney graft) in a subject by detecting one, or a panel of, RNA markers in a urine sample from the subject.

Enhanced therapeutic usage of a purine nucleoside phosphorylase or nucleoside hydrolase prodrug

The use of a purine nucleoside phosphorylase or nucleoside hydrolase or a vector encoding expression of one of these enzymes is detailed along with the use of a prodrug cleaved by the purine nucleoside phosphorylase or nucleoside hydrolase for the preparation of a direct injection inhibition of replicating or non-replicating targeted cells. The targeted cells do not normally express the introduced purine nucleoside phosphorylase or nucleoside hydrolase. The enzyme and prodrug are amenable to intermixing and injection as a single dose or as separate injection or administration to the targeted cells. The substance and prodrug efficacy are enhanced through exposure of the targeted cells to X-ray radiation. Administration of a prodrug regardless of administration route to the targeted cells is effective in combination with X-ray radiation therapy to kill or inhibit function of the targeted cells.

Multitargeting onocolytic adenovirus, methods of use, and methods of making

To increase the therapeutic potential of these oncolytic viruses based on a 24 base pair deletion in the viral E1 A gene (D24), a conditionally replicating adenovirus targeting multiple receptors upregulated on tumors was generated by incorporating an Ad5/3 fiber with a carboxyl terminus RGD ligand. The virus displayed full cytopathic effect in tumor lines assayed at low titers with improved cytotoxicity over Ad5-RGD D24, Ad5/3 D24 and an HSV oncolytic virus. The virus was further engineered to deliver immunotherapeutic agents such as GMCSF while maintaining enhanced heterogenic oncolysis.

Bacterial colicin-immunity protein protein purification system

Provided herein are compositions and methods for protein purification.

Direct central nervous system catheter and temperature control system

A central nervous system (CNS) catheter assembly (20) adapted for use as a ventriculostomy catheter and a spinal catheter includes a catheter body (28) defining at least one lumen (30) therethrough having a drug delivery branch (22) and a monitoring/sensing branch (24). The drug delivery branch and the monitoring/sensing branch are in fluid communication with the lumen. Openings (32) are disposed in fluid communication with the lumen and being located at proximal ends of the drug delivery branch and the monitoring/sensing branch. Another opening is disposed at a distal end of the main body. The assembly further includes a component such as an intracranial pressure/osmotic pressure monitoring system, a fluid drainage system, an attachable introduction aid, a patient surface attachment aid, a micromanipulator and a comprehensive intracranial pressure evaluation and relief system. The assembly optionally includes a filter assembly containing a proton exchange membrane.

Regenerable biosensor using total internal reflection fluorescence with electrochemical control

An improved electrochemical method for disassociating a biological binding partner from a corresponding second biological binding partner associated with a waveguide surface, the electrochemical method involving the application of an electrical potential to said waveguide surface ( 118 ), the improvement comprising: applying the electrical potential to the waveguide surface ( 118 ) as a square wave polarization function. Preferably, the waveguide surface is comprised of indium tin oxide. The biological binding partners are selected from the group consisting of antigen-antibody, avidin-biotin, enzyme-substrate, cell receptor-substrate/analog, antibody/anti-antibody, DNA, RNA, and fragments thereof. The antigen may be comprised of an epitope. The epitope is produced by a solid phase peptide synthesis performed on said waveguide surface ( 118 ).

Compounds useful as antiviral agents, compositions, and methods of use

Novel 3- N -cycloalkyl-5-substituted-2-thioxothiazolidin-4-one derivatives that are effective for use in treating viral infections are described. Also described are pharmaceutical compositions comprising the 3- N -cycloalkyl-5-substituted-2-thioxothiazolidin-4-one derivatives and methods for using the compounds or compositions.

Diagnosis and treatment of neuroectodermal tumors

The present invention provides fusion proteins for the detection and treatment of neuroectodermal tumors. Previous work demonstrated that chlorotoxin is specific for glial-derived or meningioma-derived tumor cells. The current invention has extended the use of chlorotoxin-cytotoxin fusion proteins to treat the whole class neuroectodermal tumors such as gliomas, meningiomas, ependymonas, medulloblastomas, neuroblastomas, gangliomas, pheochromocytomas, melanomas, PPNET's, small cell carcinoma of the lung, Ewing's sarcoma, and metastatic tumors in the brain. Also, diagnostic methods are provided for screening neoplastic neuroectodermal tumors.

Human anti-epidermal growth factor receptor single-chain antibodies

Human anti-epidermal growth factor receptor (EGFR) single-chain antibodies (scFvs) were isolated from a human IgM phage display library using purified epidermal growth factor receptor as antigen. Two isolates with different amino acid sequences were identified by ELISA as epidermal growth factor receptor-specific. the scFvs bind to the full length epidermal growth factor receptor and the truncated and/or mutated epidermal growth factor receptor on human cells. These anti-EGFR-scFvs are useful as therapeutic and/or diagnostic agents.

Hydroxamic acid-based bifunctional chelating compounds

The present disclosure details the preparation of hydroxamic-acid based bifunctional chelators and their use in conjugating metal ions to proteins and nucleic acids for tumor or tissue imaging or therapy purposes. Some preferred aspects of the disclosure involve the preparation of trisuccin, chemical name N- tris(2-N- benzyloxyaminocarbonylethyl)! methylsuccinamic acid, which is a hydroxamic acid/succinate based structure that is particularly useful for binding radionuclides such as 99m Tc, 186 Re and 67 Cu.