COMPOSITION AND METHODS OF USE OF SMALL MOLECULES AS BINDING LIGANDS FOR THE MODULATION OF PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9(PCSK9) PROTEIN ACTIVITY

This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels.

Deployable, multi-sided illumination devices and related methods of use

An illumination device may include a body having twelve sides, the body being formed by a first body portion including six sides of the twelve sides, and a second body portion including six sides of the twelve sides. The first body portion and the second body portion may be coupled to one another at a first interface and at a second interface disposed radially inward of the first interface, wherein the first interface may be positioned in a plurality of planes, and wherein the second interface may be positioned in a single plane. At least a portion of each of the twelve sides may include a transparent window. The illumination device may include a resilient cover disposed around the body.

PHENYLPIPERAZINE PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) MODULATORS AND THEIR USE

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels. 112.-. (canceled)14. The method of claim 13 , wherein an uptake of LDL by hepatocytes in the subject is modulated.15. The method of claim 13 , wherein said metabolic disease is diabetes.16. The method of claim 13 , wherein the compound of formula I is formulated as a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient.17. The method of claim 16 , wherein said pharmaceutical composition further comprises a second pharmaceutical drug compound.18. The method of claim 17 , wherein said second pharmaceutical drug compound is selected from the group consisting of a statin claim 17 , a cardiovascular drug claim 17 , a metabolic drug claim 17 , and an antihypertensive drug.19. The method of claim 13 , wherein the compound is selected from the group consisting of:N-phenyl-4-(piperazin-1-yl)benzenesulfonamide;N-isopropyl-4-((4-(piperazin-1-yl)phenyl)sulfonamido)benzamide;N-methyl-4-((4-(piperazin-1-yl)phenyl)sulfonamido)benzamide;N-(3,4-dimethylphenyl)-4-(piperazin-1-yl)benzenesulfonamide;N-(3,5-dimethylphenyl)-4-(piperazin-1-yl)benzenesulfonamide;N-(3,5- ...

METHOD AND APPARATUS FOR PREDICTING LIFE CYCLE OF A SPLICE

A monitoring apparatus, and method of use, that is capable of determining the joint characteristics by means of waveforms shifts at zero-crossing angular distortions through predictive failure algorithm specific to circuit under test. 1. A method in predicting the life cycle of a splice comprising:a) establishing a baseline over time for a splice of predetermined construction based on deviations in a signal curve for the splice in a vicinity of a zero crossing point of the signal curve using a sine curve and a first ratio of amplitude at a time of monitoring and an amplitude at a start time and a period change ratio based on a period at the time of monitoring and the period at the start time;b) monitoring an in-service splice in the vicinity of the zero crossing point for a signal of the in-service splice using the deviations used in step (a) for the signal of the in-service splice; andc) comparing the baseline of step (a) to information from step (b) to determine a degradation for the in-service splice and a decay rate curve, the decay rate curve providing an indication of a percentage of useful life remaining and time to failure for the in-service splice, the decay rate curve providing a guide for monitoring other splices for useful life and time to failure.2. The method of claim 1 , wherein the splice is a splice in a transmission line.3. An apparatus adapted for practicing the method of comprising;a) probes for determining instantaneous voltage potential across the splice;b) a current sense device for determining instantaneous current output based upon the splice,c) a nonconductive platform to support an associate device, the associated device collecting and analyzing data from the in-service splice being monitored; andd) means for establishing the baseline, monitoring the in-service splice, and comparing the baseline of step (a) to information from step (b) to determine a degradation for the in-service splice and the decay rate curve. This application is a ...

Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Allosteric Binding Ligands To Modulate Serum Low Density Lipoprotein (LDL) Levels

This invention is related to the field of hypercholesterolemia. In particular, the invention provides compositions and methods to modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9 using synthetic ligands and/or synthetic ligand derivative sequences of 3-8 amino acids ranging between 350-2,000 Da. Altering the conformation of PCSK9 affects the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for ligands which can raise LDL levels. 1. A method , comprising: i) a PCSK9 protein, wherein said protein comprises a binding site that induces allosteric modulation and a low density lipoprotein receptor binding site;', 'ii) a synthetic ligand consisting of a sequence ranging between 3 to 8 amino acids, capable of binding to said binding site;', 'iii) a plurality of hepatocyte cells comprising a low density lipoprotein receptor and low density lipoproteins;, 'a) providing;'}b) binding said synthetic ligand to said binding site, wherein said synthetic ligand induces a conformation shift of said protein; andc) modulating the affinity of said low density lipoprotein receptor binding site for said low density lipoprotein receptor by said conformational shift.2. The method of claim 1 , wherein said synthetic ligand is an allosteric inhibitor ligand wherein said modulating decreases the affinity of said low density lipoprotein receptor binding site for said low density lipoprotein receptor such that internalization of said low density lipoprotein by said plurality of hepatocytes is increased.3. The method of claim 1 , wherein synthetic peptide is an allosteric enhancer ligand said modulating increases the affinity of said low ...

Deployable, multi-sided illumination devices and related methods of use

An illumination device may include a body having twelve sides, the body being formed by a first body portion including six sides of the twelve sides, and a second body portion including six sides of the twelve sides. The first body portion and the second body portion may be coupled to one another at a first interface and at a second interface disposed radially inward of the first interface, wherein the first interface may be positioned in a plurality of planes, and wherein the second interface may be positioned in a single plane. At least a portion of each of the twelve sides may include a transparent window. The illumination device may include a resilient cover disposed around the body.

METHOD AND APPARATUS FOR MONITORING CONDITION OF A SPLICE

A splice monitoring apparatus and method of use is capable of determining splice characteristics by means of dynamic reactance through waveform shifts and harmonic distortions in comparison to a base frequency. 1. A method of monitoring a condition of a splice comprising:a) establishing a baseline for a splice of defined construction in terms of phase shift and harmonic shift;b) determining the phase shift and/or the harmonic shift for a splice that has been in service;c) comparing the phase shift and/or the harmonic shift of step (b) with the baseline of step (a) to determine based on differences between the values of phase shift and/or the harmonic shift for the splice in service and the baseline values whether the splice in service is experiencing degradation.2. The method of claim 1 , wherein the phase shift is used to determine degradation.3. The method of claim 1 , wherein the harmonic shift is used to determine degradation.4. The method of claim 2 , wherein a difference greater than 10 degrees in phase shift is representative of degradation of the splice.5. The method of claim 4 , wherein a difference greater than 20 degrees in phase shift is an indicator that the splice needs to be replaced.6. The method of claim 3 , wherein a difference greater than 150% in a 3or 5harmonic shift is representative of degradation of the splice.7. The method of claim 6 , wherein a difference greater than 200% in the 3or 5harmonic shift is an indicator that the splice needs to be replaced.8. The method of claim 1 , wherein instantaneous voltage potential across the splice and a current sense output of a transformer positioned downstream of the splice are used to measure phase shift and harmonic shift.9. An apparatus adapted for practicing the method of comprising:a) probes for determining instantaneous voltage potential across the splice,b) a current sense transformer for determining instantaneous current sense output based on the splice, andc) means for determining the phase ...

DEPLOYABLE, MULTI-SIDED ILLUMINATION DEVICES AND RELATED METHODS OF USE

An illumination device may include a body having twelve sides, the body being formed by a first body portion including six sides of the twelve sides, and a second body portion including six sides of the twelve sides. The first body portion and the second body portion may be coupled to one another at a first interface and at a second interface disposed radially inward of the first interface, wherein the first interface may be positioned in a plurality of planes, and wherein the second interface may be positioned in a single plane. At least a portion of each of the twelve sides may include a transparent window. The illumination device may include a resilient cover disposed around the body. 1. An illumination device , comprising:a body having twelve sides, the body being formed by a first body portion including six sides of the twelve sides, and a second body portion including six sides of the twelve sides, the first body portion and the second body portion being coupled to one another at a first interface and at a second interface disposed radially inward of the first interface, wherein the first interface is positioned in a plurality of planes, and wherein the second interface is positioned in a single plane, wherein at least a portion of each of the twelve sides includes a transparent window;a resilient cover disposed around the body, the resilient cover having twelve sides, wherein each of the twelve sides of the resilient cover extend over a respective side of the body, wherein each of the twelve sides of the resilient cover includes an opening positioned over one of the transparent windows of the body.a plurality of illumination sources, each of the plurality of illumination sources being positioned on an interior side of a transparent window of the body;a power source configured to deliver power to each of the plurality of illumination sources;a controller coupled to the power source and to the plurality of illumination sources;a charging port disposed in one of ...

COMPOSITION AND METHODS OF USE OF NOVEL PHENYLALANINE SMALL ORGANIC COMPOUNDS TO DIRECTLY MODULATE PCSK9 PROTEIN ACTIVITY

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels. 112.-. (canceled)14. The method of claim 13 , further comprising administering to the mammal a second active pharmaceutical.15. The method of claim 13 , comprising administering a pharmaceutical composition comprising the compound of Formula I and a pharmaceutically acceptable carrier or excipient.16. The method of claim 15 , wherein said pharmaceutical composition further comprises a second active ingredient.19. The method of claim 18 , further comprising administering to the mammal a second active pharmaceutical.20. The method of claim 18 , comprising administering a pharmaceutical composition comprising the compound of Formula I and a pharmaceutically acceptable carrier or excipient.21. The method of claim 20 , wherein said pharmaceutical composition further comprises a second active ingredient.22. The method of claim 21 , wherein said second active ingredient is selected from the group consisting of a statin claim 21 , a cardiovascular drug claim 21 , a metabolic drug claim 21 , and an antihypertensive drug.25. The method of claim 24 , further comprising administering to the mammal a ...

COMPOSITION AND METHODS OF USE OF NOVEL PHENYLALANINE SMALL ORGANIC COMPOUNDS TO DIRECTLY MODULATE PCSK9 PROTEIN ACTIVITY

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels. 2. The compound of claim 1 , formulated as a pharmaceutical composition.3. The compound of claim 2 , wherein said pharmaceutical composition further comprises a pharmaceutical drug.4. The compound of claim 3 , wherein said pharmaceutical drug is selected from the group consisting of a statin claim 3 , a cardiovascular drug claim 3 , a metabolic drug claim 3 , and an antihypertensive drug.5. A method claim 3 , comprising: i) a PCSK9 protein, wherein said protein comprises a binding site that induces allosteric modulation and a low density lipoprotein receptor binding site;', 'ii) a small organic compound capable of binding to said binding site, and selected from the group consisting of a compound of a phenylalanine scaffold of Formula I; and', 'iii) a plurality of hepatocyte cells comprising a low density lipoprotein receptor and low density lipoproteins;, 'a) providing;'}b) binding said small organic compound to said binding site, wherein said small organic compound induces a conformational shift of said protein; andc) modulating the rate of low density lipoprotein receptor ...

Method to treat lipid dysregulation by modulation of proprotein convertase subtilisin/kexin type 9 (pcsk9) protein activity with small molecule ligands

This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol, High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels.

COMPOSITION AND METHODS OF USE OF NOVEL PHENYLALANINE SMALL ORGANIC COMPOUNDS TO DIRECTLY MODULATE PCSK9 PROTEIN ACTIVITY

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels. 2. The compound of claim 1 , formulated as a pharmaceutical composition.3. The compound of claim 2 , wherein said pharmaceutical composition further comprises a pharmaceutical drug.4. The compound of claim 3 , wherein said pharmaceutical drug is selected from the group consisting of a statin claim 3 , a cardiovascular drug claim 3 , a metabolic drug claim 3 , and an antihypertensive drug.5. A method claim 3 , comprising: i) a PCSK9 protein, wherein said protein comprises a binding site that induces allosteric modulation and a low density lipoprotein receptor binding site;', 'ii) a small organic compound capable of binding to said binding site, and selected from the group consisting of a compound of a phenylalanine scaffold of Formula I; and', 'iii) a plurality of hepatocyte cells comprising a low density lipoprotein receptor and low density lipoproteins;, 'a) providing;'}b) binding said small organic compound to said binding site, wherein said small organic compound induces a conformational shift of said protein; andc) modulating the rate of low density lipoprotein receptor ...

Phenylpiperazine proprotein convertase subtilisin/kexin type 9 (pcsk9) modulators and their use

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels.

METHOD TO TREAT HYPERCHOLESTEROLEMIA BY MODULATION OF PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) PROTEIN ACTIVITY WITH SMALL MOLECULE LIGANDS

This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels. 1. A method , comprising binding an allosteric small molecule compound to a PCSK9 protein to modulate the uptake of low-density lipoprotein by a plurality of hepatocytes.2. The method of claim 1 , further comprising treating hypercholesterolemia with said allosteric small molecule compound.3. The method of claim 2 , wherein said modulation comprises increased uptake of low-density lipoprotein by a plurality of hepatocytes.4. The method of claim 3 , wherein said allosteric small molecule is selected from the group consisting of SRX75 claim 3 , SRX76 claim 3 , SRX204 claim 3 , SRX208 claim 3 , SRX209 claim 3 , SRX210 claim 3 , SRX211 claim 3 , SRX212 claim 3 , SRX 213 claim 3 , SRX214 claim 3 , SRX215 claim 3 , SRX216 claim 3 , SRX217 claim 3 , SRX218 claim 3 , SRX219 claim 3 , SRX220 claim 3 , SRX221 claim 3 , SRX222 claim 3 , SRX223 claim 3 , SRX224 claim 3 , and SRX225.5. The method of claim 3 , wherein said allosteric small molecule compound is further combined with a second pharmaceutical compound.6. The method of claim 1 , wherein said modulation comprises decreased uptake of low-density lipoprotein by a ...

COMPOSITION AND METHODS OF USE OF SMALL MOLECULES AS BINDING LIGANDS FOR THE MODULATION OF PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9(PCSK9) PROTEIN ACTIVITY

This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels. 1. A method , comprising: i) a PCSK9 protein, wherein said protein comprises a binding site that induces allosteric modulation and a low density lipoprotein receptor binding site;', 'ii) a pharmaceutical formulation comprising a small molecule ligand capable of binding said binding site, wherein said small molecule ligand is an allosteric inhibitor ligand;', 'iii) a plurality of hepatocyte cells comprising a population of low density lipoprotein receptors; and', 'iv) low density lipoproteins;, 'a) providing;'}b) binding said small molecule ligand to said binding site, wherein said small molecule ligand induces a conformational shift of said protein; andc) modulating said population of said low density lipoprotein receptors by said conformational shift.2. The method of claim 1 , wherein said pharmaceutical formulation further comprises a first pharmaceutical drug.3. The method of claim 2 , wherein said first pharmaceutical drug comprises a cardiovascular drug.4. The method of claim 3 , wherein said cardiovascular drug is selected from the group consisting of a statin and ezetimibe.5. The method of claim 1 , wherein ...

DEPLOYABLE, MULTI-SIDED ILLUMINATION DEVICES AND RELATED METHODS OF USE

An illumination device may include a body having twelve sides, the body being formed by a first body portion including six sides of the twelve sides, and a second body portion including six sides of the twelve sides. The first body portion and the second body portion may be coupled to one another at a first interface and at a second interface disposed radially inward of the first interface, wherein the first interface may be positioned in a plurality of planes, and wherein the second interface may be positioned in a single plane. At least a portion of each of the twelve sides may include a transparent window. The illumination device may include a resilient cover disposed around the body. 1. An illumination device , comprising:a body having twelve sides, the body being formed by a first body portion including six sides of the twelve sides, and a second body portion including six sides of the twelve sides, the first body portion and the second body portion being coupled to one another at a first interface and at a second interface disposed radially inward of the first interface, wherein the first interface is positioned in a plurality of planes, and wherein the second interface is positioned in a single plane, wherein at least a portion of each of the twelve sides includes a transparent window;a resilient cover disposed around the body, the resilient cover having twelve sides, wherein each of the twelve sides of the resilient cover extend over a respective side of the body, wherein each of the twelve sides of the resilient cover includes an opening positioned over one of the transparent windows of the body.a plurality of illumination sources, each of the plurality of illumination sources being positioned on an interior side of a transparent window of the body;a power source configured to deliver power to each of the plurality of illumination sources;a controller coupled to the power source and to the plurality of illumination sources;a charging port disposed in one of ...

Composition and Methods of Use of Small Molecules as Binding Ligands for the Modulation of Proprotein Convertase Subtilisin/Kexin Type 9(PCSK9) Protein Activity

This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels. 1. A method , comprising binding an allosteric small molecule compound to a PCSK9 protein to modulate the uptake of low-density lipoprotein by a plurality of hepatocytes.2. A method of claim 1 , to treat liver dysfunction or liver disease.3. A method of claim 2 , wherein said modulation is the increasing uptake of low-density lipoprotein by a plurality of hepatocytes.4. A method of claim 3 , wherein the allosteric small molecule is selected from the group consisting of SRX75 claim 3 , SRX76 claim 3 , SRX204 claim 3 , SRX208 claim 3 , SRX209 claim 3 , SRX210 claim 3 , SRX211 claim 3 , SRX212 claim 3 , SRX 213 claim 3 , SRX214 claim 3 , SRX215 claim 3 , SRX216 claim 3 , SRX217 claim 3 , SRX218 claim 3 , SRX219 claim 3 , SRX220 claim 3 , SRX221 claim 3 , SRX222 claim 3 , SRX223 claim 3 , SRX224 claim 3 , and SRX225.5. A method of claim 3 , wherein said allosteric small molecule compound is further combined with a second pharmaceutical compound.6. A method of claim 2 , wherein said modulation is the decreasing the uptake of low-density lipoprotein by a plurality of hepatocytes.7. A method of claim 6 , wherein the ...

Composition and methods of use of tetrahydroisoquinoline small molecules to bind and modulate pcsk9 protein activity

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL- cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels.

Deployable, multi-sided illumination devices and related methods of use

An illumination device may include a body having twelve sides, the body being formed by a first body portion including six sides of the twelve sides, and a second body portion including six sides of the twelve sides. The first body portion and the second body portion may be coupled to one another at a first interface and at a second interface disposed radially inward of the first interface, wherein the first interface may be positioned in a plurality of planes, and wherein the second interface may be positioned in a single plane. At least a portion of each of the twelve sides may include a transparent window. The illumination device may include a resilient cover disposed around the body.

Deployable, multi-sided illumination devices and related methods of use

Phenylpiperazine proprotein convertase subtilisin/kexin type 9 (PCSK9) modulators and their use

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels.

Proprotein convertase subtilisin/kexin type 9 allosteric binding ligands to modulate serum low density lipoprotein

Method to treat lipid dysregulation by modulation of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein activity with small molecule ligands

This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels.

Composition and methods of use of tetrahydroisoquinoline small molecules to bind and modulate PCSK9 protein activity

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunctions; thus, there is also utility for small organic compound ligands and can raise LDL levels.

Phenylalanine small organic compounds to directly modulate PCSK9 protein activity

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels.

Proprotein convertase subtilisin/kexin type 9 allosteric binding ligands to modulate serum low density lipoprotein

This invention is related to the field of hypercholesterolemia. In particular, the invention provides compositions and methods to modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9 using synthetic ligands and/or synthetic ligand derivative sequences of 3-8 amino acids ranging between 350 - 2,000 Da. Altering the conformation of PCSK9 affects the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for ligands which can raise LDL levels.

Proprotein convertase subtilisin/kexin type 9 (pcsk9) allosteric binding ligands to mudulate serum low density lipoprotein (ldl) levels

This invention is related to the field of hypercholesterolemia. In particular, the invention provides compositions and methods to modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9 using synthetic ligands and/or synthetic ligand derivative sequences of 3-8 amino acids ranging between 350 - 2,000 Da. Altering the conformation of PCSK9 affects the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for ligands which can raise LDL levels.

Method to treat lipid dysregulation by modulating activity of proprotein convertase subtilisin/kexin type 9 (pcsk9) protein with small molecule ligands

This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol, High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels.

Composition and methods of use of novel phenylalanine small organic compounds to directly modulate pcsk9 protein activity

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL- cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels.

Phenylpiperazine proprotein convertase subtilisin/kexin type 9 (pcsk9) modulators and their use

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels.

Method and apparatus for predicting life cycle of a splice

A monitoring apparatus, and method of use, that is capable of determining the joint characteristics by means of waveforms shifts at zero-crossing angular distortions through predictive failure algorithm specific to circuit under test.