DISPLAY DEVICE ADJUSTABLE HEAD HIGH

Un dispositif d'affichage tête haute (10) comprend un projecteur (12) pour générer un faisceau lumineux chargé d'une information à afficher, un combineur (20) ayant une position d'affichage pour afficher l'information dans le champ de vision d'un utilisateur et un système optique définissant un chemin optique entre le projecteur et le combineur lorsque celui-ci se trouve dans sa position d'affichage, pour diriger le faisceau lumineux sur le combineur. Le système optique comprend un premier et un deuxième miroirs de déviation. Le premier miroir (22) est agencé pour recevoir le faisceau lumineux du projecteur et le renvoyer vers le deuxième miroir (24), celui-ci étant agencé pour renvoyer le faisceau lumineux sur le chemin optique vers le combineur. Un système d'actionnement est prévu pour ajuster la longueur du chemin optique entre le projecteur et le combineur par positionnement des premier et deuxième miroirs de déviation.

COMBINE INSTRUMENTS FOR MOTOR VEHICLE

COMBINE INSTRUMENTS FOR MOTOR VEHICLE

Un combiné d'instruments (10), notamment pour véhicule automobile comprend un écran d'affichage (14) pour afficher des informations au conducteur du véhicule, une mémoire holographique (22) contenant les informations stockées sous forme d'hologrammes, ainsi qu'une source de lumière (18) pour générer un ou plusieurs faisceaux lumineux de lecture pour extraire les informations à afficher de la mémoire holographique et visualiser des informations extraites de la mémoire holographique sur l'écran d'affichage. Un dispositif d'affichage tête haute est intégré dans le combiné d'instruments et comprend un combineur (16) qui projette des informations extraites de la mémoire holographique dans le champ de vision tête haute du conducteur.

DIFFRACTIVE SEQUENCE SWITCH FOR BILL-POSTER HEAD HIGH COLOR

SYSTEM AND PROCEEDED OF DYNAMIC GUIDANCE Of a MOTOR VEHICLE

DIFFRACTIVE SEQUENCE SWITCH FOR BILL-POSTER HEAD HIGH COLOR

Un combineur diffractif (10) pour dispositif d'affichage tête haute couleur (18) comprend un premier réseau de diffraction optique (14) configuré pour diffracter, dans une direction de diffraction, de la lumière d'une première longueur d'onde incidente sur le premier réseau selon une direction d'incidence, un deuxième réseau de diffraction optique (16) configuré pour diffracter, dans la même direction de diffraction, de la lumière d'une deuxième longueur d'onde incidente sur le deuxième réseau selon la direction d'incidence. Les premier et deuxième réseaux de diffraction optique sont formés en relief sur une première et une deuxième face opposées du combineur. Le premier et/ou le deuxième réseau est réalisé comme réseau de diffraction optique multiplexé en longueur d'onde et configuré pour diffracter, dans la direction de diffraction, de la lumière d'une troisième longueur d'onde incidente le premier et/ou deuxième réseau de diffraction optique selon la direction d'incidence.

STABLE COMPOSITION COMPOUND SOLID AROMATIC AND USES

L'objet de l'invention est une composition sous forme solide, stable et dispersible dans l'eau, caractérisée en ce qu'elle comprend : - au moins un alcool aromatique, - au moins un agent émulsifiant, - au moins un agent texturant, et - au moins un couple acide-base effervescent. L'invention vise également ses utilisations, en particulier comme produit phytosanitaire.

DISPLAY DEVICE HEAD HIGH HAS RETRACTABLE SEQUENCE SWITCH

Un dispositif d'affichage tête haute (10) comprend un combineur (20) escamotable ayant une position d'affichage et une position de rangement, un système optique (18) et un mécanisme d'actionnement pour déplacer le combineur depuis sa position de rangement dans sa position d'affichage et inversement. Le mécanisme comprend un chariot élévateur (22) portant le combineur. Le combineur est disposé dressé sur le chariot élévateur. Le chariot élévateur exécute une course uniquement en translation pour mouvoir le combineur. Un élément obturateur (32) est prévu pour fermer l'ouverture de déploiement. L'élément obturateur est lié au mécanisme d'actionnement de sorte à fermer ou ouvrir l'ouverture de déploiement lors d'au moins une partie de la course en translation du chariot élévateur.

A DEVICE FOR HOLDING A WHEEL IN PERPETUAL MOTION

L'invention concerne un dispositif permettant de maintenir une roue en mouvement pour une utilisation de production d'énergie. Il est constitué d'une roue fixe châssis (1) présentant deux réservoirs (4) et (7), destinés à recevoir des masses type (10) sur cette roue (1) reposent une roue mobile périphérique (11) et une roue centrale mobile(13).Des compartiments type(12) parcourent les deux roues (11 et (13). Le système se met en mouvement lorsque une masse type (10) s'échappe du réservoir (4) et se loge dans un compartiment vaquant type (12) de la roue (13) et relâche en même temps une autre masse (10) dans le réservoir (7). Cette roue (13) en tournant fait trainer avec elle l'autre roue (11) qui reçoit une masse (10) du réservoir (7) dans son compartiment (12) et relâche en même temps une masse (10) dans le réservoir (4), et le processus recommence de nouveau. Le dispositif est particulièrement destiné à faire tourner les génératrices de production d'électricité.

DISPLAY SYSTEM Head high

PROCEEDED OF RESTITUTION Of INFORMATION EDGE Of a Road vehicle HAS

DISPLAY SYSTEM Head high

Unité optique indépendante pour système d'affichage tête haute pour véhicule automobile, destiné à l'affichage dans le champ de vision du conducteur (8) d'une image virtuelle obtenue à partir d'une image objet (3) provenant d'un projecteur (9, 12), comportant un premier composant optique (1) réfléchissant les rayons lumineux incidents issus du projecteur (9, 12) en direction d'un second composant optique (2) placé dans le champ de vision du conducteur (8) en vue du positionnement d'une image virtuelle finale (7), des moyens de réglage de leur position relative étant prévus.

HEAD-UP DISPLAY DEVICE RETRACTABLE COMBINER

DIFFRACTIVE DEVICE OF INDICATION FOR REAR VIEW MIRROR WITH POSTING 2D/3D

REDUCER OF SPECKLES AND UNIT OF PROJECTION INCLUDING/UNDERSTANDING A REDUCER OF SPECKLES

Le présent dispositif réducteur de speckles comprend un élément optique (20, 120) destiné à être traversé par le faisceau de lumière cohérente à traiter. Il comprend en outre des moyens (22, 123) aptes à provoquer un échauffement dudit élément optique (20, 120) ; et un élément refroidisseur (26) couplé audit élément optique (20, 120) de sorte à pouvoir refroidir ce dernier. Un module de commande (34, 134) est configuré pour commander les moyens d'échauffement et l'élément refroidisseur de sorte à créer des perturbations thermiques dans l'élément optique (20, 120), entraînant des variations correspondantes de l'indice de réfraction dudit élément optique.

REDUCER OF SPECKLES AND UNIT OF PROJECTION INCLUDING/UNDERSTANDING A REDUCER OF SPECKLES

DISPLAY DEVICE ADJUSTABLE HEAD HIGH

DIFFRACTIVE DEVICE OF INDICATION FOR REAR VIEW MIRROR WITH POSTING 2D/3D

Dispositif de signalisation (24) prévu pour être agencé sur l'élément réflectif (16) formant miroir d'un dispositif de rétrovision (12) comprenant au moins un module d'illumination (26, 28) et au moins un dispositif optique (30), caractérisé en ce que le dispositif optique (30) comporte un module générateur de symboles (30) qui est pourvu d'au moins un réseau diffractif (38) prévu pour former une image lumineuse correspondant à un premier symbole lumineux (A), ledit module générateur de symboles (30) étant globalement transparent et ledit réseau diffractif (38) étant réalisé à la surface dudit module générateur de symboles (30) sans en affecter sa transparence.

PROCESS OF DETECTION OF the PRPSC USING an ANTIBIOTIC D OF FAMILY DESAMINOGLYCOSIDES FOR the ELIMINATION AND the DETECTION OF the PRPSC IN BIOLOGICAL DESECHANTILLONS

Head-up display device for motor vehicle, has adjusting device offsetting active display area in extent area with respect to nominal position to modify inclination angle of illumination axis and cause corresponding movement of virtual image

Dispositif d'affichage tête haute (14), notamment pour un véhicule automobile (10), comportant une unité de projection (16) et un afficheur (30) comportant une zone d'affichage active (Za) destinée à former une image source (31) transmise vers le combineur diffractif (18) avant d'être projetée sous la forme d'une image virtuelle (19), caractérisé en ce que l'afficheur (30) comporte une zone d'affichage étendue (Ze) dans laquelle la zone d'affichage active (Za) est incluse, et en ce qu'un dispositif de réglage (34) de la position de l'image virtuelle (19) permet d'excentrer la zone d'affichage active (Za) dans la zone d'affichage étendue (Ze) par rapport à une position nominale (Po) de manière à provoquer un déplacement correspondant de l'image virtuelle (19).

PRP DETECTION METHOD USING A MOLECULE CONTAINING AT LEAST ONE POSITIVE CHARGE AND/OR AT LEAST ONE LINK AND AN OSIDIC LIGAND OTHER THAN A PROTEINIC LIGAND

PROCESS OF CONTROL OF THE DIRECTIVITY AND THE POLARIZATION OF COHERENT DISTRIBUTIONS OF FIELD IN A REVERBERATING MEDIUM.

DISPLAY DEVICE HEAD HIGH PROVIDED With an ADJUSTING DEVICE OF the POSITION OF the VIRTUAL IMAGE

PROCESS AND DEVICE OF ORGANIC MATERIAL DESTRUCTION LIQUID PARPLASMA COLD

REINIGUNGSVERFAHREN

Method of fabrication of construction materials from industrial solid waste

A low-pressure method for producing construction materials, such as blocks, bricks or slabs, utilizing high percentages of waste cement dust in admixture with additive material capable of effectively neutralizing the high lime content and agglomerating the extremely fine particles of the cement dust upon blending of the admixture with water. The resulting blend may simply be cast in molds of various shapes and sizes and cured under normal atmospheric pressure conditions into a hardened construction material exhibiting high strength, light weight and high thermal insulation.

Compositions and Methods for Treatment of Cancer

The present invention relates to pyrroloquinolinyl-pyrrolidine-2,5-dione compounds in combination with chemotherapeutic agents. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a pyrroloquinolinyl-pyrrole-2,5-dione compound or pyrroloquinolinyl-pyrrolidine-2,5-dione compound of the present invention and also administering a effective amount of a chemotherapeutic agent. 115-. (canceled)1716. The pharmaceutical composition of , wherein said second chemotherapeutic agent is selected from the group consisting of tamoxifen , raloxifene , anastrozole , exemestane , letrozole , trastuzumab , imatinib , paclitaxel , cyclophosphamide , lovastatin , mimosine , gemcitabine , araC , 5-fluorouracil , methotrexate , docetaxel , goserelin , vinctristine , vinblastine , nocodazole , teniposide , etoposide , gemcitabine , epothilone , navelbine , camptothecin , daunorubicin , dactinomycin , mitoxantrone , amsacrine , doxorubicin , epirubicin or idarubicin.1826-. (canceled)28. The method of claim 27 , wherein said second chemotherapeutic agent is selected from the group consisting of tamoxifen claim 27 , raloxifene claim 27 , anastrozole claim 27 , exemestane claim 27 , letrozole claim 27 , trastuzumab claim 27 , imatinib claim 27 , paclitaxel claim 27 , cyclophosphamide claim 27 , lovastatin claim 27 , mimosine claim 27 , gemcitabine claim 27 , araC claim 27 , 5-fluorouracil claim 27 , methotrexate claim 27 , docetaxel claim 27 , goserelin claim 27 , vinctristine claim 27 , vinblastine claim 27 , nocodazole claim 27 , teniposide claim 27 , etoposide claim 27 , gemcitabine claim 27 , epothilone claim 27 , navelbine claim 27 , camptothecin claim 27 , daunorubicin claim 27 , dactinomycin claim 27 , mitoxantrone claim 27 , amsacrine claim 27 , doxorubicin claim 27 , epirubicin or idarubicin.29. The method of wherein said treating said cell proliferative ...

Devices and methods for concentration and analysis of fluids

Disclosed are articles, compositions and methods for detecting analytes. The disclosed articled, compositions and methods increase the ease of detection and quantitation of the target analyte.

Determination of site of origin for a natural electrical pulse in a living body

Techniques include determining a first vector of temporal changes in electrical data measured at multiple electrical sensors positioned at corresponding locations on a surface of a living body due to a natural electrical pulse. A different vector of temporal changes in electrical data measured at the same electrical sensors is determined due to each stimulated signal of multiple stimulated signals within the living body. Stimulated position data is received, which indicates a different corresponding position within the living body where each of the stimulated signals originates. The site of origin of the natural electrical pulse is determined based on the first vector and the multiple different vectors and the stimulated position data. Among other applications, these techniques allow the rapid, automatic determination of the site of origin of ventricular tachycardia arrhythmia (VT). 1. A method for determining a site of origin of a natural electrical pulse in a living body comprising:determining a first vector of temporal changes in electrical data measured at a plurality of electrical sensors positioned at a corresponding plurality of locations on a surface of a living body due to a natural electrical pulse;determining a different vector of temporal changes in electrical data measured at the plurality of electrical sensors positioned at the corresponding plurality of locations on the surface of the living body due to each stimulated signal of a plurality of stimulated signals within the living body;receiving stimulated position data that indicates a different corresponding position within the living body where each of the plurality of stimulated signals originates; anddetermining the site of origin of the natural electrical pulse based on the first vector and the plurality of different vectors and the stimulated position data.2. A method as recited in claim 1 , wherein the natural electrical pulse is a ventricular tachycardia arrhythmia.3. A method as recited in ...

Puncture-treatment assembly

The elongated introducer assembly is configured to be selectively movable proximate to the biological feature of the patient, and puncture the biological feature of the patient and form a puncture site through the biological feature; and dilate the puncture site; and receive the auxiliary device for facilitation of movement of the auxiliary device toward the puncture site.

BETA-D-2'-DEOXY-2'-SUBSTITUTED-4'-SUBSTITUTED-2-SUBSTITUTED-N6-SUBSTITUTED-6-AMINOPURINENUCLEOTIDES FOR THE TREATMENT OF PARAMYXOVIRUS AND ORTHOMYXOVIRUS INFECTIONS

A compound or a pharmaceutically acceptable salt or composition thereof for the treatment of a host infected with or exposed to a virus of the Paramyxoviridae or Orthomyxoviridae family, or other disorders, in particular respiratory syncytial virus, more fully described herein. 2. The compound of claim 1 ,wherein{'sup': '1', 'Ris selected from methyl and cyclopropyl; and'}{'sup': '2', 'Ris hydrogen.'}3. The compound of claim 1 , wherein Ris methyl and Ris methyl.4. The compound of claim 1 , wherein Ris hydrogen.5. The compound of claim 1 , wherein Ris selected from Calkyl claim 1 , methyl claim 1 , Chaloalkyl claim 1 , and —CHCl.6. The compound of claim 1 , wherein Ris selected from Cl claim 1 , F claim 1 , and NRRwherein{'sup': '5', 'Ris hydrogen;'}{'sup': 6', '3C, 'Ris —C(O)R; and'}{'sup': '3C', 'Ris alkyl.'}7. The compound of claim 1 , wherein the stabilized phosphate prodrug is a phosphoramidate.8. The compound of claim 1 , wherein the stabilized phosphate prodrug is a thiophosphoramidate.10. The compound of claim 9 ,wherein{'sup': '1', 'Ris selected from methyl and cyclopropyl; and'}{'sup': '2', 'Ris hydrogen.'}11. The compound of claim 9 , wherein Ris methyl and Ris methyl.12. The compound of claim 9 , wherein Ris hydrogen.13. The compound of claim 9 , wherein Ris selected from Calkyl claim 9 , methyl claim 9 , Chaloalkyl claim 9 , and —CHCl.14. The compound of claim 9 , wherein Ris selected from Cl claim 9 , F claim 9 , and NRRwherein{'sup': '5', 'Ris hydrogen;'}{'sup': 6', '3C, 'Ris —C(O)R; and'}{'sup': '3C', 'Ris alkyl.'}15. The compound of claim 9 , wherein the stabilized phosphate prodrug is a phosphoramidate.16. The compound of claim 9 , wherein the stabilized phosphate prodrug is a thiophosphoramidate.18. The compound of claim 17 ,wherein{'sup': '1', 'Ris selected from methyl and cyclopropyl; and'}{'sup': '2', 'Ris hydrogen.'}19. The compound of claim 17 , wherein Ris methyl and Ris methyl.20. The compound of claim 17 , wherein Ris hydrogen.21. The ...

TREATMENT OF HCV INFECTED PATIENTS WITH CIRRHOSIS

A pharmaceutical composition that includes a compound of the structure: 2. The method of claim 1 , wherein the compound is administered orally.3. The method of claim 1 , wherein the compound is administered parentally.4. The method of claim 1 , wherein the compound is administered intravenously.5. The method of claim 1 , wherein the compound is administered via controlled release.6. The method of claim 1 , wherein at least 400 mg of the compound is administered.7. The method of claim 1 , wherein at least 500 mg of the compound is administered.8. The method of claim 1 , wherein at least 600 mg of the compound is administered.9. The method of claim 1 , wherein at least 700 mg of the compound is administered.10. The method of claim 1 , wherein the compound is administered for up to 12 weeks claim 1 , for up to 8 weeks claim 1 , or for up to 6 weeks.11. The method of claim 1 , wherein the compound is administered once a day.12. The method of claim 1 , wherein the compound is administered twice a day.13. The method of claim 1 , wherein the hepatitis C virus is Genotype 1a claim 1 , 1b claim 1 , 2a claim 1 , 2b claim 1 , 3a claim 1 , 3b claim 1 , 4a claim 1 , 4d claim 1 , 5a claim 1 , or 6.14. The method of claim 13 , wherein the hepatitis C virus is Genotype 1a.15. The method of claim 13 , wherein the hepatitis C virus is Genotype 1b.16. The method of claim 13 , wherein the hepatitis C virus is Genotype 2a or 2b.17. The method of claim 13 , wherein the hepatitis C virus is Genotype 3a or 3b.18. The method of claim 13 , wherein the hepatitis C virus is Genotype 4a or 4d.19. The method of claim 13 , wherein the hepatitis C virus is Genotype 5a.21. The method of claim 20 , wherein the compound is administered orally.22. The method of claim 20 , wherein the compound is administered parentally.23. The method of claim 20 , wherein the compound is administered intravenously.24. The method of claim 20 , wherein the compound is administered via controlled release.25. The method ...

BETA-D-2'-DEOXY-2'-ALPHA-FLUORO-2'-BETA-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT

A compound of the structure: 4. The pharmaceutical composition of claim 1 , in a dosage form.5. The pharmaceutical composition of claim 4 , in an oral dosage form.6. The pharmaceutical composition of claim 5 , in a tablet.7. The pharmaceutical composition of claim 5 , in a capsule.8. The pharmaceutical composition of claim 2 , in a dosage form.9. The pharmaceutical composition of claim 8 , in an oral dosage form.10. The pharmaceutical composition of claim 9 , in a tablet.11. The pharmaceutical composition of claim 9 , in a capsule.12. The pharmaceutical composition of claim 3 , in a dosage form.13. The pharmaceutical composition of claim 12 , in an oral dosage form.14. The pharmaceutical composition of claim 13 , in a tablet.15. The pharmaceutical composition of claim 13 , in a capsule.19. The pharmaceutical composition of claim 16 , in a dosage form.20. The pharmaceutical composition of claim 20 , in an oral dosage form.21. The pharmaceutical composition of claim 21 , in a tablet.22. The pharmaceutical composition of claim 21 , in a capsule.23. The pharmaceutical composition of claim 17 , in a dosage form.24. The pharmaceutical composition of claim 23 , in an oral dosage form.25. The pharmaceutical composition of claim 24 , in a tablet.26. The pharmaceutical composition of claim 24 , in a capsule.27. The pharmaceutical composition of claim 18 , in a dosage form.28. The pharmaceutical composition of claim 27 , in an oral dosage form.29. The pharmaceutical composition of claim 28 , in a tablet.30. The pharmaceutical composition of claim 28 , in a capsule. This application is a continuation of U.S. Ser. No. 15/063,461 filed on Mar. 7, 2016 and claims priority to U.S. Ser. No. 62/129,319 filed on Mar. 6, 2015; U.S. Ser. No. 62/253,958 filed on Nov. 11, 2015; and, U.S. Ser. No. 62/276,597 filed on Jan. 8, 2016. Each of these references is incorporated herewith in their entirety.The present invention is directed to nucleotide compounds and compositions and uses thereof ...

BETA-D-2'-DEOXY-2'-ALPHA-FLUORO-2'BETA-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT

A compound of the structure: 2. The compound of claim 1 , wherein the stabilized phosphate prodrug is a phosphoramidate.4. The compound of claim 3 , wherein Ris aryl.5. The compound of claim 4 , wherein Ris phenyl.6. The compound of claim 3 ,wherein{'sup': '16', 'Ris hydrogen;'}{'sup': '17', 'sub': 1', '8, 'Ris (C-C)alkyl;'}{'sup': '18', 'Ris hydrogen; and'}{'sup': '19', 'sub': 1', '6, 'Ris (C-C)alkyl.'}7. The compound of claim 6 , wherein Ris aryl.8. The compound of claim 7 , wherein Ris phenyl. This application is a continuation of U.S. Ser. No. 15/063,461 filed on Mar. 7. 2016 and claims priority to U.S. Ser. No. 62/129,319 filed on March 6, 2015, U.S. Ser. No. 62/253,958 filed on Nov. 11, 2015, and U.S. Ser. No. 62/276,597 filed on Jan. 8, 2016. Each of these references is incorporated herewith in their entirety.The present invention is directed to nucleotide compounds and compositions and uses thereof to treat the Hepatitis C virus (“HCV”).Hepatitis C (HCV) is an RNA single stranded virus and member of the genus. It is estimated that 75% of all cases of liver disease are caused by HCV. HCV infection can lead to cirrhosis and liver cancer, and if left to progress, liver failure which may require a liver transplant, Approximately 170-200 million people worldwide are infected, with an estimated 3-4 million infections in the United States.RNA polymerase is a key component in the targeting of RNA single stranded viruses. The HCV non-structural protein NS5B RNA-dependent RNA polymerase is a key enzyme responsible for initiating and catalyzing viral RNA synthesis. As a result, HCV NS5B is an attractive target for the current drug discovery and development of anti-HCV agents. There are two major subclasses of NS5B inhibitors: nucleoside analogs, which are anabolized to their active triphosphates—which act as alternative substrates for the polymerase—and non-nucleoside inhibitors (NNIs), which bind to allosteric regions on the protein. Nucleoside or nucleotide ...

CRYSTALLINE EPINEPHRINE MALONATE SALT

Described herein are epinephrine salts, specifically the epinephrine malonate salt; the epinephrine malonate salt in crystalline form; a pharmaceutical composition comprising epinephrine malonate; a sublingual or buccal pharmaceutical composition comprising epinephrine malonate in crystalline form; and a method for treating a patient comprising administering a pharmaceutical composition of epinephrine malonate in crystalline form. 1. An epinephrine malonate salt in crystalline form.2. The epinephrine malonate salt of claim 1 , wherein the crystalline form has an x-ray powder diffraction spectrum having one or more peaks expressed as 2 theta at about 12.1843 claim 1 , 13.4653 claim 1 , 14.2595 claim 1 , 14.6991 claim 1 , 15.8664 claim 1 , 17.3570 claim 1 , 17.9004 claim 1 , 19.5883 claim 1 , 20.4659 claim 1 , 21.5801 claim 1 , 22.3908 claim 1 , 22.9301 claim 1 , 23.8776 claim 1 , 24.6585 claim 1 , 25.3418 claim 1 , 26.0105 claim 1 , 26.4829 claim 1 , 25.3418 claim 1 , 26.0105 claim 1 , 26.4829 claim 1 , 27.2385 claim 1 , 27.8939 claim 1 , 29.4741 claim 1 , 33.2425 claim 1 , 34.2629 claim 1 , 34.8439.3. A pharmaceutical composition comprising epinephrine malonate salt and a pharmaceutically acceptable carrier.4. The pharmaceutical composition of claim 3 , wherein the pharmaceutical composition is suitable for oral claim 3 , rectal claim 3 , intragastrical claim 3 , topical claim 3 , intracranial claim 3 , intranasal claim 3 , and parenteral administration.5. The pharmaceutical composition of claim 3 , wherein the pharmaceutical composition is suitable for sublingual or buccal administration.6. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition comprises a filler and a disintegrant.7. The pharmaceutical composition of claim 6 , wherein the filler is microcrystalline cellulose and the disintigrant is cross-linked polyvinyl polypyrrolidone.8. The pharmaceutical composition of claim 7 , wherein the filler is present in an amount of 20 to 30 ...

ELONGATED MEDICAL CATHETER INCLUDING MARKER BAND

An elongated medical catheter includes a marker band with sidebands. The elongated medical catheter and the marker band have a radiopacity being different from the radiopacity of the sidebands. 1. An apparatus , comprising:an elongated medical catheter including a marker band with sidebands; andthe elongated medical catheter and the marker band having a radiopacity being different from the radiopacity of the sidebands.2. The apparatus of claim 1 , wherein:the sidebands are positioned on opposite sides of the marker band.3. The apparatus of claim 1 , wherein:the elongated medical catheter defines a catheter lumen extending through the sidebands and the marker band.4. The apparatus of claim 1 , wherein:the radiopacity of the elongated medical catheter is reduced at a near vicinity of the marker band by reducing a proportion of radiopaque materials in an area of the elongated medical catheter that is located proximate to the marker band.5. The apparatus of claim 1 , wherein:the elongated medical catheter has a decrease in radiopacity at a near vicinity of the marker band in such a way that a difference in radiopacity, between the elongated medical catheter and the marker band, is increased.6. (canceled)7. An apparatus claim 1 , comprising:an elongated medical catheter having a catheter distal portion and a catheter proximal portion; andthe elongated medical catheter having a marker band being positioned between the catheter distal portion and the catheter proximal portion; andthe marker band having a first end portion and a second end portion; andthe elongated medical catheter having a first sideband being positioned proximate to the first end portion of the marker band; andthe elongated medical catheter having a second sideband being positioned proximate to the second end portion of the marker band; andthe elongated medical catheter having a catheter radiopacity; andthe marker band having a marker-band radiopacity; andthe first sideband having a first sideband ...

Solid forms of a flaviviridae virus inhibitor compound and salts thereof

Provided herein are crystalline and salt forms of methyl N-{(1R)-2-[(2S)-2-{5-[4-(6-{2-[(2S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl} pyrrolidin-2-yl]-3H-benzimidazol-5-yl}thieno[3,2-b]thiophen-3-yl)phenyl]-1H-imidazol-2-yl}pyrrolidin-1-yl]-2-oxo-1-phenylethyl} carbamate, a Flaviviridae, including hepatitis C, virus inhibitor, pharmaceutical compositions comprising the compound, and processes of preparation thereof. Also provided are methods of its use for the treatment of a Flaviviridae, including HCV, infection in a subject in need thereof.

MID-INFRARED IMAGING OF MICROARRAYS

Described herein are methods for mid-infrared imaging of nucleic acid microarrays by employing mid-infrared reflective labels combined with detection in the reflection mode. The methods described herein provide intrinsic image contrast, and permit detection of DNA microarray hybridization on infrared absorbing substrates such as glass slides. 1. A method for detecting presence or absence of a target in a sample , the method comprising:contacting a capture probe attached to an addressable location on a solid infrared absorbing surface with the sample under conditions effective to form a hybridization complex between the capture probe and the target, and binding to the target a mid-infrared reflective metal after contacting with the capture probe;{'sup': −', '−1, 'exposing the contacted capture probe and solid surface to light having a wavenumber of 4000 cm1 to 900 cm; and'}determining, in external reflection mode, any reflectance from the solid surface with the contacted capture probes, wherein measurable mid-infrared reflectance indicates the presence of the target in the sample.2. The method of claim 1 , comprising exposing the contacted capture probe and solid surface to light having a wavenumber of 1400 cmto 956 cm.3. The method of claim 1 , wherein the target is conjugated to a nanoparticle prior to contacting with the capture probe to form the hybridization complex.4. The method of claim 3 , wherein the mid-infrared reflective metal is silver.5. The method of claim 4 , wherein the nanoparticle is a gold nanoparticle.6. The method of claim 1 , wherein the target is biotinylated and is then conjugated with a streptavidin-nanoparticle conjugated after contacting with the capture probe to form the hybridization complex.7. The method of claim 6 , wherein the mid-infrared reflective metal is silver.8. The method of claim 7 , wherein the nanoparticle is a gold nanoparticle.9. The method of claim 1 , wherein reflectance is detected with a mercury cadmium telluride ...

NUCLEOTIDE HEMI-SULFATE SALT FOR THE TREATMENT OF HEPATITIS C VIRUS

A hemi-sulfate salt of the structure: 3. The compound of wherein the compound is at least 90% free of the opposite phosphorus S-enantiomer.4. The compound of wherein the compound is at least 98% free of the opposite phosphorus S-enantiomer.6. The compound of wherein the compound is at least 90% free of the opposite phosphorus R-enantiomer.7. The compound of wherein the compound is at least 98% free of the opposite phosphorus R-enantiomer.10. The pharmaceutical composition of claim 9 , wherein the compound is at least 90% free of the opposite phosphorus S-enantiomer.11. The pharmaceutical composition of claim 10 , wherein the compound is at least 98% free of the opposite phosphorus S-enantiomer.13. The pharmaceutical composition of claim 12 , wherein the compound is at least 90% free of the opposite phosphorus R-enantiomer.14. The pharmaceutical composition of claim 13 , wherein the compound is at least 98% free of the opposite phosphorus R-enantiomer.15. The pharmaceutical composition of claim 8 , wherein the pharmaceutically acceptable carrier is suitable for oral delivery.16. The pharmaceutical composition of claim 15 , wherein the pharmaceutically acceptable dosage form suitable for oral delivery is in a solid dosage form.17. The pharmaceutical composition of claim 16 , wherein the pharmaceutically acceptable carrier is in the form of a tablet or a capsule.18. The pharmaceutical composition of claim 15 , wherein the pharmaceutically acceptable dosage form suitable for oral delivery is in a liquid dosage form.19. The pharmaceutical composition of claim 18 , wherein the pharmaceutically acceptable carrier is in the form of a suspension or solution.20. The pharmaceutical composition of claim 15 , in an intravenous formulation.21. The pharmaceutical composition of claim 15 , in a parenteral formulation. This application is a continuation of U.S. application Ser. No. 16/918,918, filed Jul. 1, 2020, which is a continuation of U.S. application Ser. No. 16/687,136, filed ...

Index based ransomware categorization

A computer implemented method of identifying a ransomware algorithm, the ransomware algorithm having associated a predetermined responsive action for mitigating the effect of the ransomware algorithm in use, the method including exposing a target computer system to the ransomware algorithm, the target computer system containing a predetermined set of sample data stored therein that is encrypted by the ransomware algorithm using a searchable encryption algorithm; intercepting an index of the searchable encryption algorithm; training an autoencoder based on the index to provide a trained autoencoder adapted to identify the ransomware algorithm based on the index.

NUCLEOTIDE HEMI-SULFATE SALT FOR THE TREATMENT OF HEPATITIS C VIRUS

A hemi-sulfate salt of the structure: 6. The solid dosage form of claim 5 , wherein the steady-state trough plasma level (C) is between approximately 20-50 ng/mL.7. The solid dosage form of claim 5 , wherein the steady-state trough plasma level (C) is between approximately 20-30 ng/mL.8. The solid dosage form of claim 5 , wherein the steady-state trough plasma level (C) is between approximately 20-25 ng/mL.10. The solid dosage form of claim 9 , wherein the area under the curve is between approximately 1 claim 9 ,800 ng*h/mL and 3 claim 9 ,000 ng*h/mL.11. The solid dosage form of claim 9 , wherein the area under the curve is between approximately 2 claim 9 ,400 ng*h/mL and 3 claim 9 ,000 ng*h/mL.12. The solid dosage form of claim 9 , wherein the area under the curve is between approximately 2 claim 9 ,700 ng*h/mL and 3 claim 9 ,000 ng*h/mL.13. The solid dosage form of claim 9 , wherein the area under the curve is between approximately 2 claim 9 ,000 ng*h/mL and 2 claim 9 ,200 ng*h/mL.16. The pharmaceutical composition of claim 14 , in a solid dosage form that delivers at least 300 mg claim 14 , at least 400 mg claim 14 , or at least 500 mg of the compound.17. The pharmaceutical composition of claim 14 , in a solid dosage form that delivers at least 600 mg of the compound.18. The pharmaceutical composition of claim 14 , in a solid dosage form that delivers at least 700 mg of the compound.19. The pharmaceutical composition of claim 15 , in a solid dosage form that delivers at least 300 mg claim 15 , at least 400 mg claim 15 , or at least 500 mg of the compound.20. The pharmaceutical composition of claim 15 , in a solid dosage form that delivers at least 600 mg of the compound.21. The pharmaceutical composition of claim 15 , in a solid dosage form that delivers at least 700 mg of the compound.22. The pharmaceutical composition of claim 14 , wherein the pharmaceutically acceptable carrier is suitable for oral delivery.23. The pharmaceutical composition of claim 15 , ...

TARGETED VIRAL-MEDIATED PLANT GENOME EDITING USING CRISPR /Cas9

The present disclosure provides a viral-mediated genome-editing platform that facilitates multiplexing, obviates stable transformation, and is applicable across plant species. The RNA2 genome of the tobacco rattle virus (TRV) was engineered to carry and systemically deliver a guide RNA molecules into plants overexpressing Cas9 endonuclease. High genomic modification frequencies were observed in inoculated as well as systemic leaves including the plant growing points. This system facilitates multiplexing and can lead to germinal transmission of the genomic modifications in the progeny, thereby obviating the requirements of repeated transformations and tissue culture. The editing platform of the disclosure is useful in plant genome engineering and applicable across plant species amenable to viral infections for agricultural biotechnology applications. 1. A method for modifying a target site in the genome of a plant cell , the method comprising providing a nucleic acid sequence encoding a guide RNA-PAM to a plant cell having a Cas endonuclease , wherein the guide RNA is delivered to the plant cell by a plant virus vector , and wherein said guide RNA and Cas endonuclease are capable of forming a complex that enables the Cas endonuclease to introduce a double strand break at said target site.2. The method of claim 1 , further comprising providing to the plant cell a heterologous donor DNA claim 1 , wherein said heterologous donor DNA comprises a polynucleotide of interest desired to be incorporated into the genome of the plant cell.3. The method of claim 1 , wherein said method further comprises identifying at least one plant cell that has a modification at said target claim 1 , wherein the modification includes at least one deletion or substitution of one or more nucleotides in said target site.4. The method of claim 1 , wherein the plant virus vector is a genome of the Tobacco Rattle Virus (TRV).5. The method of claim 1 , wherein the nucleic acid sequence encoding a ...

DOWNHOLE ASSEMBLY, TOOL AND METHOD

A reaming tool includes a body having a longitudinal axis and an upper end opposite a lower end and a blade located on said body, the blade including a reaming surface having one or more reaming inserts disposed on at least a portion thereof and a cutting surface having one or more cutters disposed on at least a portion thereof. One or more of said cutters are configured (a) so that an extended longitudinal axis of said cutter is positioned at an angle θ between 5 degrees and 85 degrees with respect to a plane perpendicular to the longitudinal axis of said body, or (b) on said cutting surface at a radial distance from said longitudinal axis less than said radial distances between said reaming inserts and said longitudinal axis. 1. A reaming tool comprising:a body having a longitudinal axis and an upper end opposite a lower end; and a reaming surface having one or more reaming inserts disposed on at least a portion thereof; and', 'a cutting surface having one or more cutters disposed on at least a portion thereof, wherein, 'a blade located on said body, said blade comprising(a) one or more of said cutters are configured so that an extended longitudinal axis of said cutter is positioned at an angle θ between 5 degrees and 85 degrees with respect to a plane perpendicular to the longitudinal axis of said body; or(b) one or more of said cutters are configured on said cutting surface at a radial distance from said longitudinal axis less than said radial distances between said reaming inserts and said longitudinal axis.2. The reaming tool of claim 1 , wherein one or more of said cutters are configured so that an extended longitudinal axis of said cutter is positioned at an angle θ between 5 degrees and 85 degrees with respect to a plane perpendicular to the longitudinal axis of said body.3. The reaming tool of claim 2 , wherein said angle θ is between 15 degrees and 25 degrees.4. The reaming tool of claim 1 , wherein one or more of said cutters are configured on said ...

Feedback Mechanisms for a Steerable Medical Device

An apparatus and method are disclosed for providing feedback for a steerable medical device assembly for deflecting a device, the assembly comprising a control handle comprising an actuation mechanism. The assembly additionally comprises a device coupled to the control handle and operable to be deflected upon actuation of the actuation mechanism, and a feedback mechanism for providing an indication of the deflection of the device, wherein the feedback mechanism is associated with the actuation mechanism for deflecting the device. 1. A steerable medical device assembly for deflecting a device comprising:a control handle comprising an actuation mechanism;a device coupled to the control handle and operable to be deflected upon actuation of the actuation mechanism; andan audible feedback mechanism for providing an audible indication of the deflection of the device;wherein the audible feedback mechanism is associated with the actuation mechanism for deflecting the device.2. The steerable medical device assembly of claim 1 , wherein the audible feedback mechanism comprises a mechanical feedback mechanism.3. The steerable medical device assembly of claim 2 , wherein the mechanical feedback mechanism comprises:a first indicator portion associate with a housing of the control handle; anda second indicator portion associated with the actuation mechanism for deflecting the device; andwherein an interaction between the first and second indicator portions corresponds to and is indicative of a deflection position of the device and a corresponding position of the actuation mechanism to provide an audible indication of the deflection position of the device upon actuation of the actuation mechanism.4. The steerable medical device assembly of claim 1 , wherein the audible feedback mechanism comprises an electrical feedback mechanism.5. The steerable medical device assembly of claim 4 , wherein the electrical feedback mechanism comprises:a sound emitting device, the sound emitting ...

Recombinant strain producing o-aminobenzoate and fermentative production of aniline from renewable resources via 2-aminobenzoic acid

The invention provides a recombinant microbial host cell capable of converting a raw material comprising a fermentable carbon substrate to o-aminobenzoate biologically. The invention further provides a method for producing aniline, comprising the steps of: a) producing o-aminobenzoate by fermentation of a raw material comprising at least one fermentable carbon substrate using the recombinant microbial host cell of the capable of converting said raw material comprising at least one fermentable carbon substrate to o-aminobenzoate biologically, wherein said o-aminobenzoate comprises anthranilate anion, b) converting said o-aminobenzoate from said anthranilate anion to anthranilic acid by acid protonation, c) recovering said anthranilic acid by precipitation or by dissolving in an organic solvent, and d) converting said anthranilic acid to aniline by thermal decarboxylation in an organic solvent.

Coupling Mechanism for Medical Devices

A releasable coupling mechanism for coupling a delivery catheter and a dilator. The delivery catheter comprising a first mating member at the proximal end and the dilator comprising a second mating member at the proximal end. The proximal end of the first mating member comprises a first coupling means for releasably receiving a second coupling means which is positioned at a distal end of the second mating member. The first mating member further comprising a coupling member the coupling member comprising a pair of engagement members positioned on opposing sides of the coupling member and configured to releasably engage the second coupling means. The first mating member further comprising at least one indicia perpendicular from the pair of engagement members. The indicia indicate an orientation of the first mating member such that the second mating member disengages from the coupling member by simultaneously deflecting the pair of engagement members. 1) A releasable coupling mechanism for coupling a delivery catheter comprising a first mating member and a dilator comprising a second mating member , enabling the delivery catheter and dilator to be coupled and advanced together , comprising:the second mating member positioned at a proximal end of the dilator, the second mating member comprising a distal end and a proximal end;the first mating member positioned at a proximal end of the delivery catheter comprising a distal end and a proximal end, wherein the proximal end of the first mating member comprises a first coupling means for releasably receiving a second coupling means positioned at a distal end of the second mating member, 'the coupling member comprising a pair of engagement members positioned on opposing sides of the coupling member and configured to releasably engage the second coupling means; and,', 'the first mating member further comprising a coupling member proximal of the proximal end of the first mating member;'} 'whereby the indicia indicates an ...

BETA-D-2'-DEOXY-2'-ALPHA-FLUORO-2'-BETA-C-SUBSTITUTED-4'-FLUORO-N6-SUBSTITUTED-6-AMINO-2-SUBSTITUTED PURINE NUCLEOTIDES FOR THE TREATMENT OF HEPATITIS C VIRUS INFECTION

Compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula VIII, Formula IX and Formula X that are highly active against the HCV virus when administered in an effective amount to a host in need thereof. The host can be a human or any animal that carries the viral infection. Methods of treating a subject suffering from a condition related to viral infections are also provided. 2. The compound of claim 1 , wherein Ris a stabilized phosphate prodrug claim 1 , a phosphoramidate claim 1 , or a thiophosphoramidate.6. The compound of claim 1 , wherein Ris hydrogen.7. The compound of claim 1 , wherein Ris methyl and Ris hydrogen.8. The compound of claim 1 , wherein both Rand Rare methyl.9. The compound of claim 1 , wherein Ris methyl and Ris cyclopropyl.22. The compound of claim 21 , wherein Ris a stabilized phosphate prodrug claim 21 , a phosphoramidate claim 21 , or a thiophosphoramidate.26. A method of treating a patient in need thereof comprising administering a therapeutically effective amount of the compound of .27. The method of claim 26 , wherein said patient suffers from an anti-HCV antibody positive condition claim 26 , an antigen positive condition claim 26 , viral-based chronic liver inflammation claim 26 , liver cancer resulting from advanced hepatitis C claim 26 , cirrhosis claim 26 , chronic or acute hepatitis C claim 26 , fulminant hepatitis C claim 26 , chronic persistent hepatitis C or anti-HCV-based fatigue.28. A pharmaceutically acceptable composition comprising the compound of and a pharmaceutically acceptable carrier.29. A method of treating a patient in need thereof comprising administering the compound of .30. A pharmaceutically acceptable composition comprising the compound of and a pharmaceutically acceptable carrier.31. The compound of claim 1 , wherein said compound comprises an alkylated or acylated nucleotide group.32. The compound of claim 21 , wherein said compound comprises an alkylated or ...

Pharmaceutical Formulations for Subcutaneous Administration

The present disclosure relates to compositions of levodopa 4′-monophosphate and carbidopa 4′-monophosphate having a weight by weight ratio of about 20:1 and methods of treating Parkinson's disease and associated conditions by subcutaneous administration of such compositions.

Single Parameter Segmentation of Images

Embodiments of methods and systems for single parameter segmentation of images are presented. In an embodiment, a method includes assigning a first label to a first pixel in an image. The method may also include measuring a characteristic of a first pixel. Additionally, the method may include measuring the characteristic of a second pixel, the second pixel being adjacent to the first pixel in the image. Also, the method may include assigning the first label to the second pixel in response to a determination that the characteristic of the second pixel has a measured value above a similarity threshold value. The method may further include assigning a second label to the second pixel in response to a determination that the measured value of the characteristic of the second pixel is below the similarity threshold value. 1. A method , comprising:assigning a first label to a first pixel in an image;measuring a characteristic of a first pixel;measuring the characteristic of a second pixel, the second pixel being adjacent to the first pixel in the image;assigning the first label to the second pixel in response to a determination that the characteristic of the second pixel has a measured value above a similarity threshold value; andassigning a second label to the second pixel in response to a determination that the measured value of the characteristic of the second pixel is below the similarity threshold value.2. The method of , further comprising repeating the steps of for each pixel in the image.3. The method of claim 2 , further comprising measuring a characteristic of a plurality of pixels adjacent to each pixel in the image claim 2 , and assigning pixels having measured values of the characteristic over the similarity threshold to a common label.4. The method of claim 3 , further comprising assigning a lowest available label to each pixel in the image claim 3 , wherein an available label is a label of one of the adjacent pixels in the image.5. The method of claim 4 , ...

BETA-D-2'-DEOXY-2'-ALPHA-FLUORO-2'-BETA-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT

A compound of the structure: This application is a continuation of U.S. Ser. No. 16/001,549 filed Jun. 6, 2018 that is a continuation of U.S. Ser. No. 15/782,628, now U.S. Pat. No. 10,000,523, filed Oct. 12, 2017 that is a continuation of U.S. Ser. No. 15/063,461, now U.S. Pat. No. 9,828,410, filed Mar. 7, 2016 that claims priority to U.S. Ser. No. 62/129,319 filed Mar. 6, 2015; U.S. Ser. No. 62/253,958 filed Nov. 11, 2015; and, U.S. Ser. No. 62/276,597 filed Jan. 8, 2016. Each of these references is incorporated herewith in their entirety.The present invention is directed to nucleotide compounds and compositions and uses thereof to treat the Hepatitis C virus (“HCV”).Hepatitis C (HCV) is an RNA single stranded virus and member of the Hepacivirus genus. It is estimated that 75% of all cases of liver disease are caused by HCV. HCV infection can lead to cirrhosis and liver cancer, and if left to progress, liver failure which may require a liver transplant. Approximately 170-200 million people worldwide are infected, with an estimated 3-4 million infections in the United States.RNA polymerase is a key component in the targeting of RNA single stranded viruses. The HCV non-structural protein NS5B RNA-dependent RNA polymerase is a key enzyme responsible for initiating and catalyzing viral RNA synthesis. As a result, HCV NS5B is an attractive target for the current drug discovery and development of anti-HCV agents. There are two major subclasses of NS5B inhibitors: nucleoside analogs, which are anabolized to their active triphosphates—which act as alternative substrates for the polymerase—and non-nucleoside inhibitors (NNIs), which bind to allosteric regions on the protein. Nucleoside or nucleotide inhibitors mimic natural polymerase substrate and act as chain terminators. They inhibit the initiation of RNA transcription and elongation of a nascent RNA chain.In addition to targeting RNA polymerase, other RNA viral proteins may also be targeted in combination therapies. For ...

CRYSTALLINE EPINEPHRINE MALONATE SALT

Described herein are epinephrine salts, specifically the epinephrine malonate salt; the epinephrine malonate salt in crystalline form; a pharmaceutical composition comprising epinephrine malonate; a sublingual or buccal pharmaceutical composition comprising epinephrine malonate in crystalline form; and a method for treating a patient comprising administering a pharmaceutical composition of epinephrine malonate in crystalline form. 1. A method for manufacturing an epinephrine malonate salt , said method comprising:adding malonic acid to a solution comprising epinephrine and a solvent;stirring the solution; andprecipitating the epinephrine malonate salt out of solution.2. The method of claim 1 , further comprising filtering the precipitate.3. The method of claim 2 , further comprising drying the precipitate.4. The method of claim 1 , wherein malonic acid is added at a ratio of about 0.01:1 to 3:1 relative to epinephrine.5. The method of claim 1 , wherein the solvent is selected from the group consisting of methanol claim 1 , ethanol claim 1 , n-propanol claim 1 , iso-propanol claim 1 , n-butanol claim 1 , sec-butanol claim 1 , tert-butanol claim 1 , n-pentanol claim 1 , 2-methyl-butanol claim 1 , 3-methyl-butanol claim 1 , and hexanol.6. The method of claim 5 , wherein the solvent is ethanol.7. A method of treating a patient suffering from an allergic condition claim 5 , said method comprising:administering a pharmaceutically effective amount of epinephrine malonate to the patient.8. The method of claim 7 , wherein the epinephrine malonate is administered orally claim 7 , rectally claim 7 , intragastrically claim 7 , topically claim 7 , intracranially claim 7 , intranasally claim 7 , or parenterally.9. The method of claim 7 , wherein the epinephrine malonate is administered via a buccal or sublingual tablet.10. The method of claim 7 , wherein the allergic condition is selected from the group consisting of anaphylaxis claim 7 , asthma claim 7 , or bronchial asthma.11. ...

Systems and methods of managing medical images

Computer-implemented methods and systems are provided for managing one or more images. An example method for indexing involves operating a processor to, divide an image portion of an image of the one or more images into a plurality of patches, for each patch of the image: detect one or more features of the patch; and assign the patch to at least one cluster of a plurality of clusters of the image, based on the one or more features of the patch. The processor is operable to, for each cluster of the image, select at least one patch from the cluster as at least one representative patch for the cluster; for each representative patch, generate an encoded representation based on one or more features of the representative patch; and generate an index identifier for the image based on the encoded representations of the representative patches of the image.

DOWNHOLE ASSEMBLY, TOOL AND METHOD

A reaming tool includes a body having a longitudinal axis and an upper end opposite a lower end and a plurality of blades located on said body. Each blade includes a reaming surface having reaming inserts arranged on at least a portion of the reaming surface such that substantially equal load is applied on the reaming inserts in the longitudinal and circumferential directions, and wherein the reaming inserts comprise a truncated dome having a substantially flat top as an exposed contact area. 1. A reaming tool comprising:a body having a longitudinal axis and an upper end opposite a lower end; and 'a reaming surface having reaming inserts arranged on at least a portion of the reaming surface such that substantially equal load is applied on the reaming inserts in the longitudinal and circumferential directions, and wherein the reaming inserts comprise a truncated dome having a substantially flat top as an exposed contact area.', 'a plurality of blades located on said body, each blade comprising2. The reaming tool of claim 1 , wherein the reaming inserts are arranged on at least a portion of the reaming surface in a number N of rows extending substantially parallel to a longitudinal axis of said reaming surface claim 1 , wherein N is equal or superior than two claim 1 , the rows being laterally spaced from each other by a predetermined distance R claim 1 , wherein the shortest distance along said longitudinal axis of said body between any two nearest inserts in two adjacent rows is a predetermined value Y and the distance between any two adjacent inserts of a same row is a distance X of value NY.3. The reaming tool of claim 1 , further comprising a cutting surface having cutters disposed on at least a portion thereof claim 1 , wherein radial distances between an outermost portion of all of said cutters and said longitudinal axis of said body are less than or equal to radial distances between an outermost portion of said reaming inserts and said longitudinal axis of ...

HIGHLY ACTIVE DRUG COMBINATION FOR TREATMENT OF HEPATITIS C VIRUS

A combination is provided of Compound 1 or a pharmaceutically acceptable salt thereof (such as Compound 1-A) and Compound 2 or a pharmaceutically acceptable salt thereof (such as Compound 2-A) 4. The pharmaceutical dosage form of claim 1 , wherein the effective amount of Compound 1 or a pharmaceutically acceptable salt thereof and the effective amount of Compound 2 or a pharmaceutically acceptable salt thereof are administered in a single fixed-dosage form.5. The pharmaceutical dosage form of claim 1 , wherein the dosage form is suitable for oral delivery.6. The pharmaceutical dosage form of claim 5 , wherein the dosage form is a tablet.7. The pharmaceutical dosage form of claim 5 , wherein the dosage form is a capsule.8. The pharmaceutical dosage form of claim 1 , wherein the composition is in a dosage form suitable for delivery selected from parenteral claim 1 , intravenous claim 1 , intramuscular claim 1 , topical claim 1 , transdermal claim 1 , buccal claim 1 , subcutaneous and suppository.10. The Compound 2-A of claim 9 , in solid form.11. The Compound 2-A of claim 10 , in a substantially crystalline form.13. The isolated crystalline form of Compound 2-A of claim 12 , characterized by an X-ray diffraction (XRPD) pattern comprising at least six 2theta values selected from 7.3±0.2° claim 12 , 7.9±0.20 claim 12 , 12.0±0.2° claim 12 , 12.2±0.2° claim 12 , 14.7±0.2° claim 12 , 15.8±0.2° claim 12 , 16.1±0.2° claim 12 , 16.5±0.2° claim 12 , 18.2±0.2° claim 12 , and 22.7±0.2°.14. The isolated crystalline form of Compound 2-A of claim 12 , characterized by an X-ray diffraction (XRPD) pattern comprising at least seven 2theta values selected from 7.3±0.2° claim 12 , 7.9±0.20 claim 12 , 12.0±0.2° claim 12 , 12.2±0.2° claim 12 , 14.7±0.2° claim 12 , 15.8±0.2° claim 12 , 16.1±0.2° claim 12 , 16.5±0.2° claim 12 , 18.2±0.2° claim 12 , and 22.7±0.2°.15. The isolated crystalline form of Compound 2-A of claim 12 , wherein the X-ray diffraction (XRPD) pattern comprises 2theta ...

Method and apparatus for modifying a computer program in a trusted manner

A computer system having a system memory and being arranged to permit a target program ( 90 ) installed on the system to be modified in a trusted manner. The system comprises a White-list Management Agent, WMA, module ( 10 ) for receiving, at a notification receiver ( 12 ), a notification that the target program ( 90 ) which is loaded into the system memory of the computer system has performed an update operation on the target program resulting in the generation and storage of a modified version of the target program on a storage device associated with the computer system. The WMA module is operable, upon receipt of a target program update notification, to determine if the program ( 90 ) as loaded into the system memory is in a trusted state by measuring the program ( 90 ) using a program measurer module ( 14 ) and comparing this, using a comparator ( 16 ), with a pre-stored value contained in a program whitelist ( 30 ), the pre-stored value being obtained from the program whitelist ( 30 ) using a whitelist reader/writer ( 18 ). If the determination is positive, the WMA module ( 10 ) generates a hash code of the modified version of the target computer program as stored on the storage device using the program measurer module ( 14 ) and stores this generated hash code as a new trusted hash code for the target program in the program whitelist ( 30 ), in order to permit subsequent verification of the modified version of the target program as being in a trusted state.

COUPLING MECHANISMS FOR MEDICAL DEVICES

Apparatus and systems are disclosed that incorporate coupling mechanisms to enable coupling of two mating member such as medical devices such as introducers, sheaths, dilators. More specifically, the disclosure relates to releasable coupling mechanisms, to allow for releasable coupling of two medical devices such as a dilator and a sheath so the devices can be maneuvered and/or manipulated together for example during a part of a medical procedure. 1. A releasable coupling mechanism comprising:a coupling member configured to be associated with a first mating member for releasably coupling a second mating member, receivable by the first mating member, to the first mating member;wherein the coupling member has a first state and a second state; andwherein the coupling member is moveable from the first state to the second state upon insertion of the second mating member into the first mating member to allow passage of the second mating member and is moveable thereafter from the second state to the first state to releasably couple the second mating member to the first mating member.2. The releasable coupling mechanism of claim 1 , wherein the releasable coupling mechanism comprises a translational locking mechanism preventing the first and second mating members from moving translationally with respect to one another.3. The releasable coupling mechanism of claim 2 , wherein the coupling member is functionally coupled to a housing of the first mating member.4. The releasable coupling mechanism of claim 3 , wherein the coupling member is held within the first mating member.5. The releasable coupling mechanism of claim 3 , wherein the coupling member is coupled to a housing of the first mating member.6. The releasable coupling mechanism of claim 5 , wherein the coupling member is attached to the housing7. The releasable coupling mechanism of claim 6 , wherein the coupling member is formed integrally with the housing.8. The releasable coupling mechanism of claim 7 , wherein ...

Intelligent and Adaptive Traffic Control System

Various embodiments include methods, systems, and devices for interactively controlling traffic. The method, which may be performed by operations of the systems and/or devices, may include receiving, for example by an interactive traffic control device, refined location and state information associated with a first vehicle on a roadway. The interactive traffic control device may also determine at least one notable element in the refined location and state information, customized dynamic traffic control instructions based on the refined location and state information, and whether the customized dynamic traffic control instructions conflict with the at least one notable element. In addition, the interactive traffic control device may transmit the customized dynamic traffic control instructions to the first vehicle in response to determining the customized dynamic traffic control instructions do not conflict with the at least one notable element.

METHOD OF ADMINISTERING A 5,5-FUSED HETEROARYLENE HEPATITIS C VIRUS INHIBITOR FOR TREATING OF PREVENTING HEPATITIS C VIRUS INFECTION

Provided herein are methods of administering a 5,5-fused heteroarylene hepatitis C virus inhibitor compound or an isotopic variant thereof, or a pharmaceutically acceptable salt or solvate thereof; for treating or preventing hepatitis C virus infection in a subject. 1. A method for treating or preventing a hepatitis C virus infection in a human patient , comprising administering to the patient a therapeutically effective amount of [(S)-1-((S)-2-{6-[6-(4-{(S)-2-[1-((R)-2-methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-thieno[3 ,2-b]thiophen-3-yl]-1H-benzoimidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester or an isotopic variant thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein the therapeutically effective amount is at least 1 mg per day.28-. (canceled)9. The method of claim 1 , wherein the therapeutically effective amount is about 5 mg per day claim 1 , about 10 mg per day claim 1 , about 25 mg per day claim 1 , about 50 mg per day claim 1 , or about 100 mg per day.10. A method for treating or preventing a hepatitis C virus infection in a human patient claim 1 , comprising administering to the patient a therapeutically effective amount of [(S)-1-((S)-2-{6-[6-(4-{(S)-2-[1-((R)-2-methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-thieno[3 claim 1 ,2-b]thiophen-3-yl]-1H-benzoimidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester or an isotopic variant thereof; or a pharmaceutically acceptable salt or solvate thereof; wherein the therapeutically effective amount is from about 0.02 to about 20 mg/kg/day.1116-. (canceled)17. The method of claim 10 , wherein the therapeutically effective amount is about 0.02 mg/kg/day claim 10 , about 0.1 mg/kg/day claim 10 , about 0.2 mg/kg/day claim 10 , about 0.5 mg/kg/day claim 10 , about 1 mg/kg/day claim 10 , or about 2 mg/kg/day.18. A method for treating or preventing a hepatitis C virus ...

Feedback Mechanisms for a Steerable Medical Device

An apparatus and method are disclosed for providing feedback for a steerable medical device assembly for deflecting a device, the assembly comprising a control handle comprising an actuation mechanism. The assembly additionally comprises a device coupled to the control handle and operable to be deflected upon actuation of the actuation mechanism, and a feedback mechanism for providing an indication of the deflection of the device, wherein the feedback mechanism is associated with the actuation mechanism for deflecting the device. 1. A steerable medical device assembly for deflecting a device comprising:a control handle comprising an actuation mechanism;a device coupled to the control handle and operable to be deflected upon actuation of the actuation mechanism; anda feedback mechanism for providing an indication of the deflection of the device;wherein the feedback mechanism associated with the actuation mechanism for deflecting the device.2. The steerable medical device assembly of claim 1 , wherein the feedback mechanism provides sensory feedback.3. The steerable medical device assembly of claim 1 , wherein the feedback mechanism comprises a visual feedback mechanism that provides a visual indication.4. The steerable medical device assembly of claim 1 , wherein the feedback mechanism provides comprises a tactile feedback mechanism that provides a tactile indication.5. The steerable medical device assembly of claim 1 , wherein the feedback mechanism comprises an audible feedback mechanism that provides an audible indication.6. The steerable medical device assembly of claim 3 , wherein the visual feedback mechanism comprises a mechanical feedback mechanism.7. The steerable medical device assembly of claim 6 , wherein the mechanical feedback mechanism comprises:a window that is formed within a housing of the control handle; andone or more alignment markings associated with the actuation mechanism for deflecting the device; andwherein a visibility of the one or more ...

NUCLEOTIDE HEMI-SULFATE SALT FOR THE TREATMENT OF HEPATITIS C VIRUS

A hemi-sulfate salt of the structure: 3. The solid dosage form of claim 2 , wherein the steady-state trough plasma level (C) is between approximately 20-50 ng/mL.4. The solid dosage form of claim 2 , wherein the steady-state trough plasma level (C) is between approximately 20-45 ng/mL.5. The solid dosage form of claim 2 , wherein the steady-state trough plasma level (C) is between approximately 20-30 ng/mL.6. The solid dosage form of claim 2 , wherein the steady-state trough plasma level (C) is between approximately 20-25 ng/mL.8. The solid dosage form of claim 7 , wherein the area under the curve is between approximately 1 claim 7 ,800 ng*h/mL and 3 claim 7 ,000 ng*h/mL.9. The solid dosage form of claim 7 , wherein the area under the curve is between approximately 2 claim 7 ,100 ng*h/mL and 3 claim 7 ,000 ng*h/mL.10. The solid dosage form of claim 7 , wherein the area under the curve is between approximately 2 claim 7 ,400 ng*h/mL and 3 claim 7 ,000 ng*h/mL.11. The solid dosage form of claim 7 , wherein the area under the curve is between approximately 2 claim 7 ,700 ng*h/mL and 3 claim 7 ,000 ng*h/mL.12. The solid dosage form of claim 7 , wherein the area under the curve is between approximately 2 claim 7 ,000 ng*h/mL and 2 claim 7 ,200 ng*h/mL.14. The pharmaceutical composition of claim 13 , in a solid dosage form that delivers approximately 300 mg of the compound.15. The pharmaceutical composition of claim 13 , in a solid dosage form that delivers approximately 400 mg of the compound.16. The pharmaceutical composition of claim 13 , in a solid dosage form that delivers approximately 500 mg of the compound.17. The pharmaceutical composition of claim 13 , in a solid dosage form that delivers approximately 600 mg of the compound.18. The pharmaceutical composition of claim 13 , in a solid dosage form that delivers approximately 700 mg of the compound.19. The pharmaceutical composition of claim 13 , in a solid dosage form that delivers approximately 800 mg of the ...

SENSOR PLACEMENT AND METHODS FOR AIDING NAVIGATION DURING GNSS SIGNAL OUTAGE

Systems and methods for use in aiding an inertial navigation system during a GNSS signal outage. An ultrasonic transceiver is positioned adjacent a wheel of a vehicle and reflections of the emitted signal are used to determine changes of direction and/or to determine a distance traveled by the vehicle. For changes of direction, the transceiver is adjacent to a front wheel such that left or right turns cause the wheel to interrupt a signal path from the transceiver to a reflector. For distance estimates, the transceiver is adjacent a back wheel of the vehicle. The ultrasonic signal is reflected off of solid sections of the wheel or passes through void sections of the wheel. The measurements obtained can be processed in various ways to estimate number of rotations of the wheel and, accordingly, the distance traveled by the vehicle. 2. The system according to claim 1 , wherein when said vehicle is turning claim 1 , at least a portion of said wheel is placed in a path between said transceiver and said reflector.3. The system according to claim 1 , wherein said second value and said third value are both less than said first value.4. The system according to claim 1 , wherein said wheel is a front wheel of said vehicle.5. The system according to claim 4 , wherein said wheel is a left front wheel of said vehicle.6. The system according to claim 4 , wherein said wheel is a right front wheel of said vehicle.7. The system according to claim 1 , wherein raw data obtained using said system is preprocessed to filter out at least one of: outliers and noise.8. The system according to claim 1 , wherein data obtained using said system is used to determine a change of heading of said vehicle.9. The system according to claim 8 , wherein a linear regression model is used with said data obtained using said system is used to determine said change of heading of said vehicle.10. The system according to claim 8 , wherein said change of heading is provided as updates to an Inertial Navigation ...

HIGHLY ACTIVE COMPOUNDS AGAINST COVID-19

The present invention is the use of a small group of purine nucleotide phosphoramidate disclosed herein or a pharmaceutically acceptable salt thereof in an effective amount for the treatment or prevention of the novel 2019 coronavirus disease (COVID-19) in a host, for example a human, in need thereof. 5. The method of claim 1 , wherein Ris Rand Ris a stabilized phosphate prodrug that metabolizes in vivo to a monophosphate claim 1 , diphosphate claim 1 , or triphosphate.9. The method of claim 1 , wherein the pharmaceutically acceptable carrier is a dosage form suitable for oral administration.10. The method of claim 9 , wherein the dosage form is a solid dosage form.11. The method of claim 10 , wherein the dosage form is a tablet.12. The method of claim 10 , wherein the dosage form is a capsule.13. The method of claim 9 , wherein the dosage form is a liquid dosage form.14. The method of claim 13 , wherein the dosage form is a suspension.15. The method of claim 13 , wherein the dosage form is a solution.16. The method of claim 1 , wherein the pharmaceutically acceptable carrier is a dosage form suitable for intravenous administration.17. The method of claim 1 , wherein the pharmaceutically acceptable carrier is a dosage form suitable for parenteral administration. This application is a continuation of U.S. Ser. No. 17/017,443, filed Sep. 10, 2020, which claims the benefit of U.S. Provisional Application No. 62/982,670, filed Feb. 27, 2020; U.S. Provisional Application No. 62/994,206, filed Mar. 24, 2020; U.S. Provisional Application No. 63/032,247, filed May 29, 2020; U.S. Provisional Application No. 63/039,352, filed Jun. 15, 2020; U.S. Provisional Application No. 63/040,985, filed Jun. 18, 2020; U.S. Provisional Application No. 63/054,680, filed Jul. 21, 2020; and U.S. Provisional 63/073,328 file Sep. 1, 2020. These applications are incorporated by reference in their entireties for all purposes.The present invention is directed to the use of selected purine ...

Process for Making Nucleoside Phosphoramidate Compounds

The present invention is directed to a process for making Nucleoside Phosphoramidate Compounds of formula (I): which are useful for the treatment and prophylaxis of HCV infection. The present invention is also directed to compounds that are useful as synthetic intermediates for making the compounds of formula (I).

Beta-D-2'-DEOXY-2'-alpha-FLUORO-2'-beta-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT

A compound of the structure: This application claims priority to U.S. Ser. No. 62/129,319 filed on Mar. 6, 2015, U.S. Ser. No. 62/253,958 filed on Nov. 11, 2015, and U.S. Ser. No. 62/276,597 filed on Jan. 8, 2016, each of which is incorporated herewith in their entirety.The present invention is directed to nucleotide compounds and compositions and uses thereof to treat the Hepatitis C virus (“HCV”).Hepatitis C (HCV) is an RNA single stranded virus and member of the Hepacivirus genus. It is estimated that 75% of all cases of liver disease are caused by HCV. HCV infection can lead to cirrhosis and liver cancer, and if left to progress, liver failure which may require a liver transplant. Approximately 170-200 million people worldwide are infected, with an estimated 3-4 million infections in the United States.RNA polymerase is a key component in the targeting of RNA single stranded viruses. The HCV non-structural protein NS5B RNA-dependent RNA polymerase is a key enzyme responsible for initiating and catalyzing viral RNA synthesis. As a result, HCV NS5B is an attractive target for the current drug discovery and development of anti-HCV agents. There are two major subclasses of NS5B inhibitors: nucleoside analogs, which are anabolized to their active triphosphates—which act as alternative substrates for the polymerase—and non-nucleoside inhibitors (NNIs), which bind to allosteric regions on the protein. Nucleoside or nucleotide inhibitors mimic natural polymerase substrate and act as chain terminators. They inhibit the initiation of RNA transcription and elongation of a nascent RNA chain.In addition to targeting RNA polymerase, other RNA viral proteins may also be targeted in combination therapies. For example, HCV proteins that are additional targets for therapeutic approaches are NS3/4A (a serine protease) and NS5A (a non-structural protein that is an essential component of HCV replicase and exerts a range of effects on cellular pathways).In December 2013, the first ...

BETA-D-2'-DEOXY-2'-ALPHA-FLUORO-2'-BETA-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT

A compound of the structure: 4. The method of claim 1 , wherein the compound is administered orally.5. The method of claim 4 , wherein the compound is administered in a tablet or a capsule.6. The method of claim 1 , wherein the host is a human.7. The method of claim 2 , wherein the compound is administered orally.8. The method of claim 7 , wherein the compound is administered in a tablet or a capsule.9. The method of claim 2 , wherein the host is a human.10. The method of claim 3 , wherein the compound is administered orally.11. The method of claim 10 , wherein the compound is administered in a tablet or a capsule.12. The method of claim 3 , wherein the host is a human.16. The method of claim 13 , wherein the compound is administered orally.17. The method of claim 16 , wherein the compound is administered in a tablet or a capsule.18. The method of claim 13 , wherein the host is a human.19. The method of claim 14 , wherein the compound is administered orally.20. The method of claim 19 , wherein the compound is administered in a tablet or a capsule.21. The method of claim 14 , wherein the host is a human.22. The method of claim 15 , wherein the compound is administered orally.23. The method of claim 22 , wherein the compound is administered in a tablet or a capsule.24. The method of claim 15 , wherein the host is a human. This application is a continuation of U.S. Ser. No. 15/782,628 filed Oct. 12, 2017 that is a continuation of U.S. Ser. No. 15/063,461, now U.S. Pat. No. 9,828,410, filed Mar. 7, 2016 that claims priority to U.S. Ser. No. 62/129,319 filed Mar. 6, 2015; U.S. Ser. No. 62/253,958 filed Nov. 11, 2015; and, U.S. Ser. No. 62/276,597 filed Jan. 8, 2016. Each of these references is incorporated herewith in their entirety.The present invention is directed to nucleotide compounds and compositions and uses thereof to treat the Hepatitis C virus (“HCV”).Hepatitis C (HCV) is an RNA single stranded virus and member of the Hepacivirus genus. It is estimated that 75% ...

Beta-D-2'-DEOXY-2'-Alpha-FLUORO-2'-Beta-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT

A compound of the structure: 4. The pharmaceutical composition of claim 1 , in a dosage form.5. The pharmaceutical composition of claim 4 , in a solid dosage form.6. The pharmaceutical composition of claim 5 , in a solid oral dosage form.7. The pharmaceutical composition of claim 6 , in a tablet.8. The pharmaceutical composition of claim 6 , in a capsule.9. The pharmaceutical composition of claim 2 , in a dosage form.10. The pharmaceutical composition of claim 9 , in a solid dosage form.11. The pharmaceutical composition of claim 9 , in a solid oral dosage form.12. The pharmaceutical composition of claim 11 , in a tablet.13. The pharmaceutical composition of claim 11 , in a capsule.14. The pharmaceutical composition of claim 3 , in a dosage form.15. The pharmaceutical composition of claim 14 , in a solid dosage form.16. The pharmaceutical composition of claim 14 , in a solid oral dosage form.17. The pharmaceutical composition of claim 16 , in a tablet.18. The pharmaceutical composition of claim 16 , in a capsule.22. The pharmaceutical composition of claim 19 , in a dosage form.23. The pharmaceutical composition of claim 22 , in a solid dosage form.24. The pharmaceutical composition of claim 22 , in a solid oral dosage form.25. The pharmaceutical composition of claim 24 , in a tablet.26. The pharmaceutical composition of claim 24 , in a capsule.27. The pharmaceutical composition of claim 20 , in a dosage form.28. The pharmaceutical composition of claim 27 , in a solid dosage form.29. The pharmaceutical composition of claim 27 , in a solid oral dosage form.30. The pharmaceutical composition of claim 29 , in a tablet.31. The pharmaceutical composition of claim 29 , in a capsule.32. The pharmaceutical composition of claim 21 , in a dosage form.33. The pharmaceutical composition of claim 32 , in a solid dosage form.34. The pharmaceutical composition of claim 32 , in a solid oral dosage form.35. The pharmaceutical composition of claim 34 , in a tablet.36. The ...

NUCLEOTIDE HEMI-SULFATE SALT FOR THE TREATMENT OF HEPATITIS C VIRUS

A hemi-sulfate salt of the structure: 2. The compound of claim 1 , wherein the compound is at least 98% free of the opposite phosphorus R-enantiomer.3. The compound of claim 1 , wherein the compound is at least 99% free of the opposite phosphorus R-enantiomer.5. The pharmaceutical composition of claim 4 , wherein the compound is at least 98% free of the opposite phosphorus R-enantiomer.6. The pharmaceutical composition of claim 4 , wherein the compound is at least 99% free of the opposite phosphorus R-enantiomer.7. The pharmaceutical composition of claim 4 , in an oral dosage form.8. The pharmaceutical composition of claim 7 , wherein the oral dosage form is a solid dosage form.9. The pharmaceutical composition of claim 8 , wherein the solid dosage form is a tablet.10. The pharmaceutical composition of claim 8 , wherein the solid dosage form is a capsule.11. The pharmaceutical composition of claim 4 , wherein the oral dosage form is a liquid dosage form.12. The pharmaceutical composition of claim 11 , wherein the liquid dosage form is a suspension or solution.13. The pharmaceutical composition of claim 4 , in an intravenous formulation.14. The pharmaceutical composition of claim 4 , in a parenteral formulation.16. The pharmaceutical composition of claim 15 , wherein the steady-state trough plasma level (C) is between approximately 20-50 ng/mL.17. The pharmaceutical composition of claim 15 , wherein the steady-state trough plasma level (C) is between approximately 20-30 ng/mL.18. The pharmaceutical composition of claim 15 , wherein the steady-state trough plasma level (C) is between approximately 20-25 ng/mL.20. The pharmaceutical composition of claim 19 , wherein the area under the curve is between approximately 1 claim 19 ,800 ng*h/mL and 3 claim 19 ,000 ng*h/mL.21. The pharmaceutical composition of claim 19 , wherein the area under the curve is between approximately 2 claim 19 ,400 ng*h/mL and 3 claim 19 ,000 ng*h/mL.22. The pharmaceutical composition of claim 19 ...

BETA-D-2'-DEOXY-2'-ALPHA-FLUORO-2'-BETA-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT

A compound of the structure: 2. The compound of claim 1 , wherein the compound is at least 98% free of the opposite phosphorus R-enantiomer.3. The compound of claim 1 , wherein the compound is at least 99% free of the opposite phosphorus R-enantiomer.5. The pharmaceutical composition of claim 4 , wherein the compound is at least 98% free of the opposite phosphorus R-enantiomer.6. The pharmaceutical composition of claim 4 , wherein the compound is at least 99% free of the opposite phosphorus R-enantiomer.7. The pharmaceutical composition of claim 4 , in an oral dosage form.8. The pharmaceutical composition of claim 7 , wherein the oral dosage form is a solid dosage form.9. The pharmaceutical composition of claim 8 , wherein the solid dosage form is a tablet.10. The pharmaceutical composition of claim 8 , wherein the solid dosage form is a capsule.11. The pharmaceutical composition of claim 4 , wherein the oral dosage form is a liquid dosage form.12. The pharmaceutical composition of claim 11 , wherein the liquid dosage form is a suspension or solution.13. The pharmaceutical composition of claim 4 , in an intravenous formulation.14. The pharmaceutical composition of claim 4 , in a parenteral formulation. This application is a continuation of U.S. Ser. No. 16/900,397, filed Jun. 12, 2020, which is a continuation of U.S. Ser. No. 16/278,621 filed Feb. 18, 2019, which is a continuation U.S. Ser. No. 16/001,549 filed Jun. 6, 2018, now U.S. Pat. No. 10,239,911 which is a continuation of U.S. Ser. No. 15/782,628, now U.S. Pat. No. 10,000,523, filed Oct. 12, 2017 which is a continuation of U.S. Ser. No. 15/063,461, now U.S. Pat. No. 9,828,410, filed Mar. 7, 2016 which claims priority to U.S. Ser. No. 62/129,319 filed Mar. 6, 2015; U.S. Ser. No. 62/253,958 filed Nov. 11, 2015; and, U.S. Ser. No. 62/276,597 filed Jan. 8, 2016. Each of these references is incorporated herewith in their entirety.The present invention is directed to nucleotide compounds and compositions and uses ...

BETA-D-2'-DEOXY-2'-ALPHA-FLUORO-2'-BETA-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT

A compound of the structure: 2. The compound of claim 1 , wherein the compound is at least 98% free of the opposite phosphorus S-enantiomer.3. The compound of claim 1 , wherein the compound is at least 99% free of the opposite phosphorus S-enantiomer.5. The pharmaceutical composition of claim 4 , wherein the compound is at least 98% free of the opposite phosphorus S-enantiomer.6. The pharmaceutical composition of claim 4 , wherein the compound is at least 99% free of the opposite phosphorus S-enantiomer.7. The pharmaceutical composition of claim 4 , in an oral dosage form.8. The pharmaceutical composition of claim 7 , wherein the oral dosage form is a solid dosage form.9. The pharmaceutical composition of claim 8 , wherein the solid dosage form is a tablet.10. The pharmaceutical composition of claim 8 , wherein the solid dosage form is a capsule.11. The pharmaceutical composition of claim 4 , wherein the oral dosage form is a liquid dosage form.12. The pharmaceutical composition of claim 11 , wherein the liquid dosage form is a suspension or solution.13. The pharmaceutical composition of claim 4 , in an intravenous formulation.14. The pharmaceutical composition of claim 4 , in a parenteral formulation. This application is a continuation of U.S. Ser. No. 16/900,397, filed Jun. 12, 2020, which is a continuation of U.S. Ser. No. 16/278,621 filed Feb. 18, 2019, which is a continuation U.S. Ser. No. 16/001,549 filed Jun. 6, 2018, now U.S. Pat. No. 10,239,911 which is a continuation of U.S. Ser. No. 15/782,628, now U.S. Pat. No. 10,000,523, filed Oct. 12, 2017 which is a continuation of U.S. Ser. No. 15/063,461, now U.S. Pat. No. 9,828,410, filed Mar. 7, 2016 which claims priority to U.S. Ser. No. 62/129,319 filed Mar. 6, 2015; U.S. Ser. No. 62/253,958 filed Nov. 11, 2015; and, U.S. Ser. No. 62/276,597 filed Jan. 8, 2016. Each of these references is incorporated herewith in their entirety.The present invention is directed to nucleotide compounds and compositions and uses ...

Methods for prognosis or treatment of parkinson's disease

Provided herein are methods for prognosing and treating a patient with Parkinson's disease (PD) or Parkinsonian symptoms. The prognosis and appropriate treatments can be determined by correlating the level of gene expression of SKP1a, UBE2K, ALDH1A1, PSMC4, HSPA8 and LAMB2 with a Parkinson's Disease rating scale, thereby prognosing slow or rapid progression of the symptoms or disease.

SYSTEM AND METHOD FOR DETERMINING AIRSPEED

Systems and methods for use in determining a device's speed. The system uses a plate having a front side that is perpendicular to the device's direction of travel. The airflow caused by the device's motion causes the plate to deflect from a resting position and the amount of deflection of the plate is proportional to the speed of the device. The amount of deflection is measured by a rotary encoder coupled to the plate. By properly calibrating the system, the system can determine the device's velocity simply from the airflow caused by the device's motion. 1. A system for use in determining a speed of a moving device , the system comprising:a plate having a front side exposed to an airflow outside of said device as said device is moving, said airflow causing said plate to deflect from a predefined resting position;a subsystem for measuring an amount of deflection of said plate as said plate deflects due to said airflow as said device is in motion;wherein said amount of deflection of said plate from said resting position is proportional to a speed of said airflow, said speed of said airflow being related to said speed of said moving device.2. The system according to claim 1 , wherein said subsystem comprises:a magnet coupled to said plate such that said deflection of said plate causes said magnet to rotate about an axis;a Hall effect sensor for detecting changes in peaks in a magnetic field due to said magnet, changes in said peaks of said magnetic field being proportional to said amount of deflection of said plate.3. The system according to claim 1 , wherein said subsystem comprises a rotational encoder coupled to said plate such that said deflection of said plate is encoded by said rotational encoder.4. The system according to claim 1 , wherein when said plate is at said resting position claim 1 , said front side is perpendicular to a direction of travel of said device.5. The system according to claim 1 , wherein said speed of said device as determined by said system ...

HIGHLY ACTIVE COMPOUNDS AGAINST COVID-19

The present invention is the use of purine nucleotide phosphoramidates or pharmaceutically acceptable salts thereof administered in an effective amount for the treatment or prevention of COVID-19, an infection caused by the SARS CoV-2 virus in a host, for example a human, in need thereof. 6. The method of claim 1 ,wherein:{'sup': '2', 'Ris phenyl;'}{'sup': '3', 'Ris hydrogen;'}{'sup': '4a', 'Ris methyl;'}{'sup': '4b', 'Ris hydrogen; and'}{'sup': '5', 'Ris isopropyl.'}7. The method of claim 1 ,wherein:{'sup': '2', 'Ris phenyl;'}{'sup': '3', 'Ris hydrogen;'}{'sup': '4a', 'Ris methyl;'}{'sup': '4b', 'Ris hydrogen;'}{'sup': '5', 'Ris isopropyl; and'}{'sub': 'p', 'the phosphoramidate is in the S-configuration.'}8. The method of claim 1 ,wherein:{'sup': '2', 'Ris phenyl;'}{'sup': '3', 'Ris hydrogen;'}{'sup': '4a', 'Ris methyl;'}{'sup': '4b', 'Ris hydrogen;'}{'sup': '5', 'Ris isopropyl; and'}{'sub': 'p', 'the phosphoramidate is in the R-configuration.'}9. The method of claim 1 , wherein Ris aryl.10. The method of claim 1 , wherein Ris hydrogen.11. The method of claim 1 , wherein Ris methyl and Ris hydrogen.12. The method of claim 1 , wherein Ris Calkyl.13. The method of claim 1 , wherein Ris isopropyl.23. The method of claim 1 , wherein the pharmaceutically acceptable carrier is in a dosage form suitable for oral administration.24. The method of claim 23 , wherein the dosage form is a solid dosage form.25. The method of claim 24 , wherein the solid dosage form is a tablet or capsule.26. The method of claim 23 , wherein the dosage form is a liquid dosage form.27. The method of claim 26 , wherein the liquid dosage form is a solution or a suspension.28. The method of claim 1 , wherein the pharmaceutically acceptable carrier is in a dosage form suitable for intravenous administration.29. The method of claim 1 , wherein the pharmaceutically acceptable carrier is in a dosage form suitable for parenteral administration.30. The method of claim 1 , wherein the compound is ...

Method of fabrication of construction materials from industrial solid waste

A low-pressure method for producing construction materials, such as blocks, bricks or slabs, utilizing high percentages of waste cement dust in admixture with additive material capable of effectively neutralizing the high lime content and agglomerating the extremely fine particles of the cement dust upon blending of the admixture with water. The resulting blend may simply be cast in molds of various shapes and sizes and cured under normal atmospheric pressure conditions into a hardened construction material exhibiting high strength, light weight and high thermal insulation.

Method of fabrication of construction materials from industrial solid waste

A low-pressure method for producing construction materials, such as blocks, bricks or slabs, utilizing high percentages of waste cement dust in admixture with additive material capable of effectively neutralizing the high lime content and agglomerating the extremely fine particles of the cement dust upon blending of the admixture with water. The resulting blend may simply be cast in molds of various shapes and sizes and cured under normal atmospheric pressure conditions into a hardened construction material exhibiting high strength, light weight and high thermal insulation.

HYDRAULIC BINDER

Bei einem hydraulischen Bindemittel enthaltend 25 bis 85 Gew.-% Zementklinker, 0 bis 7 Gew.-% CaSO4 sowie mineralische Zusatzstoffe in einer Menge von insgesamt 15 bis 75 Gew.-%, bezogen auf das hydraulische Bindemittel, sind 1 bis 10 Gew.-% eines dualen Abbindesteuerungssystems enthalten, das einen Aktivator und einen Verzögerer umfasst, wobei das Gewichts-Verhältnis von Aktivator zu Verzögerer, bezogen auf die Trockensubstanz, größer als 85:15, insbesondere größer als 90:10, insbesondere größer als 95:5, insbesondere größer als 98:2 gewählt ist. In a hydraulic binder containing 25 to 85 wt .-% cement clinker, 0 to 7 wt .-% CaSO4 and mineral additives in a total amount of 15 to 75 wt .-%, based on the hydraulic binder, are 1 to 10 wt. contain% of a dual Abbindesteuerungssystems comprising an activator and a retarder, wherein the weight ratio of activator to retarder, based on the dry matter, greater than 85:15, in particular greater than 90:10, in particular greater than 95: 5, especially greater than 98: 2 is selected.

Method of checking the directivity and polarization of coherent field distributions in a reverberant medium

A method for generating and checking a spatio-temporal field distribution having predefined characteristics such as one or more directions of propagation, a high level of field intensity and a polarization in a reverberant chamber. To do this, two separate networks of transducers are provided so as to estimate a transfer function between these two networks and to determine excitation signals using the principle of temporal return. The excitation signals are used to generate the spatio-temporal field according to the predefined characteristics.

Hair cutter

A hair cutter has a vacuum source connected tubular barrel and an interior shaft mounted turbine assembly. The turbine assembly includes a turbine coupled to a flywheel which in turn is coupled to a rotary blade assembly. A stationary radially disposed blade arrangement engages the rotatory blade arrangement. A pivot shaft arrangement is supported on the inside of the barrel joined to a longitudinal movable sleeve for adjusting the positioning of the internal assembly and couples the turbine to the flywheel and the flywheel to the rotary blade assembly. The turbine is coupled to the rotary blade assembly to create a rotary force to both rotate the rotary blade against the fixed blade, and to enhance the scissors force of the rotatory blade against the first blade by longitudinally urging the rotary blade toward the turbine. A vacuum source coupled to the barrel drives the turbine at one end of the barrel and the blade assembly is disposed adjacent an opening at the opposite end of the barrel. A grating is adjacent to and spaced apart from the blades.

Pharmaceutical compositions containing an omega-3 fatty acid oil

Self-emulsifying microemulsion or emulsion preconcentrate pharmaceutical compositions containing an omega-3 fatty acid oil such as a fish oil and a poorly water soluble therapeutic agent such as cyclosporin are formulated for administration, particularly oral administration to a human. The preconcentrates, which are substantially free of or contain only minor amounts of a hydrophilic solvent system, contain a pharmaceutically effective amount of an omega-3 fatty acid oil; a therapeutically effective amount of a poorly water soluble therapeutic agent that is substantially soluble in the omega-3 fatty acid oil; and a surfactant system comprising at least one surfactant. Microemulsions or emulsions formed by diluting the self-emulsifying preconcentrate with an aqueous solution are also provided.

Solid forms of an anti-HIV phosphoindole compound

Solid forms comprising a compound useful in the treatment, prevention and management of various conditions and diseases are provided herein. In particular, provided herein are solid forms comprising (2-carbamoyl-5-chloro-1H-indol-3-yl)-[3-((E)-2-cyano-vinyl)-5-methyl-phenyl]-(R)-phosphinic acid methyl ester, including salts thereof, having utility for the treatment, prevention and management of conditions and disorders including, but not limited to, human immunodeficiency virus infection.

Pharmaceutical compositions of 2'-c-methyl-guanosine, 5'-[2-[(3-hydroxy-2,2-dimethyl-1-oxopropyl)thio]ethyl n-(phenylmethyl)phosphoramidate]

Provided herein are stable pharmaceutical compositions comprising 2'-C-methyl-guanosine, 5'-[2-[(3-hydroxy-2,2-dimethyl-l-oxopropyl) thio]ethyl N-(phenylmethyl)phosphoramidate (also known s IDX-184), and in particular, oral pharmaceutical compositions such as tablets. The compositions are designed to avoid the formation of diethylene sulfide upon storage. Discosed are also methods of using these pharmaceutical compositions in the treatment of viral infections, including hepatitis C virus infections in hosts in need thereof.

D-amino acid compounds for liver disease

Provided herein are compounds comprising a D-amino acid, compositions and methods for the treatment of liver disease and conditions, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

3',5'-cyclic phosphoramidate prodrugs for hcv infection

Provided herein are compounds of formula (I) compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. Formula (I) or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein: each X is independently alkoxyl, hydrogen, or hydroxyl; each Y is independently hydroxyl, acetoxyl, or fluoro; each Z is independently substituted alkyl; and each R is independently hydrogen, alkyl, substituted alkyl, cycloalkyl, aryl, or heteroaryl.

2'-chloro nucleoside analogs for hcv infection

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 2'-chloro nucleosides according to Formula 2001: (2001); or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein B, Z and PD are as described herein.

Dinucleotide compounds for hcv infection

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds comprise two 2 '-methyl nucleotides linked according to Formula (I): N 1 - L - N 2 or a pharmaceutically acceptable salt, ester, solvate, stereoisomer, isomeric form, tautomeric form or polymorphic form thereof; wherein N 1 , L and N 2 are as described herein.

2',4'-bridged nucleosides for hcv infection

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 2',4'-bridged nucleosides which display remarkable efficacy and bioavailability for the treatment of, for example, HCV infection in a human. In certain embodiments, the 2',4'-bridged nucleosides are of Formula 3001:(I) (3001); or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, where PD, B, W, X, R A , R B , R C and R D are as described herein.

D-alanine ester of rp-nucleoside analog

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, provided herein is an isolated compound according to Formula 1a: or a pharmaceutically acceptable salt or solvate thereof.

D-alanine ester of sp-nucleoside analog

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, provided herein is an isolated compound according to Formula Ib: or a pharmaceutically acceptable salt or solvate thereof.

4'-fluoro nucleosides for the treatment of hcv

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are according to Formula (1501): or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein B, PD, R A , R B , R C , L, M and Z are as described herein.

3'-deoxy nucleosides for the treatment of hcv

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 3'- deoxy nucleoside compounds according to Formula 3001a or 3001b: or a pharmaceutically acceptable salts, solvates, stereoisomeric forms, tautomeric forms, or polymorphic forms thereof, wherein PD, Base 1 and Base 2 are as provided herein.

Thiophosphate nucleosides for the treatment of hcv

Provided herein are compounds, compositions, and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, the compounds are according to Formula 2001; where PD, Base, R A and R B are as provided herein. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

2',4'-fluoro nucleosides for the treatment of hcv

Provided herein are compounds, methods and pharmaceutical compositions for use in treatment of viral infections, including hepatitis C virus (HCV) infections, in hosts in need thereof. In certain embodiments, the compounds are 2',4'-fluoro nucleosides according to Formula 1001: (1001); or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form, or polymorphic form thereof, wherein Base, RA, and PD are as described herein. In certain embodiments, 2',4'-fluoro nucleosides are provided which display remarkable efficacy and bioavailability for the treatment of, for example, HCV infection in a human.

D-amino acid phosphoramidate pronucleotides of halogeno pyrimidine compounds for liver disease

Provided herein are compounds, compositions, and methods for the treatment of viral infections, for example, Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are D-amino acid phosphoramidate halogeno pyrimidine nucleoside analog compounds which display remarkable efficacy and bioavailability for the treatment of, for example, HCV infection in a human. In certain embodiments, the compounds are of Formula (I); or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form, or polymorphic form thereof, wherein: PD, X, R 1 , R 2 , R A , and R B are as described herein.

D-amino acid phosphoramidate and d-alanine thiophosphoramidate pronucleotides of nucleoside compounds useful for the treatment of hcv

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are of Formula AI or 1001 or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof.

D-alanine phosphoramidate pronucleotides of 2'-methyl 2'-fluoro guanosine nucleoside compounds for the treatment of hcv

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are D-alanine phosphoramidate pronucleotides of 2'-methyl 2'-fluoro guanosine nucleoside which display remarkable efficacy and bioavailability for the treatment of, for example, HCV infection in a human. In certain embodiments, the compounds are of Formula I or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof; where W and R are as described herein.

4'-or nucleosides for the treatment of hcv

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 4'-OR nucleosides of Formula I: (I); or a pharmaceutically acceptable salt thereof, wherein Base, PD, R, Z 1 , Z 2 , Z 3 , and Z 4 are as defined herein.

Pharmaceutical compositions comprising a 5,5-fused heteroarylene flaviviridae inhibitor and their use for treating or preventing flaviviridae infection

Provided herein are spray-dried particles comprising a 5,5-fused heteroarylene hepatitis C virus inhibitor compound and methods of their preparation. Also provided herein are pharmaceutical compositions comprising a 5,5-fused heteroarylene hepatitis C virus inhibitor compound, method of their preparation, and their use for treating or preventing hepatitis C virus infection.

Solid forms of a flaviviridae virus inhibitor compound and salts thereof

Provided herein are crystalline and salt forms of methyl N -{(1R)-2-[(2S)-2-{5-[4-(6- {2- [(2S)- 1 - {(2S)-2- [(methoxycarbonyl)amino] -3 -methylbutanoyl} pyrro lidin-2-yl]-3 H - benzimidazol-5-y1}thieno[3,2- b ]thiophen-3-y1)phenyl]-1 H -imidazol-2-yl}pyrrolidin-1-y1]-2- oxo-1-phenylethyl} carbamate, a Flaviviridae, including hepatitis C, virus inhibitor, pharmaceutical compositions comprising the compound, and processes of preparation thereof. Also provided are methods of its use for the treatment of a Flaviviridae, including HCV, infection in a subject in need thereof.

Solid prodrug forms of 2'-chloro-2'-methyl uridine for hcv

Provided herein are compounds, compositions and methods for the treatment of Flavivirida e infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are solid forms of Compound I: (Compound I)

Esters and malonates of sate prodrugs

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, provided herein are compounds according to Formula 1001: or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein Base, Y, Z, A, R C and R D are as described herein.

Process for the production of 2-C-methyl-D-ribonolactone

The present invention provides an improved process for preparing 2-C-methyl-D-ribonolactone.

2’-chloro nucleoside analogs for hcv infection

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 2’-chloro nucleosides according to Formula 2001: (2001); or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein B, Z and PD are as described herein.

Dinucleotide compounds for hcv infection

Thiophosphate nucleosides for the treatment of HCV

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, the compounds are according to Formula 2001: where PD, Base, R A and R B are as provided herein. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

3′-deoxy nucleosides for the treatment of HCV

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 3′-deoxy nucleoside compounds according to Formula 3001a or 3001b: or a pharmaceutically acceptable salts, solvates, stereoisomeric forms, tautomeric forms, or polymorphic forms thereof, wherein PD, Base 1 and Base 2 are as provided herein.

2′,4′-fluoro nucleosides for the treatment of HCV

Provided herein are compounds, methods and pharmaceutical compositions for use in treatment of viral infections, including hepatitis C virus (HCV) infections, in hosts in need thereof. In certain embodiments, the compounds are 2′,4′-fluoro nucleosides according to Formula 1001: or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form, or polymorphic form thereof, wherein Base, R A , and PD are as described herein. In certain embodiments, 2′,4′-fluoro nucleosides are provided which display remarkable efficacy and bioavailability for the treatment of, for example, HCV infection in a human.

D-amino acid phosphoramidate pronucleotides of halogeno pyrimidine compounds for liver disease

4′-or nucleosides for the treatment of HCV

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 4′-OR nucleosides of Formula I: or a pharmaceutically acceptable salt thereof, wherein Base, PD, R, Z 1 , Z 2 , Z 3 , and Z 4 are as defined herein.

Enantiomerically pure phosphoindoles as HIV inhibitors

Un compuesto de la siguiente fórmula o una de sus sales farmacéuticamente aceptables:**Fórmula**

Hydraulic binder

Bei einem hydraulischen Bindemittel enthaltend 25 bis 85 Gew.-% Zementklinker, 0 bis 7 Gew.-% CaSO4 sowie mineralische Zusatz- stoffe, sind 1 bis 10 Gew.-% eines dualen Abbindesteuerungssys- tems enthalten, das einen Aktivator und einen Verzögerer um- fasst, wobei das Gewichts-Verhältnis von Aktivator zu Verzöge- rer, bezogen auf die Trockensubstanz, größer als 85:15, insbe- sondere größer als 90:10, insbesondere größer als 95:5, insbe- sondere größer als 98:2 gewählt ist.

R-enantiomers of n-propargyl-1-aminoindan compounds, their preparation and pharmaceutical compositions containing them

R(+)-N-propargyl-1-aminoindan, its preparation and use and pharmaceutical compositions containing it. The novel compound was found to be useful for the treatment of human patients for Parkinson's disease, memory disorders, dementia of the Alzheimer type (DAT), depression and the hyperactive syndrome.

R(+)-n-propargyl-1-aminoindane, pharmaceutical compositions comprising such compound and their preparation

A találmány tárgya R(+)-N-propargil-1-amino-N-propargil-1-amino-indán[a továbbiakban R(+)PAI] eljárás ennek előállítására és ezt tartalmazógyógyszerkészítmények. Az új vegyületeket úgy állítják elő, hogy a) 1-amino-indán-R(–)-enantiomert propargil-bromiddal vagy propargil-kloriddal reagáltatnak szerves vagy szervetlen bázis jelenlétében,adott esetben oldószerben, és az N-propargil-1-amino-indán R(+)-enantiomerjét kromatográfiásan, desztillációval, szelektívextrahálással izolálják, és kívánt esetben a szabad bázist savaddícióssóvá alakítják vagy b) a racém 1-amino-indánt propargil-bromiddal vagypropargil-kloriddal reagáltatják szerves vagy szervetlen bázisjelenlétében, adott esetben oldószerben, és az N-propargil-1-amino-indán R(+)-enantiomerjét kromatográfiásan, desztillációval, szelektívextrahálással izolálják, és kívánt esetben a szabad bázist savaddícióssóvá alakítják vagy c) a racém N-propargil-1-amino-indán szabad bázistoptikailag aktív savval reagáltatják, majd a kapott diasz- tereomersópárból ismert módon a kívánt R(+)-N-propargil-1-amino-indán-sótelválasztják, és kívánt esetben a szabad bázist visszanyerik. Avegyület a monoamin-oxidáz enzim B formájának (MAO–B) szelektívirreverzíbilis inhibitora. Az R(+)PAI-t tartalmazógyógyszerkészítmények Parkinson-kór, memória-rendellenességek,depresszió, Alzheimer-típusú demencia és gyerek hiperaktívszindrómájának kezelésére alkalmasak. ŕ

Derivate of 1-aminoindane, preparation process therefor and pharmaceutical composition containing this derivate

R(+)-N-propargyl-1-aminoindan, its preparation and use and pharmaceutical compositions containing it. The novel compound was found to be useful for the treatment of human patients for Parkinson's disease, memory disorders, dementia of the Alzheimer type (DAT), depression and the hyperactive syndrome.

R(+)-n-propargyl-1-aminoindan compunds, process for their preparation, their use, and pharmaceuticals containing them

A process for the preparation of a compound of the formula (I) and acid addition salts thereof, comprising reacting the R(-)-enantiomer of 1-aminoindan with propargyl bromide or propargyl chloride in the presence of an organic or inorganic base, optionally in the presence of a suitable solvent and isolating the R(+)-enantiomer of the N-propargyl-1-aminoindan by chromatography, distillation, selective extraction and, if desired, converting the free base obtained into an acid addition salt thereof. Pharmaceuticals usable in the treatment of Parkinson's disease, memory disorders, dementia of the Alzheimer type (DAT), depression and the hyperactive syndrome, which pharmaceuticals contain R(+)-N-propargyl-1-aminoindan, optionally in combination with Levodopa and decarboxylase inhibitor, e.g. L-Carbidopa or benserazide. The use of the compund of the formula (I) for the preparation of preparations usable in the treatement of the aforementioned dieseases.

Use of R-enantiomer of N-propargyl-1-aminoindan, salts, and compositions thereof

The subject invention provides R(+)-N-propargyl-1-aminoindan and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions containing same. The subject invention also provides methods of treating a subject afflicted with Parkinson's disease, a memory disorder, dementia, depression, hyperactive syndrome, an affective illness, a neurodegenerative disease, a neurotoxic injury, stroke, brain ischemia, a head trauma injury, a spinal trauma injury, neurotrauma, schizophrenia, an attention deficit disorder, multiple sclerosis, or withdrawal symptoms, using R(+)-N-propargyl-1-aminoindan or the pharmaceutically acceptable salt of the subject invention. The subject invention further provides a method of preventing nerve damage in a subject. Finally, the subject invention provides methods of preparing R(+)-N-propargyl-1-aminoindan, a salt thereof, and racemic N-propargyl-1-aminoindan.

Neuroprotective iron chelators and pharmaceutical compositions comprising them

Novel iron chelators exhibiting neuroprotective and good transport properties are useful in iron chelation therapy for treatment of a disease, disorder or condition associated with iron overload and oxidative stress, eg. a neurodegenerative or cerebrovascular disease or disorder, a neoplastic disease, hemochromatosis, thalassemia, a cardiovascular disease, diabetes, a inflammatory disorder, anthracycline cardiotoxicity, a viral infection, a protozoal infection, a yeast infection, retarding ageing, and prevention and/or treatment of skin ageing and skin protection against sunlight and/or UV light. The iron chelator function is provided by a 8-hydroxyquinoline, a hydroxypyridinone or a hydroxamate moiety, the neuroprotective function is imparted to the compound e.g. by a neuroprotective peptide, and a combined antiapoptotic and neuroprotective function by a propargyl group.

Compositions and methods for treatment of cardiovascular disorders and diseases

Propargylamine, propargylamine derivatives including N-propargyl-1-aminoindan and analogs thereof, and pharmaceutically acceptable salts thereof, are useful for prevention or treatment of cardiovascular disorders and diseases.

Methods for treatment of cardiovascular disorders and diseases

Propargylamine, propargylamine derivatives including N-propargyl-1-aminoindan, enantiomers and analogs thereof, and pharmaceutically acceptable salts thereof, are useful for prevention or treatment of cardiovascular disorders, diseases and conditions.

Methods for treatment of renal failure

Propargylamine, propargylamine derivatives N-propargyl-1-aminoindan and analogs thereof, and pharmaceutically acceptable salts thereof, are useful for administration to a subject at high risk for or suffering from acute renal failure (ARF).

R-enantiomers of N-propargyl-aminoindan compounds, their preparation and pharmaceutical compositions containing them

R(+)-N-propargyl-1-aminoindan, its preparation and use and pharmaceutical compositions containing it. The novel compound was found to be useful for the treatment of human patients for Parkinson's disease, memory disorders, dementia of the Alzheimer type (DAT), depression and the hyperactive syndrome.

Use of the R-enantiomers of N-propargyl 1-aminoindan compounds for treating Parkinson's disease.

R(+)-N-p-opargyl-1-aminoindan, its preparation and use and pharmaceutical compositions containing it. The novel compound was found to be useful for the treatment of human patients for Parkinson's disease, memory disorders, dementia of the Alzheimer type (DAT), depression and the hyperactive syndrome.

R-enantiomer of N-propargyl-1-aminoindan, salts, compositions and uses thereof

The subject invention provides R(+)-N-propargyl-1-aminoindan and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions containing same. The subject invention also provides methods of treating a subject afflicted with Parkinson's disease, a memory disorder, dementia, depression, hyperactive syndrome, an affective illness, a neurodegenerative disease, a neurotoxic injury, brain ischemia, a head trauma injury, a spinal trauma injury, schizophrenia, an attention deficit disorder, multiple sclerosis, or withdrawal symptoms, using R(+)-N-propargyl-1-aminoindan or the pharmaceutically acceptable salt of the subject invention. The subject invention further provides a method of preventing nerve damage in a subject. Finally, the subject invention provides methods of preparing R(+)-N-propargyl-1-aminoindan, a salt thereof, and racemic N-propargyl-1-aminoindan.

Use of the R-enantiomers of N-propargyl-1-aminoindan compounds for the treatment of depression

This invention relates to the use of R(+)-N-propargyl-1-aminoindan.

Method of treating memory disorders using R-enantiomers of N-propargyl-aminoindan compounds

R(+)-N-propargyl-1-aminoindan, its preparation and use and pharmaceutical compositions containing it. The novel compound was found to be useful for the treatment of human patients for Parkinson's disease, memory disorders, dementia of the Alzheimer type (DAT), depression and the hyperactive syndrome.

R-enantiomer of n-propargyl-1-aminoindan, salts, compositions and uses thereof

The subject invention provides R(+)-N-propargyl-1-aminoindan and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions containing same. The subject invention also provides methods of treating a subject afflicted with Parkinson's disease, a memory disorder, dementia, depression, hyperactive syndrome, an affective illness, a neurodegenerative disease, a neurotoxic injury, brain ischemia, a head trauma injury, a spinal trauma injury, schizophrenia, an attention deficit disorder, multiple sclerosis, or withdrawal symptoms, using R(+)-N-propargyl-1-aminoindan or the pharmaceutically acceptable salt of the subject invention. The subject invention further provides a method of preventing nerve damage in a subject. Finally, the subject invention provides methods of preparing R(+)-N-propargyl-1-aminoindan, a salt thereof, and racemic N-propargyl-1-aminoindan.

Esylate and sulfate salts of R(+)-N-propargyl-1-aminoindan

The subject invention provides R(+)-N-propargyl-1-aminoindan and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions containing same. The subject invention also provides methods of treating a subject afflicted with Parkinson's disease, a memory disorder, dementia, depression, hyperactive syndrome, an affective illness, a neurodegenerative disease, a neurotoxic injury, brain ischemia, a head trauma injury, a spinal trauma injury, schizophrenia, an attention deficit disorder, multiple sclerosis, or withdrawal symptoms, using R(+)-N-propargyl-1-aminoindan or the pharmaceutically acceptable salt of the subject invention. The subject invention further provides a method of preventing nerve damage in a subject. Finally, the subject invention provides methods of preparing R(+)-N-propargyl-1-aminoindan, a salt thereof, and racemic N-propargyl-1-aminoindan.