Abstract: The present invention concerns a method for biological treatment of carbon, nitrogen and optionally phosphorus in water, in a reactor system (1) comprising a sequencing batch reactor (SBR) (2) and a moving bed biofilm reactor (MBBR) (3). The method comprises a step (10) of filling said SBR reactor (2) with water to be treated (5), a step (20) of anoxic/aerobic biological treatment in said reactor system (1) and a step (30) of discharging treated water (35) from said SBR reactor (2). The anoxic/aerobic biological treatment step (20) comprises: a biological treatment (210) under largely anoxic conditions in the SBR reactor (2), producing a first effluent (215), a biological treatment (220) under aerobic conditions in the MBBR reactor (3), producing a second effluent (225), and a continuous recirculation of the first and second effluents. The present invention also concerns a corresponding facility.

Abstract: The present invention concerns a method for biological treatment of carbon, nitrogen and optionally phosphorus in water, in a reactor system (1) comprising a sequencing batch reactor (SBR) (2) and a moving bed biofilm reactor (MBBR) (3). The method comprises a step (10) of filling said SBR reactor (2) with water to be treated (5), a step (20) of anoxic/aerobic biological treatment in said reactor system (1) and a step (30) of discharging treated water (35) from said SBR reactor (2). The anoxic/aerobic biological treatment step (20) comprises: a biological treatment (210) under largely anoxic conditions in the SBR reactor (2), producing a first effluent (215), a biological treatment (220) under aerobic conditions in the MBBR reactor (3), producing a second effluent (225), and a continuous recirculation of the first and second effluents. The present invention also concerns a corresponding facility.

Abstract: Disclosed herein is a compound of Formula I or a pharmaceutically acceptable salt thereof, in which A, G, R1 and R2 are as defined herein. The compounds and pharmaceutical compositions of the compounds are suitable for the treatment of HCV infection in mammals and are also useful to modulate or inhibit NS3/4 dimerization.

Abstract: The present invention concerns the development of a cell-based assay system having improved sensitivity to HCV NS3 protease activity when compared to known assays, which is useful for screening test compounds capable of modulating (particularly inhibiting) HCV NS3 protease activity. This system provides a first construct comprising a transactivator domain joined downstream of the NS3-5 domains of HCV under the control of a non-cytopathic viral promoter system. A second construct is also provided that comprises a reporter gene under the control of an operator sensitive to the binding of the transactivator. The NS3-5 domains encodes the NS3 polyprotein which comprises: the NS3 protease, followed by the NS4A co-factor, the NS4B and NS5A proteins (including any derivative, variant or fragment thereof, terminated by the NS5B protein (including any derivative, variant or fragment thereof) sufficient to constitute a NS5A/5B cleavage site.

Abstract: The present invention concerns the development of a cell-based assay system having improved sensitivity to HCV NS3 protease activity when compared to known assays, which is useful for screening test compounds capable of modulating (particularly inhibiting) HCV NS3 protease activity. This system provides a first construct comprising a transactivator domain joined downstream of the NS3–5 domains of HCV under the control of a non-cytopathic viral promoter system. A second construct is also provided that comprises a reporter gene under the control of an operator sensitive to the binding of the transactivator. The NS3–5 domains encodes the NS3 polyprotein which comprises: the NS3 protease, followed by the NS4A co-factor, the NS4B and NS5A proteins (including any derivative, variant or fragment thereof), terminated by the NS5B protein (including any derivative, variant or fragment thereof) sufficient to constitute a NS5A/5B cleavage site.

Abstract: A method for producing a refolded, inactive form of recombinantly produced NS2/3 protease which comprises the steps of: a) purifying the protease from inclusion bodies in the presence of a chaotropic agent; and b) refolding the purified protease by contacting it with a reducing agent and lauryldiethylamine oxide (LDAO) in the presence of reduced concentration of chaotropic agent or polar additive. The invention further comprises a method for activating this refolded inactive NS2/3 protease by adding an activation detergent. This method produces large amounts of the active NS2/3 protease to allow small molecules and ligands to be screened as potential inhibitors of NS2/3 protease, which may be useful as therapeutic agents against HCV.

Abstract: A method for producing a refolded, inactive form of recombinantly produced NS2/3 protease which comprises the steps of: a) purifying the protease from inclusion bodies in the presence of a chaotropic agent; and b) refolding the purified protease by contacting it with a reducing agent and lauryldiethylamine oxide (LDAO) in the presence of reduced concentration of chaotropic agent or polar additive. The invention further comprises a method for activating this refolded inactive NS2/3 protease by adding an activation detergent. This method produces large amounts of the active NS2/3 protease to allow small molecules and ligands to be screened as potential inhibitors of NS2/3 protease, which may be useful as therapeutic agents against HCV.

Abstract: A method for producing a refolded, inactive form of recombinantly produced NS2/3 protease which comprises the steps of: a) purifying the protease from inclusion bodies in the presence of a chaotropic agent; and b) refolding the purified protease by contacting it with a reducing agent and lauryldiethylamine oxide (LDAO) in the presence of reduced concentration of chaotropic agent or polar additive. The invention further comprises a method for activating this refolded inactive NS2/3 protease by adding an activation detergent. This method produces large amounts of the active NS2/3 protease to allow small molecules and ligands to be screened as potential inhibitors of NS2/3 protease, which may be useful as therapeutic agents against HCV.

Abstract: An inhibitor-resistant HCV NS3 protease is provided which is useful to screen for compounds having therapeutic value against drug resistant HCV strains. In particular, the inhibitor-resistant HCV NS3 protease comprises an amino acid sequence which is mutated in the substrate binding pocket thereof rendering the protease resistant to inhibitor. In a specific aspect of the present invention, at least one of the amino acids at position 155, 156 and 168 of the HCV NS3 protease is mutated to yield an inhibitor-resistant protease.

Abstract: The present invention concerns the development of a cell-based assay system having improved sensitivity to HCV NS3 protease activity when compared to known assays, which is useful for screening test compounds capable of modulating (particularly inhibiting) HCV NS3 protease activity. This system provides a first construct comprising a transactivator domain joined downstream of the NS3-5 domains of HCV under the control of a non-cytopathic viral promoter system. A second construct is also provided that comprises a reporter gene under the control of an operator sensitive to the binding of the transactivator. The NS3-5 domains encodes the NS3 polyprotein which comprises: the NS3 protease, followed by the NS4A co-factor, the NS4B and NS5A proteins (including any derivative, variant or fragment thereof, terminated by the NS5B protein (including any derivative, variant or fragment thereof) sufficient to constitute a NS5A/5B cleavage site.

Abstract: Compositions, use, article of manufacture and method for the treatment of a mammal infected with a virus of the Flaviviridae family are provided comprising administration to the infected mammal of a compound having the Formula I: wherein, A is selected from: C1 to C6 alkyl and C3 to C6 cycloalkyl; and B is selected from: phenyl or thiazolyl, both of which optionally substituted with a group selected from NH(R1) and NH(CO)R1, wherein R1 is C1 to C6 alkyl; R is OH or a sulfonamide derivative; or a pharmaceutically acceptable salt thereof.

Abstract: An inhibitor-resistant HCV NS3 protease is provided which is useful to screen for compounds having therapeutic value against drug resistant HCV strains. In particular, the inhibitor-resistant HCV NS3 protease comprises an amino acid sequence which is mutated in the substrate binding pocket thereof rendering the protease resistant to inhibitor. In a specific aspect of the present invention, at least one of the amino acids at position 155, 156 and 168 of the HCV NS3 protease is mutated to yield an inhibitor-resistant protease.

Abstract: A method for producing a refolded, inactive form of recombinantly produced NS2/3 protease which comprises the steps of: a) purifying the protease from inclusion bodies in the presence of a chaotropic agent; and b) refolding the purified protease by contacting it with a reducing agent and lauryldiethylamine oxide (LDAO) in the presence of reduced concentration of chaotropic agent or polar additive. The invention further comprises a method for activating this refolded inactive NS2/3 protease by adding an activation detergent. This method produces large amounts of the active NS2/3 protease to allow small molecules and ligands to be screened as potential inhibitors of NS2/3 protease, which may be useful as therapeutic agents against HCV.

Abstract: A method for producing a refolded, inactive form of recombinantly produced NS2/3 protease which comprises the steps of: a) purifying the protease from inclusion bodies in the presence of a chaotropic agent; and b) refolding the purified protease by contacting it with a reducing agent and lauryidiethylamine oxide (LDAO) in the presence of reduced concentration of chaotropic agent or polar additive. The invention further comprises a method for activating this refolded inactive NS2/3 protease by adding an activation detergent. This method produces large amounts of the active NS2/3 protease to allow small molecules and ligands to be screened as potential inhibitors of NS2/3 protease, which may be useful as therapeutic agents against HCV.

Abstract: The present invention concerns the development of a cell-based assay system having improved sensitivity to HCV NS3 protease activity when compared to known assays, which is useful for screening test compounds capable of modulating (particularly inhibiting) HCV NS3 protease activity. This system provides a first construct comprising a transactivator domain joined downstream of the NS3-5 domains of HCV under the control of a non-cytopathic viral promoter system. A second construct is also provided that comprises a reporter gene under the control of an operator sensitive to the binding of the transactivator. The NS3-5 domains encodes the NS3 polyprotein which comprises: the NS3 protease, followed by the NS4A co-factor, the NS4B and NS5A proteins (including any derivative, variant or fragment thereof), terminated by the NS5B protein (including any derivative, variant or fragment thereof) sufficient to constitute a NS5A/5B cleavage site.

Abstract: The present invention concerns the development of a cell-based assay system having improved sensitivity to HCV NS3 protease activity when compared to known assays, which is useful for screening test compounds capable of modulating (particularly inhibiting) HCV NS3 protease activity. This system provides a first construct comprising a transactivator domain joined downstream of the NS3-5 domains of HCV under the control of a non-cytopathic viral promoter system. A second construct is also provided that comprises a reporter gene under the control of an operator sensitive to the binding of the transactivator. The NS3-5 domains encodes the NS3 polyprotein which comprises: the NS3 protease, followed by the NS4A co-factor, the NS4B and NS5A proteins (including any derivative, variant or fragment thereof), terminated by the NS5B protein (including any derivative, variant or fragment thereof) sufficient to constitute a NS5A/5B cleavage site.

Abstract: A method for producing a refolded, inactive form of recombinantly produced NS2/3 protease which comprises the steps of: a) purifying the protease from inclusion bodies in the presence of a chaotropic agent; and b) refolding the purified protease by contacting it with a reducing agent and lauryldiethylamine oxide (LDAO) in the presence of reduced concentration of chaotropic agent or polar additive. The invention further comprises a method for activating this refolded inactive NS2/3 protease by adding an activation detergent. This method produces large amounts of the active NS2/3 protease to allow small molecules and ligands to be screened as potential inhibitors of NS2/3 protease, which may be useful as therapeutic agents against HCV.

Abstract: New methods and apparatus for the measurement of thermal conductivity of gases employ a single katharometer element comprising a thermistor. In one circuit the thermistor is part of a first potential divider whose output voltage is compared to that of a second reference potential divider by applying them to the inputs of a differential amplifier supplying heating current to the element. In another circuit, in which the katharometer element may be other than a thermistor, the element and a resistor are connected in series to a common reference point of the circuit and are supplied with current so that the voltages across them correspond to their respective resistances; the voltage cross the item not connected to the reference point is transferred to another circuit element that is connected to the reference point so that they can be compared directly.

Abstract: A new method and apparatus for the measurement of thermal conductivity of gases employs a single katharometer element, which preferably is a thermistor, but may be a heated filament. In a preferred circuit the element is part of a first potential divider whose output voltage is compared to that of a second reference potential divider by applying them to the inputs of a differential amplifier supplying heating current to the element. If the temperature of the element changes, changing its resistance, the amplifier output changes the amount of power supplied to the katharometer element to restore it to the predetermined temperature. Passage of a gas with a different thermal characteristic over the element changes its temperature which is corrected by the circuit so that the element operates at a constant temperature. The output of the amplifier to maintain the constant temperature is therefore a measure of the gas thermal conductivity.

Abstract: A simulator is used with an optical locking device such as a cinetheodolite to provide inexpensive, convenient operator training. The simulator has a video monitor mounted on the viewer of the theodolite to display simulation images to an operator. A television camera mounted on the main telescope of the theodolite feeds a background image to the monitor. A graphics generator superimposes a target image on the background image. The movement of the telescope is coordinated with the movement of the target image on the monitor to provide a realistic simulation.