Abstract: The invention provides novel compounds having a substituted imidazole ring, and methods of using such compounds for the treatment of certain disorders such as hematological cancers and solid tumors. The compounds of the invention are tri-substituted imidazole derivatives that inhibit KSP. These compounds are also useful for the treatment of drug resistant tumors, such as solid tumors that express elevated levels of P-glycoprotein.

Abstract: The invention provides methods of monitoring differential gene expression of pharmacodynamic (PD) markers in a patient treated with a Cyclin Dependent Kinase Inhibitor (CDKI), methods of determining the sensitivity of a cell to a CDKI by measuring PD markers and methods of screening for candidate CKDI.

Abstract: The present invention provides a method for determining a response of a mammalian subject having melanoma tumor cells to treatment with a melanoma inhibitory agent. In one aspect, the method comprises (a) determining a first concentration of melanoma inhibitory activity protein (MIA) in a first biological sample taken from the mammalian subject before treatment with the melanoma inhibitory agent; (b) determining a second concentration of MIA in a second biological sample from the mammalian subject taken after treatment with the melanoma, inhibitory agent; and (c) comparing the first and second concentrations of MIA, wherein a decrease in the second concentration of MIA measured in the second biological sample as compared to the first concentration of MIA measured in the first biological sample indicates a positive response to the treatment with the melanoma inhibitory agent.

Abstract: The invention provides novel compounds having a substituted imidazole ring, and methods of using such compounds for the treatment of certain disorders such as hematological cancers and solid tumors. The compounds of the invention are tri-substituted imidazole derivatives that inhibit KSP. These compounds are also useful for the treatment of drug resistant tumors, such as solid tumors that express elevated levels of P-glycoprotein.

Abstract: The present invention provides a method for determining a response of a mammalian subject having melanoma tumor cells to treatment with a melanoma inhibitory agent. In one aspect, the method comprises (a) determining a first concentration of melanoma inhibitory activity protein (MIA) in a first biological sample taken from the mammalian subject before treatment with the melanoma inhibitory agent; (b) determining a second concentration of MIA in a second biological sample from the mammalian subject taken after treatment with the melanoma inhibitory agent; and (c) comparing the first and second concentrations of MIA, wherein a decrease in the second concentration of MIA measured in the second biological sample as compared to the first concentration of MIA measured in the first biological sample indicates a positive response to the treatment with the melanoma inhibitory agent.

Abstract: The invention provides novel compounds having a substituted imidazole ring, and methods of using such compounds for the treatment of certain disorders such as hematological cancers and solid tumors. The compounds of the invention are tri-substituted imidazole derivatives that inhibit KSP. These compounds are also useful for the treatment of drug resistant tumors, such as solid tumors that express elevated levels of P-glycoprotein.

Abstract: The present invention provides a method for determining a response of a mammalian subject having melanoma tumor cells to treatment with a melanoma inhibitory agent. In one aspect, the method comprises (a) determining a first concentration of melanoma inhibitory activity protein (MIA) in a first biological sample taken from the mammalian subject before treatment with the melanoma inhibitory agent; (b) determining a second concentration of MIA in a second biological sample from the mammalian subject taken after treatment with the melanoma inhibitory agent; and (c) comparing the first and second concentrations of MIA, wherein a decrease in the second concentration of MIA measured in the second biological sample as compared to the first concentration of MIA measured in the first biological sample indicates a positive response to the treatment with the melanoma inhibitory agent.

Abstract: The invention provides novel compounds having a substituted imidazole ring, and methods of using such compounds for the treatment of certain disorders such as hematological cancers and solid tumors. The compounds of the invention are tri-substituted imidazole derivatives that inhibit KSP. These compounds are also useful for the treatment of drug resistant tumors, such as solid tumors that express elevated levels of P-glycoprotein.

Abstract: The present invention provides novel biomarkers for cancer: the phosphorylation of ZC1 and/or ZC3 kinase substrates, particularly p120 catenin and Abi-1. Accordingly, the invention provides methods of determining whether a compound modulates ZC1 or ZC3 kinase activity, methods of determining whether a mammal is responding to a compound that modulates ZC1 or ZC3 kinase activity, and methods of predicting whether a mammal will respond therapeutically to a method of treating cancer by administering a modulator of ZC1 or ZC3 kinase.

Abstract: A switch comprises a long, slender stationary contact means and a movable contact means moving between an open position and a closed position. The contact zone of the contact means is separated from the electrical connection zone by a slot which opens out on the side where the movable contact means are situated in the open position. The depth of the slot is sufficient so that, when opening takes place, the current lines passing through the contact means are curved and run approximately parallel to the flank of the slot. This arrangement prevents the foot of the electrical arc from being directed towards the free end of the contact means, away from the arc extinguishing chamber.

Abstract: A multipole switch comprises a plurality of single-pole switch modules arranged side by side in compartments of the insulating case. Each switch module comprises an individual switching bar supporting the movable contact, said bar being formed by a vertical-axis rotary insulating stud having an end-piece for guiding in rotation at one of its ends, and driving means at the other end. A pair of actuating rods is mechanically coupled to the driving means of all the switching bars, and cooperates with connecting rods of the operating mechanism to perform movement of the actuating rods in translation in opposite directions when moving from the open position to the closed position, and vice-versa, said elongate actuating rods extending parallel to one another in a horizontal plane perpendicular to the different rotary studs.

Abstract: A circuit breaker equipped with an add-on remote control unit comprises a mechanical transmission link independent from the main mechanism, to transmit the position of the movable contact to an indicator, which automatically unlocks a latch in the open position to enable padlocking of a rack. The mechanical link is in two parts, composed of a push-rod associated with an operating lever on which the indicator is arranged, and a link rod articulated on the switching bar.

Abstract: Apparatus for detecting irregularities in the diameter of a filament has a small light source placed at the focus of an objective lens system. A horizontal slot constitutes a diaphragm for the objective lens system. A first optical system forms an image of the slot in a plane in which the filament runs past. Detectors detect the beam intercepted by the filament. An optical splitting system (P1) is interposed in the path of the beam (A), downstream of the slot (3) and upstream of the filament (5). The system is designed to form two sharp images (3', 3") of the slot (3) in a plane (4). The detectors are two oppositely-connected detectors (D1, D2) each receiving a respective beam (C, C') intercepted by the filament (5).

Abstract: An automatic sheet metal cutting machine has a continuous supply of metal strips in adjustable lengths, at will. A reciprocating cutter cuts laminations from the metal strip and a receiver receives the laminations. The receiver includes a swiveling plate movable through an angle .alpha. at will about a pin perpendicular to the direction motion of the laminations. The receiver is lowered and moved downstream relative to the direction of motion of the laminations received thereby.

Abstract: A rotary sealing device for connecting a fixed gas supply pipe to a tube rotating about its axis. It comprises a first rotary member for receiving the fixed pipe, a second rotary member for receiving and sealing the rotary pipe and fixed to the first member, and a filter placed in a chamber made in the aforementioned members and forming an obstacle to the gas flow and consequently to an overpressure of said gas, opposing the entry into the said chamber of gas coming from outside the device.

Abstract: The present invention relates to a device for handling a load, particularly an immersed load, by means of a shaft having a polygonal cross-section.The shaft, which can move along its axis, is maintained by a bearing connected to rotation means, so that a rotation of the bearing about the axis of the shaft leads to an identical rotation of the latter. The supply fluid for the bearing can be that in which the load to be manipulated is immersed.Application to the control and inspection of fuel rods.

Abstract: The invention relates to an apparatus for producing a preform for constituting an optical fiber. This apparatus essentially comprises a glass maker's lathe and a motor which holds and rotates a hollow silica tube, a torch making it possible to heat a cross-section of the tube and which can be translated along the tube and means for supplying the gaseous compounds consisting of silicon chloride, oxygen and doping agents decomposing under the action of the heat. Part of the products obtained is deposited on the walls of the tube. The supply means comprise a pipe entering the tube in axial manner and at the end of which are provided two radially directed arms, which terminate with an outlet normal to the pipe and arm, said pipe moving in translation integrally with the torch.

Abstract: This induction winding includes a magnetic core formed by a vertical stack of iron disks separated by air gaps. The disks (8) include a plurality of sector-shaped portions (1) each of which is constituted by a succession of magnetic laminations (6), a first part (12,13) of these laminations are all of identical length and a second part (14) are of regularly decreasing length from one lamination to the next. The direction (F.sub.1) in which the laminations are rolled in the mill is perpendicular to the axis (7) of the winding. The increased magnetic loss that this causes is compensated by the improved filling coefficient that can then be readily obtained.

Abstract: The invention relates to a device for tightening the core and the upper and lower cross pieces of a shunt inductance winding by means of a plurality of tie rods (5, 6, 7) which are preferably seven in number and which pass through the central hole of the core. A cup-shaped part (12) held by nuts (13) is fitted onto the tie rods, the outer wall of this part is threaded, a nut (14) is screwed onto this part (12) and bears against axially elastic washers (15).

Abstract: Highly accurate centering of an optical fiber within a primary cladding deposited by a coating device is carried out by automatic regulation during the fiber-drawing process in order to optimize the mechanical properties of the fiber. The position of the coating device is controlled in dependence on the position of the fiber with respect to an origin of coordinates (O) determined by optoelectronic means. The frusto-conical lower end of the coating die is maintained at each instant by electronic and electromechanical means at the point (O') located at this level on the straight-line segment (OR) which joins the origin to the first point of contact of the fiber with the pulley used for guiding the fiber towards a storage drum.