Abstract: Evaluating an effect of one or more perturbations on cells of a first cell type is described. One method includes obtaining a screen definition for a screen, where the screen includes a cell-based assay that is run on a temporarily contiguous basis using a plurality of multi-well plates. The method includes obtaining control vectors including measurements of corresponding features of cells in control wells. The method includes obtaining test vectors including measurements of corresponding features of cells in test wells. The method includes forming a variability model based on a variance across the of control vectors, and embedding test vectors onto the variability model, thereby obtaining a set of variability model values. The method includes using the set of variability model values to resolve an effect of at least one data perturbation in the plurality of data perturbations on the first cell type.

Abstract: Systems and methods for determining whether a set of test perturbations discriminates over a null distribution for an on target effect against a first component of an entity are disclosed. The perturbations are perturbations of the first component and the entity comprises a plurality of components. For each perturbation in the set, a corresponding vector comprising a plurality of elements, is obtained. Each element comprises a distribution metric of measurements of a feature across instances of the entity upon exposure to the respective perturbation or (ii) a distribution metric of a respective dimension reduction component computed using the measurement of the plurality of features across instances of the entity upon the perturbation exposure. A composite metric is computed, using the vectors, and compared to a null distribution.

Abstract: A method for determining whether a set of perturbations discriminates over a null distribution for an on target effect against a first component of an entity is provided. The set of perturbations comprises perturbations of the first component and the entity comprises components including the first component. There is obtained, for each respective perturbation, a corresponding vector, thereby obtaining a plurality of vectors. Each such vector comprises a plurality of elements. Each element comprises (i) a distribution metric of a different feature, in a plurality of features, across a plurality of instances of the entity upon exposure of the plurality of instances of the entity to the respective perturbation or (ii) a distribution metric of a respective dimension reduction component computed using the plurality of features for a plurality of instances of the entity upon exposure of the plurality of instances of the entity to the respective perturbation.

Abstract: Systems and methods for determining whether a set of test perturbations discriminates over a null distribution for an on target effect against a first component of an entity are disclosed. The perturbations are perturbations of the first component and the entity comprises a plurality of components. For each perturbation in the set, a corresponding vector comprising a plurality of elements, is obtained. Each element comprises a distribution metric of measurements of a feature across instances of the entity upon exposure to the respective perturbation or (ii) a distribution metric of a respective dimension reduction component computed using the measurement of the plurality of features across instances of the entity upon the perturbation exposure. A composite metric is computed, using the vectors, and compared to a null distribution.

Abstract: A compound having the structure of Formula I, wherein A is a substituted or unsubstituted aryl or heteroaryl group, D is a substituted or unsubstituted 5- or 6-membered heteroaryl or heterocyclyl group and E is a substituted or unsubstituted aryl, heteroaryl, cycloalkyl or heterocyclyl group. The compounds are used for the treatment of androgen modulated indications including cancer (prostate, breast, ovarian, endometrial or bladder cancer), hair loss, acne, hirsutism, ovarian cysts, polycystic ovary disease, precocious puberty and age related macular degeneration. The use of the compounds for the manufacture of a medicament for modulating AR activity, a method of treatment using such compounds and a pharmaceutical composition and a commercial package comprising said compounds are also described.

Abstract: A compound having the structure of Formula I, wherein A is a substituted or unsubstituted aryl or heteroaryl group, D is a substituted or unsubstituted 5- or 6-membered heteroaryl or heterocyclyl group and E is a substituted or unsubstituted aryl, heteroaryl, cycloalkyl or heterocyclyl group. The compounds are used for the treatment of androgen modulated indications including cancer (prostate, breast, ovarian, endometrial or blader cancer), hair loss, acne, hirsutism, ovarian cysts, polycystic ovary disease, precocious puberty and age related macular degeneration. The use of the compounds for the manufacture of a medicament for modulating AR activity, a method of treatment using such compounds and a pharmaceutical composition and a commercial package comprising said compounds arc also described.

Abstract: Protoporphyrinogen oxidase enzyme-inhibiting herbicides are useful in a method for controlling unwanted ground shoots of vines and other trunk vegetation. Of particular interest is the use of carfentrazone ethyl and certain metabolites thereof for control of unwanted ground shoots of vines and other trunk vegetation.

Abstract: In the proposed fuel injection pump of the radial-piston pump type, the fuel injection rate can be controlled exactly by means of an electrically controlled valve which monitors a relief channel (66) of the pump working space (53) and which, by means of its closing time, determines the period of high-pressure injection during the pump-piston feed strokes. In order utilize the total length of the flanks of the drive cams as efficiently as possible, additionally injection adjustment is carried out as a result of the rotation of an essentially stationary part (13, 33) of the cam drive of the pump pistons (37) of the fuel injection pump relative to the rotary-driven part (8,9) of this cam drive. At the same time, on a fuel injection pump with a rotary-driven cam ring (9), there is a separation between a roller-carrying part (13) and a part (33) carrying pistons (37).

Abstract: A distributor fuel injection radial piston pump comprising a distributor piston movable between first and second axial positions to communicate a pump working space with an injection nozzle and to prevent communication between the pump working space with the injection nozzle, a control valve for controlling a quantity of fuel fed to the injection nozzle and movable between open and closed position to communicate the pump working space with the pump interior therethrough in the open position thereof to prevent feeding of fuel to the injection nozzle and blocking communication between the pump working space and the pump interior therethrough in the closing position thereof to provide for feeding fuel to the injection nozzle, and means for preventing excessive feeding of fuel to the nozzle in case of failure of the first control valve to move from the closing position thereof to the open position thereof in response to a predetermined control signal, the preventing means including a control space defined at leas

Abstract: A fuel injection device having a pump piston which during the supply stroke pumps fuel from a pump work chamber into an injection line which leads to a fuel injection valve. Directly adjacent to the branching off of the injection line from the pump work chamber, at the diameter of the injection line, a valve seat is provided, at which the injection line then merges with a chamber into which a pressure valve closing member plunges. The valve closing member is tightly guided in a guide bore, loaded by a valve spring, and in the chamber has a pressure shoulder adjoining the sealing surface that cooperates with the valve seat. The rear side of the pressure valve closing member communicates with a continuously open relief line.

Abstract: A plug-in pump, which is controlled by a beveled edge, is inserted in a pump installation bore of the internal combustion engine with the aid of an adjusting arrangement and ensures a uniform feed quantity in all plug-in pumps of an engine without subsequent feed quantity adjustment. When the feed quantity adjusting element is fixed in the testing position, the plug-in pump, which is inserted in the test base, is rotated until the feed quantity corresponds to the desired feed quantity and a positioning peg of the adjusting arrangement, which is supported in the flange of the plug-in pump and received by a recess in the test base, is adjusted and fixed in this rotational position. When the control rod of the engine is blocked in the basic testing position, a positioning groove (33) of an adjusting plate (32) of the adjusting arrangement is put into a corresponding rotational position by means of a pump dummy.

Abstract: A fuel injection device having a pump piston which during the supply stroke pumps fuel from a pump work chamber into an injection line which leads to a fuel injection valve. Directly adjacent to the branching off of the injection line from the pump work chamber, at the diameter of the injection line, a valve seat is provided, at which the injection line then merges with a chamber into which a pressure valve closing member plunges. The valve closing member is tightly guided in a guide bore, loaded by a valve spring, and in the chamber has a pressure shoulder adjoining the sealing surface that cooperates with the valve seat. The rear side of the pressure valve closing member communicates with a continuously open relief line.

Abstract: A fuel injection apparatus which the termination of the effective pump supply stroke is effected by exposing a relief conduit with the aid of a valve having for instance a control edge, whereupon a highly pressurized fuel flows out via the relief conduit and is directed into a pressure chamber defined by a rear face of a pressure valve closing member. The pressure valve closing member is located in a connection with a fuel injection line that leads from the pump work chamber to the fuel injection valve and is acted upon by a valve spring to effect closing of this injection line. The impact of fuel that reaches the pressure chamber via the releif conduit reinforces a fast closure of the pressure valve closing member at the end of injection, which leads to an abrupt termination of an injection cycle. In addition, or altenatively, the fuel injection valve closing member can also be acted upon by the impact of fuel diversion.

Abstract: A fuel injection pump has a work space which at a certain position of the pumping piston communicates with a tapping opening through which delivered fuel flows into an offtake space. The angular position at which the connection between the pumping space and the fuel offtake space is established, is adjustable in order to control the amount of injected fuel. The fuel offtake space is adjustable by means of a spring-biased piston. The position of the tapping opening to a distributing channel is adjustable by a movable supporting member communicating with a rotary distributor.

Abstract: The unit fuel injector has a pump piston driven at a constant stroke length, which pumps fuel at injection pressure to an injection nozzle as long as an electrically actuated overflow valve blocks the flow of the fuel flowing from the pump work chamber to a low-pressure chamber via an overflow conduit. The overflow valve is inserted between a first section which communicates continuously with the pump work chamber and a second section leading to the low-pressure chamber of the overflow conduit and is secured to a housing part laterally projecting from the pump housing. The first section of the overflow conduit comprises a connecting bore leading away from the pump work chamber, a control conduit controlled by the overflow valve, and a transverse conduit connecting these two.

Abstract: A pump/nozzle unit having a piston injection pump and an injection nozzle which includes a pump piston that is driven via a drive tappet and is rotatable via a regulating sleeve. The regulating sleeve is inserted into a recess on the end face of the pump housing and is axially secured in its installed state by means of a guide bushing. The guide bushing comprises a guide part for the drive tappet and a flange radially protruding beyond the outer diameter of the tappet spring, the flange being secured on the pump housing by a holder mechanism. The forces exerted upon the pump/nozzle unit during operation are absorbed by a securing arrangement.

Abstract: An apparatus for adjusting the spring characteristic of a helical spring has a manually actuatable adjusting element, which comprises a rotational support for the windings of a spiral spring. The apparatus further has a retaining member and an arresting member for retaining and securing the adjusting element in the adjusted positions. To provide a separate adjustability of the spring pitch and the spring biasing, the retaining member and arresting member are embodied such that the adjusting tang is rotatable without its axial position being varied, and is fixable in any rotated position.

Abstract: A pump/nozzle unit having an injection nozzle installed at at least approximately right angles to the longitudinal axis (A) on the pump housing of the piston injeciton pump. The injection pump is supported with a support face, which embodies its most extreme axial extension, on a support bearing located on the cylinder head of the engine. The support face is embodied by an outwardly pointing end face of a counterpart piston which is inserted into the pump cylinder in an extension of the longitudinal axis (A) and, with an inner end face, seals off the pump work chamber in a pressure-tight manner. As a result, the pumping forces resulting from the fuel which is placed under pressure in the pump work chamber are kept from affecting the pump housing and intercepted at a location on the cylinder head which is remote from a receiving bore for the injection nozzle.

Abstract: A fuel injection pump is proposed in which the fuel metering takes place during the intake stroke of the pump pistons via a fuel supply line in which a switching valve is mounted, which is opened upon the onset of the intake stroke of the pump pistons, closes in the course of this intake stroke and with this closing point also determines the injection onset upon the ensuing supply stroke of the pump pistons. The quantity of fuel to be injected is then limited by means of a pump-guided control edge, which is disposed on an annular slide provided on a free end of the distributor of the fuel injection pump; when a first control opening on the distributor which communicates with the pump work chamber coincides with a second control opening on the annular slide, the pump work chamber is relieved. The diversion or gradual shutoff point is controlled in the course of the compression stroke movement of the pump pistons by means of the relative rotation of the working point of the second control opening.

Abstract: A fuel injection pump in which for the purpose of controlling the injection quantity and in particular to determine the onset and end of injection, a hydraulically actuatable piston slide is provided, which controls a connection between the pump work chamber and a fuel supply line or the fuel supply container. The control is effected via two magnetic valves acting in opposite directions, by means of which two different, high control pressures acting upon the piston slide can be exerted. The control pressures are made available either with a single pressure control valve and by blocking off the relief of the supply side of the fuel supply pump, or else by means of two pressure control valves.