Abstract: The present invention relates to morpholine and thiomorpholine derivatives of the general formula I or pharmaceutically acceptable salts thereof and their use.

Abstract: The present invention relates to aniline derivatives of the general formula I or salts thereof and their use.

Abstract: The present invention provides protein single-color and multi-color protein fragment complementation assays for drug discovery, in particular to identify compounds that activate or inhibit cellular pathways. Based on the selection of an interacting protein pair combined with an appropriate PCA reporter such as monomeric enzymes and fluorescent proteins, the assays may be run in high-throughput or high-content mode and may be used in automated screening of libraries of compounds. Methods are described for constructing such assays for one or more steps in a biochemical pathway; testing the effects of compounds from combinatorial, natural product, peptide, antibody, nucleic acid or other diverse libraries on the protein or pathway(s) of interest; and using the results of the screening to identify specific compounds that activate or inhibit the protein or pathway(s) of interest. The development of such assays provides for a broad, flexible and biologically relevant platform for drug discovery.

Abstract: A rules analyzer system and method is provided for an enterprise system to evaluate and rank exact and probabilistic search rules for searching a computer database of records according to the efficiency of each search rule. The rules analyzer collects statistics on the performance of each search rule and assigns a priority value for each search rule according to the collected statistics. The priority values are based on the efficiency or precision of each search rule. Thereafter, the rules analyzer ranks the search rules according to the assigned priority.

Abstract: A transmission lubrication system for a vehicle transmission includes a fluid collection chamber positioned to collect fluid thrown by a rotatable member within the transmission. Structure forming a flow passage extending from the fluid collection chamber is in fluid communication with a transmission component so that the collected fluid flows from the fluid collection chamber via the flow passage to the transmission component to lubricate the transmission component.

Abstract: The present invention describes a method for detecting biomolecular interactions said method comprising: (a) selecting an appropriate reporter molecule selected from the group consisting of a protein, a fluorescent protein, a luminescent protein and a phosphorescent protein; (b) effecting fragmentation of said reporter molecule such that said fragmentation results in reversible loss of reporter function; (c) fusing or attaching fragments of said reporter molecule separately to other molecules; followed by (d) reassociation of said reporter fragments through interactions of the molecules that are fused to said fragments; and (e) detecting said biomolecular interactions by reconstitution of activity of the reporter molecule with the proviso that said protein is not ubiquitin.

Abstract: Oxygen or oxygen-enriched air is employed to support combustion in furnaces (16) and (26) of part of the hydrogen sulphide content of a first feed gas stream. Sulphur vapour is extracted in condenser (32) from the resulting gas mixture so as to form a sulphur vapour depleted gas stream. The sulphur vapour depleted gas stream is passed into a catalytic reduction reactor (40) in which all the residual sulphur dioxide is reduced to hydrogen sulphide. This reduced gas mixture has water vapour extracted therefrom in a quench tower (52). The resulting water vapour depleted gas stream flows to a Claus plant for treatment typically together with a second feed gas steam comprising hydrogen sulphide. Employing both furnaces (16) and (26) makes it possible to obtain effective conversions to sulphur of the hydrogen sulphide in the feed gas without having the recycle any of the water vapour depleted gas.

Abstract: The present invention describes a rapid and efficient in vivo library-versus-library screening strategy for identifying optimally interacting pairs of heterodimerizing polypeptides. It allows for the screening of a protein library against a second protein library, rather than against a single bait protein, and thus has numerous applications in the study of protein-protein interactions. Additionally, it allows for the application of different selection stringencies. Two leucine zipper libraries, semi-randomized at the positions adjacent to the hydrophobic core, were genetically fused to either one of two designed fragments of the enzyme murine dihydrofolate reductase (mDHFR), and cotransformed into E. coli. Interaction between the library polypeptides was required for reconstitution of the enzymatic activity of mDHFR, allowing bacterial growth.

Abstract: Oxygen or oxygen-enriched air is employed to support combustion in furnace (16) of part of the hydrogen sulphide content of a first feed gas stream. Sulphur is extracted from the resulting gas stream in a sulphur condenser (26). Catalyst Claus reaction between hydrogen sulphide and sulphur dioxide in the resulting sulphur vapour depleted gas stream takes place in a catalytic reactor (32). Sulphur is extracted in a further sulphur condenser (34). The resulting sulphur vapour depleted gas stream is passed into a catalytic reduction reactor (40) in which all the residual sulphur dioxide and any sulphur vapour are reduced to hydrogen sulphide. The resulting reduced gas mixture has water vapour extracted there from in a quench tower (52). The resulting water vapour depleted gas stream flows to a Claus plant for further treatment typically together with a second feed gas stream.

Abstract: A first magnetic field generated by a first coil operatively associated with a first portion of a vehicle interacts with at least one conductive element operatively associated with or at least a part of a second portion of the vehicle so as to generate an eddy current in the conductive element, which affects the magnetic field sensed by a magnetic sensor. A conductive element operatively coupled to a portion of the vehicle susceptible to a crash, e.g. a bumper or a door, provides for sensing a crash with the signal from the magnetic sensor. In another aspect, a second magnetic field is generated in the frame of a vehicle by a second coil wherein the frame is adapted so that the reluctance of the associated magnetic circuit is responsive to a crash. Signals from the first or second coils may be used to sense the associated magnetic fields.

Abstract: A signal generated responsive to a magnetic field in a magnetic circuit is decomposed into first and second filtered signals, wherein, at at least one first frequency, a magnitude of a component of the first filtered signal is greater than that of the second filtered signal, and at at least one second frequency greater than the at least one first frequency, a magnitude of a component of the second filtered signal is greater than that of the first filtered signal. A condition of a magnetic circuit is sensed responsive to the first and second filtered signals. In one embodiment, actuation of a safety restraint actuator of a vehicle is controlled responsive to the sensed condition of the magnetic circuit that includes a portion of the vehicle susceptible to a crash. A deployment threshold is adjusted responsive to a door opening state.

Abstract: Protein Fragment Complementation Assays (PCA) are done in plant material using enzyme fragment constructs, for example, dihydrofolate reductase (DHFR) fragment constructs. Plant material is transformed with at least two different constructs that form different products capable of interacting to reconstitute enzymatic activity in the plant material. Detection of the activity can be done using a substrate for the enzyme in the culture medium which, when reacted with the enzyme, is converted to a detectable product. One embodiment uses a substrate that can be enzymatically converted to a detectable fluorescent product. An inducer such as rapamycin or salicylic acid can be added to the culture medium to increase the level of detectable product.

Abstract: A tray unloader for rod-like articles of the tobacco industry includes a horizontally-movable, slidable carriage supporting an independently-driven tray inverting carrier arranged to pick up an upright full tray from a receiving position and invert it during movement to an unloading position. In the unloading position articles are received directly over opposed horizontal bands having a delivery channel between confronting ends and defining the initial level at which articles are received over most of the width of the tray. Downstream of the channel is a conveyor which operates at a relatively high rate during a first phase of unloading for each tray and at a reduced rate during a second phase, so as to allow controlled emptying of the tray and establishment of the residual level of articles in the channel after completion of unloading of each tray.

Abstract: A rules analyzer system and method is provided for an enterprise system to evaluate and rank exact and probabilistic search rules for searching a computer database of records according to the efficiency of each search rule. The rules analyzer collects statistics on the performance of each search rule and assigns a priority value for each search rule according to the collected statistics. The priority values are based on the efficiency or precision of each search rule. Thereafter, the rules analyzer ranks the search rules according to the assigned priority.

Abstract: The present invention describes an assay method comprising: (A) generating (1) at least a first fragment of a reporter molecule linked to a first interacting domain and at least a second fragment of a reporter molecule linked to a second interacting domain, or (2) nucleic acid molecules that code for (A)(1) and subsequently allowing said nucleic acid molecules to produce their coded products; then, (B) allowing interaction of said domains; and (C) detecting reconstituted reporter molecule activity, where said reporter molecule can react with a penicillin- or a cephalosporin-class substrate.

Abstract: The cell-based assays described in the present invention can be used to directly assess the sensitivity and specificity of the gene annotation reagent against its target, and to determine if a non-targeted gene participates in a pathway of interest or is functionally linked to another gene or protein. The combination of annotation reagents with such cell-based assays is useful for mapping genes (proteins) into cellular pathways on a genome-wide scale. Preferred assay embodiments include fluorescence or luminescence assays in intact (live or fixed) cells. Such fluorescence or luminescence assays include high-throughput or high-content assays for protein activity, subcellular localization, post-translational modifications, or interactions of proteins. Suitable assays may include protein-protein interaction assays; protein translocation assays; and post-translational modification assays.

Abstract: The present invention describes rapid and efficient methods to screen for biomolecular interactions in vivo based on protein fragment complementation assays (PCA). Examples are given that demonstrate the utility of the invention and the specific advantages of PCA that are not met by other library screening methods. In a first example, we demonstrate an in vivo library-versus-library screening strategy that has numerous applications in the identification of novel protein-protein interactions and in directed evolution. In another example we demonstrate the detection of protein-protein interactions starting with defined (full-length) cDNAs, and the concomitant generation of functional assays that provide initial validation of the cDNA products as being biologically relevant. In yet another example we demonstrate cDNA library screening in mammalian cells using a bait-vs.-library strategy combined with fluorescence detection.

Abstract: The present invention provides protein fragment complementation assays for drug discovery, in particular to identify compounds that activate or inhibit cellular pathways. Based on the selection of an interacting protein pair combined with an appropriate PCA reporter, the assays may be run in high-throughput or high-content mode and may be used in automated screening of libraries of compounds. The interacting pair may be selected by cDNA library screening; by gene-by-gene interaction mapping; or by prior knowledge of a pathway. Fluorescent and luminescent assays can be constructed using the methods provided herein. The selection of suitable PCA reporters for high-throughput or high-content (high-context) assay formats is described for a diversity of reporters, with particular detail provided for examples of monomeric enzymes and fluorescent proteins.

Abstract: The present invention is directed to Protein-fragment Complementation Assays (PCAs) and assay compositions based on fluorescent proteins. The invention provides methods for fragmenting fluorescent proteins and generating mutant fragments with desired spectral characteristics for PCA. The invention encompasses assays and compositions based on fluorescent proteins from the species Aequorea, Anemonia and Anthozoa. In particular, the invention is directed to fragments of mutant fluorescent proteins having improved spectral properties over the wild-type proteins. The invention encompasses fragments of mutant versions of A. Victoria green fluorescent protein (GFP), in particular yellow fluorescent proteins (EYFP and super-EYFP), ‘Venus’, cyan, ‘citrine’, blue, cyan-green, and photoactivatable variants of GFP The invention also encompasses red fluorescent PCAs based on Discosoma red fluorescent protein (RFP PCA) and a kindling fluorescent protein PCA (KFPL PCA) derived from Anemonia sulcata.

Abstract: Oxygen or oxygen-enriched air is employed to support combustion in furnaces (16) and (26) of part of the hydrogen sulphide content of a first feed gas stream. Sulphur vapour is extracted in condenser (32) from the resulting gas mixture so as to form a sulphur vapour depleted gas stream comprising hydrogen sulphide, sulphur dioxide, hydrogen and water vapour. The sulphur vapour depleted gas stream is passed into a catalytic reduction reactor (40) in which all the residual sulphur dioxide is reduced to hydrogen sulphide. The resulting reduced gas mixture has water vapour extracted therefrom in a quench tower (52). The resulting water vapour depleted gas stream flows to a Claus plant for further treatment typically together with a second geed gas steam comprising hydrogen sulphide. Employing both furnaces (16) and (26) makes it possible to obtain highly effective conversions to sulphur of the hydrogen sulphide on the feed gas without having the recycle any of the water vapour depleted gas.