Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.

Abstract: The present invention provides a method for designing a re-targeted toxin conjugate for use in treating a medical condition or disease. Also provided, is the use of said conjugates in the manufacture of a medicament for treating medical conditions or diseases. The conjugates include a Targeting Moiety, which directs the conjugate to a desired target cell, and are characterised by a Targeting Moiety that increases exocytic fusion in the target cell. The present invention also provides methods for identifying agonists suitable for use as Targeting Moieties, and methods for preparing conjugates comprising said Targeting Moieties, to re-target a toxin to a cell of therapeutic interest. In particular, the present invention describes a method for designing a toxin conjugate, and describes therapeutic applications of said conjugates to inhibit or reduce cellular processes.

Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.

Abstract: Fixed conveyor slats (12) in the nature of beams extend over a window in support framework (53, 100, 102, 116, 118) for the movable and fixed slats (10, 12) in a reciprocating slat conveyor. The fixed slats (12) support the movable slats (20), including in the region of the window. The movable slats (10) are in the nature of box beams, providing them with strength and stiffness in the region of the window. At the rear end of the conveyor, the movable slats (10) move onto support brackets (120) which prevent the rear end portions of the slats (10) from being damaged when they are in a position overhanging a rear wall (84) and material is dropped from above down onto the rear end portions of the slats (10).

Abstract: A screw (114) is rotated to move a head (110, 110?) against a first squeeze bar (30) and through a threaded opening (114) in a second squeeze bar (32), for moving the squeeze bars (30, 32) relatively together. This movement rotates cam bars (100, 102, 104, 106) in position, causing them to move a lower spread bar (24) away from an upper spread bar (22). This pulls downwardly on a bolt (16) which is connected to the lower spread bar (24). As the bolt (16) moves downwardly, its head (18) pushes downwardly on an upper clamp member (52?), moving it towards a lower clamp member (54?). This firmly clamps bottom flanges (78, 80) on a conveyor slat (70) between the upper and lower clamps member (52?, 54?), firmly securing the slat (70) to a transverse drive beam (56?).

Abstract: A method of playing a casino table version of cribbage using at least one deck of conventional playing cards, having at least one player making a wager and a dealer that deals the cards. The method includes having at least one player making a wager to receive a plurality of cards. Next, the cards are dealt to each player and the dealer is dealt a plurality of cards, wherein four random cards are dealt to create the dealer hand. The players discard either one or two cards depending on the method chosen. The dealer then exposes his cards and discards two cards. Next, the starter card is exposed. Finally, the players' cards are exposed and values of the hands are computed and compared to the dealer's hand. The method includes determining whether the players win or lose their wager.

Abstract: A conveyor comprises laterally spaced apart lifting/holding slats (12) and laterally spaced apart conveying slats (10) between the lifting/holding slats (12). The conveying slats (10) are advanced in a first direction for conveying a load and are retracted in a second direction for returning them to a start position. The lifting/holding slats (12) have lower portions (62) which reciprocate and upper portions (60) which move up and down. Cams (92, 94) operate in response to longitudinal movement of the lower portions (62) to raise and lower the upper portions (60).

Abstract: A method of treating mucus hypersecretion, the causative factor in chronic obstructive pulmonary disease (COPD), asthma and other clinical conditions involving COPD, comprises administering a compound that inhibits exocytosis in mucus secreting cells or neurones that control or direct mucus secretion. Also described is a compound, for use in the treatment of hypersecretion of mucus, which inhibits mucus secretion by inhibiting mucus secretion by mucus secreting cells, and/or inhibiting neurotransmitter release from neuronal cells controlling or directing mucus secretion.

Abstract: Fixed conveyor slats (12) in the nature of beams extend over a window in support framework (53, 100, 102, 116, 118) for the movable and fixed slats (10, 12) in a reciprocating slat conveyor. The fixed slats (12) support the movable slats (20), including in the region of the window. The movable slats (10) are in the nature of box beams, providing them with strength and stiffness in the region of the window. At the rear end of the conveyor, the movable slats (10) move onto support brackets (120) which prevent the rear end portions of the slats (10) from being damaged when they are in a position overhanging a rear wall (84) and material is dropped from above down onto the rear end portions of the slats (10).

Abstract: A method of treatment of disease by inhibition of cellular secretory processes is provided. The method has particular application in the treatment of diseases dependent upon the exocytotic activity of endocrine cells, exocrine cells, inflammatory cells, cells of the immune system, cells of the cardiovascular system, and bone cells. Agents and compositions therefor, as well as methods for manufacturing these agents and compositions, are provided. In a preferred embodiment a clostridial neurotoxin, substantially devoid of holotoxin binding affinity for neuronal cells of the presynaptic muscular junction, is associated with a targeting moiety. The targeting moiety is selected such that the clostridial toxin conjugate so formed may be directed to a non-neuronal target cell to which the conjugate may bind. Following binding, a neurotoxin component of the conjugate, which is capable of inhibition of cellular secretion, passes into the cytosol of the target cell by cellular internalisation mechanisms.

Abstract: An inflatable bladder (50) is positioned between the top (24) of a lower slat (22) and the top (36) of an upper slat (20). An air supply/exhaust conduit (52) extends upwardly from a transverse manifold (76) to the inflatable bladders (50). Flanges (32, 34) on the lower slat (22) contact flanges (42, 44) on the upper slat (20) to stop upward movement of the upper slat (20).

Abstract: The present invention is a method for determining the center to center spacing of conductors in an insulated, multi-conductor, flat cable. The method comprising applying an X-ray field to the cable, detecting the X-ray field intensity that passes through the cable, obtaining a digitized output waveform of the X-ray field intensity as a function of cable position, and determining a trough location of the waveform by averaging calculated position values for the center of the conductor at several longitudinal positions along a cross section of the conductor.

Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide, is possible and the polypeptide can be incorporated into vaccines and toxin assays.

Abstract: Transverse frame members (14, 16) extend across and are connected to longitudinal frame members (10, 12). Frame member (14) divides longitudinal frame members (10, 12) into major and minor parts (20, 22, 24, 26). The minor parts (24, 26) are braced by gussets (70, 72) which extend between the minor parts (24, 26) and a vertical web portion (68) of the transverse beam (14). The minor parts (24, 26) of the frame members (10, 12) and the central portion of the frame member (14) form a nook (76) in the cylinder components (80, 82, 84, 102, 104) are received. Piston rod portions (92, 94, 96) of the assembly of linear motors extend from the cylinder component portions to guide bearings (100) mounted in openings (56, 58, 60) formed in the vertical web (54) of the second transverse beam (16). Bolts are used to connect the inner corner portions of the assembly of linear hydraulic motors to mounting pads (34, 36).

Abstract: This invention describes a novel agent for the targeted control of a mammalian cell activity, in particular the agent is used to control the interaction of particular cell types with their external environment. The agent has applications as a pharmaceutical for the treatment of a variety of disorders. An agent according to the invention comprises three Domains B, T and E linked together in the following manner: Domain B-Domain T-Domain E where Domain B is the Binding Domain which binds the agent to a Binding Site on the cell which undergoes endocytosis to produce an endosome, Domain T is the Translocation Domain which translocates the agent (with or without the Binding Site) from within the endosome across the endosomal membrane into the cytosol of the cell, Domain E is the Effector Domain which inhibits the ability of the Recyclable Membrane Vesicles to transport the Integral Membrane Proteins to the surface of the cell.

Abstract: A threaded nipple (26) at the closed end of a linear hydraulic motor (12) is received within a recess (82) in a frame member (78). Single clamp members, or individual clamp members (88), have recesses (92) that receive lower portions of the nipples (26). Bolts (94) extend through the clamp members (88) and screw into threaded openings in the frame member (78). This clamps the nipples (26) between the frame member (78) and the removable clamp members (88). End members (22) at the rod ends of the cylinders (12) include keys (66) that are received within recesses (80) formed in another frame member (76). Bolts (76) extend through the end member (22) and screw into threaded openings (84) in the member (76). A mounting frame has transverse mounting frame members (74, 102, 74?, 102?) that are used for mounting the drive assembly in an installation. The mounting frame members (74?, 102?) may have end portions (208, 210, 212, 214, 240, 242) that serve as cells in a trailer installation.

Abstract: A door closer includes an anchor assembly for mounting on a door frame, an actuator assembly for mounting within the thickness of a door which is hinged for movement between open and closed positions, an operating member coupled by a linkage to the anchor assembly and mounted for a range of movements between a retracted position and an extended position, a resilient driving apparatus arranged to exert a driving force on the operating member, a damper mechanism operatively connected to the operating member so as to damp movement of the operating member at least in a direction towards the retracted position, and a resilient thrust device arranged to exert an increased driving force on the operating member over a defined part of its range of movement as the operating member approaches the retracted position.

Abstract: Antigenic compositions are provided comprising a single chain polypeptide comprising first and second domains, wherein said first domain is a clostridial neurotoxin light chain or a fragment or a variant thereof and is capable of cleaving one or more vesicle or plasma membrane associated proteins essential to exocytosis; and said second domain is a clostridial neurotoxin heavy chain HN portion or a fragment or a variant thereof, wherein said second domain is capable of (i) translocating the polypeptide into a cell or (ii) increasing the solubility of the polypeptide compared to the solubility of the first domain on its own or (iii) both translocating the polypeptide into a cell and increasing the solubility of the polypeptide compared to the solubility of the first domain on its own; and wherein the second domain lacks a functional C-terminal part of a clostridial neurotoxin heavy chain designated HC thereby rendering the polypeptide incapable of binding to cell surface receptors that are the natural cell sur

Abstract: A plurality of hold-down bearings (12) are locked into position on longitudinal guide beams (12, 12?). Anti-splash bearings (10) are positioned on the guide beams (12, 12?) longitudinally between the hold-down bearings (12). The anti-splash bearings have bottom flaps (46, 48) which contact bottom flanges (36, 38) on the floor slats (20) and block the upward flow of water into the region below the conveyor slats (20). The hold-down bearings (20) also block to a considerable extent the upward movement of water into the underneath regions of the conveyor slats (20).

Abstract: A door closer having a pair of main driving springs, a fluid-filled damper arrangement and a pair of thrust springs is provided, the thrust springs coming into effect during the latter part of a door closing operation, so as to provide an augmented closing force at that point. The position at which the augmented closing force is applied is variable, with a cam mechanism being used to control application of the increased closing force.