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.

Abstract: A trailer (T) and a dock (D) are provided with substantially identical slat conveyors (10, 12). Each conveyor (10, 12) has alternating conveyor slats (36, 36?) and lifting/holding slats (38, 38?). The trailer (T) is backed up to the dock (D). Upper portions of the lifting/holding slats (38, 38?) are coupled together at their ends. The confronting ends of the conveying slats (36, 36?) are also coupled together. A mechanism carried by the dock (D) raises and lowers the upper portions of the two sets of lifting/holding slats (38, 38?) a drive mechanism carried by the dock (D) where it reciprocates both sets of conveying slats (36, 36?).

Abstract: A non-cytotoxic protein conjugate for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell, comprising: (i) a Targeting Moiety (TM), wherein said TM is an agonist of a receptor present on said nociceptive sensory afferent cell, and wherein said receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of said nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are also described.

Abstract: A plow (P) sits down on movable slats (10) of a reciprocating slat conveyor formed of the movable slats (10) and fixed slats (12) which are between the movable slats (10). The movable slats (10) and fixed slats (12) define valley regions between the movable slats (10). The plow (P) has fingers (92, 106) which extend into the valley regions. During the unloading operations, the plow (P) is moved rearwardly by the moveable slats (10), together with the load (L) that is on the conveyor. When the plow (P) reaches the rear end of the conveyor, it tips rearwardly and discharges the remaining portions of the load (L) off from the conveyor. Then, a teather (T) is wound onto a winch and used for pulling the plow (P) forwardly back into a forward parked position (FIG. 15).

Abstract: A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a Targeting Moiety that is capable of binding to a Binding Site on the nociceptive sensory afferent, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the Targeting Moiety; and a translocation domain that is capable of translocating the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described.

Abstract: A plow (P) sits down on movable slats (10) of a reciprocating slat conveyor formed of the movable slats (10) and fixed slats (12) which are between the movable slats (10). The movable slats (10) and fixed slats (12) define valley regions between the movable slats (10). The plow (P) has fingers (92, 106) which extend into the valley regions. During the unloading operations, the plow (P) is moved rearwardly by the moveable slats (10), together with the load (L) that is on the conveyor. When the plow (P) reaches the rear end of the conveyor, it tips rearwardly and discharges the remaining portions of the load (L) off from the conveyor. Then, a teather (T) is wound onto a winch and used for pulling the plow (P) forwardly back into a forward parked position (FIG. 15).

Abstract: A non-cytotoxic protein conjugate for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell, comprising: (i) a Targeting Moiety (TM), wherein said TM is an agonist of a receptor present on said nociceptive sensory afferent cell, and wherein said receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of said nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are also described.

Abstract: A trailer (T) and a dock (D) are provided with substantially identical slat conveyors (10, 12). Each conveyor (10, 12) has alternating conveyor slats (36, 36?) and lifting/holding slats (38, 38?). The trailer (T) is backed up to the dock (D). Upper portions of the lifting/holding slats (38, 38?) are coupled together at their ends. The confronting ends of the conveying slats (36, 36?) are also coupled together. A mechanism carried by the dock (D) raises and lowers the upper portions of the two sets of lifting/holding slats (38, 38?) a drive mechanism carried by the dock (D) where it reciprocates both sets of conveying slats (36, 36?).

Abstract: A trailer (T) and a dock (D) are provided with substantially identical slat conveyors (10, 12). Each conveyor (10, 12) has alternating conveyor slats (36, 36?) and lifting/holding slats (38, 38?). The trailer (T) is backed up to the dock (D). Upper portions of the lifting/holding slats (38, 38?) are coupled together at their ends. The confronting ends of the conveying slats (36, 36?) are also coupled together. A mechanism carried by the dock (D) raises and lowers the upper portions of the two sets of lifting/holding slats (38, 38?) a drive mechanism carried by the dock (D) where it reciprocates both sets of conveying slats (36, 36?).

Abstract: A connection for releasable connecting confronting first and second portions of first and second members. The first portion has a first passageway has a second portion has a second passageway. An elongated coupler member is in the first passageway. A shim projects endwise outwardly from the first portion on one side of the first passageway. A coupler member is extendable endwise outwardly from the first passageway beyond the shim. When so extended, the coupler member is insertable into an entry portion of the second passageway. The first portion is movable relatively towards the second portion when the coupler member is extended. The extended coupler portion is moved into and through the entry portion of the second passageway. The shim is moved into the entry portion of the second passageway along side the coupler member.

Abstract: Separate manifold blocks are connected to the ends of tubular piston rod end portions of linear hydraulic motors that are parts of a drive assembly for a reciprocating slat conveyor. The manifold blocks are removably connected together by bolts and when connected complete passageways in the manifold block assembly that connect the linear hydraulic motors with each other and with pressure and return conduits. The end portions of the linear hydraulic motors are connected to transverse mounting frame members by spaced apart clamp assemblies. The clamp connections stiffen the end portions of the linear hydraulic motors and minimize deflection at the centers of the linear hydraulic motors.

Abstract: Fixed conveyor slats (12) in the nature of beams extend over a window in a support framework (70, 72, 74, 76, 86, 88) for the movable and fixed slats (10, 12) of the reciprocating slat conveyor. The fixed slats (12) support the movable slats (10), including in the region of the window. The fixed and movable slats (12, 10) are box beams, providing them with strength and stiffness in the region of the window. The fixed slats (12) are covered by planks of bearing material (46). Side portions (14, 16) of the movable slats (10) set down on side portions (50, 48) of the planks of bearing material (46). The planks of bearing material (46) are connected at one end only to the fixed slats (12). The bearing material (46) is capable of withstanding the heat of hot asphalt concrete and protects the fixed slats (12) from contact with the asphalt concrete.

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: 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 Translation 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: The invention provides a single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of a target cell; a Targeting Moiety that is capable of binding to a Binding Site on the target cell, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the target cell; a protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the Targeting Moiety; and a translocation domain that is capable of translocating the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the target cell.

Abstract: The present invention relates to treatment of disease by inhibition of cellular secretory processes, to agents and compositions therefor, and to manufacture of those agents and compositions. The present invention relates particularly, to treatment of disease 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.

Abstract: The present invention relates to treatment of mucus hypersecretion, to compositions therfor and manufacture of those compositions. The present invention relates particularly, though not exclusively, to the treatment of chronic bronchitis in chronic obstructive pulmonary disease (COPD), asthma and other clinical conditions involving COPD.

Abstract: An elongated plastic slide bearing (10) comprises a top (30), sidewalls (32, 34) depending from the top (30), and connecting to walls (36, 44, 48 and 38, 46, 50) that form laterally inwardly extending recesses (40, 42). Lock ribs (62, 64) extend upwardly and inwardly from the inner walls (44, 46) of the recesses (40, 42) to upper edges (66, 68). The upper edges (66, 68) are spaced below the bearing top (30). The bearing (10) is adapted to be set down onto a support beam (14) that includes laterally outwardly projecting lock flanges (22, 24) at its top. The lock ribs (62, 64) contact the lock flanges (22, 24). When the bearing (10) is pushed downwardly, the lock ribs (62, 64) bend outwardly and allow the lock ribs (62, 64) to move into a position below the lock flanges (22, 24). When that happens, the lock ribs (62, 64) assume substantially unstressed positions in which their upper edges (66, 68) are below the lock flanges (22, 24).

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.