Abstract: This invention is directed to preparation and expression of synthetic genes encoding polypeptides containing protective epitopes of botulinum neurotoxin (BoNT). The invention is also directed to production of immunogenic peptides encoded by the synthetic genes, as weel as recovery and purification of the immunogenic peptides from recombinant organisms. The invention is also directed to methods of vaccination against botulism using the expressed peptides.

Abstract: Botulinum neurotoxins, the most potent of all toxins, induce lethal neuromuscular paralysis by inhibiting exocytosis at the neuromuscular junction. The light chains (LC) of these dichain neurotoxins are a new class of zinc-endopeptidases that specifically cleave the synaptosomal proteins, SNAP-25, VAMP, or syntaxin at discrete sites. The present invention relates to the construction, expression, purification, and use of synthetic or recombinant botulinum neutoroxin genes. For example, a synthetic gene for the LC of the botulinum neurotoxin serotype A (BoNT/A) was constructed and overexpressed in Escherichia coli. The gene product was purified from inclusion bodies. The methods of the invention can provide 1.1 g of the LC per liter of culture. The LC product was stable in solution at 4° C. for at least 6 months. This rBoNT/A LC was proteolytically active, specifically cleaving the Glu-Arg bond in a 17-residue synthetic peptide of SNAP-25, the reported cleavage site of BoNT/A.

Abstract: Urea derivatives of formula I are disclosed: The compounds are inhibitors of ?-secretase, and hence useful in the treatment or prevention of Alzheimer's Disease

Abstract: Botulinum neurotoxins, the most potent of all toxins, induce lethal neuromuscular paralysis by inhibiting exocytosis at the neuromuscular junction. The light chains (LC) of these dichain neurotoxins are a new class of zinc-endopeptidases that specifically cleave the synaptosomal proteins, SNAP-25, VAMP, or syntaxin at discrete sites. The present invention relates to the construction, expression, purification, and use of synthetic or recombinant botulinum neutoroxin genes. For example, a synthetic gene for the LC of the botulinum neurotoxin serotype A (BoNT/A) was constructed and overexpressed in Escherichia coli. The gene product was purified from inclusion bodies. The methods of the invention can provide 1.1 g of the LC per liter of culture. The LC product was stable in solution at 4° C. for at least 6 months. This rBoNT/A LC was proteolytically active, specifically cleaving the Glu-Arg bond in a 17-residue synthetic peptide of SNAP-25, the reported cleavage site of BoNT/A.

Abstract: The present invention provides a container for dispensing individual paper products that includes a housing, a cover hingedly or removably attached to the housing wherein the cover defines a dispensing opening, a means for elevating paper products, and a plunger disposed in the interior area of the housing. The plunger is urged toward the dispensing opening by the means for elevating paper products. The container may be included in a system for dispensing paper products that further includes a cartridge containing paper products. The cartridge defines a dispensing opening and a second opening wherein the means for elevating paper products extends through the second opening into the interior area of the cartridge to contact the paper products and urge the paper products toward the dispensing opening. The cartridge and container may be configured wherein the second opening is formed by removal of a removable portion during the process of inserting the cartridge into the container.

Abstract: This invention relates to a method of automatically setting the gain of an echo signal in a Doppler ultrasound haemodynamic monitor. In essence the invention comprises monitoring the strength of velocity components measured by the apparatus, and identifying a group of such components occupying a particular band within the overall velocity spectrum. The signal gain is then adjusted so that the perceived with of the band falls within predetermined limits. The monitoring or assessment of the velocity components is preferably undertaken when the overall flow velocity is high e.g. during systole.

Abstract: A class of compounds is disclosed, comprising sulphonamido-substituted bridged bicycloalkyl structures. The compounds are inhibitors of gamma-secretase, and hence are useful in the treatment of and/or prevention of Alzheimer's disease.

Abstract: A method of preparing a bioactive polypeptide in a stable, inactivated form, the method comprising the step of treating the polypeptide with ozonated water in order to oxidize and/or stabilize the cysteine residues, and in turn, prevent the formation of disulfide bridges necessary for bioactivity. The method can involve the use of ozonated water to both oxidize the disulfide bridges in a bioactive polypeptide, and to then stabilize the resultant cysteine residues. Optionally, and preferably, the method can involve the use of ozonated water to stabilize the cysteine residues, and thereby prevent the formation of disulfide bridges, in a polypeptide produced by recombinant means in a manner that allows the polypeptide to be recovered with the disulfide bridges unformed.

Abstract: A method of preparing a bioactive polypeptide in a stable, inactivated form, the method comprising the step of treating the polypeptide with ozonated water in order to oxidize and/or stabilize the cysteine residues, and in turn, prevent the formation of disulfide bridges necessary for bioactivity. The method can involve the use of ozonated water to both oxidize the disulfide bridges in a bioactive polypeptide, and to then stabilize the resultant cysteine residues. Optionally, and preferably, the method can involve the use of ozonated water to stabilize the cysteine residues, and thereby prevent the formation of disulfide bridges, in a polypeptide produced by recombinant means in a manner that allows the polypeptide to be recovered with the disulfide bridges unformed.

Abstract: A linear ignition fuze has a sheath, the inner surface of which has an irregular cross section such that the sheath is capable of forming a gas channel against a single strand core having a substantially circular (e.g. circular or elliptical) cross section. According to one embodiment of the invention, the sheath wall is of a non-uniform thickness having a cylindrical outer surface and a polygonal inner surface. The gap formed between the apexes of the polygonal inner surface and the substantially cylindrical core form the gas channels, while the contact between the side walls of the polygonal inner surface and the cylindrical core confine the core within the sheath.

Abstract: The invention provides an ultrasound probe for use in a Doppler ultrasound haemodynamic monitor having a host signal processor and an interconnect cable. The probe includes a memory device, preferable in the form of E 2PROM which communicates with the host processor to limit the life of the probe and to render the probe inoperable in the event an attempt is made to use the probe in conjunction with more than one patient.

Abstract: 1 Novel urea derivatives of formula I are disclosed: The compounds are inhibitors of &ggr;-secretase, and hence useful in the treatment or prevention of Alzheimer's disease.

Abstract: This invention is directed to preparation and expression of synthetic genes encoding polypeptides containing protective epitopes of botulinum neurotoxin (BoNT). The invention is also directed to production of immunogenic peptides encoded by the synthetic genes, as weel as recovery and purification of the immunogenic peptides from recombinant organisms. The invention is also directed to methods of vaccination against botulism using the expressed peptides.

Abstract: A linear ignition fuze has a sheath, the inner surface of which has an irregular cross section such that the sheath is capable of forming a gas channel against a single strand core having a substantially circular (e.g. circular or elliptical) cross section. According to one embodiment of the invention, the sheath wall is of a non-uniform thickness having a cylindrical outer surface and a polygonal inner surface. The gap formed between the apexes of the polygonal inner surface and the substantially cylindrical core form the gas channels, while the contact between the side walls of the polygonal inner surface and the cylindrical core confine the core within the sheath.

Abstract: Using the nontoxic heavy chain fragment from botulinum neurotoxins A-G, compositions and methods of use in inducing an immune response which is protective against intoxication with botulinum in subjects is described.

Abstract: A class of tryptamine analogues bearing an optionally substituted phenyl nucleus at the 2-position are selective antagonists of the human 5-HT2A receptor and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of adverse neurological conditions, including psychotic disorders such as schizophrenia.

Abstract: Botulinum neurotoxins, the most potent of all toxins, induce lethal neuromuscular paralysis by inhibiting exocytosis at the neuromuscular junction. The light chains (LC) of these dichain neurotoxins are a new class of zinc-endopeptidases that specifically cleave the synaptosomal proteins, SNAP-25, VAMP, or syntaxin at discrete sites. The present invention relates to the construction, expression, purification, and use of synthetic or recombinant botulinum neutoroxin genes. For example, a synthetic gene for the LC of the botulinum neurotoxin serotype A (BoNT/A) was constructed and overexpressed in Escherichia coli. The gene product was purified from inclusion bodies. The methods of the invention can provide 1.1 g of the LC per liter of culture. The LC product was stable in solution at 4° C. for at least 6 months. This rBoNT/A LC was proteolytically active, specifically cleaving the Glu-Arg bond in a 17-residue synthetic peptide of SNAP-25, the reported cleavage site of BoNT/A.

Abstract: A method of preparing a bioactive polypeptide in a stable, inactivated form, the method comprising the step of treating the polypeptide with ozonated water in order to oxidize and/or stabilize the cysteine residues, and in turn, prevent the formation of disulfide bridges necessary for bioactivity. The method can involve the use of ozonated water to both oxidize the disulfide bridges in a bioactive polypeptide, and to then stabilize the resultant cysteine residues. Optionally, and preferably, the method can involve the use of ozonated water to stabilize the cysteine residues, and thereby prevent the formation of disulfide bridges, in a polypeptide produced by recombinant means in a manner that allows the polypeptide to be recovered with the disulfide bridges unformed.

Abstract: Using the nontoxic heavy chain fragment from botulinum neurotoxins A-G, compositions and methods of use in inducing an immune response which is protective against intoxication with botulinum in subjects is described.

Abstract: A photolithographically patterned spring contact is formed on a substrate and electrically connects contact pads on two devices. The spring contact also compensates for thermal and mechanical variations and other environmental factors. An inherent stress gradient in the spring contact causes a free portion of the spring contact to bend up and away from the substrate. An anchor portion remains fixed to the substrate and is electrically connected to a first contact pad on the substrate. The spring contact is made of an elastic material and the free portion compliantly contacts a second contact pad, thereby electrically interconnecting the two contact pads. The free portion is initially fixed to the substrate to intentionally form the inherent stress gradient in the elastic member. The free portion is released from the substrate by etching a release layer deposited on the substrate so the inherent stress gradient in the elastic member biases the free portion away from the substrate.