Abstract: A strategy for suppressing specifically or partially specifically an endogenous gene and introducing a replacement gene, said strategy comprising the steps of: 1. providing suppressing nucleic acids or other suppression effectors able to bind to an endogenous gene, gene transcript or gene product to be suppressed and 2. providing genomic DNA or cDNA (complete or partial) encoding a replacement gene wherein the suppressing nucleic acids are unable to bind to equivalent regions in the genomic DNA or cDNA to prevent expression of the replacement gene. The replacement nucleic acids have modifications in one or more third base (wobble) positions such that replacement nucleic acids still code for the wild type or equivalent amino acids.

Abstract: A strategy for suppressing specifically or partially specifically an endogenous gene and introducing a replacement gene, said strategy comprising the steps of: 1. providing suppressing nucleic acids or other suppression effectors able to bind to an endogenous gene, gene transcript or gene product to be suppressed and 2. providing genomic DNA or cDNA (complete or partial) encoding a replacement gene wherein the suppressing nucleic acids are unable to bind to equivalent regions in the genomic DNA or cDNA to prevent expression of the replacement gene. The replacement nucleic acids have modifications in one or more third base (wobble) positions such that replacement nucleic acids still code for the wild type or equivalent amino acids.

Abstract: The invention provides a strategy for suppressing expression of an endogenous gene, wherein said strategy comprises providing suppression effectors able to bind to the non-coding regions of a gene to be suppressed, to prevent the functional expression thereof. The suppression effectors may be nucleic acids, and the non-coding regions can include the transcribed but non-translated regions of a gene. The strategy can also introduce a replacement gene.

Abstract: Methods and agents for suppressing expression of a mutant allele of a gene and providing a replacement nucleic acid are provided. The methods of the invention provide suppression effectors such as, for example, antisense nucleic acids, ribozymes, or RNAi, that bind to the gene or its RNA. The invention further provides for the introduction of a replacement nucleic acid with modified sequences such that the replacement nucleic acid is protected from suppression by the suppression effector. The replacement nucleic acid is modified at degenerate wobble positions in the target region of the suppression effector and thereby is not suppressed by the suppression effector. In addition, by altering wobble positions, the replacement nucleic acid can still encode a wild type gene product. The invention has the advantage that the same suppression strategy could be used to suppress, in principle, many mutations in a gene.

Abstract: The invention provides strategy for suppressing expression of an endogenous gene, wherein said strategy comprises providing suppression effectors able to bind to the non-coding regions of a gene to be suppressed, to prevent the functional expression thereof. The suppression effectors may be antisense nucleic acids, and the non-coding regions can include the transcribed but non-translated regions of a gene. The strategy can also introduce a replacement gene.

Abstract: A process of producing from an elongate tube a tubular structural component having a first longitudinal section integrally connected to a second longitudinal section, the second section being located at the end of the tube and being of a desired cross-sectional shape and size, the cross-sectional size of the second section being greater than that of the first section, the process including selecting a mandrel having a cross-sectional shape and size corresponding to the second section, relatively axially feeding said end of the tube over the mandrel in order to form said second section, the choice of the size of mandrel and the rate of feed and the axial pressure applied to said tube being controlled such that the wall thickness of the second section is on average at least 70 percent of the average wall thickness of the first wall section.

Abstract: The invention provides strategy for suppressing expression of an endogenous gene, wherein said strategy comprises providing suppression effectors able to bind to the non-coding regions of a gene to be suppressed, to prevent the functional expression thereof. The suppression effectors may be antisense nucleic acids, and the non-coding regions can include the transcribed but non-translated regions of a gene. The strategy can also introduce a replacement gene.

Abstract: Methods and agents for suppressing expression of a mutant allele of a gene having a polymorphism are provided. The methods of the invention provide suppression effectors such as antisense nucleic acids or ribozymes, that bind to nucleic acid regions having a polymorphism within a gene such that one allele of a gene is exclusively or preferentially suppressed. The method also provides the administration of a replacement nucleic acid, if required. The invention has the advantage that the same suppression strategy, when directed to polymorphisms, could be used to suppress, in principle, many mutations in a polymorphic gene. This is particularly relevant when large numbers of mutations within a single gene cause disease pathology.

Abstract: A process of producing from an elongate tube a tubular structural component having a first longitudinal section integrally connected to a second longitudinal section, the second section being located at the end of the tube and being of a desired cross-sectional, shape and size, the cross-sectional size of the second section being greater than that of the first section, the process including selecting a mandrel having a cross-sectional shape and size corresponding to the second section, relatively axially feeding said end of the tube over the mandrel in order to form said second, section, the choice of the size of mandrel and the rate of feed and the axial pressure applied to said tube being controlled such that the wall thickness of the second section is on average at least 70 percent of the average wall thickness of the first wall section.

Abstract: A digital alarm system of the type having first and second electrically conductive loops connected by an alarm switch. The alarm switch is normally open, but can be closed when an alarm state exists to electrically short one loop to the other. Currents are generated in each of the loops for use in detecting either the closing of the alarm switch or the occurrence of a fault in one of the loops. Resistors are connected to each of the loops for use in detecting the presence or absence of the currents. A first pair of transistor switches alternatingly short-circuit one resistor then the other; and a second pair of transistor switches, synchronized with the first pair, alternatingly short the ends of one loop then those of the other so that when the alarm switch is closed the first pair of transistor switches simultaneously short-circuit both resistors even if a fault occurs anywhere in one of the loops.