Abstract: In various embodiments method are provided for generating expression cassettes and gene therapy vectors comprising those cassettes that recapitulate the spatiotemporal pattern of expression of the endogenous gene. In certain embodiments the methods comprise (i) selecting a target gene; (ii) identifying putative regulatory elements associated with the target gene; (iii) determining if the regulatory element is a key regulatory element and (iv) providing a list of the key regulatory elements identified in step (iii).

Abstract: In certain embodiments a lentiviral vector for the treatment of Recombination-Activating Gene 1 Severe Combined Immunodeficiency (RAG1 SCID) is provided. In certain embodiments the vector comprises an expression cassette comprising a nucleic acid construct comprising an effective fragment of the endogenous promoter of the RAG1 gene and a nucleic acid that encodes the RAG1 protein operably linked to the effective fragment of the endogenous promoter of the RAG1 gene.

Abstract: In certain embodiments a lentiviral vector for the treatment of Wiskott-Aldrich Syndrome (WAS) is provided. In certain embodiments the vector comprises an expression cassette comprising a nucleic acid construct comprising an effective fragment of the endogenous promoter of the WAS gene where said promoter has maximum length of 600 bp and contains the sequence of HS1pro, and a nucleic acid that encodes the Wiskott-Aldrich Syndrome protein (WASp) operably linked to the effective fragment of the endogenous promoter of the WAS gene.

Abstract: In certain embodiments a lentiviral vector for the treatment of X-linked chronic granulomatous disease (X-CGD) is provided. In certain embodiments the vector comprises an expression cassette comprising a nucleic acid construct comprising a CYBB promoter or effective fragment thereof; and a nucleic acid that encodes gp91phox operably linked to the CYBB promoter or promoter fragment.

Abstract: In certain embodiments a lentiviral vector having an LCR comprising HS1 ENCODE core (EC1) sequence (SEQ ID NO:1), and one or more of an HS2 core sequence (ecHS2), an HS3 core sequence (ecHS3), an HS4 core sequence (ecHS4), a full length HS2, a full length HS3, and/or a full length HS4 sequence is provided. In certain embodiments the vector comprises a modified ?AS3-globin transgene, where transgene comprises a codon optimized exon 1, and/or a codon optimized exon 2, and/or a codon optimized exon 3.

Abstract: In certain embodiments a lentiviral vector having optimized reduced size LCR with improved enhancer activity is provided. In certain embodiments direct treatment of a subject by direct introduction of the vector(s) described herein is contemplated. The lentiviral compositions may be formulated for delivery by any available route including, but not limited to parenteral (e.g., intravenous), intradermal, subcutaneous, oral (e.g., inhalation), transdermal (topical), transmucosal, rectal, and vaginal.

Abstract: In various embodiments, lentiviral vectors expressing FoxP3 using the endogenous gene elements to regulate physiologic gene expression of FoxP3 are provided herein as well as uses of such vectors.

Abstract: A mezzanine header connector includes header modules stacked side-by-side having housing frames holding contact assemblies. Each contact assembly includes header contacts held by at least one dielectric holder. The header contacts have mating segments for termination to corresponding receptacle contacts of a mezzanine receptacle connector and terminating segments for termination to a circuit board. Each of the header contacts extend along a linear path between the corresponding mating segment and the corresponding terminating segment. Each housing frame has walls defining pockets receiving corresponding header contacts of the contact assembly. The housing frame is conductive and provides shielding around the associated header contacts of the contact assemblies. The header contacts face associated walls with air separating the header contacts and the walls along a majority of the header contacts.

Abstract: A mezzanine header connector includes header modules stacked side-by-side having housing frames holding contact assemblies. Each contact assembly includes header contacts held by at least one dielectric holder. The header contacts have mating segments for termination to corresponding receptacle contacts of a mezzanine receptacle connector and terminating segments for termination to a circuit board. Each of the header contacts extend along a linear path between the corresponding mating segment and the corresponding terminating segment. Each housing frame has walls defining pockets receiving corresponding header contacts of the contact assembly. The housing frame is conductive and provides shielding around the associated header contacts of the contact assemblies. The header contacts face associated walls with air separating the header contacts and the walls along a majority of the header contacts.

Abstract: A method of negotiating a call capability between signalling points in a telecommunications system. The method comprises sending a capability preference or prioritised list of preferences from an originating signalling point to a terminating signalling point or signalling transfer point, at the Call Control level. A capability acceptance is returned from the terminating signalling point or signalling transfer point to the originating signalling point at the Call Control level, if the terminating signalling point or signalling transfer point accepts a preference sent by the originating signalling point.

Abstract: A de-coupled memory access system including a memory access control circuit configured to generate first and second independent, de-coupled time references. The memory access control circuit includes a read initiate circuit responsive to the first time reference and a read signal for generating a read enable signal, and a write initiate circuit responsive to the second time reference and a write signal for generating a write enable signal independent of the read enable signal for providing independent, de-coupled write access to a memory array.

Abstract: A method of negotiating a call capability between signalling points in a telecommunications system. The method comprises sending a capability preference or prioritised list of preferences from an originating signalling point to a terminating signalling point or signalling transfer point, at the Call Control level. A capability acceptance is returned from the terminating signalling point or signalling transfer point to the originating signalling point at the Call Control level, if the terminating signalling point or signalling transfer point accepts a preference sent by the originating signalling point.

Abstract: A method of negotiating a call capability between signalling points in a telecommunications system. The method comprises sending a capability preference or prioritised list of preferences from an originating signalling point to a terminating signalling point or signalling transfer point, at the Call Control level. A capability acceptance is returned from the terminating signalling point or signalling transfer point to the originating signalling point at the Call Control level, if the terminating signalling point or signalling transfer point accepts a preference sent by the originating signalling point.

Abstract: The present invention relates to a method for evaluating biological effects in a substance which method comprises sampling the substance, subjecting the sample to an assay in the presence of a biosensor engineered with a gene which expresses a light emitting protein and noting the light output; characterized in that the biosensor is eukaryotic and the substance is assayable over any pH between pH1 and pH12. Such a eukaryotic sensor may be derived from Saccharomyces cerevisiae and is useful in assaying potable waters.