Expression vectors are disclosed that are comprised of (a) one or more silencer elements and conditionally inducible elements to form silencer-inducible regions and (b) promoters in operative linkage upstream of at least one expressed region. The expression vector thereby regulates expression of at least one downstream region by conditional silencing in which an expressed DNA region of a gene is transcribed to produce RNA transcripts, which may or may not be translated to produce polypeptides. Genetically engineered mammalian cells and non-human mammals can be made using such expression vectors through transfection and transgenesis techniques. Moreover, processes of making and using the aforementioned products are disclosed (e. g. , the expression vector may be used diagnostically, therapeutically, or prophylactically).
Hypoxia-acidosis-associated cell death is mediated by BNIP3, a member of the Bcl-2 family of apoptosis-regulating proteins. Chronic hypoxia induced the expression and accumulation of BNIP3 mRNA and protein in cardiac myocytes but acidosis was required to activate the death pathway. Acidosis stabilized BNIP3 protein and increased the association with mitochondria. Cell death by hypoxia-acidosis was blocked by pretreatment with antisense BNIP3 oligonucleotides. The pathway included extensive DNA fragmentation and opening of the mitochondrial permeability transition pore but no apparent caspase activation. Overexpression of wild type BNIP3, but not a translocation-defective mutant activated cardiac myocyte death when the myocytes were acidotic or hypoxic.
Molecular Switch For Regulating Mammalian Gene Expression
Expression vectors are disclosed that are comprised of (a) one or more silencer elements and conditionally inducible elements to form silencer-inducible regions and (b) promoters in operative linkage upstream of at least one expressed region. The expression vector thereby regulates expression of at least one downstream region by conditional silencing in which an expressed DNA region of a gene is transcribed to produce RNA transcripts, which may or may not be translated to produce polypeptides. Genetically engineered mammalian cells and non-human mammals can be made using such expression vectors through transfection and transgenic techniques. Moreover, processes of making and using the aforementioned products are disclosed (e.g., the expression vector may be used diagnostically, therapeutically, or prophylactically).
Apparatus And Methods For Synchronized Distributed Controllers
Robert A. Bigler - Cupertino CA, US Scott A. Morrill - Webster NY, US Carl R. Vogt - Rochester NY, US Keith R. Webster - Fairport NY, US
Assignee:
Animatics Corporation - Santa Clara CA
International Classification:
G05B 19/25 G05B 11/32
US Classification:
318570, 318625
Abstract:
Intelligent servomotor controller, including integrated servomotor controller having motor with rotor in first housing; rotor position encoder producing measured position of rotor; microprocessor within second housing mating to first housing, electrically connected to rotor position encoder, serial communications port connecting to another integrated servomotor controller communicating desired rotor position command using serial digital data, microprocessor having software receiving desired position commands through communications port, computing error between desired position command and encoder-transmitted measured rotor reducing error signals to zero. Microprocessor is a position based servo system within second housing and rotor within first housing to desired position defined by communication with another integrated servo element. Microprocessor produces actuation signal to direct PID filter connected to microprocessor, PID filter providing drive amplifier servo control of supplying current to the motor. Cooperative communication facilitates synchronized action with integrated servo element. Embodiments also include method of operating IISMC group, including setting combined path target acceleration for IISMC; setting combined target velocity for IISMC; setting individual target position for IISMC; and initiating synchronized motion in the IISMC.
Methods and compositions for the treatment of hypoxia associated disorders by directional angiogenesis/arteriogenesis. Conditionally silenced vectors expressing a therapeutic molecule under hypoxic conditions avoid chaotic vascularization and allow for the orderly growth of new vessels into damaged tissue.
Methods, Compositions, Cells, And Kits For Treating Ischemic Injury
The methods, compositions, cells and kits described herein are based on the discovery that stem cells, when injected into ischemic tissue of mammals, can be protected by preconditioning of the ischemic tissue with hypoxia-regulated human VEGF and human IGF-1. Methods, compositions, cells and kits for treating tissue injured by ischemia or at risk of ischemic injury in a subject are thus described herein.
Compositions, Cells, Kits And Methods For Autologous Stem Cell Therapy
Described herein are compositions, kits and methods for stimulating angiogenic functions of stem cells and/or progenitor cells having pro-angiogenic potential (e.g., endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs)) before transplantation (e.g., ex vivo cell therapy) based on the discovery that functional recovery of CD34+ cells from coronary artery disease (CAD) patients is improved by transfection of antagomirs against one or more miRs of a plurality of miRs identified to be over-expressed in cells from CAD patients. Described herein are methods to recover the functions of EPCs isolated from patients with cardiovascular disease (e.g., CAD or peripheral artery disease (PAD)) by bioengineering the cells with antagomirs and/or premirs to specific micro-RNAs. The bioengineered cells can then be used to treat patients with ischemic or ischemic-related disease (e.g., CAD or PAD) by autologous stem cell therapy.
Tissue Specific Hypoxia Regulated Therapeutic Constructs
Keith A. Webster - Palo Alto CA Nanette H. Bishopric - Palo Alto CA
Assignee:
SRI International - Menlo Park CA
International Classification:
C12N 1500 C07H 2104
US Classification:
4353201
Abstract:
Methods and compositions relating to chimeric genes containing (i) a tissue-specific promoter and (ii) a hypoxia response enhancer element, both of which are operably linked to a selected gene, such as a reporter gene, therapeutic gene (e. g. , bcl-2, NOS, catalase and SOD), or deleterious gene are disclosed. Expression of the selected gene is enhanced in the target tissue under hypoxic conditions, such as conditions encountered during episodes of ischemia and reperfusion. The methods and compositions may be used as therapeutics and/or diagnostics.
Resumes
Owner/Winemaker At Keith M. Webster Cellars, Principal At Keith M. Webster Construction Management
Winemaker- Owner at Keith M. Webster Cellars, Owner at Keith M. Webster Construction
Location:
Saint Helena, California
Industry:
Wine and Spirits
Work:
Keith M. Webster Cellars - St Helena, California since Jan 2010
Winemaker- Owner
Keith M. Webster Construction since Jan 1975
Owner
Saddleback Cellars - Oakville, California Jan 2011 - Dec 2011
General Manager
Education:
Texas A&M University 1972 - 1974
University of Oklahoma 1968 - 1971
Founder and President at Integene International LLC, Director at VBI, Professor of Pharmacology at University of Miami, Professor at University of Miami
Location:
Miami/Fort Lauderdale Area
Industry:
Biotechnology
Work:
Integene International LLC since Jun 2009
Founder and President
VBI since Jun 2004
Director
University of Miami since Sep 2003
Professor of Pharmacology
University of Miami since Sep 1995
Professor
Miami Cardiovascular Innovations Jun 2008 - Jun 2009
Founder, CSO
Education:
University of York 1974 - 1981
PH.D., Biochemistry
Languages:
French, Middle (ca.1400-1600)
Assistant Director Of Administration At Vi Government Department Of Public Works
, so the team is remembered for its free-throw shooting. But we had terrific players, including Joe Carrabino, who became the programs career leading scorer; Bob Ferry, Danny Ferrys older brother; Arne Duncan, now the United States secretary of education; point guard Pat Smith; and a terrific shooter in Keith Webster, a freshman that year.