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  • Articles  (13)
  • Male  (8)
  • Engineering General  (5)
  • 1995-1999  (13)
  • 1
    Publication Date: 1999-04-24
    Description: The von Hippel-Lindau (VHL) tumor suppressor gene is mutated in most human kidney cancers. The VHL protein is part of a complex that includes Elongin B, Elongin C, and Cullin-2, proteins associated with transcriptional elongation and ubiquitination. Here it is shown that the endogenous VHL complex in rat liver also includes Rbx1, an evolutionarily conserved protein that contains a RING-H2 fingerlike motif and that interacts with Cullins. The yeast homolog of Rbx1 is a subunit and potent activator of the Cdc53-containing SCFCdc4 ubiquitin ligase required for ubiquitination of the cyclin-dependent kinase inhibitor Sic1 and for the G1 to S cell cycle transition. These findings provide a further link between VHL and the cellular ubiquitination machinery.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kamura, T -- Koepp, D M -- Conrad, M N -- Skowyra, D -- Moreland, R J -- Iliopoulos, O -- Lane, W S -- Kaelin, W G Jr -- Elledge, S J -- Conaway, R C -- Harper, J W -- Conaway, J W -- AG-11085/AG/NIA NIH HHS/ -- GM41628/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 23;284(5414):657-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10213691" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Carrier Proteins/chemistry/genetics/*metabolism ; Cell Cycle ; Cell Cycle Proteins/metabolism ; Cell Line ; *Cullin Proteins ; Cyclin-Dependent Kinase Inhibitor Proteins ; *F-Box Proteins ; Fungal Proteins/metabolism ; *Ligases ; Liver ; Male ; Molecular Sequence Data ; Peptide Synthases/*metabolism ; Proteins/*metabolism ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins/metabolism ; S-Phase Kinase-Associated Proteins ; SKP Cullin F-Box Protein Ligases ; Saccharomyces cerevisiae/metabolism ; *Saccharomyces cerevisiae Proteins ; Sequence Alignment ; Transcription Factors/metabolism ; *Tumor Suppressor Proteins ; *Ubiquitin-Protein Ligases ; Ubiquitins/*metabolism ; Von Hippel-Lindau Tumor Suppressor Protein
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1997-06-27
    Description: Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. A mutation was identified in the alpha-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype. This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Polymeropoulos, M H -- Lavedan, C -- Leroy, E -- Ide, S E -- Dehejia, A -- Dutra, A -- Pike, B -- Root, H -- Rubenstein, J -- Boyer, R -- Stenroos, E S -- Chandrasekharappa, S -- Athanassiadou, A -- Papapetropoulos, T -- Johnson, W G -- Lazzarini, A M -- Duvoisin, R C -- Di Iorio, G -- Golbe, L I -- Nussbaum, R L -- New York, N.Y. -- Science. 1997 Jun 27;276(5321):2045-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-1430, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9197268" target="_blank"〉PubMed〈/a〉
    Keywords: Age of Onset ; Amino Acid Sequence ; Animals ; Base Sequence ; Chromosome Mapping ; Chromosomes, Human, Pair 4 ; Female ; Genes, Dominant ; Genetic Markers ; Greece ; Humans ; Italy ; Male ; Molecular Sequence Data ; Nerve Tissue Proteins/chemistry/*genetics/physiology ; Parkinson Disease/*genetics ; Pedigree ; Phenotype ; *Point Mutation ; Polymerase Chain Reaction ; Protein Structure, Secondary ; Synucleins ; alpha-Synuclein
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-05-12
    Description: Mutations in genes required for associative learning and memory in Drosophila exist, but isolation of the genes has been difficult because most are defined by a single, chemically induced allele. Here, a simplified genetic screen was used to identify candidate genes involved in learning and memory. Second site suppressors of the dunce (dnc) female sterility phenotype were isolated with the use of transposon mutagenesis. One suppressor mutation that was recovered mapped in the amnesiac (amn) gene. Cloning of the locus revealed that amn encodes a previously uncharacterized neuropeptide gene. Thus, with the cloning of amn, specific neuropeptides are implicated in the memory process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feany, M B -- Quinn, W G -- New York, N.Y. -- Science. 1995 May 12;268(5212):869-73.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7754370" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cloning, Molecular ; Codon ; DNA Transposable Elements ; DNA, Complementary/genetics ; Drosophila/*genetics/physiology ; *Drosophila Proteins ; Female ; *Genes, Insect ; Growth Hormone-Releasing Hormone/chemistry/genetics ; Male ; Memory/*physiology ; Molecular Sequence Data ; Mutagenesis, Insertional ; Mutation ; Neuropeptides/chemistry/*genetics ; Pituitary Adenylate Cyclase-Activating Polypeptide ; Sequence Homology, Amino Acid ; Suppression, Genetic
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 1995-11-17
    Description: Strategies for the treatment of human immunodeficiency virus-type 1 (HIV-1) infection must contend with the obstacle of drug resistance. HIV-1 nucleocapsid protein zinc fingers are prime antiviral targets because they are mutationally intolerant and are required both for acute infection and virion assembly. Nontoxic disulfide-substituted benzamides were identified that attack the zinc fingers, inactivate cell-free virions, inhibit acute and chronic infections, and exhibit broad antiretroviral activity. The compounds were highly synergistic with other antiviral agents, and resistant mutants have not been detected. Zinc finger-reactive compounds may offer an anti-HIV strategy that restricts drug-resistance development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rice, W G -- Supko, J G -- Malspeis, L -- Buckheit, R W Jr -- Clanton, D -- Bu, M -- Graham, L -- Schaeffer, C A -- Turpin, J A -- Domagala, J -- Gogliotti, R -- Bader, J P -- Halliday, S M -- Coren, L -- Sowder, R C 2nd -- Arthur, L O -- Henderson, L E -- New York, N.Y. -- Science. 1995 Nov 17;270(5239):1194-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Antiviral Drug Mechanisms, PRI/DynCorp., National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7502043" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antiviral Agents/chemistry/pharmacokinetics/*pharmacology ; Benzamides/chemistry/pharmacokinetics/*pharmacology ; Biological Availability ; Capsid/chemistry/*metabolism ; *Capsid Proteins ; Cell Line ; Disulfides/chemistry/pharmacokinetics/*pharmacology ; Drug Resistance, Microbial ; Drug Synergism ; Gene Products, gag/*antagonists & inhibitors/chemistry ; HIV-1/*drug effects/physiology ; Humans ; Male ; Mice ; Molecular Sequence Data ; *Viral Proteins ; Zinc Fingers/*drug effects ; gag Gene Products, Human Immunodeficiency Virus
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 1995-10-06
    Description: BAX, a heterodimeric partner of BCL2, counters BCL2 and promotes apoptosis in gain-of-function experiments. A Bax knockout mouse was generated that proved viable but displayed lineage-specific aberrations in cell death. Thymocytes and B cells in this mouse displayed hyperplasia, and Bax-deficient ovaries contained unusual atretic follicles with excess granulosa cells. In contrast, Bax-deficient males were infertile as a result of disordered seminiferous tubules with an accumulation of atypical premeiotic germ cells, but no mature haploid sperm. Multinucleated giant cells and dysplastic cells accompanied massive cell death. Thus, the loss of Bax results in hyperplasia or hypoplasia, depending on the cellular context.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knudson, C M -- Tung, K S -- Tourtellotte, W G -- Brown, G A -- Korsmeyer, S J -- CA49712/CA/NCI NIH HHS/ -- HD27500/HD/NICHD NIH HHS/ -- P30-HD28934/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1995 Oct 6;270(5233):96-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7569956" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; B-Lymphocytes/cytology ; Female ; Granulosa Cells/cytology ; Hyperplasia/pathology ; Infertility, Male/*pathology ; Lymphoid Tissue/*pathology ; Male ; Mice ; Mice, Knockout ; Ovary/cytology ; Proto-Oncogene Proteins/*deficiency/genetics/physiology ; *Proto-Oncogene Proteins c-bcl-2 ; Seminiferous Tubules/*pathology ; Spermatids/pathology ; Spermatocytes/ultrastructure ; Spermatogenesis ; Spermatozoa/*pathology ; T-Lymphocytes/cytology ; bcl-2-Associated X Protein
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 1996-11-15
    Description: Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 1 percent of the population over age 50. Recent studies have confirmed significant familial aggregation of PD and a large number of large multicase families have been documented. Genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Zmax = 6.00 for marker D4S2380. This finding will facilitate identification of the gene and research on the pathogenesis of PD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Polymeropoulos, M H -- Higgins, J J -- Golbe, L I -- Johnson, W G -- Ide, S E -- Di Iorio, G -- Sanges, G -- Stenroos, E S -- Pho, L T -- Schaffer, A A -- Lazzarini, A M -- Nussbaum, R L -- Duvoisin, R C -- New York, N.Y. -- Science. 1996 Nov 15;274(5290):1197-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetic Disease Research, National Center for Human Genome Research, National Institutes of Health, Bethesda, MD 20892-1430, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8895469" target="_blank"〉PubMed〈/a〉
    Keywords: *Chromosome Mapping ; *Chromosomes, Human, Pair 4 ; Female ; Genetic Linkage ; Genetic Markers ; Humans ; Lod Score ; Male ; Parkinson Disease/*genetics ; Pedigree ; Phenotype
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    International Journal for Numerical Methods in Fluids 20 (1995), S. 671-693 
    ISSN: 0271-2091
    Keywords: airfoil ; artificial viscosity ; upwinding ; Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: The numerical solution of the compressible Euler and Navier-Stokes equations in primitive variables form requires the use of artificial viscosity or upwinding. Methods that are first-order-accurate are too dissipative and reduce the effective Reynolds number substantially unless a very fine grid is used. A first-order finite element method for the solution of the Euler and Navier-Stokes equations can be constructed by adding Laplacians of the primitive variables to the governing equations. Second-order schemes may require a fourth-order dissipation and higher-order elements. A finite element approach is proposed in which the fourth-order dissipation is recast as the difference of two Laplacian operators, allowing the use of bilinear elements. The Laplacians of the primitive variables of the first-order scheme are thus balanced by additional terms obtained from the governing equations themselves, tensor identities or other forms of nodal averaging. To demonstrate formally the accuracy of this scheme, an exact solution is introduced which satisfies the continuity equation identically and the momentum equations through forcing functions. The solutions of several transonic and supersonic inviscid and laminar viscous test cases are also presented and compared to other available numerical data.
    Additional Material: 17 Ill.
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  • 8
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    International Journal for Numerical Methods in Fluids 22 (1996), S. 603-618 
    ISSN: 0271-2091
    Keywords: shallow water equations ; wave continuity equation ; boundary conditions ; finite elements ; generalized functions ; Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Finite element solution of the shallow water wave equations has found increasing use by researchers and practitioners in the modelling of oceans and coastal areas. Wave equation models, most of which use equal-orderC0 interpolants for both the velocity and the surface elevation, do not introduce spurious oscillation modes, hence avoiding the need for artificial or numerical damping. An important question for both primitive equation and wave equation models is the interpretation of boundary conditions. Analysis of the characteristics of the governing equations shows that for most geophysical flows a single condition at each boundary is sufficient, yet there is not a consensus in the literature as to what that boundary condition must be or how it should be implemented in a finite element code. Traditionally (partly because of limited data), surface elevation is specified at open ocean boundaries while the normal flux is specified as zero at land boundaries. In most finite element wave equation models both of these boundary conditions are implemented as essential conditions. Our recent work focuses on alternative ways to numerically implement normal flow boundary conditions with an eye towards improving the mass-conserving properties of wave equation models. A unique finite element formulation using generalized functions demonstrates that boundary conditions should be implemented by treating normal fluxes as natural conditions with the flux interpreted as external to the computational domain. Results from extensive numerical experiments show that the scheme does conserve mass for all parameter values. Furthermore, convergence studies demonstrate that the algorithm is consistent, as residual errors at the boundary diminish as the grid is refined.
    Additional Material: 6 Ill.
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  • 9
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    International Journal for Numerical Methods in Fluids 23 (1996), S. 673-690 
    ISSN: 0271-2091
    Keywords: Euler equations ; directionally adaptive meshes ; edge-based error estimate ; structured grids ; mesh movement ; finite element method ; high-speed flows ; Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: The present paper describes a directionally adaptive finite element method for high-speed flows, using an edge-based error estimate on quadrilateral grids. The error of the numerical solution is estimated through its second derivatives and the resulting Hessian tensor is used to define a Riemannian metric. An improved mesh movement strategy, based on a spring analogy, but with no orthogonality constraints, is introduced to equidistribute the lengths of the edges of the elements in the defined metric. The grid adaptation procedure is validated on an analytical test case and the efficiency of the overall methodology is investigated on supersonic and hypersonic benchmarks.
    Additional Material: 21 Ill.
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  • 10
    Publication Date: 1998-02-07
    Description: Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winkler, C -- Modi, W -- Smith, M W -- Nelson, G W -- Wu, X -- Carrington, M -- Dean, M -- Honjo, T -- Tashiro, K -- Yabe, D -- Buchbinder, S -- Vittinghoff, E -- Goedert, J J -- O'Brien, T R -- Jacobson, L P -- Detels, R -- Donfield, S -- Willoughby, A -- Gomperts, E -- Vlahov, D -- Phair, J -- O'Brien, S J -- New York, N.Y. -- Science. 1998 Jan 16;279(5349):389-93.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Science Applications International Corporation (SAIC), National Cancer Institute, Frederick, MD 21702, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9430590" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/genetics/*immunology/virology ; Adult ; Chemokine CXCL12 ; Chemokines/chemistry/*genetics/physiology ; *Chemokines, CXC ; Cohort Studies ; Continental Population Groups ; Disease Progression ; Genes ; Genetic Variation ; Genotype ; HIV Infections/genetics/*immunology/virology ; HIV-1/*physiology ; Heterozygote ; Humans ; Male ; Molecular Sequence Data ; Odds Ratio ; Polymorphism, Genetic ; Receptors, CCR2 ; Receptors, CCR5/genetics/physiology ; Receptors, CXCR4/metabolism ; Receptors, Chemokine/genetics/physiology ; Survival Analysis ; T-Lymphocytes/virology
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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