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  • American Association for the Advancement of Science (AAAS)  (605)
  • Blackwell Science Ltd  (305)
  • American Association for the Advancement of Science  (225)
  • 2000-2004  (1,135)
  • 1980-1984
  • 2003  (1,135)
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Publisher
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  • 2000-2004  (1,135)
  • 1980-1984
Year
  • 1
    Publication Date: 2003-11-01
    Description: Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Changelian, Paul S -- Flanagan, Mark E -- Ball, Douglas J -- Kent, Craig R -- Magnuson, Kelly S -- Martin, William H -- Rizzuti, Bonnie J -- Sawyer, Perry S -- Perry, Bret D -- Brissette, William H -- McCurdy, Sandra P -- Kudlacz, Elizabeth M -- Conklyn, Maryrose J -- Elliott, Eileen A -- Koslov, Erika R -- Fisher, Michael B -- Strelevitz, Timothy J -- Yoon, Kwansik -- Whipple, David A -- Sun, Jianmin -- Munchhof, Michael J -- Doty, John L -- Casavant, Jeffrey M -- Blumenkopf, Todd A -- Hines, Michael -- Brown, Matthew F -- Lillie, Brett M -- Subramanyam, Chakrapani -- Shang-Poa, Chang -- Milici, Anthony J -- Beckius, Gretchen E -- Moyer, James D -- Su, Chunyan -- Woodworth, Thasia G -- Gaweco, Anderson S -- Beals, Chan R -- Littman, Bruce H -- Fisher, Douglas A -- Smith, James F -- Zagouras, Panayiotis -- Magna, Holly A -- Saltarelli, Mary J -- Johnson, Kimberly S -- Nelms, Linda F -- Des Etages, Shelley G -- Hayes, Lisa S -- Kawabata, Thomas T -- Finco-Kent, Deborah -- Baker, Deanna L -- Larson, Michael -- Si, Ming-Sing -- Paniagua, Ricardo -- Higgins, John -- Holm, Bari -- Reitz, Bruce -- Zhou, Yong-Jie -- Morris, Randall E -- O'Shea, John J -- Borie, Dominic C -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):875-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunology Group, Department of Antibacterials and Immunology, Pfizer Global Researchand Development, Groton, CT 06340, USA. paul_s_changelian@groton.pfizer.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593182" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Enzyme Inhibitors/administration & dosage/pharmacology/therapeutic use/toxicity ; Gene Expression Regulation/drug effects ; Graft Rejection/*prevention & control ; Graft Survival/drug effects ; *Heart Transplantation ; Humans ; Immunosuppressive Agents/administration & dosage/*pharmacology/therapeutic ; use/toxicity ; Interleukin-2/immunology ; Janus Kinase 3 ; *Kidney Transplantation ; Lymphocyte Activation/drug effects ; Lymphocyte Count ; Lymphocyte Culture Test, Mixed ; Lymphocyte Subsets/drug effects ; Macaca fascicularis ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Myocardium/metabolism ; Piperidines ; Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism ; Pyrimidines/administration & dosage/*pharmacology/therapeutic use/toxicity ; Pyrroles/administration & dosage/*pharmacology/therapeutic use/toxicity ; Transplantation, Heterotopic ; Transplantation, Homologous ; Tumor Cells, Cultured
    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
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 In the present investigation we examined the regulation of calmodulin (CaM)- and protein kinase C (PKC)-dependent pathways by cytosolic Ca2+ in the contraction of cat lower oesophageal sphincter (LES). 2 Force developed in response to increasing doses of acetylcholine (ACh) was directly related to the increase of the [Ca2+]i measured by fura-2. Thapsigargin, which depletes Ca2+ stores, reduced the contraction and the [Ca2+]i. In addition, contraction in response to maximal ACh was reduced by the CaM inhibitor CGS9343B but not by the PKC inhibitor chelerythrine. The contraction in response to submaximal ACh was reduced by chelerythrine but not by CGS9343B. 3 In permeabilized cells, the contraction in response to low Ca2+ (0.54 μm) was also reduced by CGS9343B. 4 The response to high Ca2+ (1.0 μm) was reduced by CGS9343B. ACh also inhibited PKC activation induced by diacylglycerol, which activation is inhibited by the N-myristoylated peptide inhibitor derived from pseudosubstrate sequences of PKCαβγ (myr-PKC-αβγ), but not of myr-PKC-α. 5 These data are consistent with the view that activated CaM-dependent pathways inhibit PKC-dependent pathways, this switch mechanism might be regulated by Ca2+ in the LES.
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of fish biology 62 (2003), S. 0 
    ISSN: 1095-8649
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Social control of maturation is a common phenomenon in fishes, yet associated mechanisms are often unidentified. An examination of interactions between mature and juvenile male bluegill Lepomis macrochirus in mesocosms, isolating visual, chemical and physical interactions, suggested that chemical cues are responsible for inhibiting maturation of juvenile males.
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  • 4
    Publication Date: 2003-04-12
    Description: DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882961/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882961/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scherer, Stephen W -- Cheung, Joseph -- MacDonald, Jeffrey R -- Osborne, Lucy R -- Nakabayashi, Kazuhiko -- Herbrick, Jo-Anne -- Carson, Andrew R -- Parker-Katiraee, Layla -- Skaug, Jennifer -- Khaja, Razi -- Zhang, Junjun -- Hudek, Alexander K -- Li, Martin -- Haddad, May -- Duggan, Gavin E -- Fernandez, Bridget A -- Kanematsu, Emiko -- Gentles, Simone -- Christopoulos, Constantine C -- Choufani, Sanaa -- Kwasnicka, Dorota -- Zheng, Xiangqun H -- Lai, Zhongwu -- Nusskern, Deborah -- Zhang, Qing -- Gu, Zhiping -- Lu, Fu -- Zeesman, Susan -- Nowaczyk, Malgorzata J -- Teshima, Ikuko -- Chitayat, David -- Shuman, Cheryl -- Weksberg, Rosanna -- Zackai, Elaine H -- Grebe, Theresa A -- Cox, Sarah R -- Kirkpatrick, Susan J -- Rahman, Nazneen -- Friedman, Jan M -- Heng, Henry H Q -- Pelicci, Pier Giuseppe -- Lo-Coco, Francesco -- Belloni, Elena -- Shaffer, Lisa G -- Pober, Barbara -- Morton, Cynthia C -- Gusella, James F -- Bruns, Gail A P -- Korf, Bruce R -- Quade, Bradley J -- Ligon, Azra H -- Ferguson, Heather -- Higgins, Anne W -- Leach, Natalia T -- Herrick, Steven R -- Lemyre, Emmanuelle -- Farra, Chantal G -- Kim, Hyung-Goo -- Summers, Anne M -- Gripp, Karen W -- Roberts, Wendy -- Szatmari, Peter -- Winsor, Elizabeth J T -- Grzeschik, Karl-Heinz -- Teebi, Ahmed -- Minassian, Berge A -- Kere, Juha -- Armengol, Lluis -- Pujana, Miguel Angel -- Estivill, Xavier -- Wilson, Michael D -- Koop, Ben F -- Tosi, Sabrina -- Moore, Gudrun E -- Boright, Andrew P -- Zlotorynski, Eitan -- Kerem, Batsheva -- Kroisel, Peter M -- Petek, Erwin -- Oscier, David G -- Mould, Sarah J -- Dohner, Hartmut -- Dohner, Konstanze -- Rommens, Johanna M -- Vincent, John B -- Venter, J Craig -- Li, Peter W -- Mural, Richard J -- Adams, Mark D -- Tsui, Lap-Chee -- 38103/Canadian Institutes of Health Research/Canada -- P01 GM061354/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 May 2;300(5620):767-72. Epub 2003 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8. steve@genet.sickkids.on.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690205" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/genetics ; Chromosome Aberrations ; Chromosome Fragile Sites ; Chromosome Fragility ; Chromosome Mapping ; Chromosomes, Human, Pair 7/*genetics ; Computational Biology ; Congenital Abnormalities/genetics ; CpG Islands ; DNA, Complementary ; Databases, Genetic ; Euchromatin/genetics ; Expressed Sequence Tags ; Gene Duplication ; Genes, Overlapping ; Genetic Diseases, Inborn/genetics ; Genomic Imprinting ; Humans ; In Situ Hybridization, Fluorescence ; Limb Deformities, Congenital/genetics ; Mice ; Molecular Sequence Data ; Mutation ; Neoplasms/genetics ; Pseudogenes ; RNA/genetics ; Retroelements ; *Sequence Analysis, DNA ; Williams Syndrome/genetics
    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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  • 5
    Publication Date: 2003-07-19
    Description: The cascade from tides to turbulence has been hypothesized to serve as a major energy pathway for ocean mixing. We investigated this cascade along the Hawaiian Ridge using observations and numerical models. A divergence of internal tidal energy flux observed at the ridge agrees with the predictions of internal tide models. Large internal tidal waves with peak-to-peak amplitudes of up to 300 meters occur on the ridge. Internal-wave energy is enhanced, and turbulent dissipation in the region near the ridge is 10 times larger than open-ocean values. Given these major elements in the tides-to-turbulence cascade, an energy budget approaches closure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rudnick, Daniel L -- Boyd, Timothy J -- Brainard, Russell E -- Carter, Glenn S -- Egbert, Gary D -- Gregg, Michael C -- Holloway, Peter E -- Klymak, Jody M -- Kunze, Eric -- Lee, Craig M -- Levine, Murray D -- Luther, Douglas S -- Martin, Joseph P -- Merrifield, Mark A -- Moum, James N -- Nash, Jonathan D -- Pinkel, Robert -- Rainville, Luc -- Sanford, Thomas B -- New York, N.Y. -- Science. 2003 Jul 18;301(5631):355-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Scripps Institution of Oceanography, La Jolla, CA 92093-0213, USA. drudnick@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12869758" target="_blank"〉PubMed〈/a〉
    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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  • 6
    Publication Date: 2003-01-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, Stephen T -- Benson, Bill G -- Bramson, H Neal -- Chapman, Dennis E -- Dickerson, Scott H -- Dold, Karen M -- Eberwein, Derek J -- Edelstein, Mark -- Frye, Stephen V -- Gampe, Robert T Jr -- Grifffen, Robert J -- Harris, Philip A -- Hassell, Anne M -- Holmes, William D -- Hunter, Robert N -- Knick, Victoria B -- Lackey, Karen -- Lovejoy, Brett -- Luzzio, Michael J -- Murray, Doris -- Parker, Patricia -- Rocque, Warren J -- Shewchuk-Chapman, Lisa -- Veal, James M -- Walker, Duncan H -- Kuyper, Lee F -- New York, N.Y. -- Science. 2002 Dec 20;298(5602):2327.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Trans Tech Pharmaceuticals, 4170 Mendenhall Oaks Parkway, High Point, NC 27265, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12526115" target="_blank"〉PubMed〈/a〉
    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
    Publication Date: 2003-05-06
    Description: We sequenced the 29,751-base genome of the severe acute respiratory syndrome (SARS)-associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using polymerase chain reaction and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marra, Marco A -- Jones, Steven J M -- Astell, Caroline R -- Holt, Robert A -- Brooks-Wilson, Angela -- Butterfield, Yaron S N -- Khattra, Jaswinder -- Asano, Jennifer K -- Barber, Sarah A -- Chan, Susanna Y -- Cloutier, Alison -- Coughlin, Shaun M -- Freeman, Doug -- Girn, Noreen -- Griffith, Obi L -- Leach, Stephen R -- Mayo, Michael -- McDonald, Helen -- Montgomery, Stephen B -- Pandoh, Pawan K -- Petrescu, Anca S -- Robertson, A Gordon -- Schein, Jacqueline E -- Siddiqui, Asim -- Smailus, Duane E -- Stott, Jeff M -- Yang, George S -- Plummer, Francis -- Andonov, Anton -- Artsob, Harvey -- Bastien, Nathalie -- Bernard, Kathy -- Booth, Timothy F -- Bowness, Donnie -- Czub, Martin -- Drebot, Michael -- Fernando, Lisa -- Flick, Ramon -- Garbutt, Michael -- Gray, Michael -- Grolla, Allen -- Jones, Steven -- Feldmann, Heinz -- Meyers, Adrienne -- Kabani, Amin -- Li, Yan -- Normand, Susan -- Stroher, Ute -- Tipples, Graham A -- Tyler, Shaun -- Vogrig, Robert -- Ward, Diane -- Watson, Brynn -- Brunham, Robert C -- Krajden, Mel -- Petric, Martin -- Skowronski, Danuta M -- Upton, Chris -- Roper, Rachel L -- New York, N.Y. -- Science. 2003 May 30;300(5624):1399-404. Epub 2003 May 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉British Columbia Cancer Agency (BCCA) Genome Sciences Centre, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada. mmarra@bccgsc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12730501" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; 5' Untranslated Regions ; Animals ; Base Sequence ; Conserved Sequence ; Coronavirus/classification/genetics ; DNA, Complementary ; Frameshifting, Ribosomal ; *Genome, Viral ; Humans ; Membrane Glycoproteins/chemistry/genetics ; Nucleocapsid Proteins/chemistry/genetics ; Open Reading Frames ; Phylogeny ; RNA Replicase/chemistry/genetics ; RNA, Viral/*genetics/isolation & purification ; Regulatory Sequences, Nucleic Acid ; SARS Virus/classification/*genetics/isolation & purification ; Sequence Analysis, DNA ; Severe Acute Respiratory Syndrome/virology ; Spike Glycoprotein, Coronavirus ; Viral Envelope Proteins/chemistry/genetics ; Viral Matrix Proteins/chemistry/genetics ; Viral Proteins/chemistry/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Weed research 43 (2003), S. 0 
    ISSN: 1365-3180
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Two Sonchus asper (spiny annual sow-thistle) biotypes, suspected of being resistant to the sulfonylurea herbicide metsulfuron-methyl, were collected in 1996 from two barley (Hordeum vulgare) fields in central Alberta, Canada. Both fields had received at least six applications of acetolactate synthase (ALS)-inhibiting herbicide(s). The responses of the two resistant (R) biotypes and two susceptible (S) biotypes to several sulfonylurea herbicides, and to herbicides and herbicide mixtures with other mechanisms of action, were compared. Both R biotypes were highly resistant to all sulfonylurea herbicides, but their control with other herbicides and mixtures was effective and comparable to that of the S biotypes. ALS extracted from an R biotype was about 440 times more resistant to metsulfuron-methyl than that of an S biotype, indicating that resistance was conferred by an ALS enzyme that was less sensitive to inhibition by the herbicide. Competitiveness and seed production of S. asper varied among biotypes, but the differences were probably the result of ecotype differences rather than resistance or susceptibility to sulfonylurea herbicides. This is the first reported occurrence of target site-based S. asper resistance to ALS-inhibiting herbicides.
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  • 9
    ISSN: 1365-2389
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: There is an increasing interest in agricultural systems in which the use of herbicides is forbidden. Therefore, soils treated with herbicides atrazine and metolachlor for the last 20 years were compared with soil samples from the same field that had never been treated (control soil). We determined the pollution induced community tolerance (PICT) by evaluating the methane oxidation capacity of soil samples after adding increasing amounts of a methane oxidation inhibitor, 2,4-dichlorophenoxyacetic acid (2,4-D). Denaturing gradient gel electrophoresis (DGGE) of 16S rRNA genes assessed whether the soil methanotrophic community differed between the two treatments. Addition of 60 µg 2,4-D per g soil clearly inhibited methane oxidation in both soils but increased the time needed to oxidize 5% methane in the headspace by 250% for the control soil compared with 175% for the herbicide-treated soil. This indicates that the soil with a long-term herbicide history had a greater tolerance to the methane oxidation inhibitor than did the control soil. The DGGE of 16S rRNA genes amplified directly from soil community DNA could also distinguish the two treatments. The banding patterns of the Type I methanotrophs contained fewer bands in the herbicide-treated soil. It seems that both the PICT approach and DGGE analysis are effective assays to distinguish a long-term herbicide-treated soil from an untreated soil.
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Plant pathology 52 (2003), S. 0 
    ISSN: 1365-3059
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: A function was derived to predict fungicide efficacy when more than one application of a single active ingredient is made to a crop, given parameters describing the dose–response curves of the component single-spray applications. In the function, a second application is considered to act on that proportion of the total pathogen population which was uncontrollable at the time of the first application (represented by the lower asymptote of the dose–response curve for the first treatment), plus any additional part of the population which survived the first application as a result of a finite dose being applied. Data to estimate the single-spray dose–response curve parameters and validate predictions of two-spray programme efficacy were obtained from separate subsets of treatments in four field experiments. A systemic fungicide spray was applied to wheat at a range of doses, at one or both of two times (t1 and t2), in all dose combinations. Observed values of the area under the disease progress curve (AUDPC) for septoria leaf blotch (Mycosphaerella graminicola) were used to construct response surfaces of dose at t1 by dose at t2 for each culm leaf layer. Parameters were estimated from single-spray and zero-dose treatment data only. The model predicted a high proportion (R2 = 71–95%) of the variation in efficacy of the two-spray programmes. AUDPC isobols showed that the dose required at t2 was inversely related to the dose at t1, but the slope of the relationship varied with the relative timings of t1 and t2 in relation to culm leaf emergence. Isobols were curved, so the effective dose – the total dose required to achieve a given level of disease suppression – was lower when administered as two applications.
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