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  • Articles  (18)
  • Articles: DFG German National Licenses  (18)
  • Annual Reviews  (18)
  • American Meteorological Society
  • Blackwell Publishers Inc.
  • Elsevier
  • 2010-2014
  • 2000-2004  (11)
  • 1960-1964
  • 1955-1959  (7)
  • 1920-1924
  • 2000  (11)
  • 1957  (3)
  • 1956  (4)
  • Chemistry and Pharmacology  (12)
  • Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition  (6)
Collection
  • Articles  (18)
Source
Years
  • 2010-2014
  • 2000-2004  (11)
  • 1960-1964
  • 1955-1959  (7)
  • 1920-1924
Year
  • 1
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 40 (2000), S. 67-95 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Abstract We propose a framework for considering the role of pharmacokinetic/ pharmacodynamic modeling in drug development and an appraisal of its current and potential impact on that activity. After some introduction, definitions, and background information on drug development, we discuss subject-matter models that underlie pharmacokinetic/pharmacodynamic modeling and show how they determine appropriate statistical models. We discuss the broad role modeling can play in drug development, enhancing primarily the "learning" steps, i.e. acquiring the information needed for the label and for planning efficient confirmatory clinical trials. Examples of past applications of modeling to drug development are presented in tabular form, followed by a discussion of some practical issues in application. Modeling will not reach its potential utility until it is manifest as a visible and separate work unit within a drug development program. We suggest that that work unit is the "in numero" study: a protocol-driven exercise designed to extract additional information, and/or answer a specific drug-development question, through an integrated model-based (meta-) analysis of existent raw data, often pooled across separate (clinical) studies.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 69 (2000), S. 145-182 
    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The prostaglandin endoperoxide H synthases-1 and 2 (PGHS-1 and PGHS-2; also cyclooxygenases-1 and 2, COX-1 and COX-2) catalyze the committed step in prostaglandin synthesis. PGHS-1 and 2 are of particular interest because they are the major targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen, and the new COX-2 inhibitors. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. In this review, we examine how the structures of these enzymes relate mechanistically to cyclooxygenase and peroxidase catalysis, and how differences in the structure of PGHS-2 confer on this isozyme differential sensitivity to COX-2 inhibitors. We further examine the evidence for independent signaling by PGHS-1 and PGHS-2, and the complex mechanisms for regulation of PGHS-2 gene expression.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 26 (1957), S. 209-242 
    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 26 (1957), S. 275-306 
    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physical Chemistry 7 (1956), S. 43-66 
    ISSN: 0066-426X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 40 (2000), S. 43-65 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Abstract The chlorinated methanes, particularly carbon tetrachloride and chloroform, are classic models of liver injury and have developed into important experimental hepatoxicants over the past 50 years. Hepatocellular steatosis and necrosis are features of the acute lesion. Mitochondria and the endoplasmic reticulum as target sites are discussed. The sympathetic nervous system, hepatic hemodynamic alterations, and role of free radicals and biotransformation are considered. With carbon tetrachloride, lipid peroxidation and covalent binding to hepatic constituents have been dominant themes over the years. Potentiation of chlorinated methane-induced liver injury by alcohols, aliphatic ketones, ketogenic compounds, and the pesticide chlordecone is discussed. A search for explanations for the potentiation phenomenon has led to the discovery of the role of tissue repair in the overall outcome of liver injury. Some final thoughts about future research are also presented.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 40 (2000), S. 295-317 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Abstract A potentially powerful approach to drug delivery in the treatment of disease involves the use of cells to introduce genes encoding therapeutic proteins into the body. Candidate genes for delivery include those encoding secreted factors that could have broad applications ranging from treatment of inherited single-gene deficiencies to acquired disorders of the vasculature or cancer. Myoblasts, the proliferative cell type of skeletal muscle tissues, are potent tools for stable delivery of a gene of interest into the body, as they become an integral part of the muscle into which they are injected, in close proximity to the circulation. The recent development of improved tetracycline-inducible retroviral vectors allows for fine control of recombinant gene expression levels. The combination of ex vivo gene transfer using myoblasts and regulatable retroviral vectors provides a powerful toolbox with which to develop gene therapies for a number of human diseases.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 69 (2000), S. 183-215 
    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract Most prokaryotic signal-transduction systems and a few eukaryotic pathways use phosphotransfer schemes involving two conserved components, a histidine protein kinase and a response regulator protein. The histidine protein kinase, which is regulated by environmental stimuli, autophosphorylates at a histidine residue, creating a high-energy phosphoryl group that is subsequently transferred to an aspartate residue in the response regulator protein. Phosphorylation induces a conformational change in the regulatory domain that results in activation of an associated domain that effects the response. The basic scheme is highly adaptable, and numerous variations have provided optimization within specific signaling systems. The domains of two-component proteins are modular and can be integrated into proteins and pathways in a variety of ways, but the core structures and activities are maintained. Thus detailed analyses of a relatively small number of representative proteins provide a foundation for understanding this large family of signaling proteins.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Phytopathology 38 (2000), S. 181-205 
    ISSN: 0066-4286
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Biology
    Notes: Abstract Several economically important diseases of unknown or recently determined cause are reviewed. Citrus blight (CB), first described over 100 years ago, was shown in 1984 to be transmitted by root-graft inoculations; the cause remains unknown and is controversial. Based on graft transmission, it is considered to be an infectious agent by some; others suggest that the cause of CB is abiotic. Citrus variegated chlorosis, although probably long present in Argentina, where it was considered to be a variant of CB, was identified as a specific disease and shown to be caused by a strain of Xylella fastidiosa after if reached epidemic levels in Brazil in 1987. Citrus psorosis, described in 1933 as the first virus disease of citrus, is perhaps one of the last to be characterized. In 1988, it was shown to be caused by a very unusual virus. The cause of lettuce big vein appears to be a viruslike agent that is transmitted by a soilborne fungus. Double-stranded RNAs were associated with the disease, suggesting it may be caused by an unidentified RNA virus. Rio Grande gummosis, dry rot root, peach tree short life, and some replant diseases may be diseases of complex etiology. Various microorganisms have been isolated from trees with these diseases, but the diseases may be attributable in part to environmental factors. Determination of the cause of these diseases of complex etiology has proven difficult, in part, because they affect only mature trees.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Phytopathology 38 (2000), S. 541-576 
    ISSN: 0066-4286
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Biology
    Notes: Abstract Diseases caused by species in the genus Phytophthora are responsible for significant economic losses on a wide range of host plants. Spatial pattern is one of the most characteristic ecological properties of a species, and reflects environmental and genetic heterogeneity and reproductive population growth acting on the processes of reproduction, dispersal, and mortality. Species of Phytophthora can be dispersed either in soil, via surface water movement down rows, from rain splash dispersal, by air, or via movement by humans or invertebrate activity. Dispersal results in patchiness in patterns of disease or inoculum in soil. In this chapter we discuss the mechanisms of dispersal of members of this important genus and describe several methods that can be used to statistically analyze data for which spatial coordinates are known. The methods include testing spatial autocorrelation for binary data or continuous data, semivariograms, and regression models for spatial data. The goal of spatial pattern analysis is to gain an understanding of the mechanisms of dispersal of propagules and to sort out the physical and biological factors that are important for spread of plant pathogens and ultimately, for disease management.
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