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  • 1
    ISSN: 0948-5023
    Keywords: HIV-1 reverse transcriptase ; Minor groove binding track ; Particle-mesh Ewald
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract We have built a molecular dynamics model for human immunodeficiency virus (HIV-1) reverse transcriptase (RT) complexed with a 19/18-mer template/primer by combining the structural information of a low resolution crystal structure of a HIV-1 RT/DNA complex (1hmi) with that of a high resolution crystal structure of unliganded HIV-1 RT (1rtj). The process involved slow forcing of the α-carbons of 1rtj onto those of 1hmi using constrained MD simulations, while immersing the protein in aqueous solution. A similar technique was used to build the bent all-atom DNA duplex, which was then docked into the modeled protein. The resulting model complex was refined using molecular dynamics simulation with the Particle-mesh Ewald method employed to accommodate long-range electrostatic interactions. New parameters of the Amber force field that affect DNA twist are tested and largely validated. The model has been used successfully to explain the results of vertical scanning mutagenesis of residue 266 (Trp266). Recently, the low resolution crystal structure of the HIV-1 RT/DNA complex has been refined to a 2.8 Å resolution (2hmi) and a crystal structure of a HIV-1/RT/dTTP ternary complex has been determined at 3.2 Å resolution (1rtd). A detailed structural comparison of the prior model structure and the two experimental structures becomes possible. Overall, the three structures share many similarities. The root mean square deviations of the α-carbons for the individual subdomains among the three structures are within the same ranges. The secondary structure assignments in the three structures are nearly identical. Key protein-DNA contacts such as those in the region of the primer grip are also similar in the three structures.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 112 (2000), S. 2265-2273 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: Quantum mechanical calculations on the vibrational predissociation dynamics of NeBr2 in the B electronic state have been performed and the results compared with both experimental data and other computational studies. For vibrational levels with v≤20 we find that the vibrational state dependence of the predissociation lifetimes is in qualitative agreement with experimental measurements, as are the calculated Br2 fragment rotational distributions. For higher vibrational levels, the B←X excitation profiles are well represented by a sum of two Lorentzian line shapes. We attribute this result to the presence of long-lived resonances in the dissociative continuum that are reminiscent of long-lived dissociative trajectories in previous classical studies of NeBr2. © 2000 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 112 (2000), S. 10042-10048 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: We demonstrate a variant of the bond fluctuation lattice Monte Carlo model in which moves through cis conformations are forbidden. Ring polymers in this model have a conserved quantity that amounts to a topological linking number. Increased linking number reduces the radius of gyration mildly. A linking number of order 0.2 per bond leads to an 8% reduction of the radius for 128-bond chains. This percentage appears to rise with increasing chain length, contrary to expectation. For ring chains evolving without the conservation of linking number, we demonstrate a substantial anticorrelation between the twist and writhe variables whose sum yields the linking number. We raise the possibility that our observed anticorrelations may have counterparts in the most important practical polymer that conserves linking number, DNA. © 2000 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK and Boston, USA : Blackwell Publishers Ltd
    Bulletin of economic research 54 (2002), S. 0 
    ISSN: 1467-8586
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Economics
    Notes: This research examines the location choice of private schools entering the California schooling market in 1979–80. We find that entrants are more likely to locate in public school districts with lower levels of per–pupil expenditure and higher fractions of public school students who reside in low–income households. In addition, we provide evidence of differences in the responsiveness of different types of private schools to the underlying conditions. Also, in comparing our results to those of previous research, we find that the determinants of the location choices of entrants appear to be the same as the determinants of the location pattern of incumbent private schools.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 425-456 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract IL-13 was first recognized for its effects on B cells and monocytes, where it upregulated class II expression, promoted IgE class switching and inhibited inflammatory cytokine production. It was also thought to be functionally redundant with IL-4. However, studies conducted with knockout mice, neutralizing antibodies, and novel antagonists demonstrate that IL-13 possesses several unique effector functions that distinguish it from IL-4. Resistance to most gastrointestinal nematodes is mediated by type-2 cytokine responses, in which IL-13 plays a dominant role. By regulating cell-mediated immunity, IL-13 modulates resistance to intracellular organisms including Leishmania major, Leishmania mexicana, and Listeria monocytogenes. In the lung, IL-13 is the central mediator of allergic asthma, where it regulates eosinophilic inflammation, mucus secretion, and airway hyperresponsiveness. Manipulation of IL-13 effector function may also prove useful in the treatment of some cancers like B-cell chronic lymphocytic leukemia and Hodgkin's disease, where IL-13 modulates apoptosis or tumor cell growth. IL-13 can also inhibit tumor immunosurveillance. As such, inhibitors of IL-13 might be effective as cancer immunotherapeutics by boosting type-1-associated anti-tumor defenses. Finally, IL-13 was revealed as a potent mediator of tissue fibrosis in both schistosomiasis and asthma, which indicates that it is a key regulator of the extracellular matrix. The mechanisms that regulate IL-13 production and/or function have also been investigated, and IL-4, IL-12, IL-18, IFN-gamma, IL-10, TGF-beta, TNF-alpha, and the IL-4/IL-13 receptor complex play important roles. This review highlights the effector functions of IL-13 and describes multiple pathways for modulating its activity in vivo.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 1-27 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract My work on basic and clinical immunology has focused on the regulation of the human immune response and how its dysregulation can lead to immunodeficiency, autoimmune, and malignant disorders. The early focus in our laboratory was on pathogenic mechanisms underlying hypogammaglobulinemia. Our demonstration of active suppression by human suppressor T cells changed thinking about the pathogenesis of certain immunodeficiency disorders. Recently we have focused on the cytokines interleukin-2 (IL-2) and IL-15, which have competitive functions in adaptive immune responses. IL-2 is necessary to destroy self-reactive lymphocytes and thus favors peripheral tolerance to self-antigens, whereas IL-15 favors the persistence of lymphocytes involved in the memory and effector responses to invading pathogens but risks the development of inflammatory autoimmune diseases. Our murine anti-Tac monoclonal antibody exploits these differences, as does a humanized form (daclizumab) now approved for the prevention of renal allograft rejection. New forms of therapy directed at IL-2 and IL-15 receptors may be effective against certain neoplastic diseases and autoimmune disorders and in the prevention of allograft rejection.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical psychology 8 (2001), S. 0 
    ISSN: 1468-2850
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Psychology
    Notes: Wood, Nezworski, Garb, and Lilienfeld provide a compelling critique of the norms developed by Exner for the Rorschach Comprehensive System. There does appear to be a systematic error that results in clinicians and researchers identifying pathology that may not in fact be present. Wood and his colleagues recommend that the Comprehensive System not be used in clinical or forensic work. The Rorschach is prone to excessive interpretation and should perhaps not have an appreciable or significant impact on the resolution of legal disputes. However, even Wood and Lilienfeld previously concluded that valid information can be obtained within a Rorschach protocol. The dispute over the Rorschach may be a flashpoint of a wider and more fundamental dispute within the profession.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical psychology 10 (2003), S. 0 
    ISSN: 1468-2850
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Psychology
    Notes: Lenzenweger (2003, this issue) objected to my suggestion that Lenzenweger and Korfine (1992) interpreted their taxometric study as support for Meehl's (1962, 1990) single major gene model of schizophrenia. I suggest in this brief response that my representation of Lenzenweger and Korfine was consistent with the statements they had made. However, I do welcome the clarification that there are alternative explanations for the manifest class taxon identified by Lenzenweger and Korfine (e.g., see Widiger, 2001) and I would encourage future taxometric studies to explore these alternatives.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical psychology 8 (2001), S. 0 
    ISSN: 1468-2850
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Psychology
    Notes: Taxometric analyses can be useful in indicating that a particular set of beliefs, attitudes, feelings, or behaviors have coherence as manifest class taxa. However, there is little reason to believe that taxometric analyses identify latent class taxa with specific etiologies, pathologies, or treatment implications. Taxometric analyses can, in fact, be quite misleading if their results are taken too seriously. Mental disorders are most likely the result of polygenetic dispositions and multifactorial etiologies. The optimal understanding of the etiology, pathology, and treatment of mental disorders is more likely to be multifactorial than taxonic.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1468-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Media Resources and Communication Sciences, Journalism
    Notes: The availability of statistical software packages has led to a sharp increase in use of complex research designs and complex statistical analyses in communication research. An informal examination of studies from 2 leading communication journals suggests that the analysis of variance (ANOVA) is often the statistic of choice, and a substantial proportion of published research reports using ANOVA employ complex (k ≥ 3) factorial designs, often involving multiple dependent variables. This article reports a series of Monte Carlo simulations which demonstrate that this complexity may come at a heavier cost than many communication researchers realize. As frequently used, complex factorial ANOVA yield Type I and Type II error rates that many communication scholars would likely consider unacceptable. Consequently, quality of statistical inference in many studies is highly suspect. Communication researchers are warned about problems associated with design and statistical complexity and solutions are suggested.
    Type of Medium: Electronic Resource
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