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  • 1
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] We have designed short peptides composed of two functional domains, one a tumor blood vessel 'homing' motif and the other a programmed cell death-inducing sequence, and synthesized them by simple peptide chemistry. The 'homing' domain was designed to guide the peptide to targeted cells and allow ...
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  • 2
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 99 (1993), S. 9930-9937 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: Phenomenological models have been quite successful in characterizing both the various complex phases and the corresponding phase diagrams of microemulsions. In some approaches, e.g., the random mixing model (RMM), the lattice parameter is of the order of the dimension of an oil or water domain and has been used as a length scale for computing a configurational entropy, the so-called entropy of mixing, of the microemulsion. In the central and material section of this paper (Sec. III), we show that the fundamental length scale for the calculation of the entropy of mixing is of the order of the cube root of the volume per molecule—orders of magnitude smaller than the dimension of such a domain. This length scale is specifically the scale for the configurational entropy—not that which measures either the curvature of the interface, the "granularity'' of the microemulsion, or the persistence length. Furthermore, we demonstrate, in general, that mixing entropy, evaluated in configuration space as opposed to phase space, will not be physically correct unless it is made to be consistent with the phase space evaluation. Following this core section, we give a one-dimensional illustration of the problem (Sec. IV), and discuss the consequences of our general result with respect to the RMM (Sec. V). The RMM not only seriously underestimates the entropy of mixing but exhibits a dependence on composition that is qualitatively very different from the correct dependence. Furthermore, for oil or water rich compositions of the microemulsion, the correct mixing entropy reinforces effects that would normally be attributed to bending energy, i.e., it destabilizes the system.
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  • 3
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 95 (1991), S. 9209-9218 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: A statistical-mechanical theory of vapor-phase nucleation is developed which improves on that introduced by Reiss, Katz, and Cohen (RKC), and revised by Reiss, Tabazadeh, and Talbot (RTT) by identifying a physical embryo appropriate to the nucleation process. Put in the simplest manner, the goals of this paper are (1) to define embryos in such a manner that their thermodynamic properties can be easily calculated by means of computer simulation; (2) to define embryos in such a manner that (ideally) they can be used as entities in terms of which the systematic exact evaluation of the classical phase integral can be performed, and the equilibrium distribution of embryos therefore determined. This model of a pre-nucleating embryo prevents redundant counting of configurations in the partition function needed to derive the metastable equilibrium distribution of embryos. The embryo definition does not artificially constrain the molecules within the embryo, but remains only a procedural device for organizing the counting. The present treatment also resolves a problem not noticed by RTT involving an inconsistency concerning dimensions in their theory. Using the embryo definition the metastable equilibrium distribution of embryos is derived. Finally, a brief discussion of how the distribution can be used in a theory of nucleation rate is provided. Work is presently under way on the rate theory.
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  • 4
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Expression of the protooncogene bcl-2 inhibits both apoptotic and in some cases necrotic cell death in many cell types, including neural cells, and in response to a wide variety of inducers. The mechanism by which the Bcl-2 protein acts to prevent cell death remains elusive. One mechanism by which Bcl-2 has been proposed to act is by decreasing the net cellular generation of reactive oxygen species. To evaluate this proposal, we measured activities of antioxidant enzymes as well as levels of glutathione and pyridine nucleotides in control and bcl-2 transfectants in two different neural cell lines—rat pheochromocytoma PC12 and the hypothalamic GnRH cell line GT1-7. Both neural cell lines overexpressing bcl-2 had elevated total glutathione levels when compared with control transfectants. The ratios of oxidized glutathione to total glutathione in PC12 and GT1-7 cells overexpressing bcl-2 were significantly reduced. In addition, the NAD+/NADH ratio of bcl-2-expressing PC12 and GT1-7 cells was two- to threefold less than that of control cell lines. GT1-7 cells overexpressing bcl-2 had the same level of glutathione peroxidase, catalase, superoxide dismutase, and glutathione reductase activities as control cells. PC12 cells overexpressing bcl-2 had a twofold increase in superoxide dismutase and catalase activity when compared with matched control transfected cells. The levels of glutathione peroxidase and glutathione reductase in PC12 cells overexpressing bcl-2 were similar to those of control cells. These results indicate that the overexpression of bcl-2 shifts the cellular redox potential to a more reduced state, without consistently affecting the major cellular antioxidant enzymes.
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  • 5
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract : X-linked spinal and bulbar muscular atrophy (SBMA),Kennedy's disease, is a degenerative disease of the motor neurons that isassociated with an increase in the number of CAG repeats encoding apolyglutamine stretch within the androgen receptor (AR). Recent work hasdemonstrated that the gene products associated with open reading frame tripletrepeat expansions may be substrates for the cysteine protease cell deathexecutioners, the caspases. However, the role that caspase cleavage plays inthe cytotoxicity associated with expression of the disease-associated allelesis unknown. Here, we report the first conclusive evidence that caspasecleavage is a critical step in cytotoxicity ; the expression of the AR with anexpanded polyglutamine stretch enhances its ability to induce apoptosis whencompared with the normal AR. The AR is cleaved by a caspase-3 subfamilyprotease at Asp146, and this cleavage is increased duringapoptosis. Cleavage of the AR at Asp146 is critical for theinduction of apoptosis by AR, as mutation of the cleavage site blocks theability of the AR to induce cell death. Further, mutation of the caspasecleavage site at Asp146 blocks the ability of the SBMA AR to form perinuclear aggregates. These studies define a fundamental role for caspase cleavage in the induction of neural cell death by proteins displaying expanded polyglutamine tracts, and therefore suggest a strategy that may be useful to treat neurodegenrative diseases associated with polyglutamine repeat expansions.
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  • 6
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 97 (1992), S. 5766-5772 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: A statistical mechanical theory of the cluster distribution involved in homogeneous vapor-phase nucleation is presented based on the stochastic nature of physical clusters. This new approach supports the work of Ellerby, Weakliem, and Reiss (Paper I of this series) by deriving their results by a different, though equally rigorous method. Furthermore, the present treatment is more direct and transparent, avoiding completely the need to construct the partition function for the entire vapor, requiring instead the consideration only of the probability of an individual cluster. This circumvents the problem of complicated configuration counting involved in the partition function approach, and therefore eliminates the potentially tedious explanations corresponding to it. The increased simplicity and clarity of the method presented here result in new insights and discoveries concerning the cluster distribution. For example, the distribution is now understood in relation to fluctuation theory, and is cast in terms of an equilibrium constant for cluster formation. Beyond this, the meaning of the free energy of cluster formation in the theory is now thoroughly understood. This approach complements that of Ellerby, Weakliem, and Reiss, and advances the understanding and exposition of a viable theory of vapor-phase nucleation.
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