220 research outputs found

    Classification of integrable Weingarten surfaces possessing an sl(2)-valued zero curvature representation

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    In this paper we classify Weingarten surfaces integrable in the sense of soliton theory. The criterion is that the associated Gauss equation possesses an sl(2)-valued zero curvature representation with a nonremovable parameter. Under certain restrictions on the jet order, the answer is given by a third order ordinary differential equation to govern the functional dependence of the principal curvatures. Employing the scaling and translation (offsetting) symmetry, we give a general solution of the governing equation in terms of elliptic integrals. We show that the instances when the elliptic integrals degenerate to elementary functions were known to nineteenth century geometers. Finally, we characterize the associated normal congruences

    Biological activity differences between TGF-β1 and TGF-β3 correlate with differences in the rigidity and arrangement of their component monomers

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    [Image: see text] TGF-β1, -β2, and -β3 are small, secreted signaling proteins. They share 71–80% sequence identity and signal through the same receptors, yet the isoform-specific null mice have distinctive phenotypes and are inviable. The replacement of the coding sequence of TGF-β1 with TGF-β3 and TGF-β3 with TGF-β1 led to only partial rescue of the mutant phenotypes, suggesting that intrinsic differences between them contribute to the requirement of each in vivo. Here, we investigated whether the previously reported differences in the flexibility of the interfacial helix and arrangement of monomers was responsible for the differences in activity by generating two chimeric proteins in which residues 54–75 in the homodimer interface were swapped. Structural analysis of these using NMR and functional analysis using a dermal fibroblast migration assay showed that swapping the interfacial region swapped both the conformational preferences and activity. Conformational and activity differences were also observed between TGF-β3 and a variant with four helix-stabilizing residues from TGF-β1, suggesting that the observed changes were due to increased helical stability and the altered conformation, as proposed. Surface plasmon resonance analysis showed that TGF-β1, TGF-β3, and variants bound the type II signaling receptor, TβRII, nearly identically, but had small differences in the dissociation rate constant for recruitment of the type I signaling receptor, TβRI. However, the latter did not correlate with conformational preference or activity. Hence, the difference in activity arises from differences in their conformations, not their manner of receptor binding, suggesting that a matrix protein that differentially binds them might determine their distinct activities

    HIV Types, Groups, Subtypes and Recombinant Forms: Errors in Replication, Selection Pressure and Quasispecies

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    HIV-1 is a chimpanzee virus which was transmitted to humans by several zoonotic events resulting in infection with HIV-1 groups M P, and in parallel transmission events from sooty mangabey monkey viruses leading to infections with HIV-2 groups A H. Both viruses have circulated in the human population for about 80 years. In the infected patient, HIV mutates, and by elimination of some of the viruses by the action of the immune system individual quasispecies are formed. Along with the selection of the fittest viruses, mutation and recombination after superinfection with HIV from different groups or subtypes have resulted in the diversity of their patterns of geographic distribution. Despite the high variability observed, some essential parts of the HIV genome are highly conserved. Viral diversity is further facilitated in some parts of the HIV genome by drug selection pressure and may also be enhanced by different genetic factors, including HLA in patients from different regions of the world. Viral and human genetic factors influence pathogenesis. Viral genetic factors are proteins such as Tat, Vif and Rev. Human genetic factors associated with a better clinical outcome are proteins such as APOBEC, langerin, tetherin and chemokine receptor 5 (CCR5) and HLA B27, B57, DRB1{*}1303, KIR and PARD3B. Copyright (C) 2012 S. Karger AG, Base

    Notes on the Third Law of Thermodynamics.I

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    We analyze some aspects of the third law of thermodynamics. We first review both the entropic version (N) and the unattainability version (U) and the relation occurring between them. Then, we heuristically interpret (N) as a continuity boundary condition for thermodynamics at the boundary T=0 of the thermodynamic domain. On a rigorous mathematical footing, we discuss the third law both in Carath\'eodory's approach and in Gibbs' one. Carath\'eodory's approach is fundamental in order to understand the nature of the surface T=0. In fact, in this approach, under suitable mathematical conditions, T=0 appears as a leaf of the foliation of the thermodynamic manifold associated with the non-singular integrable Pfaffian form δQrev\delta Q_{rev}. Being a leaf, it cannot intersect any other leaf S=S= const. of the foliation. We show that (N) is equivalent to the requirement that T=0 is a leaf. In Gibbs' approach, the peculiar nature of T=0 appears to be less evident because the existence of the entropy is a postulate; nevertheless, it is still possible to conclude that the lowest value of the entropy has to belong to the boundary of the convex set where the function is defined.Comment: 29 pages, 2 figures; RevTex fil

    СОВРЕМЕННЫЕ ВОЗМОЖНОСТИ СНИЖЕНИЯ ИНТЕНСИВНОСТИ ГИПЕРМЕТАБОЛИЗМА ПРИ ТЯЖЕЛОЙ ТЕРМИЧЕСКОЙ ТРАВМЕ (ОБЗОР ЛИТЕРАТУРЫ)

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    The review focuses on key aspects  of complex hypermetabolic response modulation which improve treatment outcomes  in patients with severe thermal  trauma: pharmacologic and non-pharmacologic approaches, early enteral feeding and micronutrients, physiatrics, estimation of individual nutritional requirements and monitoring  of the nutritional support  adequacy.В обзоре освещены ключевые аспекты комплексного подхода к модулированию гиперметаболического ответа, позволяющего улучшить результаты лечения пострадавших с тяжелой ожоговой травмой — фармакологические и нефармакологические методы,  раннее энтеральное  питание и дополнительное  назначение  микронутриентов, ранняя  реабилитация  пациентов, индивидуальная оценка потребностей больного в питательных веществах и контроль адекватности проводимой терапии

    An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

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    Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays
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