1,474 research outputs found
Effect of Recrystallized Texture on the Deep-Drawability of 17% Cr-Ferritic Stainless Steel
No full text
Determination of the limited trypsinolysis pathways of tumor necrosis factor-alpha and its mutant by electrospray ionization mass spectrometry
No full textElectrospray ionization mass spectrometry (ESI-MS) is employed to directly analyze the limited trypsinolysis products of wild-type tumor necrosis factor-alpha (wtTNF-alpha) and its mutant, M3S. To determine the charge numbers of peaks of relatively small peptides in the ESI mass spectrum of a digest, a series of sodium-adduct ion peaks of each peptide are generated by adding a small quantity of NaCl to the digest before taking the spectrum. From the monitoring of the composition of proteolytic mixture as the incubation time is lengthened, it has been learned that the proteolysis of wtTNF-alpha by trypsin occurs sequentially: Arg(2), Arg(6), Arg(32), Arg(31), and Arg(44), and that M3S is strongly resistant to the proteolysis. Since the cleavage sequence of wtTNF-alpha and the mutation-induced resistance of M3S are consistent with the structural features of the proteins, we can suggest a mutant more resistant to proteolysis than M3S, which has an additional point mutation, Ala35Leu or Ala35Ile. (C) 1999 Academic Press.X111sciescopu
High resolution crystal structure of a human tumor necrosis factor-alpha mutant with low systemic toxicity
No full textA human tumor necrosis factor-alpha (TNF-alpha) mutant (M3S) with low systemic toxicity in vivo was designed, and its structures in two different crystal packings were determined crystallographically at 1.8 and 2.15-Angstrom resolution, respectively, to explain altered biological activities of the mutant, M3S contains four changes: a hydrophilic substitution of L29S,two hydrophobic substitutions of S52I and Y56F, and a deletion of the N-terminal seven amino acids that is disordered in the structure of wild type TNF-alpha. Compared with wild-type TNF-alpha, it exhibits 11- and 71-fold lower binding affinities for the human TNF-R55 and TNF-R75 receptors, respectively, and in vitro cytotoxic effect and in vivo systemic toxicity of M3S are 20 and 10 times lower, respectively, However, in a transplanted solid tumor mouse model, M3S suppresses tumor growth more efficiently than wild-type TNF-alpha, M3S is highly resistant to proteolysis by trypsin, and it exhibits increased thermal stability and a prolonged half-life in vivo, The L29S mutation causes substantial restructuring of the loop containing residues 29-36 into a rigid segment as a consequence of induced formation of intra-and intersubunit interactions, explaining the altered receptor binding affinity and thermal stability, A mass spectrometric analysis identified major proteolytic cleavage sites located on this loop, and thus the increased resistance of M3S to the proteolysis is consistent with the increased rigidity of the loop, The S52I and Y56F mutations do not induce a noticeable conformational change, The side chain of Phe(56) projects into a hydrophobic cavity, while Ile(52) is exposed to the bulk solvent, Ile(52) should be involved in hydrophobic interactions with the receptors, since a mutant containing the same mutations as in M3S except for the L29S mutation exhibits an increased receptor binding affinity. The low systemic toxicity of M3S appears to be the effect of the reduced and selective binding affinities for the TNF receptors, and the superior tumor-suppression of M3S appears to be the effect of its weak but longer antitumoral activity in vivo compared with wild-type TNF-alpha, It is also expected that the 1.8-Angstrom resolution structure will serve as an accurate model for explaining the structure-function relationship of wild-type TNF-alpha and many TNF-alpha mutants reported previously and for the design of new TNF-alpha mutants.X1135sciescopu
Interpolating sequences for H∞(BH)
No full textWe prove that under the extended Carleson’s condition, a sequence (xn) ⊂ BH is linear interpolating for H∞(BH) for an infinite dimensional Hilbert space H. In particular, we construct the interpolating functions for each sequence and find a bound for the constant of interpolation.The author is supported by Project MTM 2011-22457 (Ministerio de Economía y Competitividad, Spain) and Project P1-1B2014-35 (Universitat Jaume I, Spain
Evaluation and ranking of researchers--Bh Index.
No full textEvaluation and ranking of every author is very crucial as it is widely used to evaluate the performance of the researcher. This article proposes a new method, called Bh-Index, to evaluate the researchers based on the publications and citations. The method is built on h-Index and only the h-core articles are taken into consideration. The method assigns value additions to those articles that receive significantly high citations in comparison to the h-Index of the researcher. It provides a wide range of values for a given h-Index and effective evaluation even for a short period. Use of Bh-Index along with the h-Index gives a powerful tool to evaluate the researchers
ROVIBRATIONAL CHARACTERIZATION OF X BH BY THE EXTRAPOLATION OF PHOTOSELECTED HIGH-RYDBERG SERIES IN BH
No full textAuthor Institution: Department of Chemistry, Purdue University, West Lafayette, IN 47907; Department of Chemistry, University of British Columbia, 6174 University Boulevard,; Vancouver, BC, Canada V6T 1Z3Optical-optical-optical triple resonance spectroscopy of BH isolates high-Rydberg states that form series converging to rotational state specific ionization potentials in the vibrational levels of BH from through . Limits defined by a comprehensive fit of these series to state-detailed thresholds yield rovibrational constants describing the X state of BH. The data provide a first determination of the vibration-rotation interaction parameter cm and a more accurate estimate of cm together with the higher-order anharmonic terms cm and cm. The deperturbation and global fit of series to state-detailed limits also yields a precise value of the adiabatic ionization potential of BH of cm, or eV. High precision is afforded here by the use of graphical analysis techniques, narrow bandwidth laser systems, and an analysis of newly observed, high-principal quantum number Rydberg states that conform well with a Hund's case (d) electron-core coupling limit
Activities of Transmitted/Founder and Chronic Clade B HIV-1 Vpu and a C-Terminal Polymorphism Specifically Affecting Virion Release
No full textAcute HIV-1 infection is characterized by a type I interferon response, resulting in the induction of host restriction factors. HIV-1 has evolved to counteract these factors, and one such adaptation, the ability of Vpu to counteract BST2/tetherin, is associated with the evolution of simian immunodeficiency virus (SIVcpz) into pandemic group M human immunodeficiency virus type 1 (HIV-1). During transmission between individuals, very few viruses or even a single virus, the "transmitted/founder" (T/F) virus, gives rise to the new infection, but in the new host the selective pressure of the immune response yields the diverse "quasispecies" of chronic infection. Here we examine the functional characteristics of Vpu proteins encoded by T/F viruses compared to acute and chronic viruses from longitudinally sampled subjects. The studied T/F Vpu proteins showed a trend toward optimized CD4 downregulation compared to chronic Vpu proteins but did not differ substantially in their ability to downregulate BST2 or enhance virion release, although individual clones from each group were impaired in these activities. Analysis of the functionally impaired clones identified a C-terminal residue, W76, as important specifically for Vpu enhancement of virion release. Primary Vpu clones encoding a W76G polymorphism, or site-directed mutants encoding a W76G substitution, were impaired in their ability to enhance virion release, but they were not defective for BST2 surface downregulation. Conversely, the virion release function of impaired primary clones was restored by creating a G76W substitution. The identification of W76 as important for virion release enhancement that is independent of BST2 surface downregulation supports the potential to mechanistically separate these functions of Vpu.
IMPORTANCE: To establish infection in a host, HIV-1 must evade the host's immune response, including the production of antiviral factors. HIV-1 encodes proteins that antagonize these defenses, including Vpu. Vpu counteracts the host protein BST2, which blocks the release of progeny viruses from the host cell. To determine the importance of Vpu activity to HIV-1 transmission, this study assessed the functionality of Vpu from viruses isolated soon after transmission ("transmitted/founder" viruses) compared to isolates from chronic infection. Although the anti-BST2 activity of Vpu proteins from the tested transmitted/founder viruses did not differ from the activity of the chronic Vpu proteins, the transmitted/founder Vpu proteins trended toward having superior activity against another host protein, CD4. Further, this study identified an amino acid near the C terminus of Vpu that is specifically important for Vpu's ability to enhance the release of progeny virus from the host cell, supporting the notion of a new mechanism for this function of Vpu
More on finite groups with few defining relations
No full textMennicke J, Neumann BH. More on finite groups with few defining relations. Journal of the Australian Mathematical Society. 1989;46(1):132-136.Certain central products of the binary polyhedral groups with finite cyclic groups are here shown to have presentations with two generators and two defining relations; this disproves a conjecture of the second author, stated in J. Austral. Math. Soc. Ser. A 38 (1985), 230–240
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