567 research outputs found

    A typology of masspersonal information seeking repertoires (MISR): Global implications for political participation and subjective well-being

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    Masspersonal information seeking repertoires are a person-centered method of gaining insight into the relationship between Internet use, subjective well-being, and political participation. Through latent profile analysis, three person types were identified in two waves of stratified samples in 18 countries (N = 8352). In accord with the β€œaugmentation hypothesis,” high levels of interpersonal contact and traditional mass media usage covaried with high Internet use for the highly engaged type, that had highest political participation and life satisfaction, political knowledge, low depressive symptoms and also high anxiety. The other two types fit the β€œdisplacement hypothesis,” where Internet-based media displaces traditional media and face-to-face communication. Compared with the digitally immersed, the traditional repertoire was more knowledgeable and politically engaged, and had better well-being. Latent transition analysis showed these repertoires were stable over 6 months. Identifying different types of people with different information seeking styles clarifies mixed results on effects of online mass media use

    Effects of Noise, Correlations and errors in the preparation of initial states in Quantum Simulations

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    In principle a quantum system could be used to simulate another quantum system. The purpose of such a simulation would be to obtain information about problems which cannot be simulated with a classical computer due to the exponential increase of the Hilbert space with the size of the system and which cannot be measured or controlled in an actual experiment. The system will interact with the surrounding environment, with the other particles in the system and be implemented using imperfect controls making it subject to noise. It has been suggested that noise does not need to be controlled to the same extent as it must be for general quantum computing. However the effects of noise in quantum simulations and how to treat them are not completely understood. In this paper we study an existing quantum algorithm for the one-dimensional Fano-Anderson model to be simulated using a liquid-state NMR device. We calculate the evolution of different initial states in the original model, and then we add interacting spins to simulate a more realistic situation. We find that states which are entangled with their environment, and sometimes correlated but not necessarily entangled have an evolution which is described by maps which are not completely positive. We discuss the conditions for this to occur and also the implications.Comment: Revtex 4-1, 14 pages, 21 figures, version 2 has typos corrected and acknowledgement adde

    Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the Ξ±3 domain of MHC I molecules

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    THE Ξ±1 and Ξ±2 domains of major histocompatibility complex (MHC) class I molecules function in the binding and presentation of foreign peptides to the T-cell antigen receptor and control both negative and positive selection of the T-cell repertoire. Although the Ξ±3 domain of class I is not involved in peptide binding, it does interact with the T-cell accessory molecule, CDS. CDS is important in the selection of T cells as anti-CDS antibody injected into perinatal mice interfers with this process. We previously used a hybrid class I molecule with the Ξ±1/Ξ±2 domains from L^d and the Ξ±3 domain from Q7^b and showed that this molecule binds an L^d-restricted peptide but does not interact with CD8-dependent cytotoxic T lymphocytes. Expression of this molecule in transgenic mice fails to negatively select a subpopulation of anti-L^d cytotoxic T lymphocytes. In addition, positive selection of virus-specific L^d-restricted cytotoxic T lymphocytes does not occur. We conclude that besides the Ξ±1/Ξ±2 domains of class I, the Ξ±3 domain plays an important part in both positive and negative selection of antigen-specific cells

    Dirac Equation with Spin Symmetry for the Modified P\"oschl-Teller Potential in DD-dimensions

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    We present solutions of the Dirac equation with spin symmetry for vector and scalar modified P\"oschl-Teller potential within framework of an approximation of the centrifugal term. The relativistic energy spectrum is obtained using the Nikiforov-Uvarov method and the two-component spinor wavefunctions are obtain are in terms of the Jacobi polynomials. It is found that there exist only positive-energy states for bound states under spin symmetry, and the energy levels increase with the dimension and the potential range parameter Ξ±\alpha.Comment: 9 pages and 1tabl

    Leptin induces cell migration and invasion in a FAK-Src- dependent manner in breast cancer cells

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    Breast cancer is the most common invasive neoplasia, and the second leading cause of the cancer deaths in women worldwide. Mammary tumorigenesis is severely linked to obesity, one potential connection is leptin. Leptin is a hormone secreted by adipocytes, which contributes to the progression of breast cancer. Cell migration, metalloproteases secretion, and invasion are cellular processes associated with various stages of metastasis. These processes are regulated by the kinases FAK and Src. In this study, we utilized the breast cancer cell lines MCF7 and MDA-MB-231 to determine the effect of leptin on FAK and Src kinases activation, cell migration, metalloprotease secretion, and invasion. We found that leptin activates FAK and Src, and induces the localization of FAK to the focal adhesions. Interestingly, leptin promotes the activation of FAK through a Src and STAT3-dependent canonical pathway. Specific inhibitors of FAK, Src and STAT3 showed that the effect exerted by leptin in cell migration in breast cancer cells is dependent on these proteins. Moreover, we established that leptin promotes the secretion of the extracellular matrix remodelers, MMP-2 and MMP-9 and invasion in a FAK and Src dependent manner. Our findings strongly suggest that leptin promotes the development of a more aggressive invasive phenotype in mammary cancer cells

    Gelatin porous scaffolds fabricated using a modified gas foaming technique: Characterisation and cytotoxicity assessment

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    The current study presents an effective and simple strategy to obtain stable porous scaffolds from gelatin via a gas foaming method. The technique exploits the intrinsic foaming ability of gelatin in the presence of CO2 to obtain a porous structure stabilised with glutaraldehyde. The produced scaffolds were characterised using physical and mechanical characterisation methods. The results showed that gas foaming may allow the tailoring of the 3-dimensional structure of the scaffolds with an interconnected porous structure. To assess the effectiveness of the preparation method in mitigating the potential cytotoxicity risk of using glutaraldehyde as a crosslinker, direct and in-direct cytotoxicity assays were performed at different concentrations of glutaraldehyde. The results indicate the potential of the gas foaming method, in the preparation of viable tissue engineering scaffolds

    Negative Smad Expression and Regulation in the Developing Chick Limb

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    The inhibitory or negative Smads, Smad6 and Smad7, block TGFΞ² superfamily signals of both the BMP and TGFΞ² classes by antagonizing the intracellular signal transduction machinery. We report the cloning of one Smad6 and two Smad7 (Smad7a and Smad7b) chick homologs and their expression and regulation in the developing limb. Smad6 and Smad7a are expressed in dynamic patterns reflecting the domains of BMP gene expression in the limb. Activation and inhibition of the BMP signaling pathway in limb mesenchyme indicates that negative Smad gene expression is regulated, at least in part, by BMP family signals

    Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

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    The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

    Iterative Structure-Based Peptide-Like Inhibitor Design against the Botulinum Neurotoxin Serotype A

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    The botulinum neurotoxin serotype A light chain (BoNT/A LC) protease is the catalytic component responsible for the neuroparalysis that is characteristic of the disease state botulism. Three related peptide-like molecules (PLMs) were designed using previous information from co-crystal structures, synthesized, and assayed for in vitro inhibition against BoNT/A LC. Our results indicate these PLMS are competitive inhibitors of the BoNT/A LC protease and their Ki values are in the nM-range. A co-crystal structure for one of these inhibitors was determined and reveals that the PLM, in accord with the goals of our design strategy, simultaneously involves both ionic interactions via its P1 residue and hydrophobic contacts by means of an aromatic group in the P2β€² position. The PLM adopts a helical conformation similar to previously determined co-crystal structures of PLMs, although there are also major differences to these other structures such as contacts with specific BoNT/A LC residues. Our structure further demonstrates the remarkable plasticity of the substrate binding cleft of the BoNT/A LC protease and provides a paradigm for iterative structure-based design and development of BoNT/A LC inhibitors

    Kidney Development in the Absence of Gdnf and Spry1 Requires Fgf10

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    GDNF signaling through the Ret receptor tyrosine kinase (RTK) is required for ureteric bud (UB) branching morphogenesis during kidney development in mice and humans. Furthermore, many other mutant genes that cause renal agenesis exert their effects via the GDNF/RET pathway. Therefore, RET signaling is believed to play a central role in renal organogenesis. Here, we re-examine the extent to which the functions of Gdnf and Ret are unique, by seeking conditions in which a kidney can develop in their absence. We find that in the absence of the negative regulator Spry1, Gdnf, and Ret are no longer required for extensive kidney development. Gdnfβˆ’/βˆ’;Spry1βˆ’/βˆ’ or Retβˆ’/βˆ’;Spry1βˆ’/βˆ’ double mutants develop large kidneys with normal ureters, highly branched collecting ducts, extensive nephrogenesis, and normal histoarchitecture. However, despite extensive branching, the UB displays alterations in branch spacing, angle, and frequency. UB branching in the absence of Gdnf and Spry1 requires Fgf10 (which normally plays a minor role), as removal of even one copy of Fgf10 in Gdnfβˆ’/βˆ’;Spry1βˆ’/βˆ’ mutants causes a complete failure of ureter and kidney development. In contrast to Gdnf or Ret mutations, renal agenesis caused by concomitant lack of the transcription factors ETV4 and ETV5 is not rescued by removing Spry1, consistent with their role downstream of both RET and FGFRs. This shows that, for many aspects of renal development, the balance between positive signaling by RTKs and negative regulation of this signaling by SPRY1 is more critical than the specific role of GDNF. Other signals, including FGF10, can perform many of the functions of GDNF, when SPRY1 is absent. But GDNF/RET signaling has an apparently unique function in determining normal branching pattern. In contrast to GDNF or FGF10, Etv4 and Etv5 represent a critical node in the RTK signaling network that cannot by bypassed by reducing the negative regulation of upstream signals
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