286 research outputs found

    Guest Artist:Leslie Tung, Fortepiano

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    Kemp Recital Hall Thursday Evening November 7, 2002 8:00p.m

    Choice Overload, Attitude Formation Hierarchy, and Online Approach/Avoidance Behavior

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    This study examined how the number of choices offered on a website influences consumers’ attitude formation and their approach/avoidance behavior (email subscription) and whether the presentation consistency can mitigate the effect of choice overload during online apparel shopping

    The Reduction in Electroporation Voltages by the Addition of a Surfactant to Planar Lipid Bilayers

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    AbstractThe effects of a nonionic surfactant, octaethyleneglycol mono n-dodecyl ether (C12E8), on the electroporation of planar bilayer lipid membranes made of the synthetic lipid 1-pamitoyl 2-oleoyl phosphatidylcholine (POPC), was studied. High-amplitude (∼100–450mV) rectangular voltage pulses were used to electroporate the bilayers, followed by a prolonged, low-amplitude (∼65mV) voltage clamp to monitor the ensuing changes in transmembrane conductance. The electroporation thresholds of the membranes were found for rectangular voltage pulses of given durations. The strength-duration relationship was determined over a range from 10μs to 10s. The addition of C12E8 at concentrations of 0.1, 1, and 10μM to the bath surrounding the membranes decreased the electroporation threshold monotonically with concentration for all durations (p<0.0001). The decrease from control values ranged from 10% to 40%, depending on surfactant concentration and pulse duration. For a 10-μs pulse, the transmembrane conductance 150μs after electroporation (G150) increased monotonically with the surfactant concentration (p=0.007 for 10μM C12E8). These findings suggest that C12E8 incorporates into POPC bilayers, allowing electroporation at lower intensities and/or shorter durations, and demonstrate that surfactants can be used to manipulate the electroporation threshold of lipid bilayers

    Physical developmental cues for the maturation of human pluripotent stem cell-derived cardiomyocytes

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    Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are the most promising source of cardiomyocytes (CMs) for experimental and clinical applications, but their use is largely limited by a structurally and functionally immature phenotype that most closely resembles embryonic or fetal heart cells. The application of physical stimuli to influence hPSC-CMs through mechanical and bioelectrical transduction offers a powerful strategy for promoting more developmentally mature CMs. Here we summarize the major events associated with in vivo heart maturation and structural development. We then review the developmental state of in vitro derived hPSC-CMs, while focusing on physical (electrical and mechanical) stimuli and contributory (metabolic and hypertrophic) factors that are actively involved in structural and functional adaptations of hPSC-CMs. Finally, we highlight areas for possible future investigation that should provide a better understanding of how physical stimuli may promote in vitro development and lead to mechanistic insights. Advances in the use of physical stimuli to promote developmental maturation will be required to overcome current limitations and significantly advance research of hPSC-CMs for cardiac disease modeling, in vitro drug screening, cardiotoxicity analysis and therapeutic applications.published_or_final_versio

    Exploiting physico-chemical properties in string kernels

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    <p>Abstract</p> <p>Background</p> <p>String kernels are commonly used for the classification of biological sequences, nucleotide as well as amino acid sequences. Although string kernels are already very powerful, when it comes to amino acids they have a major short coming. They ignore an important piece of information when comparing amino acids: the physico-chemical properties such as size, hydrophobicity, or charge. This information is very valuable, especially when training data is less abundant. There have been only very few approaches so far that aim at combining these two ideas.</p> <p>Results</p> <p>We propose new string kernels that combine the benefits of physico-chemical descriptors for amino acids with the ones of string kernels. The benefits of the proposed kernels are assessed on two problems: MHC-peptide binding classification using position specific kernels and protein classification based on the substring spectrum of the sequences. Our experiments demonstrate that the incorporation of amino acid properties in string kernels yields improved performances compared to standard string kernels and to previously proposed non-substring kernels.</p> <p>Conclusions</p> <p>In summary, the proposed modifications, in particular the combination with the RBF substring kernel, consistently yield improvements without affecting the computational complexity. The proposed kernels therefore appear to be the kernels of choice for any protein sequence-based inference.</p> <p>Availability</p> <p>Data sets, code and additional information are available from <url>http://www.fml.tuebingen.mpg.de/raetsch/suppl/aask</url>. Implementations of the developed kernels are available as part of the Shogun toolbox.</p

    Landscape and well-being: A conceptual framework and an example

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    This article explores why landscape is a crucial element in researching the relationship between environment and well-being. The main point we make is that human social agents are embedded in particular landscapes, and it is in landscapes that environmental changes are experienced, which can have implications for well-being. We draw from a variety of perspectives on landscape that understands a fundamental creative relation between humans and landscape and recent developments in neo-materialism theorising. Landscape is understood here as an assemblage of different forms of matter, animate and inanimate objects, as well as symbolic and cultural processes. A case study is also presented to indicate how landscape can be studied in relation to environment and change. Using the conceptual ideas laid out in the first section of the article, we analyse landscape, environment and well-being in Xuan Thuy National Park in North Vietnam. The area is part of a precarious coastal region where extreme weather events have impacted on the well-being of both humans and other matter. This article concludes with suggestions on the use of this landscape approach in researching environment and well-being

    Amino acid classification based spectrum kernel fusion for protein subnuclear localization

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    <p>Abstract</p> <p>Background</p> <p>Prediction of protein localization in subnuclear organelles is more challenging than general protein subcelluar localization. There are only three computational models for protein subnuclear localization thus far, to the best of our knowledge. Two models were based on protein primary sequence only. The first model assumed homogeneous amino acid substitution pattern across all protein sequence residue sites and used BLOSUM62 to encode <it>k</it>-mer of protein sequence. Ensemble of SVM based on different <it>k</it>-mers drew the final conclusion, achieving 50% overall accuracy. The simplified assumption did not exploit protein sequence profile and ignored the fact of heterogeneous amino acid substitution patterns across sites. The second model derived the <it>PsePSSM </it>feature representation from protein sequence by simply averaging the profile PSSM and combined the <it>PseAA </it>feature representation to construct a kNN ensemble classifier <it>Nuc-PLoc</it>, achieving 67.4% overall accuracy. The two models based on protein primary sequence only both achieved relatively poor predictive performance. The third model required that GO annotations be available, thus restricting the model's applicability.</p> <p>Methods</p> <p>In this paper, we only use the amino acid information of protein sequence without any other information to design a widely-applicable model for protein subnuclear localization. We use <it>K</it>-spectrum kernel to exploit the contextual information around an amino acid and the conserved motif information. Besides expanding window size, we adopt various amino acid classification approaches to capture diverse aspects of amino acid physiochemical properties. Each amino acid classification generates a series of spectrum kernels based on different window size. Thus, (I) window expansion can capture more contextual information and cover size-varying motifs; (II) various amino acid classifications can exploit multi-aspect biological information from the protein sequence. Finally, we combine all the spectrum kernels by simple addition into one single kernel called <it>SpectrumKernel+ </it>for protein subnuclear localization.</p> <p>Results</p> <p>We conduct the performance evaluation experiments on two benchmark datasets: <it>Lei </it>and <it>Nuc-PLoc</it>. Experimental results show that <it>SpectrumKernel+ </it>achieves substantial performance improvement against the previous model <it>Nuc-PLoc</it>, with overall accuracy <it>83.47% </it>against <it>67.4%</it>; and <it>71.23% </it>against <it>50% </it>of <it>Lei SVM Ensemble</it>, against 66.50% of <it>Lei GO SVM Ensemble</it>.</p> <p>Conclusion</p> <p>The method <it>SpectrumKernel</it>+ can exploit rich amino acid information of protein sequence by embedding into implicit size-varying motifs the multi-aspect amino acid physiochemical properties captured by amino acid classification approaches. The kernels derived from diverse amino acid classification approaches and different sizes of <it>k</it>-mer are summed together for data integration. Experiments show that the method <it>SpectrumKernel</it>+ significantly outperforms the existing models for protein subnuclear localization.</p

    Elaborating a people-centered approach to understanding sustainable livelihoods under climate and environmental change: Thang Binh District, Quang Nam Province, Vietnam

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    This paper explores the maintenance of livelihoods under climate, environmental, and economic development pressures, through the case of Thang Binh District in Quang Nam Province, Vietnam. Within widespread recognition of the need to link sustainable livelihoods approaches with climate change adaptation, there is growing awareness of the importance of people-centered approaches which keep the diverse experience, capabilities, and knowledges of the most vulnerable at the heart of sustainable livelihoods thinking. In response, this paper explores the conditions for changes in modes of livelihoods in a case study area where top-down strategies for sustainable livelihoods are met with residents’ diverse experiences of vulnerability, and where climate and environmental changes shape residents’ relations with the landscape. The research is undertaken via interviews with residents, farmers/fishers, and local government officials. Our study finds that whilst government-led initiatives for sustainable livelihoods are welcomed in the locality, inflexible policies can make it challenging for the most vulnerable people to access support. Moreover, residents see the capacity to live with and respond to extreme weather events as a critical component of maintaining a sustainable livelihood. Our findings reinforce international literature, showing that ‘the poor’ are not a homogenous category, and illustrate the importance of attention to the smallest levels of government who are tasked with putting sustainable livelihoods initiatives into practice in relation to people’s daily lives

    Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicing

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    RBM15, an RNA binding protein, determines cell-fate specification of many tissues including blood. We demonstrate that RBM15 is methylated by protein arginine methyltransferase 1 (PRMT1) at residue R578 leading to its degradation via ubiquitylation by an E3 ligase (CNOT4). Overexpression of PRMT1 in acute megakaryocytic leukemia cell lines blocks megakaryocyte terminal differentiation by downregulation of RBM15 protein level. Restoring RBM15 protein level rescues megakaryocyte terminal differentiation blocked by PRMT1 overexpression. At the molecular level, RBM15 binds to pre-mRNA intronic regions of genes important for megakaryopoiesis such as GATA1, RUNX1, TAL1 and c-MPL. Furthermore, preferential binding of RBM15 to specific intronic regions recruits the splicing factor SF3B1 to the same sites for alternative splicing. Therefore, PRMT1 regulates alternative RNA splicing via reducing RBM15 protein concentration. Targeting PRMT1 may be a curative therapy to restore megakaryocyte differentiation for acute megakaryocytic leukemia

    The C-terminal fragment of the ribosomal P protein complexed to trichosanthin reveals the interaction between the ribosome-inactivating protein and the ribosome

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    Ribosome-inactivating proteins (RIPs) inhibit protein synthesis by enzymatically depurinating a specific adenine residue at the sarcin-ricin loop of the 28S rRNA, which thereby prevents the binding of elongation factors to the GTPase activation centre of the ribosome. Here, we present the 2.2 Å crystal structure of trichosanthin (TCS) complexed to the peptide SDDDMGFGLFD, which corresponds to the conserved C-terminal elongation factor binding domain of the ribosomal P protein. The N-terminal region of this peptide interacts with Lys173, Arg174 and Lys177 in TCS, while the C-terminal region is inserted into a hydrophobic pocket. The interaction with the P protein contributes to the ribosome-inactivating activity of TCS. This 11-mer C-terminal P peptide can be docked with selected important plant and bacterial RIPs, indicating that a similar interaction may also occur with other RIPs
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