581 research outputs found

    A User-centric Framework for Accessing Biological Sources and Tools

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    Biologists face two problems in interpreting their experiments: the integration of their data with information from multiple heterogeneous sources and data analysis with bioinformatics tools. It is difficult for scientists to choose between the numerous sources and tools without assistance. Following a thorough analysis of scientists’ needs during the querying process, we found that biologists express preferences concerning the sources to be queried and the tools to be used. Interviews also showed that the querying process itself – the strategy followed – differs between scientists. In response to these findings, we have introduced a user-centric framework allowing to specify various querying processes. Then we have developed the BioGuide system which helps the scientists to choose suitable sources and tools, find complementary information in sources, and deal with divergent data. It is generic in that it can be adapted by each user to provide answers respecting his/her preferences, and obtained following his/her strategies

    A Focus on Subtle Signs and Motor Behavior to Unveil Awareness in Unresponsive Brain-Impaired Patients: The Importance of Being Clinical.

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    Brain-injured patients in a state of cognitive motor dissociation (CMD) exhibit a lack of command following using conventional neurobehavioral examination tools but a high level of awareness and language processing when assessed using advanced imaging and electrophysiology techniques. Because of their behavioral unresponsiveness, patients with CMD may seem clinically indistinguishable from those with a true disorder of consciousness that affects awareness on a substantial level (coma, vegetative state/unresponsive wakefulness state, or minimally conscious state minus). Yet, by expanding the range of motor testing across limb, facial, and ocular motricity, we may detect subtle, purposeful movements even in the subset of patients classified as vegetative state/unresponsive wakefulness state. We propose the term of clinical CMD to describe patients showing these slight but determined motor responses and exhibiting a characteristic akinetic motor behavior as opposed to a pyramidal motor system behavior. These patients may harbor hidden cognitive capabilities and significant potential for a good long-term outcome. Indeed, we envision CMD as ranging from complete (no motor response) to partial (subtle clinical motor response) forms, falling within a spectrum of progressively better motor output in patients with considerable cognitive capabilities. In addition to providing a decisional flowchart, we present this novel approach to classification as a graphical model that illustrates the range of clinical manifestations and recovery trajectories fundamentally differentiating true disorders of consciousness from the spectrum of CMD

    Ultrafast quasiparticle relaxation dynamics in normal metals and heavy fermion materials

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    We present a detailed theoretical study of the ultrafast quasiparticle relaxation dynamics observed in normal metals and heavy fermion materials with femtosecond time-resolved optical pump-probe spectroscopy. For normal metals, a nonthermal electron distribution gives rise to a temperature (T) independent electron-phonon relaxation time at low temperatures, in contrast to the T^{-3}-divergent behavior predicted by the two-temperature model. For heavy fermion compounds, we find that the blocking of electron-phonon scattering for heavy electrons within the density-of-states peak near the Fermi energy is crucial to explain the rapid increase of the electron-phonon relaxation time below the Kondo temperature. We propose the hypothesis that the slower Fermi velocity compared to the sound velocity provides a natural blocking mechanism due to energy and momentum conservation laws.Comment: 10 pages, 11 figure

    Ultrafast photoinduced reflectivity transients in (Nd0.5Sr0.5)MnO3(Nd_{0.5}Sr_{0.5})MnO_3

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    The temperature dependence of ultrafast photoinduced reflectivity transients is reported in Nd0.5_{0.5}Sr0.5_{0.5}MnO3_{3} thin film. The photoinduced reflectivity shows a complex response with very different temperature dependences on different timescales. The response on the sub-ps timescale appears to be only weakly sensitive to the 270K-metal-insulator phase transition. Below 160\sim 160 K the sub-ps response displays a two component behavior indicating inhomogeneity of the film resulting from the substrate induced strain. On the other hand, the slower response on the 10-100 ps timescale is sensitive only to the metal-insulator phase transition and is in agreement with some previously published results. The difference in the temperature dependences of the responses on nanosecond and μ\mu s timescales indicates that thermal equilibrium between the different degrees of fredom is established relatively slowly - on a nanosecond timescale

    Carnitine Acetyltransferase Mitigates Metabolic Inertia and Muscle Fatigue during Exercise

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    SummaryAcylcarnitine metabolites have gained attention as biomarkers of nutrient stress, but their physiological relevance and metabolic purpose remain poorly understood. Short-chain carnitine conjugates, including acetylcarnitine, derive from their corresponding acyl-CoA precursors via the action of carnitine acetyltransferase (CrAT), a bidirectional mitochondrial matrix enzyme. We show here that contractile activity reverses acetylcarnitine flux in muscle, from net production and efflux at rest to net uptake and consumption during exercise. Disruption of this switch in mice with muscle-specific CrAT deficiency resulted in acetyl-CoA deficit, perturbed energy charge, and diminished exercise tolerance, whereas acetylcarnitine supplementation produced opposite outcomes in a CrAT-dependent manner. Likewise, in exercise-trained compared to untrained humans, post-exercise phosphocreatine recovery rates were positively associated with CrAT activity and coincided with dramatic shifts in muscle acetylcarnitine dynamics. These findings show acetylcarnitine serves as a critical acetyl buffer for working muscles and provide insight into potential therapeutic strategies for combatting exercise intolerance

    Drying nano particles solution on an oscillating tip at an air liquid interface: what we can learn, what we can do

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    Evaporation of fluid at micro and nanometer scale may be used to self-assemble nanometre-sized particles in suspension. Evaporating process can be used to gently control flow in micro and nanofluidics, thus providing a potential mean to design a fine pattern onto a surface or to functionalize a nanoprobe tip. In this paper, we present an original experimental approach to explore this open and rather virgin domain. We use an oscillating tip at an air liquid interface with a controlled dipping depth of the tip within the range of the micrometer. Also, very small dipping depths of a few ten nanometers were achieved with multi walls carbon nanotubes glued at the tip apex. The liquid is an aqueous solution of functionalized nanoparticles diluted in water. Evaporation of water is the driving force determining the arrangement of nanoparticles on the tip. The results show various nanoparticles deposition patterns, from which the deposits can be classified in two categories. The type of deposit is shown to be strongly dependent on whether or not the triple line is pinned and of the peptide coating of the gold nanoparticle. In order to assess the classification, companion dynamical studies of nanomeniscus and related dissipation processes involved with thinning effects are presented

    Comparison of s- and d-wave gap symmetry in nonequilibrium superconductivity

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    Recent application of ultrafast pump/probe optical techniques to superconductors has renewed interest in nonequilibrium superconductivity and the predictions that would be available for novel superconductors, such as the high-Tc cuprates. We have reexamined two of the classical models which have been used in the past to interpret nonequilibrium experiments with some success: the mu* model of Owen and Scalapino and the T* model of Parker. Predictions depend on pairing symmetry. For instance, the gap suppression due to excess quasiparticle density n in the mu* model, varies as n^{3/2} in d-wave as opposed to n for s-wave. Finally, we consider these models in the context of S-I-N tunneling and optical excitation experiments. While we confirm that recent pump/probe experiments in YBCO, as presently interpreted, are in conflict with d-wave pairing, we refute the further claim that they agree with s-wave.Comment: 14 pages, 11 figure

    Preprint: Overdose prevention centres as spaces of safety, trust and inclusion: a causal pathway based on a realist review

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    Background: Overdose prevention centres (OPCs) are non-residential spaces where people can use illicit drugs (that they have obtained elsewhere) in the presence of staff who can intervene in order to prevent and reverse any overdoses that occur. Many reviews of OPCs exist, but few explain how OPCs work. Methods: We carried out a realist review, using the RAMESES reporting standards. We systematically searched for and then thematically analysed 391 documents that provide information on the contexts, mechanisms, and outcomes of OPCs. Findings: Our retroductive analysis identified a causal pathway that highlights the feeling of safety – and the immediate outcome of not dying - as conditions of possibility for the people who use OPCs to build trust and experience social inclusion. The combination of safety, trust, and social inclusion that is triggered by OPCs can – depending on the contexts in which they operate - generate other positive outcomes, which may include less risky drug use practices, reductions in blood borne viruses and injection-related infections and wounds, and access to housing. Interpretation: OPCs can enable people who live with structural violence and vulnerability to develop feelings of safety and trust that help them stay alive and to build longer term trajectories of social inclusion, with potential to improve other aspects of their health and living conditions

    Adverse effects of fenofibrate in mice deficient in the protein quality control regulator, CHIP

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    We previously reported how the loss of CHIP expression (Carboxyl terminus of Hsc70-Interacting Protein) during pressure overload resulted in robust cardiac dysfunction, which was accompanied by a failure to maintain ATP levels in the face of increased energy demand. In this study, we analyzed the cardiac metabolome after seven days of pressure overload and found an increase in long-chain and medium-chain fatty acid metabolites in wild-type hearts. This response was attenuated in mice that lack expression of CHIP (CHIP-/-). These findings suggest that CHIP may play an essential role in regulating oxidative metabolism pathways that are regulated, in part, by the nuclear receptor PPARα (Peroxisome Proliferator-Activated Receptor alpha). Next, we challenged CHIP-/- mice with the PPARα agonist called fenofibrate. We found that treating CHIP-/- mice with fenofibrate for five weeks under non-pressure overload conditions resulted in decreased skeletal muscle mass, compared to wild-type mice, and a marked increase in cardiac fibrosis accompanied by a decrease in cardiac function. Fenofibrate resulted in decreased mitochondrial cristae density in CHIP-/- hearts as well as decreased expression of genes involved in the initiation of autophagy and mitophagy, which suggests that a metabolic challenge, in the absence of CHIP expression, impacts pathways that contribute to mitochondrial quality control. In conclusion, in the absence of functional CHIP expression, fenofibrate results in unexpected skeletal muscle and cardiac pathologies. These findings are particularly relevant to patients harboring loss-of-function mutations in CHIP and are consistent with a prominent role for CHIP in regulating cardiac metabolism
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