7,874 research outputs found

    A versatile interface model for thermal conduction phenomena and its numerical implementation by XFEM

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    International audienceA general interface model is presented for thermal conduction and characterized by two jump relations. The first one expresses that the temperature jump across an interface is proportional to the interfacial average of the normal heat flux while the second one states that the normal heat flux jump is proportional to the surface Laplacian of the interfacial average of the temperature. By varying the two scalar proportionality parameters, not only the Kapitza resistance and highly conducting interface models can be retrieved but also all the intermediate cases can be covered. The general interface model is numerically implemented by constructing its weak form and by using the level-set method and XFEM. The resulting numerical procedure, whose accuracy and robustness are thoroughly tested and discussed with the help of a benchmark problem, is shown to be efficient for solving the problem of thermal conduction in particulate composites with various imperfect interfaces

    Potentiation of sensory responses in ventrobasal thalamus in vivo via selective modulation of mGlu1 receptors with a positive allosteric modulator.

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    Metabotropic glutamate subtype 1 (mGlu1) receptor is thought to play a role in synaptic responses in thalamic relay nuclei. The aim of this study was to evaluate the positive allosteric modulator (PAM) Ro67-4853 as a tool to modulate thalamic mGlu1 receptors on single thalamic neurones in vivo. Ro67-4853, applied by iontophoresis onto ventrobasal thalamus neurones of urethane-anaesthetised rats, selectively enhanced responses to the agonist (S)-3,5-dihydroxy-phenylglycine (DHPG), an effect consistent with mGlu1 potentiation. The PAM was also able to enhance maintained responses to 10 Hz trains of sensory stimulation of the vibrissae, but had little effect on responses to single sensory stimuli. Thus Ro67-4853 appears to be a highly selective tool that can be useful in investigating how mGlu1 receptor potentiation can alter neural processing in vivo. Our results show the importance of mGlu1 in sensory processing and attention mechanisms at the thalamic level and suggest that positive modulation of mGlu1 receptors might be a useful mechanism for enhancing cognitive and attentional processes

    Rare B Decays with a HyperCP Particle of Spin One

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    In light of recent experimental information from the CLEO, BaBar, KTeV, and Belle collaborations, we investigate some consequences of the possibility that a light spin-one particle is responsible for the three Sigma^+ -> p mu^+ mu^- events observed by the HyperCP experiment. In particular, allowing the new particle to have both vector and axial-vector couplings to ordinary fermions, we systematically study its contributions to various processes involving b-flavored mesons, including B-Bbar mixing as well as leptonic, inclusive, and exclusive B decays. Using the latest experimental data, we extract bounds on its couplings and subsequently estimate upper limits for the branching ratios of a number of B decays with the new particle. This can serve to guide experimental searches for the particle in order to help confirm or refute its existence.Comment: 17 pages, 3 figures; discussion on spin-0 case modified, few errors corrected, main conclusions unchange

    Essential requirement for JPT2 in NAADP-evoked Ca²⁺ signaling

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    Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that releases Ca2+ from acidic organelles through the activation of two-pore channels (TPCs) to regulate endolysosomal trafficking events. NAADP action is mediated by NAADP-binding protein(s) of unknown identity that confer NAADP sensitivity to TPCs. Here, we used a “clickable” NAADP-based photoprobe to isolate human NAADP-binding proteins and identified Jupiter microtubule-associated homolog 2 (JPT2) as a TPC accessory protein required for endogenous NAADP-evoked Ca2+ signaling. JPT2 was also required for the translocation of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus through the endolysosomal system. Thus, JPT2 is a component of the NAADP receptor complex that is essential for TPC-dependent Ca2+ signaling and control of coronaviral entry

    Tumor-Secreted LOXL2 Activates Fibroblasts through FAK Signaling

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    Cancer-associated fibroblasts enhance cancer progression when activated by tumor cells through mechanisms not yet fully understood. Blocking mammary tumor cell-derived lysyl oxidase-like 2 (LOXL2) significantly inhibited mammary tumor cell invasion and metastasis in transgenic and orthotopic mouse models. Here, we discovered that tumor-derived LOXL2 directly activated stromal fibroblasts in the tumor microenvironment. Genetic manipulation or antibody inhibition of LOXL2 in orthotopically grown mammary tumors reduced the expression of alpha-smooth muscle actin (alpha-SMA). Using a marker for reticular fibroblasts, it was determined that expression of alpha-SMA was localized to fibroblasts recruited from the host tissue. This marker also revealed that the matrix present in tumors with reduced levels of LOXL2 was more scattered compared with control tumors which exhibited matrices with dense, parallel alignments. Importantly, in vitro assays revealed that tumor-derived LOXL2 and a recombinant LOXL2 protein induced fibroblast branching on collagen matrices, as well as increased fibroblast-mediated collagen contraction and invasion of fibroblasts through extracellular matrix. Moreover, LOXL2 induced the expression of alpha-SMA in fibroblasts grown on collagen matrices. Mechanistically, it was determined that LOXL2 activated fibroblasts through integrin mediated focal adhesion kinase activation. These results indicate that inhibition of LOXL2 in tumors not only reduces tumor cell invasion but also attenuates the activation of host cells in the tumor microenvironment. (C) 2013 AACR

    Metal-based imaging agents: progress towards interrogating neurodegenerative disease.

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    Central nervous system (CNS) neurodegeneration is defined by a complex series of pathological processes that ultimately lead to death. The precise etiology of these disorders remains unknown. Recent efforts show that a mechanistic understanding of the malfunctions underpinning disease progression will prove requisite in developing new treatments and cures. Transition metals and lanthanide ions display unique characteristics (i.e., magnetism, radioactivity, and luminescence), often with biological relevance, allowing for direct application in CNS focused imaging modalities. These techniques include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and luminescent-based imaging (LumI). In this Tutorial Review, we have aimed to highlight the various metal-based imaging techniques developed in the effort to understand the pathophysiological processes associated with neurodegeneration. Each section has been divided so as to include an introduction to the particular imaging technique in question. This is then followed by a summary of key demonstrations that have enabled visualization of a specific neuropathological biomarker. These strategies have either exploited the high binding affinity of a receptor for its corresponding biomarker or a specific molecular transformation caused by a target species, all of which produce a concomitant change in diagnostic signal. Advantages and disadvantages of each method with perspectives on the utility of molecular imaging agents for understanding the complexities of neurodegenerative disease are discussed

    Gluino Decay as a Probe of High Scale Supersymmetry Breaking

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    A supersymmetric standard model with heavier scalar supersymmetric particles has many attractive features. If the scalar mass scale is O(10 - 10^4) TeV, the standard model like Higgs boson with mass around 125 GeV, which is strongly favored by the LHC experiment, can be realized. However, in this scenario the scalar particles are too heavy to be produced at the LHC. In addition, if the scalar mass is much less than O(10^4) TeV, the lifetime of the gluino is too short to be measured. Therefore, it is hard to probe the scalar particles at a collider. However, a detailed study of the gluino decay reveals that two body decay of the gluino carries important information on the scalar scale. In this paper, we propose a test of this scenario by measuring the decay pattern of the gluino at the LHC.Comment: 29 pages, 9 figures; version published in JHE

    Observation of eight-photon entanglement

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    Using ultra-bright sources of pure-state entangled photons from parametric down conversion, an eight-photon interferometer and post-selection detection, we demonstrate the ability to experimentally manipulate eight individual photons and report the creation of an eight-photon Schr\"odinger cat state with an observed fidelity of 0.708±0.0160.708 \pm 0.016.Comment: 6 pages, 4 figure

    Prognostic Factors in Arthroplasty in the Rheumatoid Shoulder

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    Total shoulder arthroplasty is commonly considered a good option for treatment of the rheumatoid shoulder. However, when the rotator cuff and glenoid bone stock are not preserved, the clinical outcome of arthroplasty in the rheumatoid patients remains unclear. Aim of the study is to explore the prognostic value of multiple preoperative and peroperative variables in total shoulder arthroplasty and shoulder hemiarthroplasty in rheumatoid patients. Clinical Hospital for Special Surgery Shoulder score was determined at different time points over a mean period of 6.5 years in 66 rheumatoid patients with total shoulder arthroplasty and 75 rheumatoid patients with shoulder hemiarthroplasty. Moreover, radiographic analysis was performed to assess the progression of humeral head migration and glenoid loosening. Advanced age and erosions or cysts at the AC joint at time of surgery were associated with a lower postoperative Clinical Hospital for Special Surgery Shoulder score. In total shoulder arthroplasty, status of the rotator cuff and its repair at surgery were predictive of postoperative improvement. Progression of proximal migration during the period after surgery was associated with a lower clinical score over time. However, in hemiarthroplasty, no relation was observed between the progression of proximal or medial migration during follow-up and the clinical score over time. Status of the AC joint and age at the time of surgery should be taken into account when considering shoulder arthroplasty in rheumatoid patients. Total shoulder arthroplasty in combination with good cuff repair yields comparable clinical results as total shoulder arthroplasty when the cuff is intact
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