1,514 research outputs found

    Nanoelectromechanical Resonator Arrays for Ultrafast, Gas-Phase Chromatographic Chemical Analysis

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    Miniaturized gas chromatography (GC) systems can provide fast, quantitative analysis of chemical vapors in an ultrasmall package. We describe a chemical sensor technology based on resonant nanoelectromechanical systems (NEMS) mass detectors that provides the speed, sensitivity, specificity, and size required by the microscale GC paradigm. Such NEMS sensors have demonstrated detection of subparts per billion (ppb) concentrations of a phosphonate analyte. By combining two channels of NEMS detection with an ultrafast GC front-end, chromatographic analysis of 13 chemicals was performed within a 5 s time window

    Magnetic structure of Yb2Pt2Pb: Ising moments on the Shastry-Sutherland lattice.

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    Neutron diffraction measurements were carried out on single crystals and powders of Yb2Pt2Pb, where Yb moments form two interpenetrating planar sublattices of orthogonal dimers, a geometry known as Shastry-Sutherland lattice, and are stacked along the c axis in a ladder geometry. Yb2Pt2Pb orders antiferromagnetically at TN=2.07K, and the magnetic structure determined from these measurements features the interleaving of two orthogonal sublattices into a 5×5×1 magnetic supercell that is based on stripes with moments perpendicular to the dimer bonds, which are along (110) and (−110). Magnetic fields applied along (110) or (−110) suppress the antiferromagnetic peaks from an individual sublattice, but leave the orthogonal sublattice unaffected, evidence for the Ising character of the Yb moments in Yb2Pt2Pb that is supported by point charge calculations. Specific heat, magnetic susceptibility, and electrical resistivity measurements concur with neutron elastic scattering results that the longitudinal critical fluctuations are gapped with ΔE≃0.07meV

    A New Model for the Spiral Structure of the Galaxy. Superposition of 2+4-armed patterns

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    We investigate the possibility of describing the spiral pattern of the Milky Way in terms of a model of superposition 2- and 4-armed wave harmonics (the simplest description, besides pure modes). Two complementary methods are used: a study of stellar kinematics, and direct tracing of positions of spiral arms. In the first method, the parameters of the galactic rotation curve and the free parameters of the spiral density waves were obtained from Cepheid kinematics, under different assumptions. To turn visible the structure corresponding to these models, we computed the evolution of an ensemble of N-particles, simulating the ISM clouds, in the perturbed galactic gravitational field. In the second method, we present a new analysis of the longitude-velocity (l-v) diagram of the sample of galactic HII regions, converting positions of spiral arms in the galactic plane into locii of these arms in the l-v diagram. Both methods indicate that the ``self-sustained'' model, in which the 2-armed and 4-armed mode have different pitch angles (6 arcdeg and 12 arcdeg, respectively) is a good description of the disk structure. An important conclusion is that the Sun happens to be practically at the corotation circle. As an additional result of our study, we propose an independent test for localization of the corotation circle in a spiral galaxy: a gap in the radial distribution of interstellar gas has to be observed in the corotation region.Comment: 17 pages, 9 figures, Latex, uses aas2pp4.st

    Human Physiological Responses to Cycle Ergometer Leg Exercise During +Gz Acceleration

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    Spaceflight and bed-rest deconditioning decrease maximal oxygen uptake (aerobic power), strength, endurance capacity, and orthostatic tolerance. In addition to extensive use of muscular exercise conditioning as a countermeasure for the reduction in aerobic power (VO(sub 2max)), stimuli from some form of +Gz acceleration conditioning may be necessary to attenuate the orthostatic intolerance component of this deconditioning. Hypothesis: There will be no significant difference in the physiological responses (oxygen uptake, heart rate, ventilation, or respiratory exchange ratio) during supine exercise with moderate +Gz acceleration

    Free Energy Simulations of a GTPase: GTP and GDP Binding to Archaeal Initiation Factor 2

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    International audienceArchaeal initiation factor 2 (aIF2) is a protein involved in the initiation of protein biosynthesis. In its GTP-bound, "ON" conformation, aIF2 binds an initiator tRNA and carries it to the ribosome. In its GDP-bound, "OFF" conformation, it dissociates from tRNA. To understand the specific binding of GTP and GDP and its dependence on the ON or OFF conformational state of aIF2, molecular dynamics free energy simulations (MDFE) are a tool of choice. However, the validity of the computed free energies depends on the simulation model, including the force field and the boundary conditions, and on the extent of conformational sampling in the simulations. aIF2 and other GTPases present specific difficulties; in particular, the nucleotide ligand coordinates a divalent Mg(2+) ion, which can polarize the electronic distribution of its environment. Thus, a force field with an explicit treatment of electronic polarizability could be necessary, rather than a simpler, fixed charge force field. Here, we begin by comparing a fixed charge force field to quantum chemical calculations and experiment for Mg(2+):phosphate binding in solution, with the force field giving large errors. Next, we consider GTP and GDP bound to aIF2 and we compare two fixed charge force fields to the recent, polarizable, AMOEBA force field, extended here in a simple, approximate manner to include GTP. We focus on a quantity that approximates the free energy to change GTP into GDP. Despite the errors seen for Mg(2+):phosphate binding in solution, we observe a substantial cancellation of errors when we compare the free energy change in the protein to that in solution, or when we compare the protein ON and OFF states. Finally, we have used the fixed charge force field to perform MDFE simulations and alchemically transform GTP into GDP in the protein and in solution. With a total of about 200 ns of molecular dynamics, we obtain good convergence and a reasonable statistical uncertainty, comparable to the force field uncertainty, and somewhat lower than the predicted GTP/GDP binding free energy differences. The sign and magnitudes of the differences can thus be interpreted at a semiquantitative level, and are found to be consistent with the experimental binding preferences of ON- and OFF-aIF2

    Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group.

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    Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs\u27 therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs are mild to moderate in severity; however, serious and occasionally life-threatening irAEs are reported in the literature, and treatment-related deaths occur in up to 2% of patients, varying by ICI. Immunotherapy-related irAEs typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies. There is an urgent need for multidisciplinary guidance reflecting broad-based perspectives on how to recognize, report and manage organ-specific toxicities until evidence-based data are available to inform clinical decision-making. The Society for Immunotherapy of Cancer (SITC) established a multidisciplinary Toxicity Management Working Group, which met for a full-day workshop to develop recommendations to standardize management of irAEs. Here we present their consensus recommendations on managing toxicities associated with immune checkpoint inhibitor therapy
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