833 research outputs found

    Influence of a magnetic field on the viscosity of a dilute gas consisting of linear molecules.

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    The viscomagnetic effect for two linear molecules, N2 and CO2, has been calculated in the dilute-gas limit directly from the most accurate ab initio intermolecular potential energy surfaces presently available. The calculations were performed by means of the classical trajectory method in the temperature range from 70 K to 3000 K for N2 and 100 K to 2000 K for CO2, and agreement with the available experimental data is exceptionally good. Above room temperature, where no experimental data are available, the calculations provide the first quantitative information on the magnitude and the behavior of the viscomagnetic effect for these gases. In the presence of a magnetic field, the viscosities of nitrogen and carbon dioxide decrease by at most 0.3% and 0.7%, respectively. The results demonstrate that the viscomagnetic effect is dominated by the contribution of the jj¯ polarization at all temperatures, which shows that the alignment of the rotational axes of the molecules in the presence of a magnetic field is primarily responsible for the viscomagnetic effect

    Dostarlimab for primary advanced or recurrent endometrial cancer

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    BACKGROUND: Dostarlimab is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor. The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer. METHODS: We conducted a phase 3, global, double-blind, randomized, placebo-controlled trial. Eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer were randomly assigned in a 1:1 ratio to receive either dostarlimab (500 mg) or placebo, plus carboplatin (area under the concentration-time curve, 5 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area), every 3 weeks (six cycles), followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. The primary end points were progression-free survival as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, and overall survival. Safety was also assessed. RESULTS: Of the 494 patients who underwent randomization, 118 (23.9%) had mismatch repair-deficient (dMMR), microsatellite instability-high (MSI-H) tumors. In the dMMR-MSI-H population, estimated progression-free survival at 24 months was 61.4% (95% confidence interval [CI], 46.3 to 73.4) in the dostarlimab group and 15.7% (95% CI, 7.2 to 27.0) in the placebo group (hazard ratio for progression or death, 0.28; 95% CI, 0.16 to 0.50; P\u3c0.001). In the overall population, progression-free survival at 24 months was 36.1% (95% CI, 29.3 to 42.9) in the dostarlimab group and 18.1% (95% CI, 13.0 to 23.9) in the placebo group (hazard ratio, 0.64; 95% CI, 0.51 to 0.80; P\u3c0.001). Overall survival at 24 months was 71.3% (95% CI, 64.5 to 77.1) with dostarlimab and 56.0% (95% CI, 48.9 to 62.5) with placebo (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.87). The most common adverse events that occurred or worsened during treatment were nausea (53.9% of the patients in the dostarlimab group and 45.9% of those in the placebo group), alopecia (53.5% and 50.0%), and fatigue (51.9% and 54.5%). Severe and serious adverse events were more frequent in the dostarlimab group than in the placebo group. CONCLUSIONS: Dostarlimab plus carboplatin-paclitaxel significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer, with a substantial benefit in the dMMR-MSI-H population. (Funded by GSK; RUBY ClinicalTrials.gov number, NCT03981796.)

    Facile crystallization of Escherichia coli ketol-acid reductoisomerase

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    Ketol-acid reductoisomerase (EC 1.1.1.86) catalyses the second reaction in the biosynthesis of branched-chain amino acids. The reaction involves an Mg2+-dependent alkyl migration followed by an NADPH-dependent reduction of the 2-keto group. Here, the crystallization of the Escherichia coli enzyme is reported. A form with a C-terminal hexahistidine tag could be crystallized under 18 different conditions in the absence of NADPH or Mg2+ and a further six crystallization conditions were identified with one or both ligands. With the hexahistidine tag on the N-terminus, 20 crystallization conditions were found, some of which required the presence of NADPH, NADP(+), Mg2+ or a combination of ligands. Finally, the selenomethionine-substituted enzyme with the N-terminal tag crystallized under 15 conditions. Thus, the enzyme is remarkably easy to crystallize. Most of the crystals diffract poorly but several data sets were collected at better than 3.2 Angstrom resolution; attempts to phase them are currently in progress

    Structural Origins of Chiral Second-Order Optical Nonlinearity in Collagen: Amide I Band

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    AbstractThe molecular basis of nonlinear optical (NLO) chiral effects in the amide I region of type I collagen was investigated using sum-frequency generation vibrational spectroscopy; chiral and achiral tensor elements were separated using different input/output beam polarization conditions. Spectra were obtained from native rat tail tendon (RTT) collagen and from cholesteric liquid crystal-like (LC) type I collagen films. Although RTT and LC collagen both possess long-range order, LC collagen lacks the complex hierarchical organization of RTT collagen. Their spectra were compared to assess the role of such organization in NLO chirality. No significant differences were observed between RTT and LC with respect to chiral or achiral spectra. These findings suggest that amide I NLO chiral effects in type I collagen assemblies arise predominantly from the chiral organization of amide chromophores within individual collagen molecules, rather than from supramolecular structures. The study suggests that sum-frequency generation vibrational spectroscopy may be uniquely valuable in exploring fundamental aspects of chiral nonlinearity in complex macromolecular structures

    Low temperature structural phase transition and incommensurate lattice modulation in the spin gap compound BaCuSi2O6

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    Results of high resolution x-ray diffraction experiments are presented for single crystals of the spin gap compound BaCuSi2_2O6_6 in the temperature range from 16 to 300 K. The data show clear evidence of a transition from the room temperature tetragonal phase into an incommensurately modulated orthorhombic structure below ∼\sim100 K. This lattice modulation is characterized by a resolution limited wave vector {\bf q}IC_{IC}=(0,∼\sim0.13,0) and its 2nd^{nd} and 3rd^{rd} harmonics. The phase transition is first order and exhibits considerable hysteresis. This observation implies that the spin Hamiltonian representing the system is more complex than originally thought.Comment: 4 pages, 4 figure

    Bisecting the mental number line in near and far space

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    Much evidence suggests that common posterior parietal mechanisms underlie the orientation of attention in physical space and along the mental number line. For example, the small leftward bias (pseudoneglect) found in paper-and-pencil line bisection is also found when participants "bisect" number pairs, estimating (without calculating) the number midway between two others. For bisection of physical lines, pseudoneglect has been found to shift rightward as lines are moved from near space (immediately surrounding the body) to far space. We investigated whether the presentation of stimuli in near or far space also modulated spatial attention for the mental number line. Participants bisected physical lines or number pairs presented at four distances (60, 120, 180, 240 cm). Clear rightward shifts in bias were observed for both tasks. Furthermore, the rate at which this shift occurred in the two tasks, as measured by least squares regression slopes, was significantly correlated across participants, suggesting that the transition from near to far distances induced a common modulation of lateral attention in physical and numerical space. These results demonstrate a tight coupling between number and physical space, and show that even such prototypically abstract concepts as number are modulated by our on-line interactions with the world
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