517 research outputs found

    Noem vaccin-critici geen wappies, dat werkt averechts

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    The politics and administration of institutional chang

    EXAFS Structural Determination of the Pt2(P2O5H2)44– Anion in Solution

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    We present the first structural determination of the Pt2(P2O5H2)44– anion in solution by analyzing the extended X-ray absorption fine structure (EXAFS) spectrum of the Pt LIII edge. The data could be fit with a simple model involving single and multiple scattering paths to near and far P-atoms, bridging O-atoms, and the other Pt-atom in the binuclear complex. A Pt–Pt distance of 2.876(28) Å and a Pt–P bond length of 2.32(4) Å are obtained. These values are in line with distances found in previous X-ray diffraction studies. The assignment of the EXAFS spectrum of the Pt2(P2O5H2)44– anion in its ground state is required for future time-resolved X-ray absorption measurements with the goal of determining the structure and dynamics of the complex in the 1,3A2u excited states

    Retrieving photochemically active structures by time-resolved EXAFS spectroscopy

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    Describing the nature and structure of molecular excited states is important in order to understand their chemical reactivity and role as intermediates in photochemical reactions. The recent implementation of x-ray absorption spectroscopy in the ultrafast time domain allows studying the electronic and structural dynamics of photochemically active molecules in solutions. In this work we present the structural determination of a photoexcited diplatinum molecule, [Pt-2(P2O5H2)(4)](4-), which plays a photocatalytic role in important chemical conversions. A novel analysis of time-resolved EXAFS spectra based on the fitting of the experimental transients obtained from optical pump/x-ray probe experiments has been performed to derive a contraction of 0.31(5) angstrom of the two Pt atoms and a ligand expansion of 0.010(6) angstrom. The former is assigned to the formation of a transient Pt-Pt bond in the excited state, while the latter indicates a concomitant weakening of the Pt-ligand coordination bonds

    Maternal Environment Influences Cocaine Intake in Adulthood in a Genotype-Dependent Manner

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    Background: Accumulating epidemiological evidence points to the role of genetic background as a modulator of the capacity of adverse early experiences to give rise to mental illness. However, direct evidence of such gene-environment interaction in the context of substance abuse is scarce. In the present study we investigated whether the impact of early life experiences on cocaine intake in adulthood depends on genetic background. In addition, we studied other behavioral dimensions associated with drug abuse, i.e. anxiety- and depression-related behaviors. Methodology/Principal Findings: For this purpose, we manipulated the maternal environment of two inbred mouse strains, the C57BL/6J and DBA/2J by fostering them with non-related mothers, i.e. the C3H/HeN and AKR strains. These mother strains show respectively high and low pup-oriented behavior. As adults, C57BL/6J and DBA/2J were tested either for cocaine intravenous self-administration or in the elevated plus-maze and forced swim test (FST). We found that the impact of maternal environment on cocaine use and a depression-related behavior depends upon genotype, as cocaine self-administration and behavior in the FST were influenced by maternal environment in DBA/2J, but not in C57BL/6J mice. Anxiety was not influenced by maternal environment in either strain. Conclusions/Significance: Our experimental approach could contribute to the identification of the psychobiological factor

    Endosonography With or Without Confirmatory Mediastinoscopy for Resectable Lung Cancer:A Randomized Clinical Trial

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    PURPOSE:Resectable non-small-cell lung cancer (NSCLC) with a high probability of mediastinal nodal involvement requires mediastinal staging by endosonography and, in the absence of nodal metastases, confirmatory mediastinoscopy according to current guidelines. However, randomized data regarding immediate lung tumor resection after systematic endosonography versus additional confirmatory mediastinoscopy before resection are lacking.METHODS:Patients with (suspected) resectable NSCLC and an indication for mediastinal staging after negative systematic endosonography were randomly assigned to immediate lung tumor resection or confirmatory mediastinoscopy followed by tumor resection. The primary outcome in this noninferiority trial (noninferiority margin of 8% that previously showed to not compromise survival, Pnoninferior &lt;.0250) was the presence of unforeseen N2 disease after tumor resection with lymph node dissection. Secondary outcomes were 30-day major morbidity and mortality.RESULTS:Between July 17, 2017, and October 5, 2020, 360 patients were randomly assigned, 178 to immediate lung tumor resection (seven dropouts) and 182 to confirmatory mediastinoscopy first (seven dropouts before and six after mediastinoscopy). Mediastinoscopy detected metastases in 8.0% (14/175; 95% CI, 4.8 to 13.0) of patients. Unforeseen N2 rate after immediate resection (8.8%) was noninferior compared with mediastinoscopy first (7.7%) in both intention-to-treat (Δ, 1.03%; UL 95% CIΔ, 7.2%; Pnoninferior =.0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; Pnoninferior =.0157). Major morbidity and 30-day mortality was 12.9% after immediate resection versus 15.4% after mediastinoscopy first (P =.4940).CONCLUSION:On the basis of our chosen noninferiority margin in the rate of unforeseen N2, confirmatory mediastinoscopy after negative systematic endosonography can be omitted in patients with resectable NSCLC and an indication for mediastinal staging.</p

    A New Arthritis Therapy with Oxidative Burst Inducers

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    BACKGROUND: Despite recent successes with biological agents as therapy for autoimmune inflammatory diseases such as rheumatoid arthritis (RA), many patients fail to respond adequately to these treatments, making a continued search for new therapies extremely important. Recently, the prevailing hypothesis that reactive oxygen species (ROS) promote inflammation was challenged when polymorphisms in Ncf1, that decrease oxidative burst, were shown to increase disease severity in mouse and rat arthritis models. Based on these findings we developed a new therapy for arthritis using oxidative burst-inducing substances. METHODS AND FINDINGS: Treatment of rats with phytol (3,7,11,15-tetramethyl-2-hexadecene-1-ol) increased oxidative burst in vivo and thereby corrected the effect of the genetic polymorphism in arthritis-prone Ncf1 (DA) rats. Importantly, phytol treatment also decreased the autoimmune response and ameliorated both the acute and chronic phases of arthritis. When compared to standard therapies for RA, anti-tumour necrosis factor-α and methotrexate, phytol showed equally good or better therapeutic properties. Finally, phytol mediated its effect within hours of administration and involved modulation of T cell activation, as injection prevented adoptive transfer of disease with arthritogenic T cells. CONCLUSIONS: Treatment of arthritis with ROS-promoting substances such as phytol targets a newly discovered pathway leading to autoimmune inflammatory disease and introduces a novel class of therapeutics for treatment of RA and possibly other chronic inflammatory diseases

    The influence of the accessory genome on bacterial pathogen evolution

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    Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution

    Semiclassical Mechanics of the Wigner 6j-Symbol

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    The semiclassical mechanics of the Wigner 6j-symbol is examined from the standpoint of WKB theory for multidimensional, integrable systems, to explore the geometrical issues surrounding the Ponzano-Regge formula. The relations among the methods of Roberts and others for deriving the Ponzano-Regge formula are discussed, and a new approach, based on the recoupling of four angular momenta, is presented. A generalization of the Yutsis-type of spin network is developed for this purpose. Special attention is devoted to symplectic reduction, the reduced phase space of the 6j-symbol (the 2-sphere of Kapovich and Millson), and the reduction of Poisson bracket expressions for semiclassical amplitudes. General principles for the semiclassical study of arbitrary spin networks are laid down; some of these were used in our recent derivation of the asymptotic formula for the Wigner 9j-symbol.Comment: 64 pages, 50 figure
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