949 research outputs found

    Temperature dependence of the hydrogen bond network in Trimethylamine N-oxide and guanidine hydrochloride - water solutions

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    We present an X-ray Compton scattering study on aqueous Trimethylamine N-oxide (TMAO) and guanidine hydrochloride solutions (GdnHCl) as a function of temperature. Independent from the concentration of the solvent, Compton profiles almost resemble results for liquid water as a function of temperature. However, The number of hydrogen bonds per water molecule extracted from the Compton profiles suggests a decrease of hydrogen bonds with rising temperatures for all studied samples, the differences between water and the solutions are weak. Nevertheless, the data indicate a reduced bond weakening with rising TMAO concentration up to 5M of 7.2% compared to 8 % for pure water. In contrast, the addition of GdnHCl appears to behave differently for concentrations up to 3.1 M with a weaker impact on the temperature response of the hydrogen bond structure

    Noisy frequency estimation with noisy probes

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    We consider frequency estimation in a noisy environment with noisy probes. This builds on previous studies, most of which assume that the initial probe state is pure, while the encoding process is noisy, or that the initial probe state is mixed, while the encoding process is noiseless. Our work is more representative of reality, where noise is unavoidable in both the initial state of the probe and the estimation process itself. We prepare the probe in a GHZ diagonal state, starting from n + 1 qubits in an arbitrary uncorrelated mixed state, and subject it to parameter encoding under dephasing noise. For this scheme, we derive a simple formula for the (quantum and classical) Fisher information, and show that quantum enhancements do not depend on the initial mixedness of the qubits. That is, we show that the so-called 'Zeno' scaling is attainable when the noise present in the encoding process is time inhomogeneous. This scaling does not depend on the mixedness of the initial probe state, and it is retained even for highly mixed states that can never be entangled. We then show that the sensitivity of the probe in our protocol is invariant under permutations of qubits, and monotonic in purity of the initial state of the probe. Finally, we discuss two limiting cases, where purity is either distributed evenly among the probes or concentrated in a single probe

    Distinct localization of SNAP47 protein in GABAergic and glutamatergic neurons in the mouse and the rat hippocampus

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    Synaptosomal-associated protein of 47 kDa (SNAP47) isoform is an atypical member of the SNAP family, which does not contribute directly to exocytosis and synaptic vesicle (SV) recycling. Initial characterization of SNAP47 revealed a widespread expression in nervous tissue, but little is known about its cellular and subcellular localization in hippocampal neurons. Therefore, in the present study we applied multiple-immunofluorescence labeling, immuno- electron microscopy and in situ hybridization (ISH) and analyzed the localization of SNAP47 in pre- and postsynaptic compartments of glutamatergic and GABAergic neurons in the mouse and rat hippocampus. While the immunofluorescence signal for SNAP47 showed a widespread distribution in both mouse and rat, the labeling pattern was complementary in the two species: in the mouse the immunolabeling was higher over the CA3 stratum radiatum, oriens and cell body layer. In contrast, in the rat the labeling was stronger over the CA1 neuropil and in the CA3 stratum lucidum. Furthermore, in the mouse high somatic labeling for SNAP47 was observed in GABAergic interneurons (INs). On the contrary, in the rat, while most INs were positive, they blended in with the high neuropil labeling. ISH confirmed the high expression of SNAP47 RNA in INs in the mouse. Co-staining for SNAP47 and pre- and postsynaptic markers in the rat revealed a strong co-localization postsynaptically with PSD95 in dendritic spines of pyramidal cells and, to a lesser extent, presynaptically, with ZnT3 and vesicular glutamate transporter 1 (VGLUT1) in glutamatergic terminals such as mossy fiber (MF) boutons. Ultrastructural analysis confirmed the pre- and postsynaptic localization at glutamatergic synapses. Furthermore, in the mouse hippocampus SNAP47 was found to be localized at low levels to dendritic shafts and axon terminals of putative INs forming symmetric synapses, indicating that this protein could be trafficked to both post- and presynaptic sites in both major cell types. These results reveal divergent localization of SNAP47 protein in mouse and rat hippocampus indicating species- and cell type-specific differences. SNAP47 is likely to be involved in unique fusion machinery which is distinct from the one involved in presynaptic neurotransmitter release. Nonetheless, our data suggest that SNAP47 may be involved not only postsynaptic, but also in presynaptic function

    Neuron-Derived Semaphorin 3A Is an Early Inducer of Vascular Permeability in Diabetic Retinopathy via Neuropilin-1

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    SummaryThe deterioration of the inner blood-retinal barrier and consequent macular edema is a cardinal manifestation of diabetic retinopathy (DR) and the clinical feature most closely associated with loss of sight. We provide evidence from both human and animal studies for the critical role of the classical neuronal guidance cue, semaphorin 3A, in instigating pathological vascular permeability in diabetic retinas via its cognate receptor neuropilin-1. We reveal that semaphorin 3A is induced in early hyperglycemic phases of diabetes within the neuronal retina and precipitates initial breakdown of endothelial barrier function. We demonstrate, by a series of orthogonal approaches, that neutralization of semaphorin 3A efficiently prevents diabetes-induced retinal vascular leakage in a stage of the disease when vascular endothelial growth factor neutralization is inefficient. These observations were corroborated in TgCre-Esr1/Nrp1flox/flox conditional knockout mice. Our findings identify a therapeutic target for macular edema and provide further evidence for neurovascular crosstalk in the pathogenesis of DR

    Comparing social perceptions of culturally emic protagonists using the Stereotype Content Model: A scale development and adaption process across four languages and eight countries

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    Cross-cultural comparisons are often based on a single itemset that is used in several cultures and languages being translated semantically correct. In contrast, a new, emic, approach measures the same construct with individually created items for each culture and language. To test this emic approach, the current paper used the stereotype content model (SCM) with its dimensions, warmth, and competence. It is used to compare perceptions of people, residing in different countries, speaking different languages. The current paper reports a study (N = 2,901) that tests whether an adapted scale allows reliable and structurally valid measurement and comparisons of culturally emic protagonists on SCM dimensions across four languages (English, German, Portuguese, Spanish) in eight countries (United States, United Kingdom, Germany, Switzerland, Portugal, Brazil, Spain, Argentina). The warmth dimension emerges as largely universal, but the competence dimension is a more culture-specific construct. Cross-cultural comparisons as to the competence dimension should be treated with care

    Mass and ionic composition of atmospheric fine particles over Belgium and their relation with gaseous air pollutants

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    Original article can be found at: http://www.rsc.org/publishing/journals/EM/Index.asp Copyright Royal Society of Chemistry. DOI: 10.1039/b805157gMass, major ionic components (MICs) of PM2.5, and related gaseous pollutants (SO2, NOx, NH3, HNO2, and HNO3) were monitored over six locations of different anthropogenic influence (industrial, urban, suburban, and rural) in Belgium. SO42-, NO3- NH4+, and Na+ were the primary ions of PM2.5 with averages diurnal concentrations ranging from 0.4-4.5, 0.3-7.6, 0.9-4.9, and 0.4-1.2 g/m3, respectively. MICs formed 39% of PM2.5 on an average, but it could reach up to 80-98 %. The SO2, NO, NO2, HNO2, and HNO3 levels showed high seasonal and site-specific fluctuations. The NH3 levels were similar over all the sites (2-6 g/m3), indicating its relation to the evenly distributed animal husbandry activities. The sulfur and nitrogen oxidation ratios for PM2.5 point towards a low-to-moderate formation of secondary sulfate and nitrate aerosols over five cities/towns, but their fairly intensive formation at the rural Wingene. Cluster analysis revealed the association of three groups of compounds in PM2.5; (i) NH4NO3, KNO3; (ii) Na2SO4; and (iii) MgCl2, CaCl2, MgF2, CaF2, corresponding to anthropogenic, sea-salt, and mixed (sea-salt + anthropogenic) aerosols, respectively. The neutralization and cation-to-anion ratios indicate that MICs of PM2.5 appeared mostly as (NH4)2SO4 and NH4NO3 salts. Sea-salt input was maximal during winter reaching up to 12 % of PM2.5. The overall average Cl-loss for sea-salt particles of PM2.5 at the six sites varied between 69 and 96 % with an average of 87 %. Principal component analysis revealed vehicular emission, coal/wood burning and animal farming as the dominating sources for the ionic components of PM2.5.Peer reviewe

    Tech Imaginations

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    Prof. Dr. Jens Schröter, Christoph Borbach, Max Kanderske und Prof. Dr. Benjamin Beil sind Herausgeber der Reihe. Die Herausgeber*innen der einzelnen Hefte sind renommierte Wissenschaftler*innen aus dem In- und Ausland.Technologies and especially media technologies are pervasive in modern societies. But even more omnipresent are the imaginaries of modern technologies – what technologies are thought to be capable of or what effects they are supposed to have. These imaginations reveal a lot of the political and ideological self-descriptions of societies, hence the (techno-)imaginary also functions as a kind of epistemic tool. Concepts of the imaginary therefore have experienced an increasing attention in cultural theory and the social sciences in recent years. In particular, work from political philosophy, but also approaches from science and technology studies (STS) or communication and media studies are worth mentioning here. The term "techno-imagination", coined by Vilém Flusser in the early 1990s, refers to the close interconnection of (digital) media and imaginations, whose coupling can not only be understood as a driver of future technology via fictional discourses (e.g. science fiction), but much more fundamentally also as a constitutive element of society and sociality itself, as Castoriadis has argued. In the first part of the issue several theoretical contributions add new aspects to the discussion of socio-technical imaginaries, while in the second part a workshop held in January 2022 at the CAIS in Bochum is documented, in which the case of the imaginaries of “Future Internets” was discussed

    Phase II Trial of Dabrafenib Plus Trametinib in Relapsed/Refractory BRAF V600-Mutant Pediatric High-Grade Glioma

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    PURPOSE: BRAF V600 mutation is detected in 5%-10% of pediatric high-grade gliomas (pHGGs), and effective treatments are limited. In previous trials, dabrafenib as monotherapy or in combination with trametinib demonstrated activity in children and adults with relapsed/refractory BRAF V600-mutant HGG. METHODS: This phase II study evaluated dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600-mutant pHGG. The primary objective was overall response rate (ORR) by independent review by Response Assessment in Neuro-Oncology criteria. Secondary objectives included ORR by investigator determination, duration of response (DOR), progression-free survival, overall survival (OS), and safety. RESULTS: A total of 41 pediatric patients with previously treated BRAF V600-mutant HGG were enrolled. At primary analysis, median follow-up was 25.1 months, and 51% of patients remained on treatment. Sixteen of 20 discontinuations were due to progressive disease in this relapsed/refractory pHGG population. Independently assessed ORR was 56% (95% CI, 40 to 72). Median DOR was 22.2 months (95% CI, 7.6 months to not reached [NR]). Fourteen deaths were reported. Median OS was 32.8 months (95% CI, 19.2 months to NR). The most common all-cause adverse events (AEs) were pyrexia (51%), headache (34%), and dry skin (32%). Two patients (5%) had AEs (both rash) leading to discontinuation. CONCLUSION: In relapsed/refractory BRAF V600-mutant pHGG, dabrafenib plus trametinib improved ORR versus previous trials of chemotherapy in molecularly unselected patients with pHGG and was associated with durable responses and encouraging survival. These findings suggest that dabrafenib plus trametinib is a promising targeted therapy option for children and adolescents with relapsed/refractory BRAF V600-mutant HGG
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