Bimetallic junctions

The formation of voids through interdiffusion in bimetallic welded structures exposed to high operating temperatures is inhibited by utilizing an alloy of the parent materials in the junction of the parent materials or by preannealing the junction at an ultrahigh temperature. These methods are also used to reduce the concentration gradient of a hardening agent

Brain-derived neurotrophic factor signaling in the HVC is required for testosterone-induced song of female canaries

Testosterone-induced singing in songbirds is thought to involve testosterone-dependent morphological changes that include angiogenesis and neuronal recruitment into the HVC, a central part of the song control circuit. Previous work showed that testosterone induces the production of vascular endothelial growth factor (VEGF) and its receptor (VEGFR2 tyrosine kinase), which in turn leads to an upregulation of brain-derived neurotrophic factor (BDNF) production in HVC endothelial cells. Here we report for the first time that systemic inhibition of the VEGFR2 tyrosine kinase is sufficient to block testosterone-induced song in adult female canaries, despite sustained androgen exposure and the persistence of the effects of testosterone on HVC morphology. Expression of exogenous BDNF in HVC, induced locally by in situ transfection, reversed the VEGFR2 inhibition-mediated blockade of song development, thereby restoring the behavioral phenotype associated with androgen-induced song. The VEGFR2-inhibited, BDNF-treated females developed elaborate malelike song that included large syllable repertoires and high syllable repetition rates, features known to attract females. Importantly, although functionally competent new neurons were recruited to HVC after testosterone treatment, the time course of neuronal addition appeared to follow BDNF-induced song development. These findings indicate that testosterone-associated VEGFR2 activity is required for androgen-induced song in adult songbirds and that the behavioral effects of VEGFR2 inhibition can be rescued by BDNF within the adult HVC. Copyright © 2009 Society for Neuroscience

Identification of Two Eosinophil Subsets in Induced Sputum from Patients with Allergic Asthma According to CD15 and CD66b Expression

Allergic asthma; Eosinophil subsets; Induced sputumAsma alérgica; Subconjuntos de eosinófilos; Esputo inducidoAsma al·lèrgica; Subconjunts d'eosinòfils; Esput induïtTwo subsets of eosinophils have been described: resident eosinophils with homeostatic functions (rEOS) in healthy subjects and in patients with nonallergic eosinophilic asthma, and inflammatory eosinophils (iEOS) in blood and lung samples from patients with allergic asthma. We explored if it would be possible to identify different subsets of eosinophils using flow cytometry and the gating strategy applied to induced sputum. We conducted an observational cross-sectional single-center study of 62 patients with persistent allergic asthma. Inflammatory cells from induced sputum samples were counted by light microscopy and flow cytometry, and cytokine levels in the supernatant were determined. Two subsets of eosinophils were defined that we call E1 (CD66b-high and CD15-high) and E2 (CD66b-low and CD15-low). Of the 62 patients, 24 were eosinophilic, 18 mixed, 10 paucigranulocytic, and 10 neutrophilic. E1 predominated over E2 in the eosinophilic and mixed patients (20.86% vs. 6.27% and 14.42% vs. 4.31%, respectively), while E1 and E2 were similar for neutrophilic and paucigranulocytic patients. E1 correlated with IL-5, fractional exhaled nitric oxide, and blood eosinophils. While eosinophil subsets have been identified for asthma in blood, we have shown that they can also be identified in induced sputum.This research was supported by the Spanish Allergy and Clinical Immunology Society (SEAIC) by means of a grant awarded in the call of 2017 (reference 17/06) and a BRN—Fundació Pla i Armengol grant in the call of 2018. The funds provided contributed to the acquisition of the material necessary to carry out the study, but the collaborating entities had no role in the analysis or interpretation of the results

A Metric Framework for quantifying Data Concentration

Poor performance of artificial neural nets when applied to credit-related classification problems is investigated and contrasted with logistic regression classification. We propose that artificial neural nets are less successful because of the inherent structure of credit data rather than any particular aspect of the neural net structure. Three metrics are developed to rationalise the result with such data. The metrics exploit the distributional properties of the data to rationalise neural net results. They are used in conjunction with a variant of an established concentration measure that differentiates between class characteristics. The results are contrasted with those obtained using random data, and are compared with results obtained using logistic regression. We find, in general agreement with previous studies, that logistic regressions out-perform neural nets in the majority of cases. An approximate decision criterion is developed in order to explain adverse results

Lumbar spine segmentation in MR images: a dataset and a public benchmark

This paper presents a large publicly available multi-center lumbar spine magnetic resonance imaging (MRI) dataset with reference segmentations of vertebrae, intervertebral discs (IVDs), and spinal canal. The dataset includes 447 sagittal T1 and T2 MRI series from 218 patients with a history of low back pain. It was collected from four different hospitals and was divided into a training (179 patients) and validation (39 patients) set. An iterative data annotation approach was used by training a segmentation algorithm on a small part of the dataset, enabling semi-automatic segmentation of the remaining images. The algorithm provided an initial segmentation, which was subsequently reviewed, manually corrected, and added to the training data. We provide reference performance values for this baseline algorithm and nnU-Net, which performed comparably. We set up a continuous segmentation challenge to allow for a fair comparison of different segmentation algorithms. This study may encourage wider collaboration in the field of spine segmentation, and improve the diagnostic value of lumbar spine MRI

Cytotoxic CD8+ T cell-neuron interactions: perforin-dependent electrical silencing precedes but is not causally linked to neuronal cell death

Cytotoxic CD8(+) T cells are considered important effector cells contributing to neuronal damage in inflammatory and degenerative CNS disorders. Using time-lapse video microscopy and two-photon imaging in combination with whole-cell patch-clamp recordings, we here show that major histocompatibility class I (MHC I)-restricted neuronal antigen presentation and T cell receptor specificity determine CD8(+) T-cell locomotion and neuronal damage in culture and hippocampal brain slices. Two separate functional consequences result from a direct cell-cell contact between antigen-presenting neurons and antigen-specific CD8(+) T cells. (1) An immediate impairment of electrical signaling in single neurons and neuronal networks occurs as a result of massive shunting of the membrane capacitance after insertion of channel-forming perforin (and probably activation of other transmembrane conductances), which is paralleled by an increase of intracellular Ca(2+) levels (within <10 min). (2) Antigen-dependent neuronal apoptosis may occur independently of perforin and members of the granzyme B cluster (within approximately 1 h), suggesting that extracellular effects can substitute for intracellular delivery of granzymes by perforin. Thus, electrical silencing is an immediate consequence of MHC I-restricted interaction of CD8(+) T cells with neurons. This mechanism is clearly perforin-dependent and precedes, but is not causally linked, to neuronal cell death

Theory and Applications of X-ray Standing Waves in Real Crystals

Theoretical aspects of x-ray standing wave method for investigation of the real structure of crystals are considered in this review paper. Starting from the general approach of the secondary radiation yield from deformed crystals this theory is applied to different concreat cases. Various models of deformed crystals like: bicrystal model, multilayer model, crystals with extended deformation field are considered in detailes. Peculiarities of x-ray standing wave behavior in different scattering geometries (Bragg, Laue) are analysed in detailes. New possibilities to solve the phase problem with x-ray standing wave method are discussed in the review. General theoretical approaches are illustrated with a big number of experimental results.Comment: 101 pages, 43 figures, 3 table

Identification of a Novel Signaling Pathway and Its Relevance for GluA1 Recycling

We previously showed that the serum- and glucocorticoid-inducible kinase 3 (SGK3) increases the AMPA-type glutamate receptor GluA1 protein in the plasma membrane. The activation of AMPA receptors by NMDA-type glutamate receptors eventually leads to postsynaptic neuronal plasticity. Here, we show that SGK3 mRNA is upregulated in the hippocampus of new-born wild type Wistar rats after NMDA receptor activation. We further demonstrate in the Xenopus oocyte expression system that delivery of GluA1 protein to the plasma membrane depends on the small GTPase RAB11. This RAB-dependent GluA1 trafficking requires phosphorylation and activation of phosphoinositol-3-phosphate-5-kinase (PIKfyve) and the generation of PI(3,5)P2. In line with this mechanism we could show PIKfyve mRNA expression in the hippocampus of wild type C57/BL6 mice and phosphorylation of PIKfyve by SGK3. Incubation of hippocampal slices with the PIKfyve inhibitor YM201636 revealed reduced CA1 basal synaptic activity. Furthermore, treatment of primary hippocampal neurons with YM201636 altered the GluA1 expression pattern towards reduced synaptic expression of GluA1. Our findings demonstrate for the first time an involvement of PIKfyve and PI(3,5)P2 in NMDA receptor-triggered synaptic GluA1 trafficking. This new regulatory pathway of GluA1 may contribute to synaptic plasticity and memory

The mechanism of functional up-regulation of P2X3 receptors of trigeminal sensory neurons in a genetic mouse model of Familial Hemiplegic Migraine type 1 (FHM-1)

A knock-in (KI) mouse model of FHM-1 expressing the R192Q missense mutation of the Cacna1a gene coding for the \u3b11 subunit of CaV2.1 channels shows, at the level of the trigeminal ganglion, selective functional up-regulation of ATP -gated P2X3 receptors of sensory neurons that convey nociceptive signals to the brainstem. Why P2X3 receptors are constitutively more responsive, however, remains unclear as their membrane expression and TRPV1 nociceptor activity are the same as in wildtype (WT) neurons. Using primary cultures of WT or KI trigeminal ganglia, we investigated whether soluble compounds that may contribute to initiating (or maintaining) migraine attacks, such as TNF\u3b1, CGRP, and BDNF, might be responsible for increasing P2X3 receptor responses. Exogenous application of TNF\u3b1 potentiated P2X3 receptor-mediated currents of WT but not of KI neurons, most of which expressed both the P2X3 receptor and the TNF\u3b1 receptor TNFR2. However, sustained TNF\u3b1 neutralization failed to change WT or KI P2X3 receptor currents. This suggests that endogenous TNF\u3b1 does not regulate P2X3 receptor responses. Nonetheless, on cultures made from both genotypes, exogenous TNF\u3b1 enhanced TRPV1 receptor-mediated currents expressed by a few neurons, suggesting transient amplification of TRPV1 nociceptor responses. CGRP increased P2X3 receptor currents only in WT cultures, although prolonged CGRP receptor antagonism or BDNF neutralization reduced KI currents to WT levels. Our data suggest that, in KI trigeminal ganglion cultures, constitutive up-regulation of P2X3 receptors probably is already maximal and is apparently contributed by basal CGRP and BDNF levels, thereby rendering these neurons more responsive to extracellular ATP. \ua9 2013 Hullugundi et al

Imola: A decentralised learning-driven protocol for multi-hop White-Fi

In this paper we tackle the digital exclusion problem in developing and remote locations by proposing Imola, an inexpensive learning-driven access mechanism for multi-hop wireless networks that operate across TV white-spaces (TVWS). Stations running Imola only rely on passively acquired neighbourhood information to achieve scheduled-like operation in a decentralised way, without explicit synchronisation. Our design overcomes pathological circumstances such as hidden and exposed terminals that arise due to carrier sensing and are exceptionally problematic in low frequency bands. We present a prototype implementation of our proposal and conduct experiments in a real test bed, which confirms the practical feasibility of deploying our solution in mesh networks that build upon the IEEE 802.11af standard. Finally, the extensive system level simulations we perform demonstrate that Imola achieves up to 4x\u97 more throughput than the channel access protocol defined by the standard and reduces frame loss rate by up to 100%