36 research outputs found

    Test and Analysis of a Buckling-Critical Large-Scale Sandwich Composite Cylinder

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    Structural stability is an important design consideration for launch-vehicle shell structures and it is well known that the buckling response of such shell structures can be very sensitive to small geometric imperfections. As part of an effort to develop new buckling design guidelines for sandwich composite cylindrical shells, an 8-ft-diameter honeycomb-core sandwich composite cylinder was tested under pure axial compression to failure. The results from this test are compared with finite-element-analysis predictions and overall agreement was very good. In particular, the predicted buckling load was within 1% of the test and the character of the response matched well. However, it was found that the agreement could be improved by including composite material nonlinearity in the analysis, and that the predicted buckling initiation site was sensitive to the addition of small bending loads to the primary axial load in analyses

    Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

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    Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

    Abnormal resting-state cortical coupling in chronic tinnitus

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    <p>Abstract</p> <p>Background</p> <p>Subjective tinnitus is characterized by an auditory phantom perception in the absence of any physical sound source. Consequently, in a quiet environment, tinnitus patients differ from control participants because they constantly perceive a sound whereas controls do not. We hypothesized that this difference is expressed by differential activation of distributed cortical networks.</p> <p>Results</p> <p>The analysis was based on a sample of 41 participants: 21 patients with chronic tinnitus and 20 healthy control participants. To investigate the architecture of these networks, we used phase locking analysis in the 1–90 Hz frequency range of a minute of resting-state MEG recording. We found: 1) For tinnitus patients: A significant decrease of inter-areal coupling in the alpha (9–12 Hz) band and an increase of inter-areal coupling in the 48–54 Hz gamma frequency range relative to the control group. 2) For both groups: an inverse relationship (r = -.71) of the alpha and gamma network coupling. 3) A discrimination of 83% between the patient and the control group based on the alpha and gamma networks. 4) An effect of manifestation on the distribution of the gamma network: In patients with a tinnitus history of less than 4 years, the left temporal cortex was predominant in the gamma network whereas in patients with tinnitus duration of more than 4 years, the gamma network was more widely distributed including more frontal and parietal regions.</p> <p>Conclusion</p> <p>In the here presented data set we found strong support for an alteration of long-range coupling in tinnitus. Long-range coupling in the alpha frequency band was decreased for tinnitus patients while long-range gamma coupling was increased. These changes discriminate well between tinnitus and control participants. We propose a tinnitus model that integrates this finding in the current knowledge about tinnitus. Furthermore we discuss the impact of this finding to tinnitus therapies using Transcranial Magnetic Stimulation (TMS).</p

    Optimizing Preprocessing and Analysis Pipelines for Single-Subject fMRI: 2. Interactions with ICA, PCA, Task Contrast and Inter-Subject Heterogeneity

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    A variety of preprocessing techniques are available to correct subject-dependant artifacts in fMRI, caused by head motion and physiological noise. Although it has been established that the chosen preprocessing steps (or “pipeline”) may significantly affect fMRI results, it is not well understood how preprocessing choices interact with other parts of the fMRI experimental design. In this study, we examine how two experimental factors interact with preprocessing: between-subject heterogeneity, and strength of task contrast. Two levels of cognitive contrast were examined in an fMRI adaptation of the Trail-Making Test, with data from young, healthy adults. The importance of standard preprocessing with motion correction, physiological noise correction, motion parameter regression and temporal detrending were examined for the two task contrasts. We also tested subspace estimation using Principal Component Analysis (PCA), and Independent Component Analysis (ICA). Results were obtained for Penalized Discriminant Analysis, and model performance quantified with reproducibility (R) and prediction metrics (P). Simulation methods were also used to test for potential biases from individual-subject optimization. Our results demonstrate that (1) individual pipeline optimization is not significantly more biased than fixed preprocessing. In addition, (2) when applying a fixed pipeline across all subjects, the task contrast significantly affects pipeline performance; in particular, the effects of PCA and ICA models vary with contrast, and are not by themselves optimal preprocessing steps. Also, (3) selecting the optimal pipeline for each subject improves within-subject (P,R) and between-subject overlap, with the weaker cognitive contrast being more sensitive to pipeline optimization. These results demonstrate that sensitivity of fMRI results is influenced not only by preprocessing choices, but also by interactions with other experimental design factors. This paper outlines a quantitative procedure to denoise data that would otherwise be discarded due to artifact; this is particularly relevant for weak signal contrasts in single-subject, small-sample and clinical datasets

    Age-related changes in neural functional connectivity and its behavioral relevance

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    <p>Abstract</p> <p>Background</p> <p>Resting-state recordings are characterized by widely distributed networks of coherent brain activations. Disturbances of the default network - a set of regions that are deactivated by cognitive tasks and activated during passive states - have been detected in age-related disorders such as Alzheimer's or Parkinson's disease but alterations in the course of healthy aging still need to be explored.</p> <p>Results</p> <p>Using magnetoencephalography (MEG), the present study investigated how age-related functional resting-state brain connectivity links to cognitive performance in healthy aging in fifty-three participants ranging in age from 18 to 89 years. A beamforming technique was used to reconstruct the brain activity in source space and the interregional coupling was investigated using partial directed coherence (PDC). We found significant age-related alterations of functional resting-state connectivity. These are mainly characterized by reduced information input into the posterior cingulum/precuneus region together with an enhanced information flow to the medial temporal lobe. Furthermore, higher inflow in the medial temporal lobe subsystem was associated with weaker cognitive performance whereas stronger inflow in the posterior cluster was related to better cognitive performance.</p> <p>Conclusion</p> <p>This is the first study to show age-related alterations in subsystems of the resting state network that are furthermore associated with cognitive performance.</p

    Segregation of lexical and sub-lexical reading processes in the left perisylvian cortex.

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    International audienceA fundamental issue in cognitive neuroscience is the existence of two major, sub-lexical and lexical, reading processes and their possible segregation in the left posterior perisylvian cortex. Using cortical electrostimulation mapping, we identified the cortical areas involved on reading either orthographically irregular words (lexical, "direct" process) or pronounceable pseudowords (sublexical, "indirect" process) in 14 right-handed neurosurgical patients while video-recording behavioral effects. Intraoperative neuronavigation system and Montreal Neurological Institute (MNI) stereotactic coordinates were used to identify the localization of stimulation sites. Fifty-one reading interference areas were found that affected either words (14 areas), or pseudo-words (11 areas), or both (26 areas). Forty-one (80%) corresponded to the impairment of the phonological level of reading processes. Reading processes involved discrete, highly localized perisylvian cortical areas with individual variability. MNI coordinates throughout the group exhibited a clear segregation according to the tested reading route; specific pseudo-word reading interferences were concentrated in a restricted inferior and anterior subpart of the left supramarginal gyrus (barycentre x = -68.1; y = -25.9; z = 30.2; Brodmann's area 40) while specific word reading areas were located almost exclusively alongside the left superior temporal gyrus. Although half of the reading interferences found were nonspecific, the finding of specific lexical or sublexical interferences is new evidence that lexical and sublexical processes of reading could be partially supported by distinct cortical sub-regions despite their anatomical proximity. These data are in line with many brain activation studies that showed that left superior temporal and inferior parietal regions had a crucial role respectively in word and pseudoword reading and were core regions for dyslexia
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