2,531 research outputs found

    Effects of stitching on delamination of satin weave carbon-epoxy laminates under mode I, mode II and mixed-mode I/II loadings

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    The objective of the present study is to characterize the effect of modified chain stitching on the delamination growth under mixed-mode I/II loading conditions. Delamination toughness under mode I is experimentally determined, for unstitched and stitched laminates, by using untabbed and tabbed double cantilever beam (TDCB) tests. The effect of the reinforcing tabs on mode I toughness is investigated. Stitching improves the energy release rate (ERR) up to 4 times in mode I. Mode II delamination toughness is evaluated in end-notched flexure (ENF) tests. Different geometries of stitched specimens are tested. Crack propagation occurs without any failure of stitching yarns. The final crack length attains the mid-span or it stops before and the specimen breaks in bending. The ERR is initially low and gradually increases with crack length to very high values. The mixedmode delamination behaviour is investigated using a mixed-mode bending (MMB) test. For unstitched specimens, a simple mixed-mode criterion is identified. For stitched specimens, stitching yarns do not break during 25% of mode I ratio tests and the ERR increase is relatively small compared to unstitched values. For 70% and 50% of mode I ratios, failures of yarns are observed during crack propagation and tests are able to capture correctly the effect of the stitching: it clearly improves the ERR for these two mixed modes, as much as threefold

    Mobile devices in PBL

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    Session: Digital Tsunami / Evidence and Theory - Oral Presentations & 45 Minute Workshop: no. 54INTRODUCTION/ BACKGROUND: Problem-based learning is a dynamic process through which students not only learn content knowledge but also skills important to their medical career, such as problem solving skills and communication skills. Technology can potentially contribute to this process, such as the use of mobile devices (defined in this study to include laptop or notebook computers, smartphones, and tablets) for search of information during PBL. But it presents both opportunities and challenges to the …postprin

    Asymmetric localization of DLC1 defines avian trunk neural crest polarity for directional delamination and migration

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    Following epithelial-mesenchymal transition, acquisition of avian trunk neural crest cell (NCC) polarity is prerequisite for directional delamination and migration, which in turn is essential for peripheral nervous system development. However, how this cell polarization is established and regulated remains unknown. Here we demonstrate that, using the RHOA biosensor in vivo and in vitro, the initiation of NCC polarization is accompanied by highly activated RHOA in the cytoplasm at the cell rear and its fluctuating activity at the front edge. This differential RHOA activity determines polarized NC morphology and motility, and is regulated by the asymmetrically localized RhoGAP Deleted in liver cancer (DLC1) in the cytoplasm at the cell front. Importantly, the association of DLC1 with NEDD9 is crucial for its asymmetric localization and differential RHOA activity. Moreover, NC specifiers, SOX9 and SOX10, regulate NEDD9 and DLC1 expression, respectively. These results present a SOX9/SOX10-NEDD9/DLC1-RHOA regulatory axis to govern NCC migratory polarization.published_or_final_versio

    The Role of IRE1α in the Degradation of Insulin mRNA in Pancreatic β-Cells

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    The endoplasmic reticulum (ER) is a cellular compartment for the biosynthesis and folding of newly synthesized secretory proteins such as insulin. Perturbations to ER homeostasis cause ER stress and subsequently activate cell signaling pathways, collectively known as the Unfolded Protein Response (UPR). IRE1α is a central component of the UPR. In pancreatic β-cells, IRE1α also functions in the regulation of insulin biosynthesis.Here we report that hyperactivation of IRE1α caused by chronic high glucose treatment or IRE1α overexpression leads to insulin mRNA degradation in pancreatic β-cells. Inhibition of IRE1α signaling using its dominant negative form prevents insulin mRNA degradation. Islets from mice heterozygous for IRE1α retain expression of more insulin mRNA after chronic high glucose treatment than do their wild-type littermates.These results reveal a role of IRE1α in insulin mRNA expression under ER stress conditions caused by chronic high glucose. The rapid degradation of insulin mRNA could provide immediate relief for the ER and free up the translocation machinery. Thus, this mechanism would preserve ER homeostasis and help ensure that the insulin already inside the ER can be properly folded and secreted. This adaptation may be crucial for the maintenance of β-cell homeostasis and may explain why the β-cells of type 2 diabetic patients with chronic hyperglycemia stop producing insulin in the absence of apoptosis. This mechanism may also be involved in suppression of the autoimmune type 1 diabetes by reducing the amount of misfolded insulin, which could be a source of “neo-autoantigens.

    Microguards and micromessengers of the genome

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    The regulation of gene expression is of fundamental importance to maintain organismal function and integrity and requires a multifaceted and highly ordered sequence of events. The cyclic nature of gene expression is known as ‘transcription dynamics’. Disruption or perturbation of these dynamics can result in significant fitness costs arising from genome instability, accelerated ageing and disease. We review recent research that supports the idea that an important new role for small RNAs, particularly microRNAs (miRNAs), is in protecting the genome against short-term transcriptional fluctuations, in a process we term ‘microguarding’. An additional emerging role for miRNAs is as ‘micromessengers’—through alteration of gene expression in target cells to which they are trafficked within microvesicles. We describe the scant but emerging evidence that miRNAs can be moved between different cells, individuals and even species, to exert biologically significant responses. With these two new roles, miRNAs have the potential to protect against deleterious gene expression variation from perturbation and to themselves perturb the expression of genes in target cells. These interactions between cells will frequently be subject to conflicts of interest when they occur between unrelated cells that lack a coincidence of fitness interests. Hence, there is the potential for miRNAs to represent both a means to resolve conflicts of interest, as well as instigate them. We conclude by exploring this conflict hypothesis, by describing some of the initial evidence consistent with it and proposing new ideas for future research into this exciting topic

    I-HAZE: a dehazing benchmark with real hazy and haze-free indoor images

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    Image dehazing has become an important computational imaging topic in the recent years. However, due to the lack of ground truth images, the comparison of dehazing methods is not straightforward, nor objective. To overcome this issue we introduce a new dataset -named I-HAZE- that contains 35 image pairs of hazy and corresponding haze-free (ground-truth) indoor images. Different from most of the existing dehazing databases, hazy images have been generated using real haze produced by a professional haze machine. For easy color calibration and improved assessment of dehazing algorithms, each scene include a MacBeth color checker. Moreover, since the images are captured in a controlled environment, both haze-free and hazy images are captured under the same illumination conditions. This represents an important advantage of the I-HAZE dataset that allows us to objectively compare the existing image dehazing techniques using traditional image quality metrics such as PSNR and SSIM

    Nitrogen uptake and internal recycling in Zostera marina exposed to oyster farming: eelgrass potential as a natural biofilter

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    Oyster farming in estuaries and coastal lagoons frequently overlaps with the distribution of seagrass meadows, yet there are few studies on how this aquaculture practice affects seagrass physiology. We compared in situ nitrogen uptake and the productivity of Zostera marina shoots growing near off-bottom longlines and at a site not affected by oyster farming in San Quintin Bay, a coastal lagoon in Baja California, Mexico. We used benthic chambers to measure leaf NH4 (+) uptake capacities by pulse labeling with (NH4)-N-15 (+) and plant photosynthesis and respiration. The internal N-15 resorption/recycling was measured in shoots 2 weeks after incubations. The natural isotopic composition of eelgrass tissues and vegetative descriptors were also examined. Plants growing at the oyster farming site showed a higher leaf NH4 (+) uptake rate (33.1 mmol NH4 (+) m(-2) day(-1)) relative to those not exposed to oyster cultures (25.6 mmol NH4 (+) m(-2) day(-1)). We calculated that an eelgrass meadow of 15-16 ha (which represents only about 3-4 % of the subtidal eelgrass meadow cover in the western arm of the lagoon) can potentially incorporate the total amount of NH4 (+) excreted by oysters (similar to 5.2 x 10(6) mmol NH4 (+) day(-1)). This highlights the potential of eelgrass to act as a natural biofilter for the NH4 (+) produced by oyster farming. Shoots exposed to oysters were more efficient in re-utilizing the internal N-15 into the growth of new leaf tissues or to translocate it to belowground tissues. Photosynthetic rates were greater in shoots exposed to oysters, which is consistent with higher NH4 (+) uptake and less negative delta C-13 values. Vegetative production (shoot size, leaf growth) was also higher in these shoots. Aboveground/belowground biomass ratio was lower in eelgrass beds not directly influenced by oyster farms, likely related to the higher investment in belowground biomass to incorporate sedimentary nutrients

    Factors affecting treatment-seeking for febrile illness in a malaria endemic block in Boudh district, Orissa, India: policy implications for malaria control

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    <p>Abstract</p> <p>Background</p> <p>Orissa state in eastern India accounts for the highest malaria burden to the nation. However, evidences are limited on its treatment-seeking behaviour in the state. We assessed the treatment-seeking behaviour towards febrile illness in a malaria endemic district in Orissa.</p> <p>Methods</p> <p>A cross-sectional community-based survey was carried out during the high malaria transmission season of 2006 in Boudh district. Respondents (n = 300) who had fever with chills within two weeks prior to the day of data collection were selected through a multi-stage sampling and interviewed with a pre-tested and structured interview schedule. Malaria treatment providers (n = 23) were interviewed in the district to gather their insights on factors associated with prompt and effective treatment through a semi-structured and open-ended interview guideline.</p> <p>Results</p> <p>Majority of respondents (n = 281) sought some sort of treatment e.g. government health facility (35.7%), less qualified providers (31.3%), and community level health workers and volunteers (24.3%). The single most common reason (66.9%) for choosing a provider was proximity. Over a half (55.7%) sought treatment from appropriate providers within 48 hours of onset of symptoms. Respondents under five years (OR 2.00, 95% CI 0.84-4.80, <it>P </it>= 0.012), belonging to scheduled tribe community (OR 2.13, 95% CI 1.11-4.07, <it>P </it>= 0.022) and visiting a provider more than five kilometers (OR 2.04, 95% CI 1.09-3.83, <it>P </it>= 0.026) were more likely to have delayed or inappropriate treatment. Interviews with the providers indicated that patients' lack of trust in community volunteers providing treatment led to inappropriate treatment-seeking from the less qualified providers. The reasons for the lack of trust included drug side effects, suspicions about drug quality, stock-outs of drugs and inappropriate attitude of the provider.</p> <p>Conclusion</p> <p>Large-scale involvement of less qualified providers is suggested in the malaria control programme as volunteers after appropriate capacity development since the community has more trust in them. This should be supported by uninterrupted supply of drugs to the community volunteers, and involvement of the community-based organizations and volunteers in the planning, implementation, and monitoring of malaria control services. There is also a need for continuous and rigorous impact evaluations of the program to make necessary modifications, scale up and to prevent drug resistance.</p

    Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer

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    Tissue-resident memory T (TRM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether TRM cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a TRM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander TRM-like cells present prior to tumor onset boosted immune cell recruitment, causing tumor immune evasion through loss of MHC class I protein expression and resistance to immune checkpoint inhibitors. In humans, only tumors arising in ES patients underwent clonal immune evasion, unrelated to tobacco-associated mutagenic signatures or oncogenic drivers. These data demonstrate that enhanced TRM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes

    Autoimmune and autoinflammatory mechanisms in uveitis

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    The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders
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