410 research outputs found

    Lymphoid Microenvironments in the Thymus and Lymph Node

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    The three-dimensional architecture of the thymus and mesenteric lymph node reveals several different stromal cell types important in the development and function of T cells. In the thymic cortex, T cells proliferate and differentiate in a meshwork of epithelial-reticular cells. They then migrate towards the medulla where they may interact with interdigitating cells. T cells migrate from the thymus through perivascular spaces, surrounding large vessels at the cortico-medullary boundary. In this area also large thymic cystic cavities are found, their function remains at present unclear. Mature selected T cells leave the thymus most probably by the venous bloodstream, to enter peripheral lymph nodes. Upon entering the lymph node they cross the wall of high endothelial venules. On the other hand, lymph enters the node by afferent lymphatics draining into various types of sinuses. Here, macrophages are strategically located to phagocytose and process antigen. These cells then expose antigen to T cells and B cells within the lymph node parenchyma, thus creating a microenvironment for the onset of an immune response. The various microenvironments important in T cell development and T cell function are shown in this paper using scanning electron microscopy as a dissecting tool. We discuss our morphological findings in the light of recent data on the physiology of T cell differentiation and function

    Exploiting the Passive Dynamics of a Compliant Leg to Develop Gait Transitions

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    In the area of bipedal locomotion, the spring loaded inverted pendulum (SLIP) model has been proposed as a unified framework to explain the dynamics of a wide variety of gaits. In this paper, we present a novel analysis of the mathematical model and its dynamical properties. We use the perspective of hybrid dynamical systems to study the dynamics and define concepts such as partial stability and viability. With this approach, on the one hand, we identified stable and unstable regions of locomotion. On the other hand, we found ways to exploit the unstable regions of locomotion to induce gait transitions at a constant energy regime. Additionally, we show that simple non-constant angle of attack control policies can render the system almost always stable

    Post-colonoscopy colorectal cancers in a national FIT-based CRC screening program

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    Background and study aims: Post-colonoscopy colorectal cancers (PCCRCs) decrease the effect of colorectal cancer (CRC) screening programs. To enable PCCRC incidence reduction on the long-term we classified PCCRCs diagnosed after colonoscopies performed in a fecal immunochemical test (FIT-) based screening program. Patients and methods: PCCRCs diagnosed after colonoscopies performed between 2014-2016 for positive FIT in the Dutch CRC screening program were included. PCCRCs were categorized according to the World Endoscopy Organization consensus statement into a) interval PCCRC (diagnosed before the recommended surveillance), b) non-interval-type-A (diagnosed at the recommended surveillance interval), c) non-interval-type-B (diagnosed after the recommended surveillance interval), or d) non-interval-type-C (diagnosed after the intended recommended surveillance interval, but not applied due to comorbidity). The most probable etiology was determined by root-cause analysis. Tumor stage distributions were compared between categories. Results: 116,362 colonoscopies were performed after positive FIT with 9,978 screen-detected CRCs. During follow-up, 432 PCCRCs were diagnosed. The 3-year PCCRC rate was 2.7%. PCCRCs were categorized as interval (53.5%), non-interval-type-A (14.6%), non-interval-type-B (30.6%), and non-interval-type-C (1.4%). Interval PCCRCs had as most common etiology a possible missed lesion with adequate examination (73.6%) and were more often diagnosed at an advanced stage (stage III/IV, 53.2%) compared to non-interval-type-A (15.9%, p&lt;0.001) and non-interval-type-B (40.9%, p=0.025) PCCRCs. Conclusions: The 3-year PCCRC rate was low in this FIT-based CRC screening program. Approximately half of PCCRCs were interval PCCRCs. These were mostly caused by missed lesions and were diagnosed at more advanced stage. This emphasizes the importance of high-quality colonoscopy with optimal polyp detection.</p

    Collisionality and safety factor scalings of H-mode energy transport in the MAST spherical tokamak

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    A factor of 4 dimensionless collisionality scan of H-mode plasmas in MAST shows that the thermal energy confinement time scales as BτE,th ∝ ν-0.82±0.1*e. Local heat transport is dominated by electrons and is consistent with the global scaling. The n

    Jaw Bone Invasion of Oral Squamous Cell Carcinoma Is Associated with Osteoclast Count and Expression of Its Regulating Proteins in Patients and Organoids

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    AIMS: Oral squamous cell carcinoma (OSCC) frequently invades the jaw. The exact mechanism of bone invasion remains unclear. This study investigates (premature) osteoclasts and the expression of its differentiation regulating proteins RANKL, OPG and RANK in patients with OSCC. METHODS: Resection specimens from OSCC patients were divided into NI group (No Invasion), E group (Erosion) or I group (bone Invasion). Tissue sections were stained with Cathepsin K (osteoclast-counting), RANKL, OPG and RANK. The staining intensity was scored on different regions of the tumor: front, center, back and normal mucosa. Immunohistochemistry and qPCR for RANKL/OPG/RANK were performed on five head and neck squamous cell carcinoma (HNSCC) organoids. RESULTS: The mean number of osteoclasts (I group) and premature osteoclasts (E group) was significantly higher compared to the NI group ( p = 0.003, p = 0.036). RANKL expression was significantly higher in the tumor front and tumor center compared to normal mucosa (all groups). In the I group, RANKL and RANK expression was significantly higher in the tumor front compared to the tumor back and there was a trend of higher RANKL expression in the tumor front compared to the E group and NI group. qPCR showed a 20-43 times higher RANKL mRNA expression in three out of five tumor organoids compared to a normal squamous cell organoid line. There was no correlation between protein and mRNA expression in the HNSCC organoids. CONCLUSIONS: These findings suggest that OSCCs induce bone invasion by stimulating osteoclast activation by regulating the production of RANKL and RANK proteins

    The impact of ageing reveals distinct roles for human dentate gyrus and CA3 in pattern separation and object recognition memory

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    © 2017 The Author(s). Both recognition of familiar objects and pattern separation, a process that orthogonalises overlapping events, are critical for effective memory. Evidence is emerging that human pattern separation requires dentate gyrus. Dentate gyrus is intimately connected to CA3 where, in animals, an autoassociative network enables recall of complete memories to underpin object/event recognition. Despite huge motivation to treat age-related human memory disorders, interaction between human CA3 and dentate subfields is difficult to investigate due to small size and proximity. We tested the hypothesis that human dentate gyrus is critical for pattern separation, whereas, CA3 underpins identical object recognition. Using 3 T MR hippocampal subfield volumetry combined with a behavioural pattern separation task, we demonstrate that dentate gyrus volume predicts accuracy and response time during behavioural pattern separation whereas CA3 predicts performance in object recognition memory. Critically, human dentate gyrus volume decreases with age whereas CA3 volume is age-independent. Further, decreased dentate gyrus volume, and no other subfield volume, mediates adverse effects of aging on memory. Thus, we demonstrate distinct roles for CA3 and dentate gyrus in human memory and uncover the variegated effects of human ageing across hippocampal regions. Accurate pinpointing of focal memory-related deficits will allow future targeted treatment for memory loss

    Aerodynamic investigations of ventilated brake discs.

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    The heat dissipation and performance of a ventilated brake disc strongly depends on the aerodynamic characteristics of the flow through the rotor passages. The aim of this investigation was to provide an improved understanding of ventilated brake rotor flow phenomena, with a view to improving heat dissipation, as well as providing a measurement data set for validation of computational fluid dynamics methods. The flow fields at the exit of four different brake rotor geometries, rotated in free air, were measured using a five-hole pressure probe and a hot-wire anemometry system. The principal measurements were taken using two-component hot-wire techniques and were used to determine mean and unsteady flow characteristics at the exit of the brake rotors. Using phase-locked data processing, it was possible to reveal the spatial and temporal flow variation within individual rotor passages. The effects of disc geometry and rotational speed on the mean flow, passage turbulence intensity, and mass flow were determined. The rotor exit jet and wake flow were clearly observed as characterized by the passage geometry as well as definite regions of high and low turbulence. The aerodynamic flow characteristics were found to be reasonably independent of rotational speed but highly dependent upon rotor geometry
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