1,738 research outputs found

    Effect of In-Plane Voiding on the Fracture Behavior of Laser Sintered Polyamide

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    The primary contributors to poor mechanical properties in polyamide materials used during Selective Laser Sintering® are qualified. Methods to quantify the decreased mechanical properties, including Scanning Electron Microscopy (SEM) of fracture surfaces, are compared against each other and against mechanical properties of components fabricated using multiple process parameters. Of primary interest are Ultimate Tensile Strength (UTS) and Elongation at Break (EOB) of tensile specimens fabricated under conditions that produce varying degrees of ductile and brittle fracture.Mechanical Engineerin

    Intermediate filament–membrane attachments function synergistically with actin-dependent contacts to regulate intercellular adhesive strength

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    By tethering intermediate filaments (IFs) to sites of intercellular adhesion, desmosomes facilitate formation of a supercellular scaffold that imparts mechanical strength to a tissue. However, the role IF–membrane attachments play in strengthening adhesion has not been directly examined. To address this question, we generated Tet-On A431 cells inducibly expressing a desmoplakin (DP) mutant lacking the rod and IF-binding domains (DPNTP). DPNTP localized to the plasma membrane and led to dissociation of IFs from the junctional plaque, without altering total or cell surface distribution of adherens junction or desmosomal proteins. However, a specific decrease in the detergent-insoluble pool of desmoglein suggested a reduced association with the IF cytoskeleton. DPNTP-expressing cell aggregates in suspension or substrate-released cell sheets readily dissociated when subjected to mechanical stress whereas controls remained largely intact. Dissociation occurred without lactate dehydrogenase release, suggesting that loss of tissue integrity was due to reduced adhesion rather than increased cytolysis. JD-1 cells from a patient with a DP COOH-terminal truncation were also more weakly adherent compared with normal keratinocytes. When used in combination with DPNTP, latrunculin A, which disassembles actin filaments and disrupts adherens junctions, led to dissociation up to an order of magnitude greater than either treatment alone. These data provide direct in vitro evidence that IF–membrane attachments regulate adhesive strength and suggest furthermore that actin- and IF-based junctions act synergistically to strengthen adhesion

    Cancer bioimprinting and cell shape recognition for diagnosis and targeted treatment

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    Cancer incidence and mortality have both increased in the last decade and are predicted to continue to rise. Diagnosis and treatment of cancers are often hampered by the inability to specifically target neoplastic cells. Bioimprinting is a promising new approach to overcome shortfalls in cancer targeting. Highly specific recognition cavities can be made into polymer matrices to mimic lock-and-key actions seen in in vivo biological systems. Early studies concentrated on molecules and were inhibited by template size complexity. Surface imprinting allows the capture of increasingly complex motifs from polypeptides to single cell organisms and mammalian cells. Highly specific cell shape recognition can also be achieved by cell interaction with imprints that can be made into polymer matrices to mimic biological systems at a molecular level. Bioimprinting has also been used to achieve nanometre scale resolution imaging of cancer cells. Studies of bioimprint-based drug delivery on cancer cells have been recently trialled in vitro and show that this approach can potentially improve existing chemotherapeutic approaches. This review focuses on the possible applications of bioimprinting with particular regards to cancer understanding, diagnosis and therapy. Cell imprints, incorporated into biosensors can allow the limits of detection to be improved or negate the need for extensive patient sample processing. Similar cell imprinting platforms can be used for nanoscale imaging of cancer morphology, as well as to investigate topographical signalling of cancer cells in vitro. Lastly, bioimprints also have applications as selective drug delivery vehicles to tumours with the potential to decrease chemotherapy-related side effects

    String Junctions and Bound States of Intersecting Branes

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    We study four-dimensional black hole configurations which result from wrapping M5-branes on a Calabi-Yau manifold, as well as U-dual realizations. Our aim is to understand the microscopic degrees of freedom responsible for the existence of bound states of multiple branes. The details depend on the chosen U-frame; in some cases, they are massless string junctions. We also identify a perturbative description in which these states correspond to twisted strings of intersecting D3-branes at an orbifold singularity. In each case, these are the preponderant states of the spacetime infrared conformal field theory and account for the entropy of the blackhole.Comment: 14 pages; 2 figures; uses latex with epsf and hyperref package

    Removal of Human Leukemic Cells from Peripheral Blood Mononuclear Cells by Cell Recognition Chromatography with Size Matched Particle Imprints

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    We report a cell recognition chromatography approach for blood cancer cell separation from healthy peripheral blood mononuclear cells (PBMCs) based on sizematched functionalized particle imprints. Negative imprints were prepared from layers of 15 ÎĽm polymeric microbeads closely matching the size of cultured human leukemic cells (HL60). We replicated these imprints on a large scale with UV curable polyurethane resin using nanoimprinting lithography. The imprints were functionalized with branched polyethylene imine (bPEI) and passivated by Poloxamer 407 to promote a weak attraction toward cells. When a matching cell fits into an imprint cavity, its contact area with the imprint is maximized, which amplifies the attraction and the binding selectivity. We tested these imprints specificity for depleting myeloblasts from a mixture with healthy human PBMCs in a cell recognition chromatography setup hosting the imprint. The mixture of fixed HL60/PBMCs ratio was circulated over the imprint and at each step the selectivity toward HL60 was assessed by flow cytometry. The role of the imprint length, flow rate, channel depth, and the bPEI coating concentration were examined. The results show that HL60 cells, closely matching the imprint cavities, get trapped on the imprint, while the smaller PBMCs are carried away by the drag force of the flow. Lower flow rates, longer imprints, and interim channel depth favor HL60 specific retention. The bPEI concentration higher than 1 wt % on the imprint made it less selective toward the HL60 because of indiscriminate attraction with all cells. Particle imprint based cell recognition chromatography was able to achieve selective myeloblast depletion from initial 11.7% HL60 (88.3% PBMC) to less than 1.3% HL60 for 3 h of circulation. The cell recognition chromatography with size-matched microbead imprints can be employed as an efficient cell separation technique and potentially lead to alternative therapies for myeloblasts removal from peripheral blood of patients with acute myeloid leukemia
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