Fatigue Damage Initiation of a PA66/Glass Fibers Composite Material

Fatigue damage initiation of a PA66/glass fiber composite material is studied with interrupted tests carried out with an “alternative bending device” and a small applied strain. During the damage initiation period, no change of macroscopic properties, density, cristallinity ratio, glass transition temperature, and flexural elastic modulus is observed. Polysequential tests are carried out with three rest times differing by their length. These rest times allow the relaxation of macromolecular chains in the region of the microdefects and increase the number of cycles at fracture. The most efficient stop is the one just before the final fracture. The comparison of the fatigue behavior of the composite and its neat matrix shows that the microdefects relaxed during the break are identical to those which initiate damage and final fracture

Unraveling the temperature dependence of the yield strength in single-crystal tungsten using atomistically-informed crystal plasticity calculations

We use a physically-based crystal plasticity model to predict the yield strength of body-centered cubic (bcc) tungsten single crystals subjected to uniaxial loading. Our model captures the thermally-activated character of screw dislocation motion and full non-Schmid effects, both of which are known to play a critical role in bcc plasticity. The model uses atomistic calculations as the sole source of constitutive information, with no parameter fitting of any kind to experimental data. Our results are in excellent agreement with experimental measurements of the yield stress as a function of temperature for a number of loading orientations. The validated methodology is then employed to calculate the temperature and strain-rate dependence of the yield strength for 231 crystallographic orientations within the standard stereographic triangle. We extract the strain-rate sensitivity of W crystals at different temperatures, and finish with the calculation of yield surfaces under biaxial loading conditions that can be used to define effective yield criteria for engineering design models

Single platelet and megakaryocyte morpho-dynamics uncovered by multicolor reporter mouse strains in vitro and in vivo

Visualizing cell behavior and effector function on a single cell level has been crucial for understanding key aspects of mammalian biology. Due to their small size, large number and rapid recruitment into thrombi, there is a lack of data on fate and behavior of individual platelets in thrombosis and hemostasis. Here we report the use of platelet lineage restricted multi-color reporter mouse strains to delineate platelet function on a single cell level. We show that genetic labeling allows for single platelet and megakaryocyte tracking and morphological analysis in vivo and in vitro, while not affecting lineage functions. Using Credriven Confetti expression, we provide insights into temporal gene expression patterns as well as spatial clustering of megakaryocytes in the bone marrow. In the vasculature, shape analysis of activated platelets recruited to thrombi identifies ubiquitous filopodia formation with no evidence of lamellipodia formation. Single cell tracking in complex thrombi reveals prominent myosin-dependent motility of platelets and highlights thrombus formation as a highly dynamic process amenable to modification and intervention of the acto-myosin cytoskeleton. Platelet function assays combining flow cytrometry, as well as in vivo, ex vivo and in vitro imaging show unaltered platelet functions of multicolor reporter mice compared to WT controls. In conclusion, platelet lineage multicolor reporter mice prove useful in furthering our understanding of platelet and megakaryocyte biology on a single cell level

Necrosis y perforación de un tumor de intestino delgado. Presentación de un caso.

Introducción: El intestino delgado ocupa el 75 % del tubo digestivo y el 90% de la superficie de absorción. A pesar de ser uno de los órganos de mayor extensión y más activos metabólicamente los tumores que en él se originan son raros. Por ello su diagnóstico suele realizarse en un estadío avanzado cuando las expectativas terapéuticas son más limitadas y el pronóstico más incierto. Objetivo: Exponer un caso que se interviene quirúrgicamente por un abdomen agudo y en el acto operatorio se comprueba la existencia de dos tumores de intestino delgado. Caso Clínico: Se expuso un paciente masculino de 66 años que acude a cuerpo de guardia porque hace alrededor de 3 meses presenta dolores abdominales tipo cólico leves después de la ingestión de comidas, se ingresa para estudio y tratamiento, 48 horas después se intensifica y se decide intervenir quirúrgicamente con el presunto diagnóstico de ulcera perforada. En el acto quirúrgico se aprecian 2 tumores localizados en yeyuno e íleon, y el primero de ellos perforados. Metodología: Se realizó una revisión de la bibliografía relacionada con las tumoraciones de intestino delgado y de los tumores de GIST. Mediante el análisis y la síntesis de estas consultas se elaboraron deducciones en relación al desarrollo y proyecciones futuras de casos semejantes. Conclusiones: Las neoplasias de intestino delgado en muchas ocasiones pasan inadvertidas por su baja incidencia y sus síntomas inespecíficos. Es importante incrementar el índice de sospecha clínica de estos tumores para así lograr un diagnóstico precoz, con este se podrá conseguir una adecuada resección quirúrgica; indispensable para evitar las complicaciones, mayor supervivencia y calidad de vida

Procoagulant platelet sentinels prevent inflammatory bleeding through GPIIBIIIA and GPVI

Impairment of vascular integrity is a hallmark of inflammatory diseases. We recently reported that single immune-responsive platelets migrate and reposition themselves to sites of vascular injury to prevent bleeding. However, it remains unclear how single platelets preserve vascular integrity once encountering endothelial breaches. Here we demonstrate by intravital microscopy combined with genetic mouse models that procoagulant activation (PA) of single platelets and subsequent recruitment of the coagulation cascade are crucial for the prevention of inflammatory bleeding. Using a novel lactadherin-based compound, we detect phosphatidylserine (PS)-positive procoagulant platelets in the inflamed vasculature. We identify exposed collagen as the central trigger arresting platelets and initiating subsequent PA in a CypD- and TMEM16F-dependent manner both in vivo and in vitro. Platelet PA promotes binding of the prothrombinase complex to the platelet membrane, greatly enhancing thrombin activity and resulting in fibrin formation. PA of migrating platelets is initiated by costimulation via integrin αIIbβ3 (GPIIBIIIA)/Gα13-mediated outside-in signaling and glycoprotein VI signaling, leading to an above-threshold intracellular calcium release. This effectively targets the coagulation cascade to breaches of vascular integrity identified by patrolling platelets. Platelet-specific genetic loss of either CypD or TMEM16F as well as combined blockade of platelet GPIIBIIIA and glycoprotein VI reduce platelet PA in vivo and aggravate pulmonary inflammatory hemorrhage. Our findings illustrate a novel role of procoagulant platelets in the prevention of inflammatory bleeding and provide evidence that PA of patrolling platelet sentinels effectively targets and confines activation of coagulation to breaches of vascular integrity

Prediction of thermal cross-slip stress in magnesium alloys from direct first principles data

We develop a first-principles model of thermally-activated cross-slip in magnesium in the presence of a random solute distribution. Electronic structure methods provide data for the interaction of solutes with prismatic dislocation cores and basal dislocation cores. Direct calculations of interaction energies are possible for solutes---K, Na, and Sc---that lower the Mg prismatic stacking fault energy to improve formability. To connect to thermally activated cross-slip, we build a statistical model for the distribution of activation energies for double kink nucleation, barriers for kink migration, and roughness of the energy landscape to be overcome by an athermal stress. These distributions are calculated numerically for a range of concentrations, as well as alternate approximate analytic expressions for the dilute limit. The analytic distributions provide a simplified model for the maximum cross-slip softening for a solute as a function of temperature. The direct interaction calculations predict lowered forming temperatures for Mg-0.7at.%Sc, Mg-0.4at.%K, and Mg-0.6at.%Na of approximately 250C.Comment: 26 pages, 7 figure

Thrombocytopenia and splenic platelet-directed immune responses after IV ChAdOx1 nCov-19 administration

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are based on a range of novel platforms, with adenovirus-based approaches (like ChAdOx1 nCov-19) being one of them. Recently, a novel complication of SARS-CoV-2–targeted adenovirus vaccines has emerged: immune thrombocytopenia, either isolated, or accompanied by thrombosis (then termed VITT). This complication is characterized by low platelet counts, and in the case of VITT, also by platelet-activating platelet factor 4 antibodies reminiscent of heparin-induced thrombocytopenia, leading to a prothrombotic state with clot formation at unusual anatomic sites. Here, we detected antiplatelet antibodies targeting platelet glycoprotein receptors in 30% of patients with proven VITT (n = 27) and 42% of patients with isolated thrombocytopenia after ChAdOx1 nCov-19 vaccination (n = 26), indicating broad antiplatelet autoimmunity in these clinical entities. We use in vitro and in vivo models to characterize possible mechanisms of these platelet-targeted autoimmune responses leading to thrombocytopenia. We show that IV but not intramuscular injection of ChAdOx1 nCov-19 triggers platelet-adenovirus aggregate formation and platelet activation in mice. After IV injection, these aggregates are phagocytosed by macrophages in the spleen, and platelet remnants are found in the marginal zone and follicles. This is followed by a pronounced B-cell response with the emergence of circulating antibodies binding to platelets. Our work contributes to the understanding of platelet-associated complications after ChAdOx1 nCov-19 administration and highlights accidental IV injection as a potential mechanism of platelet-targeted autoimmunity. Hence, preventing IV injection when administering adenovirus-based vaccines could be a potential measure against platelet-associated pathologies after vaccination