Toy nanoindentation model and incipient plasticity

A toy model of two dimensional nanoindentation in finite crystals is proposed. The crystal is described by periodized discrete elasticity whereas the indenter is a rigid strain field of triangular shape representing a hard knife-like indenter. Analysis of the model shows that there are a number of discontinuities in the load vs penetration depth plot which correspond to the creation of dislocation loops. The stress vs depth bifurcation diagram of the model reveals multistable stationary solutions that appear as the dislocation-free branch of solutions develops turning points for increasing stress. Dynamical simulations show that an increment of the applied load leads to nucleation of dislocation loops below the nanoindenter tip. Such dislocations travel inside the bulk of the crystal and accommodate at a certain depth in the sample. In agreement with experiments, hysteresis is observed if the stress is decreased after the first dislocation loop is created. Critical stress values for loop creation and their final location at equilibrium are calculated.Comment: 22 pages, 5 figures, to appear in Chaos, Solitons and Fractal

The N-terminal region of the atypical chemokine receptor ACKR2 is a key determinant of ligand binding

The atypical chemokine receptor, ACKR2 is a pivotal regulator of chemokine-driven inflammatory responses and works by binding, internalizing, and degrading inflammatory CC-chemokines. ACKR2 displays promiscuity of ligand binding and is capable of interacting with up to 14 different inflammatory CC-chemokines. Despite its prominent biological role, little is known about the structure/function relationship within ACKR2, which regulates ligand binding. Here we demonstrate that a conserved tyrosine motif at the N terminus of ACKR2 is essential for ligand binding, internalization, and scavenging. In addition we demonstrate that sulfation of this motif contributes to ligand internalization. Furthermore, a peptide derived from this region is capable of binding inflammatory chemokines and inhibits their interaction with their cognate signaling receptors. Importantly, the peptide is only active in the sulfated form, further confirming the importance of the sulfated tyrosines for function. Finally, we demonstrate that the bacterial protease, staphopain A, can cleave the N terminus of ACKR2 and suppress its ligand internalization activity. Overall, these results shed new light on the nature of the structural motifs in ACKR2 that are responsible for ligand binding. The study also highlights ACKR2-derived N-terminal peptides as being of potential therapeutic significance

Application of Graphene within Optoelectronic Devices and Transistors

Scientists are always yearning for new and exciting ways to unlock graphene's true potential. However, recent reports suggest this two-dimensional material may harbor some unique properties, making it a viable candidate for use in optoelectronic and semiconducting devices. Whereas on one hand, graphene is highly transparent due to its atomic thickness, the material does exhibit a strong interaction with photons. This has clear advantages over existing materials used in photonic devices such as Indium-based compounds. Moreover, the material can be used to 'trap' light and alter the incident wavelength, forming the basis of the plasmonic devices. We also highlight upon graphene's nonlinear optical response to an applied electric field, and the phenomenon of saturable absorption. Within the context of logical devices, graphene has no discernible band-gap. Therefore, generating one will be of utmost importance. Amongst many others, some existing methods to open this band-gap include chemical doping, deformation of the honeycomb structure, or the use of carbon nanotubes (CNTs). We shall also discuss various designs of transistors, including those which incorporate CNTs, and others which exploit the idea of quantum tunneling. A key advantage of the CNT transistor is that ballistic transport occurs throughout the CNT channel, with short channel effects being minimized. We shall also discuss recent developments of the graphene tunneling transistor, with emphasis being placed upon its operational mechanism. Finally, we provide perspective for incorporating graphene within high frequency devices, which do not require a pre-defined band-gap.Comment: Due to be published in "Current Topics in Applied Spectroscopy and the Science of Nanomaterials" - Springer (Fall 2014). (17 pages, 19 figures

Influence of routine computed tomography on predicted survival from blunt thoracoabdominal trauma

Item does not contain fulltextINTRODUCTION: Many scoring systems have been proposed to predict the survival of trauma patients. This study was performed to evaluate the influence of routine thoracoabdominal computed tomography (CT) on the predicted survival according to the trauma injury severity score (TRISS). PATIENTS AND METHODS: 1,047 patients who had sustained a high-energy blunt trauma over a 3-year period were prospectively included in the study. All patients underwent physical examination, conventional radiography of the chest, thoracolumbar spine and pelvis, abdominal sonography, and routine thoracoabdominal CT. From this group with routine CT, we prospectively defined a selective CT (sub)group for cases with abnormal physical examination and/or conventional radiography and/or sonography. Type and extent of injuries were recorded for both the selective and the routine CT groups. Based on the injuries found by the two different CT algorithms, we calculated the injury severity scores (ISS) and predicted survivals according to the TRISS methodology for the routine and the selective CT algorithms. RESULTS: Based on injuries detected by the selective CT algorithm, the mean ISS was 14.6, resulting in a predicted mortality of 12.5%. Because additional injuries were found by the routine CT algorithm, the mean ISS increased to 16.9, resulting in a predicted mortality of 13.7%. The actual observed mortality was 5.4%. CONCLUSION: Routine thoracoabdominal CT in high-energy blunt trauma patients reveals more injuries than a selective CT algorithm, resulting in a higher ISS. According to the TRISS, this results in higher predicted mortalities. Observed mortality, however, was significantly lower than predicted. The predicted survival according to MTOS seems to underestimate the actual survival when routine CT is used

HIV-1 Efficient Entry in Inner Foreskin Is Mediated by Elevated CCL5/RANTES that Recruits T Cells and Fuels Conjugate Formation with Langerhans Cells

Male circumcision reduces acquisition of HIV-1 by 60%. Hence, the foreskin is an HIV-1 entry portal during sexual transmission. We recently reported that efficient HIV-1 transmission occurs following 1 h of polarized exposure of the inner, but not outer, foreskin to HIV-1-infected cells, but not to cell-free virus. At this early time point, Langerhans cells (LCs) and T-cells within the inner foreskin epidermis are the first cells targeted by the virus. To gain in-depth insight into the molecular mechanisms governing inner foreskin HIV-1 entry, foreskin explants were inoculated with HIV-1-infeceted cells for 4 h. The chemokine/cytokine milieu secreted by the foreskin tissue, and resulting modifications in density and spatial distribution of T-cells and LCs, were then investigated. Our studies show that in the inner foreskin, inoculation with HIV-1-infected cells induces increased CCL5/RANTES (1.63-fold) and decreased CCL20/MIP-3-alpha (0.62-fold) secretion. Elevated CCL5/RANTES mediates recruitment of T-cells from the dermis into the epidermis, which is blocked by a neutralizing CCL5/RANTES Ab. In parallel, HIV-1-infected cells mediate a bi-phasic modification in the spatial distribution of epidermal LCs: attraction to the apical surface at 1 h, followed by migration back towards the basement membrane later on at 4 h, in correlation with reduced CCL20/MIP-3-alpha at this time point. T-cell recruitment fuels the continuous formation of LC-T-cell conjugates, permitting the transfer of HIV-1 captured by LCs. Together, these results reveal that HIV-1 induces a dynamic process of immune cells relocation in the inner foreskin that is associated with specific chemokines secretion, which favors efficient HIV-1 entry at this site

Effects of mefloquine and artesunate mefloquine on the emergence, clearance and sex ratio of Plasmodium falciparum gametocytes in malarious children

<p>Abstract</p> <p>Background</p> <p>The gametocyte sex ratio of <it>Plasmodium falciparum</it>, defined as the proportion of gametocytes that are male, may influence transmission but little is known of the effects of mefloquine or artesunate-mefloquine on gametocyte sex ratio and on the sex ratio of first appearing gametocytes.</p> <p>Methods</p> <p>350 children with uncomplicated <it>P. falciparum </it>malaria were enrolled in prospective treatment trial of mefloquine or artesunate-mefloquine between 2007 and 2008. Gametocytaemia was quantified, and gametocytes were sexed by morphological appearance, before and following treatment. The area under curve of gametocyte density <it>versus </it>time (AUC_gm) was calculated by linear trapezoidal method.</p> <p>Results</p> <p>91% and 96% of all gametocytes appeared by day 7 and day 14, respectively following treatment. The overall rate of gametocytaemia with both treatments was 31%, and was significantly higher in mefloquine than in artesunate-mefloquine treated children if no gametocyte was present a day after treatment began (25.3% <it>v </it>12.8%, P = 0.01). Gametocyte clearance was significantly faster with artesunate-mefloquine (1.8 ± 0.22 [sem] <it>v </it>5.6 ± 0.95 d; P = 0.001). AUC_gmwas significantly lower in the artesunate mefloquine group (P = 0.008). The pre-treatment sex ratio was male-biased, but post-treatment sex ratio or the sex ratio of first appearing gametocytes, was significantly lower and female-biased two or three days after beginning of treatment in children given artesunate-mefloquine.</p> <p>Conclusion</p> <p>Addition of artesunate to mefloquine significantly modified the emergence, clearance, and densities of gametocytes and has short-lived, but significant, sex ratio modifying effects in children from this endemic area.</p

Trends in the Synthesis and Functionalization of Guaianolides

Guaianolides constitute a large and diverse group of biologically active sesquiterpenes. Guaianolide and seco-guaianolides can also be used as, for example, scaffolds for the development of new active molecules that are readily accessible by synthetic methods. Nevertheless, these lactones often have complex structures that make their synthesis difficult. The aim of this microreview is to provide an overview of the developments in guaianolide synthesis by the two major synthetic strategies: semi-synthesis and total synthesis. Partial and total syntheses of guaianolides are described, with particular emphasis placed on the methods reported in the last decade. The methods discussed include rearrangements, cycloadditions, ring-closing metathesis, the use of transitionmetal catalysts, photochemical reactions, and other recently developed techniques as key steps