5,465 research outputs found

    A Case of Reactive Cervical Lymphadenopathy with Fat Necrosis Impinging on Adjacent Vascular Structures.

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    A tender neck mass in adults can be a diagnostic challenge due to a wide differential diagnosis, which ranges from reactive lymphadenopathy to malignancy. In this report, we describe a case of a young female with an unusually large and tender reactive lymph node with fat necrosis. The diagnostic imaging findings alone mimicked that of scrofula and malignancy, which prompted a complete workup. Additionally, the enlarged lymph node was compressing the internal jugular vein in the setting of oral contraceptive use by the patient, raising concern for Lemierre's syndrome or internal jugular vein thrombosis. This report shows how, in the appropriate clinical context, and especially with the involvement of adjacent respiratory or neurovascular structures, aggressive diagnostic testing can be indicated

    Silicon micromachined hollow microneedles for transdermal liquid transport

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    This paper presents a novel process for the fabrication of out-of-plane hollow microneedles in silicon. The fabrication method consists of a sequence of deep-reactive ion etching (DRIE), anisotropic wet etching and conformal thin film deposition, and allows needle shapes with different, lithography-defined tip curvature. In this study, the length of the needles varied between 150 and 350 micrometers. The widest dimension of the needle at its base was 250 /spl mu/m. Preliminary application tests of the needle arrays show that they are robust and permit skin penetration without breakage. Transdermal water loss measurements before and after microneedle skin penetration are reported. Drug delivery is increased approximately by a factor of 750 in microneedle patch applications with respect to diffusion alone. The feasibility of using the microneedle array as a blood sampler on a capillary electrophoresis chip is demonstrated

    Excitatory and inhibitory D-serine binding to the NMDA receptor

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    N-methyl-D-aspartate receptors (NMDARs) uniquely require binding of two different neurotransmitter agonists for synaptic transmission. D-serine and glycine bind to one subunit, GluN1, while glutamate binds to the other, GluN2. These agonists bind to the receptor's bi-lobed ligand-binding domains (LBDs), which close around the agonist during receptor activation. To better understand the unexplored mechanisms by which D-serine contributes to receptor activation, we performed multi-microsecond molecular dynamics simulations of the GluN1/GluN2A LBD dimer with free D-serine and glutamate agonists. Surprisingly, we observed D-serine binding to both GluN1 and GluN2A LBDs, suggesting that D-serine competes with glutamate for binding to GluN2A. This mechanism is confirmed by our electrophysiology experiments, which show that D-serine is indeed inhibitory at high concentrations. Although free energy calculations indicate that D-serine stabilizes the closed GluN2A LBD, its inhibitory behavior suggests that it either does not remain bound long enough or does not generate sufficient force for ion channel gating. We developed a workflow using pathway similarity analysis to identify groups of residues working together to promote binding. These conformation-dependent pathways were not significantly impacted by the presence of N-linked glycans, which act primarily by interacting with the LBD bottom lobe to stabilize the closed LBD

    Dihydroartemisinin ameliorates inflammatory disease by its reciprocal effects on Th and Treg cell function via modulating mTOR pathway

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    Dihydroartemisinin (DHA) is an important derivative of an herb medicine Artemisia annua L., used in ancient China. DHA is currently used world-wide to treat malaria by killing malaria-causing parasites. In addition to this prominent effect, DHA is suggested to regulate cellular functions, such as angiogenesis, tumor cell growth and immunity. Nonetheless, how DHA affects T cell function remains poorly understood. We found that DHA potently suppressed Th cell differentiation in vitro. Unexpectedly however, DHA greatly promoted Treg cell generation, in a manner dependent on TGF-βR:Smad signal. In addition, DHA treatment effectively reduced EAE onset and ameliorated ongoing EAE in mice. Administration of DHA significantly decreased Th but increased Treg cells in EAE-inflicted mice without apparent global immune suppression. Moreover, DHA modulated mTOR pathway, because mTOR signal was attenuated in T cells upon DHA treatment. Importantly, enhanced Akt activity neutralized DHA-mediated effects on T cells in an mTOR dependent fashion. This study therefore reveals a novel immune regulatory function of DHA to reciprocally regulate Th and Treg cell generation through modulating mTOR pathway. It addresses how DHA regulates immune function and suggests a new type of drug for treating diseases where mTOR activity to be tempered

    The EROS2 search for microlensing events towards the spiral arms: the complete seven season results

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    The EROS-2 project has been designed to search for microlensing events towards any dense stellar field. The densest parts of the Galactic spiral arms have been monitored to maximize the microlensing signal expected from the stars of the Galactic disk and bulge. 12.9 million stars have been monitored during 7 seasons towards 4 directions in the Galactic plane, away from the Galactic center. A total of 27 microlensing event candidates have been found. Estimates of the optical depths from the 22 best events are provided. A first order interpretation shows that simple Galactic models with a standard disk and an elongated bulge are in agreement with our observations. We find that the average microlensing optical depth towards the complete EROS-cataloged stars of the spiral arms is τˉ=0.51±.13×106\bar{\tau} =0.51\pm .13\times 10^{-6}, a number that is stable when the selection criteria are moderately varied. As the EROS catalog is almost complete up to IC=18.5I_C=18.5, the optical depth estimated for the sub-sample of bright target stars with IC<18.5I_C<18.5 (τˉ=0.39±>.11×106\bar{\tau}=0.39\pm >.11\times 10^{-6}) is easier to interpret. The set of microlensing events that we have observed is consistent with a simple Galactic model. A more precise interpretation would require either a better knowledge of the distance distribution of the target stars, or a simulation based on a Galactic model. For this purpose, we define and discuss the concept of optical depth for a given catalog or for a limiting magnitude.Comment: 22 pages submitted to Astronomy & Astrophysic

    Design and rationale of a randomized control trial testing the effectiveness of combined therapy with STAtin plus FENOfibrate and statin alone in non-diabetic, combined dyslipidemia patients with non-intervened intermediate coronary artery disease - STAFENO study

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    Background Despite the chronicled success of low-density lipoprotein cholesterol (LDLc)-lowering statin therapy, substantial residual cardiovascular (CV) disease risk remains a problem worldwide, highlighting the need to for combination therapies targeting non-LDLc factors, such as with fenofibrate. Methods/design The STAFENO trial is a prospective, randomized, open-label, multi-center trial to compare the effect of statin plus fenofibrate with statin alone on the reduction and stabilization of plaque in non-diabetic, combined dyslipidemia patients with non-intervened, intermediate coronary artery disease (CAD) using virtual histology-intravascular ultrasound at 12 months. A total of 106 eligible patients are planned to be randomized to receive either a combination therapy (rosuvastatin 10 mg plus fenofibrate 160 mg/day) or monotherapy (rosuvastatin 10 mg/day) for 12 months. The primary endpoint of this study is the percentage change in the necrotic core volume. Secondary endpoints include changes in tissue characteristics and 1-year major CV events, including all-cause mortality, CV mortality, nonfatal myocardial infarction, stroke, and revascularization of the intervened and non-intervened lesions. Discussion The STAFENO trial will address whether combination treatment of statin and fenofibrate has an additive beneficial effect compared to statin alone on the reduction and stabilization of plaque and CV events in non-diabetic, combined dyslipidemia patients with non-intervened intermediate CAD. Trial registration ClinicalTrials.gov, NCT02232360. Registered 9 February 2014. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0004ULE&selectaction=Edit&uid=U00023SZ&ts=2&cx=juppd2This is an investigator-initiated clinical trial with grant support from Daewoong Pharmaceutical Co. Ltd (Seoul, Korea). The sponsor has no role in the development of study protocols or study processes, including site selection, management, and data collection and analysis. The authors are solely responsible for the design and editing of this paper and its final content

    QCD Corrections to QED Vacuum Polarization

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    We compute QCD corrections to QED calculations for vacuum polarization in background magnetic fields. Formally, the diagram for virtual eeˉe\bar{e} loops is identical to the one for virtual qqˉq\bar{q} loops. However due to confinement, or to the growth of αs\alpha_s as p2p^2 decreases, a direct calculation of the diagram is not allowed. At large p2p^2 we consider the virtual qqˉq\bar{q} diagram, in the intermediate region we discuss the role of the contribution of quark condensates \left and at the low-energy limit we consider the π0\pi^0, as well as charged pion π+π\pi^+\pi^- loops. Although these effects seem to be out of the measurement accuracy of photon-photon laboratory experiments they may be relevant for γ\gamma-ray burst propagation. In particular, for emissions from the center of the galaxy (8.5 kpc), we show that the mixing between the neutral pseudo-scalar pion π0\pi_0 and photons renders a deviation from the power-law spectrum in the TeVTeV range. As for scalar quark condensates \left and virtual qqˉq\bar{q} loops are relevant only for very high radiation density 300MeV/fm3\sim 300 MeV/fm^3 and very strong magnetic fields of order 1014T\sim 10^{14} T.Comment: 15 pages, 4 figures; Final versio

    Structural basis for CRISPR RNA-guided DNA recognition by Cascade

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    The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and low-resolution structure of Cascade and show how it recognizes double-stranded DNA (dsDNA) targets in a sequence-specific manner. Cascade is a 405-kDa complex comprising five functionally essential CRISPR-associated (Cas) proteins (CasA1B2C6D1E1) and a 61-nucleotide CRISPR RNA (crRNA) with 5′-hydroxyl and 2′,3′-cyclic phosphate termini. The crRNA guides Cascade to dsDNA target sequences by forming base pairs with the complementary DNA strand while displacing the noncomplementary strand to form an R-loop. Cascade recognizes target DNA without consuming ATP, which suggests that continuous invader DNA surveillance takes place without energy investment. The structure of Cascade shows an unusual seahorse shape that undergoes conformational changes when it binds target DNA.
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