TREX1 is expressed by microglia in normal human brain and increases in regions affected by ischemia

BACKGROUND: Mutations in the three-prime repair exonuclease 1 (TREX1) gene have been associated with neurological diseases, including Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). However, the endogenous expression of TREX1 in human brain has not been studied. METHODS: We produced a rabbit polyclonal antibody (pAb) to TREX1 to characterize TREX1 by Western blotting (WB) of cell lysates from normal controls and subjects carrying an RVCL frame-shift mutation. Dual staining was performed to determine cell types expressing TREX1 in human brain tissue. TREX1 distribution in human brain was further evaluated by immunohistochemical analyses of formalin-fixed, paraffin-embedded samples from normal controls and patients with RVCL and ischemic stroke. RESULTS: After validating the specificity of our anti-TREX1 rabbit pAb, WB analysis was utilized to detect the endogenous wild-type and frame-shift mutant of TREX1 in cell lysates. Dual staining in human brain tissues from patients with RVCL and normal controls localized TREX1 to a subset of microglia and macrophages. Quantification of immunohistochemical staining of the cerebral cortex revealed that TREX1 CONCLUSIONS: TREX1 is expressed by a subset of microglia in normal human brain, often in close proximity to the microvasculature, and increases in the setting of ischemic lesions. These findings suggest a role for TREX

Automated Glaucoma Detection Using Hybrid Feature Extraction in Retinal Fundus Images

Glaucoma is one of the most common causes of blindness. Robust mass screening may help to extend the symptom-free life for affected patients. To realize mass screening requires a cost-effective glaucoma detection method which integrates well with digital medical and administrative processes. To address these requirements, we propose a novel low cost automated glaucoma diagnosis system based on hybrid feature extraction from digital fundus images. The paper discusses a system for the automated identification of normal and glaucoma classes using higher order spectra (HOS), trace transform (TT), and discrete wavelet transform (DWT) features. The extracted features are fed to a support vector machine (SVM) classifier with linear, polynomial order 1, 2, 3 and radial basis function (RBF) in order to select the best kernel for automated decision making. In this work, the SVM classifier, with a polynomial order 2 kernel function, was able to identify glaucoma and normal images with an accuracy of 91.67%, and sensitivity and specificity of 90% and 93.33%, respectively. Furthermore, we propose a novel integrated index called Glaucoma Risk Index (GRI) which is composed from HOS, TT, and DWT features, to diagnose the unknown class using a single feature. We hope that this GRI will aid clinicians to make a faster glaucoma diagnosis during the mass screening of normal/glaucoma images

Atomic structure of dislocation kinks in silicon

We investigate the physics of the core reconstruction and associated structural excitations (reconstruction defects and kinks) of dislocations in silicon, using a linear-scaling density-matrix technique. The two predominant dislocations (the 90-degree and 30-degree partials) are examined, focusing for the 90-degree case on the single-period core reconstruction. In both cases, we observe strongly reconstructed bonds at the dislocation cores, as suggested in previous studies. As a consequence, relatively low formation energies and high migration barriers are generally associated with reconstructed (dangling-bond-free) kinks. Complexes formed of a kink plus a reconstruction defect are found to be strongly bound in the 30-degree partial, while the opposite is true in the case of 90-degree partial, where such complexes are found to be only marginally stable at zero temperature with very low dissociation barriers. For the 30-degree partial, our calculated formation energies and migration barriers of kinks are seen to compare favorably with experiment. Our results for the kink energies on the 90-degree partial are consistent with a recently proposed alternative double-period structure for the core of this dislocation.Comment: 12 pages, two-column style with 8 postscript figures embedded. Uses REVTEX and epsf macros. Also available at http://www.physics.rutgers.edu/~dhv/preprints/index.html#rn_di

Temperature effects on dislocation core energies in silicon and germanium

Temperature effects on the energetics of the 90-degree partial dislocation in silicon and germanium are investigated, using non-equilibrium methods to estimate free energies, coupled with Monte Carlo simulations. Atomic interactions are described by Tersoff and EDIP interatomic potentials. Our results indicate that the vibrational entropy has the effect of increasing the difference in free energy between the two possible reconstructions of the 90-degree partial, namely, the single-period and the double-period geometries. This effect further increases the energetic stability of the double-period reconstruction at high temperatures. The results also indicate that anharmonic effects may play an important role in determining the structural properties of these defects in the high-temperature regime.Comment: 8 pages in two-column physical-review format with six figure

Blocking Zika virus vertical transmission.

The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs. In vivo, SOF treatment post-infection (p.i.) decreased viral burden in an immunodeficient mouse model. Finally, we show for the first time that acute SOF treatment of pregnant dams p.i. was well-tolerated and prevented vertical transmission of the virus to the fetus. Taken together, our data confirmed SOF-mediated sparing of human neural cell types from ZIKV-mediated cell death in vitro and reduced viral burden in vivo in animal models of chronic infection and vertical transmission, strengthening the growing body of evidence for SOF anti-ZIKV activity

Urgent computing of storm surge for North Carolina's coast

Forecasting and prediction of natural events, such as tropical and extra-tropical cyclones, inland flooding, and severe winter weather, provide critical guidance to emergency managers and decision-makers from the local to the national level, with the goal of minimizing both human and economic losses. This guidance is used to facilitate evacuation route planning, post-disaster response and resource deployment, and critical infrastructure protection and securing, and it must be available within a time window in which decision makers can take appropriate action. This latter element is that which induces the need for urgency in this area. In this paper, we outline the North Carolina Forecasting System (NCFS) for storm surge and waves for coastal North Carolina, which is threatened by tropical cyclones about once every three years. We initially used advanced cyberinfrastructure techniques (e.g., opportunistic grid computing) in an effort to provide timely guidance for storm surge and wave impacts. However, our experience has been that a distributed computing approach is not robust enough to consistently produce the real-time results that end users expect. As a result, our technical approach has shifted so that the reliable and timely delivery of forecast products has been guaranteed by provisioning dedicated computational resources as opposed to relying on opportunistic availability of external resources. Our experiences with this forecasting effort is discussed in this paper, with a focus on Hurricane Irene (2011) that impacted a substantial portion of the US east coast from North Carolina, up along the eastern seaboard, and into New England

Measurement of polarization-transfer to bound protons in carbon and its virtuality dependence

We measured the ratio $P_{x}/P_{z}$ of the transverse to longitudinal components of polarization transferred from electrons to bound protons in $^{12}\mathrm{C}$ by the $^{12}\mathrm{C}(\vec{e},e'\vec{p})$ process at the Mainz Microtron (MAMI). We observed consistent deviations from unity of this ratio normalized to the free-proton ratio, $(P_{x}/P_{z})_{^{12}\mathrm{C}}/(P_{x}/P_{z})_{^{1}\mathrm{H}}$, for both $s$- and $p$-shell knocked out protons, even though they are embedded in averaged local densities that differ by about a factor of two. The dependence of the double ratio on proton virtuality is similar to the one for knocked out protons from $^{2}\mathrm{H}$ and $^{4}\mathrm{He}$, suggesting a universal behavior. It further implies no dependence on average local nuclear density

Urgent computing of storm surge for North Carolina's coast

Forecasting and prediction of natural events, such as tropical and extra-tropical cyclones, inland flooding, and severe winter weather, provide critical guidance to emergency managers and decision-makers from the local to the national level, with the goal of minimizing both human and economic losses. This guidance is used to facilitate evacuation route planning, post-disaster response and resource deployment, and critical infrastructure protection and securing, and it must be available within a time window in which decision makers can take appropriate action. This latter element is that which induces the need for urgency in this area. In this paper, we outline the North Carolina Forecasting System (NCFS) for storm surge and waves for coastal North Carolina, which is threatened by tropical cyclones about once every three years. We initially used advanced cyberinfrastructure techniques (e.g., opportunistic grid computing) in an effort to provide timely guidance for storm surge and wave impacts. However, our experience has been that a distributed computing approach is not robust enough to consistently produce the real-time results that end users expect. As a result, our technical approach has shifted so that the reliable and timely delivery of forecast products has been guaranteed by provisioning dedicated computational resources as opposed to relying on opportunistic availability of external resources. Our experiences with this forecasting effort is discussed in this paper, with a focus on Hurricane Irene (2011) that impacted a substantial portion of the US east coast from North Carolina, up along the eastern seaboard, and into New England

Large Eddy Simulation based Analysis of Complex Flow Structures within the Volute of a Vaneless Centrifugal Pump

Centrifugal pumps are very common in many fluid handling industrial applications, such as petrochemicals, oil and gas etc. Although the design practices for centrifugal pumps are well established, efforts are directed towards optimising such systems for better operational efficiencies. In order to optimally design centrifugal pumps, it is beneficial to first understand the complex flow phenomena within different sections of the pump for a variety of operating conditions. This is normally achieved through the use of modern techniques, such as Computational Fluid Dynamics (CFD), where the flow within centrifugal pumps can be numerically modelled and important flow features can be analysed for better understanding of interactions amongst different process variables. CFD offers different turbulence modelling techniques with an aim to predict realistic flow approximations. Larger Eddy Simulation (LES) offers a more accurate solution to this, in which the larger eddies are resolved while smaller eddies are modelled, hence predictions using LES are more realistic. Further to turbulence modelling within centrifugal pumps, it is also important to model the complete interaction amongst different variables rather than a simplistic single blade passage flow analysis. In the present work, the complex blade-tongue interactions, and their consequent effects on the pressure fluctuations within the volute have been evaluated. It is seen that the secondary flow features in the near tongue regions due to blade interactions with the tongue, affect the flow characteristics within the volute considerably

Extended states in 1D lattices: application to quasiperiodic copper-mean chain

The question of the conditions under which 1D systems support extended electronic eigenstates is addressed in a very general context. Using real space renormalisation group arguments we discuss the precise criteria for determining the entire spertrum of extended eigenstates and the corresponding eigenfunctions in disordered as well as quasiperiodic systems. For purposes of illustration we calculate a few selected eigenvalues and the corresponding extended eigenfunctions for the quasiperiodic copper-mean chain. So far, for the infinite copper-mean chain, only a single energy has been numerically shown to support an extended eigenstate [ You et al. (1991)] : we show analytically that there is in fact an infinite number of extended eigenstates in this lattice which form fragmented minibands.Comment: 10 pages + 2 figures available on request; LaTeX version 2.0