gebhart/patrepeval huggingface dataset:
Cloning and sequencing of a highly productive, endotheliotropic virus strain derived from human cytomegalovirus TB40/E (2008)

Human cytomegalovirus (HCMV) strain TB40/E, replicates efficiently, exhibits a broad cell tropism and is widely used for infection of endothelial cells and monocyte-derived cells yet has not been available in a phenotypically homogeneous form compatible with genetic analysis. To overcome this problem, we cloned the TB40/E strain into a bacterial artificial chromosome (BAC) vector. Both highly endotheliotropic and poorly endotheliotropic virus clones, representing three distinct restriction fragment patterns, were reconstituted after transfection of BAC clones derived from previously plaque-purified strain TB40/E. For one of the highly endotheliotropic clones, TB40-BAC4, we provide the genome sequence. Two BACs with identical restriction fragment patterns but different cell tropism were further analysed in the UL128-UL131A gene region. Sequence analysis revealed one coding-relevant adenine insertion at position 332 of UL128 in the BAC of the poorly endotheliotropic virus, which caused a frameshift in the C-terminal part of the coding sequence. Removal of this insertion by markerless mutagenesis restored the highly endotheliotropic phenotype, indicating that the loss of endothelial cell tropism was caused by this insertion. In conclusion, HCMV strain TB40/E, which combines the high endothelial cell tropism of a clinical isolate with the high titre growth of a cell culture adapted strain, is now available as a BAC clone suitable for genetic engineering. The results also suggest BAC cloning as a suitable method for selection of genetically defined virus clones.
Design of a Droopnose Configuration for a Coanda Active Flap Application (2013)

The present study describes the fundamentals of droopnose design for improving the aerodynamics of airfoils with active high-lift using a Coanda ap. Increasing the stall angle of attack and reducing the power required by the high-lift system, are the main objectives. The sensitivities of the investigated geometries are described, as well as the physical phenomena that rule the aerodynamic performance.
Identification and proteomic profiling of exosomes in human urine (2004)

Urine provides an alternative to blood plasma as a potential source of disease biomarkers. One urinary biomarker already exploited in clinical studies is aquaporin-2. However, it remains a mystery how aquaporin-2 (an integral membrane protein) and other apical transporters are delivered to the urine. Here we address the hypothesis that these proteins reach the urine through the secretion of exosomes [membrane vesicles that originate as internal vesicles of multivesicular bodies (MVBs)]. Low-density urinary membrane vesicles from normal human subjects were isolated by differential centrifugation. ImmunoGold electron microscopy using antibodies directed to cytoplasmic or anticytoplasmic epitopes revealed that the vesicles are oriented "cytoplasmic-side inward," consistent with the unique orientation of exosomes. The vesicles were small (<100 nm), consistent with studies of MVBs and exosomes from other tissues. Proteomic analysis of urinary vesicles through nanospray liquid chromatography-tandem mass spectrometry identified numerous protein components of MVBs and of the endosomal pathway in general. Full liquid chromatography-tandem MS analysis revealed 295 proteins, including multiple protein products of genes already known to be responsible for renal and systemic diseases, including autosomal dominant polycystic kidney disease, Gitelman syndrome, Bartter syndrome, autosomal recessive syndrome of osteopetrosis with renal tubular acidosis, and familial renal hypomagnesemia. The results indicate that exosome isolation may provide an efficient first step in biomarker discovery in urine.
Prospective motion correction with continuous gradient updates in diffusion weighted imaging (2011)

Despite the existence of numerous motion correction methods, head motion during MRI continues to be a major source of artifacts and can greatly reduce image quality. This applies particularly to diffusion weighted imaging, where strong gradients are applied during long encoding periods. These are necessary to encode microscopic movements. However, they also make the technique highly sensitive to bulk motion. In this work, we present a prospective motion correction method where all applied gradients are adjusted continuously to compensate for changes of the object position and ensure the desired phase evolution in the image coordinate frame. Additionally, in phantom experiments this new technique is used to reproduce motion artifacts with high accuracy by changing the position of the imaging frame relative to the measured object. In vivo measurements demonstrate the validity of the new correction method.
Mild Pre- and Posttraumatic Hypothermia Attenuates Blood-Brain Barrier Damage Following Controlled Cortical Impact Injury in the Rat (1996)

Recent studies have demonstrated a neuroprotective effect of mild/moderate hypothermia in models of cerebral trauma and ischemia. In contrast, hypotension is known to exacerbate CNS injury. To better understand the mechanisms whereby hypothermia and hypotension influence secondary neural injury, the present study assessed the effects of these two variables upon blood-brain barrier (BBB) permeability following controlled cortical impact injury. Rats were subjected to either 0, 15, or 30 min of hypotension under normothermic or slightly hypothermic brain temperature conditions. Brain temperature was maintained within 0.5 degrees C of baseline (normothermic) or allowed to float freely (e.g., become hypothermic) throughout the study. Hypotension was induced immediately after head injury by rapid hemorrhage down to a mean arterial pressure of 50 mm Hg and held there for 15 or 30 min. Blood-brain barrier permeability was measured by the extravasation of plasma protein-bound Evan's blue dye into the injured cortex at 60 min postinjury. The results revealed that mild hypothermia (< 1.6 +/- 0.2 degrees C), right before and 15-30 min following head injury, significantly reduced BBB permeability 28.0, 21.8, and 26.2% in rats subjected to 0, 15, or 30 min hypotension, respectively (all p values < or = 0.05). Hypotension did not increase BBB permeability nor did it significantly interact with the brain temperature effect. Previous results, using this same model, have shown that the progressive posttraumatic increase in BBB permeability is preceded by an increase in cortical .OH and lipid hydroperoxides at the site of injury and is attenuated by the lipid peroxidation inhibitor tirilazad mesylate. Thus, the present results are discussed in terms of the role of free radical-induced lipid peroxidation in the genesis of posttraumatic BBB damage and the possible effects of hypothermia upon this injury process.
SCALP: an iterative-improvement-based low-power data path synthesis system (1997)

In this paper, we present SCALP, a comprehensive low-power data path synthesis system that performs the various high-level synthesis tasks (transformations, scheduling, clock selection, module selection, and hardware allocation and assignment) with an aim of reducing the power consumption in the synthesized data path. Focusing on only one or a small subset of the high-level synthesis tasks makes it difficult to realize the full potential for power savings at the algorithm and architecture levels. Our synthesis algorithms, which are based on an iterative improvement strategy with efficient pruning techniques, are capable of performing the various high-level synthesis tasks (and considering their interactions) in an efficient manner. Supply voltage and clock period pruning strategies are used for quickly eliminating inferior design points during the search for the minimum power solution. Estimating switched capacitance accurately at intermediate stages during high-level synthesis can be challenging since the exact structure of the circuit, which affects both physical capacitance and switching activity, may not be available, and due to the high computational complexity of running register-transfer level power analysis tools several times during high-level synthesis. SCALP overcomes the above problems by maintaining a complete image of the structural register-transfer level (RTL) circuit (this is possible since we have a complete solution at any point during iterative improvement), and employing a very fast switched capacitance estimation technique that Is based on the concept of switched capacitance matrices. Our system can handle diverse module libraries and utilize complex scheduling constructs such as multicycling, chaining, and structural pipelining. Retiming and functional pipelining are used in our system to meet tight performance constraints, and to enable the ensuing synthesis steps to better explore the implementation space. Results on several real-life examples are presented to demonstrate the effectiveness of the algorithm. Power estimates obtained using switch-level simulation after layout indicate that up to an order-of-magnitude of power savings can be obtained using our synthesis system.
Electrical Characteristics and Reliability of Pt/Ti/Pt/Au Ohmic Contacts to p-Type GaAs (1991)

The ohmic contacts to p-type GaAs formed by GaAs/Pt/Ti/Pt/Au systems were investigated. The specific contact resistance below 8×10 -7 Ω·cm 2 was achieved when the interface Pt between GaAs and Ti/Pt/Au was thicker than 50 Å, which is about one-fourth of the conventional Ti/Pt/Au contact. The activation energies of the initial degradation of the Pt/Ti/Pt/Au electrodes correspond to the reaction of GaAs and Pt to form PtAs 2 . However, even after the initial degradation, Pt/Ti/Pt/Au with the thin Pt interface layer still shows lower contact resistivity. These systems are promising for practical p-tye ohmic contacts for AlGaAs/GaAs heterojunction bipolar transistors.
Simultaneous mutation and copy number variation (CNV) detection by multiplex PCR-based GS-FLX sequencing (2008)

We evaluated multiplex PCR amplification as a front-end for high-throughput sequencing, to widen the applicability of massive parallel sequencers for the detailed analysis of complex genomes. Using multiplex PCR reactions, we sequenced the complete coding regions of seven genes implicated in peripheral neuropathies in 40 individuals on a GS-FLX genome sequencer (Roche). The resulting dataset showed highly specific and uniform amplification. Comparison of the GS-FLX sequencing data with the dataset generated by Sanger sequencing confirmed the detection of all variants present and proved the sensitivity of the method for mutation detection. In addition, we showed that we could exploit the multiplexed PCR amplicons to determine individual copy number variation (CNV), increasing the spectrum of detected variations to both genetic and genomic variants. We conclude that our straightforward procedure substantially expands the applicability of the massive parallel sequencers for sequencing projects of a moderate number of amplicons (50-500) with typical applications in resequencing exons in positional or functional candidate regions and molecular genetic diagnostics.
Metabolomic analysis of survival in carbohydrate pre-fed pigs subjected to shock and polytrauma (2016)

Abstract Hemorrhagic shock, a result of extensive blood loss, is a dominant factor in battlefield morbidity and mortality. Early rodent studies in hemorrhagic shock reported carbohydrate feeding prior to the induction of hemorrhagic shock decreased mortality. When repeated in our laboratory with a porcine model, carbohydrate pre-feed resulted in a 60% increase in death rate following hemorrhagic shock with trauma when compared to fasted animals (15/32 or 47% vs. 9/32 or 28%). In an attempt to explain the unexpected death rate for pre-fed animals, we further investigated the metabolic profiles of pre-fed non-survivors (n = 15) across 4 compartments (liver, muscle, serum, and urine) at specific time intervals (pre-shock, shock, and resuscitation) and compared them to pre-fed survivors (n = 17). As hypothesized, pre-fed pigs that died as a result of hemorrhage and trauma showed differences in their metabolic and physiologic profiles at all time intervals and in all compartments when compared to pre-fed survivors. Our data suggest that, although all animals were subjected to the same shock and trauma protocol, non-survivors exhibited altered carbohydrate processing as early as the pre-shock sampling point. This was evident in (for example) the higher levels of ATP and markers of greater anabolic activity in the muscle at the pre-shock time point. Based on the metabolic findings, we propose two mechanisms that connect pre-fed status to a higher death rate: (1) animals that die are more susceptible to opening of the mitochondrial permeability transition pore, a major factor in ischemia/reperfusion injury; and (2) loss of fasting-associated survival mechanisms in pre-fed animals.
Gap Junctions in Vascular Tissues (1996)

Integration and coordination of responses among vascular wall cells are critical to the local modulation of vasomotor tone and to the maintenance of circulatory homeostasis. This article reviews the vast literature concerning the principles that govern the initiation and propagation of vasoactive stimuli among vascular smooth muscle cells, which are nominally the final effectors of vasomotor tone. In light of the abundance of new information concerning the distribution and function of gap junctions between vascular wall cells throughout the vascular tree, particular attention is paid to this integral aspect of vascular physiology. Evidence is provided for the important contribution of intercellular communication to vascular function at all levels of the circulation, from the largest elastic artery to the terminal arterioles. The thesis of this review is that the presence of gap junctions, in concert with the autonomic nervous system, pacemaker cells, myogenic mechanisms, and/or electrotonic current spread (both hyperpolarizing and depolarizing waves through gap junctions), confers a plasticity, adaptability, and flexibility to vasculature that may well account for the observed diversity in regulation and function of vascular tissues throughout the vascular tree. It is hoped that the summary information provided here will serve as a launching pad for a new discourse on the mechanistic basis of the integrative regulation and function of vasculature, which painstakingly accounts for the undoubtedly complex and manifold role of gap junctions in vascular physiology/dysfunction.
p53: A Guide to Apoptosis (2008)

Approximately 50% of sporadic human tumors harbor somatic mutations in the p53 gene locus, while germ line mutations confer a high familial risk and are associated with Li-Fraumeni Syndrome patients. The p53 tumor suppressor protein is often referred to as the "guardian of the genome" since its response to DNA-damage or checkpoint failure gives rise to a series of anti-proliferative responses. One of the most important functions of p53 is its ability to induce apoptosis, while disruption of this route can promote tumor progression and chemo resistance. Besides its ability to promote apoptosis through transcription dependent mechanisms, p53 may also be able to activate apoptosis independent of transcriptional regulation. Therefore, to ensure normal cell growth, p53 levels and activity are tightly regulated. Upon diverse forms of cellular stress the steady state levels and transcriptional activity of p53 are considerably increased. The stabilization and activation of p53 are a result of hindered inhibition by its negative regulators, e.g. Mdmx (also known as Mdm4) and Mdm2, while on the other hand activators such as HIPK2 and DYRK2 enhance the p53 response. The continually increasing understanding of the mechanisms of regulation of p53 may provide the basis for new drug designs that could eventually lead to therapeutics to reactivate p53 in cancers.
A novel immunohistochemical detection system using mirror image complementary antibodies (MICA) (1999)

We have described and illustrated a novel immunohistochemical detection system and demonstrated greatly increased sensitivity over the commonly used ABC system. An additional advantage of the MICA system is that it is avidin-free and so avoids non-specific staining due to endogenous tissue biotin.
Platelet-derived Growth Factor Signal Transduction through the Interferon-inducible Kinase PKR (1995)

The interferon-inducible, double-stranded RNA (dsRNA)-dependent eukaryotic initiation factor-2 alpha kinase PKR has primarily been characterized as a component of the interferon-mediated cellular antiviral response. Several lines of evidence now exist that suggest that PKR plays a role in the regulation of growth in uninfected cells. The most direct examples are the finding of an oncogenic variant of PKR and the effects of activators and inhibitors of PKR phosphorylation on the expression of platelet-derived growth factor (PDGF)-inducible genes. Previous reports have shown that 1) dsRNA, a direct activator of PKR, induces the genes c-myc, c-fos, and JE; 2) 2-aminopurine, a chemical inhibitor of PKR, blocks the induction of these genes by serum; and 3) activated p21ras induces a cellular inhibitor of PKR. We report here that activation of PKR was correlated with the induction of the immediate early genes c-fos, c-myc, and JE by PDGF in the following situations: 1) PDGF induction of these genes, also inducible by dsRNA, was blocked by two inhibitors of PKR activation: 2-aminopurine and v-ras; 2) PDGF induction of another immediate early gene, egr-1, which could not be induced by dsRNA, was not blocked by 2-aminopurine or v-ras; 3) agents that reverse v-ras inhibition of PKR activation also reversed the v-ras block of PDGF induction of c-myc, c-fos, and JE; 4) down-regulation of PKR protein levels by antisense inhibition of translation blocked the induction of c-myc, c-fos, and JE by PDGF, but had no effect on egr-1 induction; and finally, 5) PKR was autophosphorylated in vivo in response to PDGF. These results provide direct evidence that PKR activation functions as a second messenger in a growth factor signal transduction pathway. Thus, PKR may serve as a common mediator of growth-promoting and growth inhibitory signals.
Molecular Scale Electronics:  A Synthetic/Computational Approach to Digital Computing (1998)

This paper outlines a design paradigm for molecular scale electronic systems. The contrast between the present bulk devices and potential molecular systems is presented along with the limitations of using bulk design philosophies for molecular-sized components. For example, the overwhelming considerations of heat dissipation on molecular scale electronic architectures are shown which demonstrate the need for dramatically different information transfer methods if these ultradense molecular devices are to be used for computation. The use of changes in electrostatic potential for information coding is suggested. The issue of signal restoration is addressed using a periodic external potential through the underlying substrate. Several convergent synthetic routes are shown to conjugated molecules with various potential digital device applications including a two-terminal molecular wire with a tunnel barrier, a molecular wire with a quantum well to serve as a resonant-tunneling diode, three-terminal systems with switch-like possibilities, and four-terminal systems that could serve as logical gates without the use of multiple transistors. Ab initio computational methods are used to show that (i) molecules can be considered active electronic devices able to transfer the information from one molecule to another, (ii) the electrostatic potential can also be used as a tool to perform logical operations, and (iii) the molecules synthesized here could perform the functions for which they were designed.
Optimal Step Nonrigid ICP Algorithms for Surface Registration (2007)

We show how to extend the ICP framework to nonrigid registration, while retaining the convergence properties of the original algorithm. The resulting optimal step nonrigid ICP framework allows the use of different regularisations, as long as they have an adjustable stiffness parameter. The registration loops over a series of decreasing stiffness weights, and incrementally deforms the template towards the target, recovering the whole range of global and local deformations. To find the optimal deformation for a given stiffness, optimal iterative closest point steps are used. Preliminary correspondences are estimated by a nearest-point search. Then the optimal deformation of the template for these fixed correspondences and the active stiffness is calculated. Afterwards the process continues with new correspondences found by searching from the displaced template vertices. We present an algorithm using a locally affine regularisation which assigns an affine transformation to each vertex and minimises the difference in the transformation of neighbouring vertices. It is shown that for this regularisation the optimal deformation for fixed correspondences and fixed stiffness can be determined exactly and efficiently. The method succeeds for a wide range of initial conditions, and handles missing data robustly. It is compared qualitatively and quantitatively to other algorithms using synthetic examples and real world data.
Multiple organ infection and the pathogenesis of SARS (2005)

After >8,000 infections and >700 deaths worldwide, the pathogenesis of the new infectious disease, severe acute respiratory syndrome (SARS), remains poorly understood. We investigated 18 autopsies of patients who had suspected SARS; 8 cases were confirmed as SARS. We evaluated white blood cells from 22 confirmed SARS patients at various stages of the disease. T lymphocyte counts in 65 confirmed and 35 misdiagnosed SARS cases also were analyzed retrospectively. SARS viral particles and genomic sequence were detected in a large number of circulating lymphocytes, monocytes, and lymphoid tissues, as well as in the epithelial cells of the respiratory tract, the mucosa of the intestine, the epithelium of the renal distal tubules, the neurons of the brain, and macrophages in different organs. SARS virus seemed to be capable of infecting multiple cell types in several organs; immune cells and pulmonary epithelium were identified as the main sites of injury. A comprehensive theory of pathogenesis is proposed for SARS with immune and lung damage as key features.
RPR120844, a Novel, Specific Inhibitor of Coagulation Factor Xa Inhibits Venous Thrombosis in the Rabbit (1999)

The in vivo antithrombotic activity of RPR 20844, a novel synthetic coagulation factor Xa (fXa) inhibitor (Ki = 7 nM), was assessed by its ability to inhibit thrombus formation in a damaged segment of the rabbit jugular vein. Intravenous dose-response studies were performed and thrombus mass (TM), activated partial thromboplastin time (APTT), prothrombin time (PT), inhibition of ex vivo fXa activity and plasma drug levels (PDL) were determined. TM, measured at the end of a 50 min infusion, was significantly reduced (p<0.05 vs. saline-treated animals) by RPR120844 at 30 and 100 microg/kg/min. At doses of 10, 30 and 100 microg/kg/min, APTT was prolonged by 2.1, 4.2 and 6.1-fold, and PT was prolonged by 1.4, 2.2 and 3.5-fold, respectively. PDL were determined by measuring anti-fXa activity using an amidolytic assay. Peak PDL were 0.8+/-0.3, 1.5+/-0.9 and 2.4+/-0.6 microM, respectively. The drug effect was reversible with APTT, PT and PDL returning toward pretreatment values 30 min after termination of treatment. The results suggest that RPR 120844, or similar compounds, may provide an efficacious, yet easily reversible, means of inhibiting thrombus formation.