gebhart/patrepeval huggingface dataset:
COVID-19 Sepsis: Pathogenesis and Endothelial Molecular Mechanisms Based on “Two-Path Unifying Theory” of Hemostasis and Endotheliopathy-Associated Vascular Microthrombotic Disease, and Proposed Therapeutic Approach with Antimicrothrombotic Therapy (2021)

COVID-19 sepsis is characterized by acute respiratory distress syndrome (ARDS) as a consequence of pulmonary tropism of the virus and endothelial heterogeneity of the host. ARDS is a phenotype among patients with multiorgan dysfunction syndrome (MODS) due to disseminated vascular microthrombotic disease (VMTD). In response to the viral septicemia, the host activates the complement system which produces terminal complement complex C5b-9 to neutralize pathogen. C5b-9 causes pore formation on the membrane of host endothelial cells (ECs) if CD59 is underexpressed. Also, viral S protein attraction to endothelial ACE2 receptor damages ECs. Both affect ECs and provoke endotheliopathy. Disseminated endotheliopathy activates two molecular pathways: inflammatory and microthrombotic. The former releases inflammatory cytokines from ECs, which lead to inflammation. The latter initiates endothelial exocytosis of unusually large von Willebrand factor (ULVWF) multimers and FVIII from Weibel-Palade bodies. If ADAMTS13 is insufficient, ULVWF multimers activate intravascular hemostasis of ULVWF path. In activated ULVWF path, ULVWF multimers anchored to damaged endothelial cells recruit circulating platelets and trigger microthrombogenesis. This process produces "microthrombi strings" composed of platelet-ULVWF complexes, leading to endotheliopathy-associated VMTD (EA-VMTD). In COVID-19, microthrombosis initially affects the lungs per tropism causing ARDS, but EA-VMTD may orchestrate more complex clinical phenotypes, including thrombotic thrombocytopenic purpura (TTP)-like syndrome, hepatic coagulopathy, MODS and combined micro-macrothrombotic syndrome. In this pandemic, ARDS and pulmonary thromboembolism (PTE) have often coexisted. The analysis based on two hemostatic theories supports ARDS caused by activated ULVWF path is EA-VMTD and PTE caused by activated ULVWF and TF paths is macrothrombosis. The thrombotic disorder of COVID-19 sepsis is consistent with the notion that ARDS is virus-induced disseminated EA-VMTD and PTE is in-hospital vascular injury-related macrothrombosis which is not directly related to viral pathogenesis. The pathogenesis-based therapeutic approach is discussed for the treatment of EA-VMTD with antimicrothrombotic regimen and the potential need of anticoagulation therapy for coinciding macrothrombosis in comprehensive COVID-19 care.
E5202: The GI Intergroup Strategy for Stage II Colon Cancer Patients (2007)

"E5202: The GI Intergroup Strategy for Stage II Colon Cancer Patients." Oncology Issues, 22(2), pp. 20–21
Fabrication and analysis of a three-layer stratified volume diffractive optical element high-efficiency grating (2003)

We have demonstrated a high-efficiency grating (>80%) using a three-layer Stratified Volume Diffractive Optical Element (SVDOE). Its angular sensitivity was measured optically and shown to agree extremely well with simulations performed using rigorous coupled wave analysis (RCWA). Further simulations predict an increase in efficiency as the number of layers is increased. An SVDOE consists of binary grating layers interleaved with homogeneous layers. The binary grating layers are shifted laterally relative to each other to emulate a volume holographic grating with slanted fringes. Creating the slanted fringe structure permits the preferred incidence angle of the SVDOE to be rotated to any arbitrary position. Achieving the relative offset between grating layers is the most challenging fabrication step and required the development of a high-precision alignment technique that was implemented on a contact mask aligner. The approach is based on monitoring the diffraction signal of a beam that is transmitted through gratings on the substrate and those on the mask as they are translated with respect to one another during pre-exposure alignment. The homogeneous layers are fabricated using a polymer material, SU-8, that is spin-coated and then planarized during its curing process.
A new proposed location registration procedure in next-generation mobile networks (NGMN) (2011)

The objective of this research is to propose a new location registration procedure for System Architecture Evolution (SAE) which is the core network architecture of 3GPP's future Long Term Evolution (LTE) wireless communication standard. Under the proposed procedure, the authentication between access systems supporting different IP versions is carried out. A signaling message for a new location registration procedure is developed to evaluate the performance of the signaling procedure. The numerical results showed that the proposed procedure reduces the registration costs and latency for location registration. Therefore, this procedure results in significant performance improvements for SAE.
Transcriptome Analysis of <i>Arabidopsis</i> Clubroots Indicate a Key Role for Cytokinins in Disease Development (2006)

The clubroot disease of the family Brassicaceae is caused by the obligate biotrophic protist Plasmodiophora brassicae. Infected roots undergo a developmental switch that results in the formation of aberrant roots (clubs). To investigate host gene expression during the development of the disease, we have used the Arabidopsis ATH1 genome array. Two timepoints were chosen, an early timepoint at which the pathogen has colonized the root but has induced only very limited change of host cell and root morphology and a later timepoint at which more than 60% of the host root cells were colonized and root morphology was drastically altered. At both timepoints, more than 1,000 genes were differentially expressed in infected versus control roots. These included genes associated with growth and cell cycle, sugar phosphate metabolism, and defense. The involvement of plant hormones in club development was further supported; genes involved in auxin homeostasis, such as nitrilases and members of the GH3 family, were upregulated, whereas genes involved in cytokinin homeostasis (cytokinin synthases and cytokinin oxidases/dehydrogenases) were already strongly downregulated at the early timepoint. Cytokinin oxidase/dehydrogenase overexpressing lines were disease resistant, clearly indicating the importance of cytokinin as a key factor in clubroot disease development.
Implementation of a new type DSP PLL using high performance DSP DSSP-1 (2005)

This paper describes a new digital processing Phase Lock Loop (PLL) implemented on a high performance DSP, the DSSP1. Called the Linear Digital PLL (L-DPLL), the new PLL has linearty in its phase comparison characteristics. It gives fast acquision without increase in jitter, its pull-in range is wider; and its steady state errors and sampling frequency are lower than with conventional PLLs. It also does not require Automatic Gain Control.
Statistical Accuracy in the Photon Counting Structure Function of Fluctuating Light Fields (1981)

An analysis of the variance of the structure function coefficients of a train of digital photodetections, both unnormalized and with various normalizations, is made and compared with known corresponding results for the photon correlation function. A gaussian-lorentzian model light field is used in both direct and homodyne detection. Numerical simulations confirm and extend the analytical results, which show certain circumstances when the structure function may be a useful alternative measure of spectral content.
Sol–gel derived organic–inorganic hybrid materials for photonic applications (1998)

The author presents recent progress on sol–gel derived organic–inorganic hybrid materials, especially with photonic applications in mind. The classification, synthesis, forming and structural characterisation of this new class of materials, based on sol–gel derived siloxane matrices, are described. These new materials potentially combine the excellent optical properties of silica with the flexibility of incorporating organic moiety at the molecular level. The organic character can facilitate low temperature (< 200°C) processing of thin films. The added organic moiety can be designed to influence the linear and nonlinear optical properties of the material. Potential photonic applications cover an enormous range, including passive and active waveguides, sensors, optical limiters and solid-state dye lasers.
Rat endopeptidase‐24.18 α subunit is secreted into the culture medium as a zymogen when expressed by COS‐1 cells (1993)

Endopeptidase-24.18 (EC 3.4.24.18, E-24.18) is an oligomeric Zn-ectoenzyme. The alpha and beta subunits have been cloned from both rat and mouse kidneys. The primary structure of these subunits revealed that they both contain the consensus Zn binding site and that they are members of the astacin family. Analysis of the hydropathy plot also suggested that they are anchored by a C-terminal hydrophobic domain. In order to verify the mode of anchoring of the rat E-24.18 alpha subunit and to test the functionality of the astacin-like domain in the alpha subunit when expressed alone, COS-1 cells were transfected with a cloned cDNA for rat alpha subunit. Despite the presence of its putative transmembrane domain, the alpha subunit was not anchored in the plasma membrane but rather secreted as a dimer into the culture medium. When the enzymatic activity of the secreted recombinant protein was tested in the azocasein degradation assay, the alpha subunit was found to be inactive. Activity could, however, be revealed after mild trypsin digestion. This activity was abolished by replacing the Glu-157 in the active site by Val. Taken together our results suggest that the alpha subunit of Endopeptidase-24.18 contains a latent astacin-like Zn metallopeptidase activity which could be secreted as a soluble enzyme by kidney and intestine.
Real-time PET image reconstruction based on regularized pseudo-inverse of the system matrix (2005)

The feasibility of tomographic image reconstruction by projection data filtering based on the singular value decomposition of the system matrix has recently been demonstrated in high-resolution animal positron emission tomography (PET). A regularization methodology involving truncation of the singular value spectrum based on the systematic spatial resolution analysis has been proposed and successfully applied. In the present paper, we show how realtime image reconstruction can be achieved using the regularized pseudo-inverse of the system matrix. An update of the current image estimate can be obtained using one column of the regularized pseudo-inverse matrix to account for the next registered event, thus allowing, in principle, for instant visualization of the radioactivity distribution while the object is still being scanned. Computed estimates converge to the minimum-norm least-squares solution of the regularized inverse problem when sufficient total counts are acquired to fulfill the assumption of the normal data error distribution. The computing expenses for image updating to account for the next registered event depend only on the total number of pixels in the discrete image representation. Data storage requirements are discussed. Limited angle tomography and non-traditional detection geometry may be handled using the described image reconstruction approach as well. The proposed method was tested with the list-mode PET data.
When mutualists are pathogens: an experimental study of the symbioses between <i>Steinernema</i> (entomopathogenic nematodes) and <i>Xenorhabdus</i> (bacteria) (2004)

In this paper, we investigate the level of specialization of the symbiotic association between an entomopathogenic nematode (Steinernema carpocapsae) and its mutualistic native bacterium (Xenorhabdus nematophila). We made experimental combinations on an insect host where nematodes were associated with non-native symbionts belonging to the same species as the native symbiont, to the same genus or even to a different genus of bacteria. All non-native strains are mutualistically associated with congeneric entomopathogenic nematode species in nature. We show that some of the non-native bacterial strains are pathogenic for S. carpocapsae. When the phylogenetic relationships between the bacterial strains was evaluated, we found a clear negative correlation between the effect a bacterium has on nematode fitness and its phylogenetic distance to the native bacteria of this nematode. Moreover, only symbionts that were phylogenetically closely related to the native bacterial strain were transmitted. These results suggest that co-evolution between the partners has led to a high level of specialization in this mutualism, which effectively prevents horizontal transmission. The pathogenicity of some non-native bacterial strains against S. carpocapsae could result from the incapacity of the nematode to resist specific virulence factors produced by these bacteria.
Efficacy of oral 9‐(2‐phosphonylmethoxyethyl)‐2,6‐diaminopurine (PMEDAP) in the treatment of retrovirus and cytomegalovirus infections in mice (1993)

9-(2-Phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) is a broad-spectrum antiviral agent with potent activity against DNA viruses and retroviruses. We now demonstrate that PMEDAP is highly efficacious when given orally to mice infected with either Moloney murine sarcoma virus (MSV), Friend leukemia virus (FLV), or murine cytomegalovirus (MCMV). PMEDAP markedly delayed MSV-induced tumor initiation when administered orally at 50, 100, or 250 mg/kg/day during 5 subsequent days. At the highest dose (250 mg/kg/day), PMEDAP completely prevented tumor formation in the MSV-infected animals. PMEDAP also caused 84-96% inhibition of FLV-induced splenomegaly when given orally to FLV-infected mice at 50-250 mg/kg/day. These PMEDAP treatment regimens were also markedly effective in increasing the survival rate of MCMV-infected mice. Intraperitoneal PMEDAP achieved a comparable antiviral activity at 2- to 5-fold lower doses than oral PMEDAP. However, the therapeutic index (ratio of the toxic dose to the antivirally effective dose) of oral PMEDAP was substantially higher than that of intraperitoneal PMEDAP. Oral PMEDAP at doses of 100, 250, or 500 mg/kg resulted in plasma PMEDAP levels of 0.5-2.5 micrograms/ml, which were sustained for 3 or 6 hours after administration and may account for the high antiviral efficacy achieved.
Expression of survivin mRNA in dog tumors (2005)

Survivin, a member of the inhibitor of apoptosis (IAP) gene family, overexpresses in various human tumors. Recently this protein has attracted strong interest as a potential prognostic marker because it promotes malignancy through anti-apoptotic activity and is associated with a more aggressive phenotype. To explore the utility of survivin as a veterinary marker of tumor malignancy, we performed molecular cloning of dog survivin cDNA and studied survivin mRNA expression in a variety of naturally occurring dog tumors. The dog cDNA contains a 426-bp open reading frame encoding 142 amino acids of polypeptide, in which a structure termed the baculovirus IAP repeat (BIR) domain, commonly observed in IAPs, is found, as it is in other mammalian survivin protein. The transcript was detected in many adult normal organs including heart, lung, liver, stomach, duodenum, colon, spleen, kidney and testis. As a result of quantitative expression analysis by real-time PCR undertaken for benign and malignant tumors, overexpression of the survivin gene was found in 3 of 18 malignant tumors and in none of the benign tumors, suggesting that survivin overexpression is associated with tumor malignancy in dog.
Murine leukemia virus envelope gp70 is a shared biomarker for the high-sensitivity quantification of murine tumor burden (2013)

The preclinical development of anticancer drugs including immunotherapeutics and targeted agents relies on the ability to detect minimal residual tumor burden as a measure of therapeutic efficacy. Real-time quantitative (qPCR) represents an exquisitely sensitive method to perform such an assessment. However, qPCR-based applications are limited by the availability of a genetic defect associated with each tumor model under investigation. Here, we describe an off-the-shelf qPCR-based approach to detect a broad array of commonly used preclinical murine tumor models. In particular, we report that the mRNA coding for the envelope glycoprotein 70 (gp70) encoded by the endogenous murine leukemia virus (MuLV) is universally expressed in 22 murine cancer cell lines of disparate histological origin but is silent in 20 out of 22 normal mouse tissues. Further, we detected the presence of as few as 100 tumor cells in whole lung extracts using qPCR specific for gp70, supporting the notion that this detection approach has a higher sensitivity as compared with traditional tissue histology methods. Although gp70 is expressed in a wide variety of tumor cell lines, it was absent in inflamed tissues, non-transformed cell lines, or pre-cancerous lesions. Having a high-sensitivity biomarker for the detection of a wide range of murine tumor cells that does not require additional genetic manipulations or the knowledge of specific genetic alterations present in a given neoplasm represents a unique experimental tool for investigating metastasis, assessing antitumor therapeutic interventions, and further determining tumor recurrence or minimal residual disease.
US FDA perspective on the regulations of medical-grade polymers: cyanoacrylate polymer medical device tissue adhesives (2007)

This article provides a brief description of the uses and clinical applications of medical-grade polymers, in particular synthetic cyanoacrylate adhesive/glue devices that have been cleared and/or approved as medical devices by the US FDA since the Medical Device Amendments of 1976 were enacted. This includes Class I cyanoacrylate devices (e.g., liquid bandages), Class II cyanoacrylate devices (e.g., dental cements), and Class III (premarket approval) cyanoacrylate devices such as Dermabond, Indermil Tissue Adhesive, Histoacryl and Histoacryl Blue Topical Skin Adhesive, and Trufill n-Butyl Cyanoacrylate Embolic Agent. By citing an example of FDA approved Class III devices in the cyanoacrylate technology, the article provides a brief discussion of the FDA approval process of medical devices. It includes the FDA issues regarding the published guidance document for 'Cyanoacrylate Topical Tissue Adhesives' that will provide guidance to regulatory personnel and manufacturers in the preparation of investigational device exception applications and in the development of valid scientific evidence to support premarket approval applications for cyanocrylate tissue adhesives intended for topical approximation of skin and others. The article provides a short regulatory description of the US FDA; under what laws its operates, how the FDA evaluates new devices for marketing, and how the device regulatory system works, for example, Class I, Class II, and Class III cyanoacrylate medical devices.
Optimization of a slow-acting automatic gain control system for use in hearing aids (1991)

This paper describes experiments evaluating and optimizing an automatic gain control system, called dual front-end AGC (abbreviated as D), intended for use in hearing aids. This system has two purposes: (1) to compensate for variations in the overall level of speech from one situation to another by slowly changing its gain; (2) to protect the user from sudden intense transients without affecting the long-term gain. This is achieved by using two control voltages to determine the gain. One changes slowly as the input varies in level. Normally this component determines the overall gain. The other comes into operation when an intense transient occurs. It acts rapidly to reduce the gain, avoiding over-amplification of the transient, but its action ceases quickly after the end of the transient. We describe four experiments measuring speech intelligibility for subjects with cochlear hearing loss in which we determine optimum values for two of the time constants of the D system, namely the recovery time of the fast component and the attack time of the slow component. The experiments also compare the D system with linear amplification (L) and 'adaptive compression' (A). The results show: (1) for the D system, optimum values are about 80-150 ms for the recovery time of the fast component and 150-325 ms for the attack time of the slow component; (2) in situations where intense transient sounds are present, and there is either no background sound (experiment 1) or continuous speech-shaped noise as a background (experiment 2), the D system gives significantly better performance than the L or A systems. When the background noise is a single voice, reversed in time (experiment 3), the D and L systems give similar performance, and both are markedly superior to the A system; (3) when the level of speech is varied over a range of 30 dB (experiment 4), both D and A systems allow good performance over the whole range of levels. Performance for the L system worsens markedly at the lower levels.
Understanding Drug Release and Absorption Mechanisms (2006)

Demand for better reliability from drug delivery systems has caused designers and researchers to move away from trial-and-error approaches and toward model-based methods of product development. Developing such models requires cross-disciplinary physical, mathematical, and physiological knowledge. Combining these areas under a single cover, Under
Cardiac metabolism in ischemic heart disease. (1999)

Myocardial ischemia is the metabolic consequence of an inadequate blood supply to the myocardium. How does the myocardium survive a severe insult? Ischemia, perhaps acting through hypoxia, is able to induce a series of cellular signals that lead to protective genetic reprogramming. Metabolic self-protection includes the new ischemic syndromes: stunning, hibernation and preconditioning. In every case it should be considered that ischemia is basically a metabolic problem, usually caused by coronary artery disease, stemming from lack of oxygen and blood flow. In principle, besides revascularization, metabolic therapy should be considered. In the past, metabolic therapies for effort angina have often been ignored. A current hypothesis is that the ischemic myocardium benefits from a switch from fatty acid to glucose metabolism. Two examples are (1) the hemodynamically neutral antianginal agent, trimetazidine, and (2) intravenous glucose-insulin-potassium (GIK). In acute myocardial infarction, GIK is undergoing a resurgence of interest due to the promising results of the large recent Argentinian trial. GIK acts in several ways, including the beneficial effects of insulin itself upon reperfusion, promotion of glycolysis, and inhibition of circulating fatty acids and hence of fatty acid oxidation. Metabolic therapy acting to protect the ischemic cell deserves more attention.
Reliability of copper wire bonds on a novel over-pad metallization (2015)

Wire bonding technology is used in most semiconductor products. Recently, high gold prices have forced semiconductor manufacturers to replace Au wires with Cu wires. Because Cu wire bonds are vulnerable to high temperature and humidity, they remain unpopular in automotive and industrial applications with narrow-bond-pad pitches and small deformed ball diameters. To avoid forming the corrosive Cu-rich intermetallic compound Cu9Al4, the use of a Ni/Pd(/Au) over-pad metallization (OPM) structure produced by electroless plating on the Al metallization has been proposed. However, certain technical issues must be overcome, such as variations in the purity and thickness of the plating. To tackle these issues, a novel OPM structure produced by physical vapor deposition is proposed and evaluated in this study.