gebhart/patrepeval huggingface dataset:
Elevated plasma interleukin-6 and increased severity and mortality in alcoholic hepatitis. (1991)

Recent studies in alcoholic hepatitis have proposed a role for the cytokine tumour necrosis factor-alpha (TNF-alpha) a mediator of endotoxic shock in sepsis. In this study plasma levels of the closely related cytokine interleukin-6 (IL-6) were assayed in 96 samples from 58 patients with severe alcoholic hepatitis, and 69 patients in control groups (21 normal, 10 alcoholic without liver disease, 10 inactive alcoholic cirrhosis, 18 chronic liver disease, 10 chronic renal failure). Plasma IL-6 levels were markedly elevated in patients with alcoholic hepatitis when compared with all control groups (P less than 0.001). IL-6 levels were higher in patients who died (P = 0.04) and correlated with the features of severe disease including: increased grade of encephalopathy, increased neutrophil count, increased prothrombin ratio, hypotension, increased serum creatinine and increased serum bilirubin. Surprisingly, no correlation was found between levels of plasma IL-6 and plasma TNF-alpha or endotoxin, or the presence of infection; an inverse correlation was found between plasma IL-6 and serum globulins. These findings provide further evidence that the IL-6/TNF cytokine system is activated in severe alcoholic hepatitis and may mediate hepatic or extra-hepatic tissue damage.
Erythropoietin: Gene Cloning, Protein Structure, and Biological Properties (1986)

The successful cloning of the gene for human erythropoietin (EPO) (Jacobs et al. 1985; Lin et al. 1985) has yielded information on the genetic organization and protein structure of this hormone and has allowed assessment of its biological properties. Biological studies have clearly indicated the clinical potential for this hormone in treatment of various anemias, and initial clinical studies of recombinant-DNA-produced human EPO (r-hEPO)1 are now under way.
Is transthoracic core needle biopsy under CT scan a good deal for benign diseases' diagnosis? (2014)

BACKGROUND: Transthoracic core needle biopsy under CT-Scan (TTNB) is frequently used for lung malignancies diagnosis. However, there is little data about its interest in the diagnosis of non-malignant diseases. This work aims to determine TTNBs diagnostic performance in this setting and whether some factors may influence diagnostic accuracy. METHOD: All TTNBs performed in three university centers of thoracic radiology between 2006 and 2012 were analyzed. Medical charts were then reviewed in order to record the final diagnosis retained (either by the TTNB, either by other exam or follow-up) by the physicians. Only TTNBs with a benign final diagnosis were included in this study while TTNBs with either no final diagnosis, either a malignant diagnosis were excluded. This study was declared to French ethic committee. Chi-square test was used for proportion comparisons. RESULTS: On the 980 TTNBs performed, 62 met the study criteria (61 patients). Final diagnosis were infectious (50%), inflammatory (23%), benign tumors (19%), and non-specific benign diseases (8%). Final diagnosis was concordant with initial diagnosis by TTNB in 68%. Sensibility and specificity for TTNB in this setting were 64% and 83%. Factors associated with a higher diagnostic accuracy were: radiologists' training (84% of diagnostic concordance if radiologist did more than 100 TTNBs during the study period vs 42%, p&amp;lt;0.001); targets' location in lower lobe (82% vs 50% in upper/median p =0.016); and needle diameter (69% for 16/18G vs 33% for 19/22G p=0.033). CONCLUSION: TTNB has moderate performance to diagnose accurately benign diseases but may be helpful if previous exams failed to find the correct diagnose.
Comparison of normalization methods for CodeLink Bioarray data (2005)

Median is insufficient either to reduce variability or to retain signal effectively for CodeLink Bioarray data. CyclicLoess is a more suitable approach for normalizing these data. CyclicLoess also seems to be the most effective method among the five different normalization strategies examined.
Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain (2000)

Although metformin is widely used for the treatment of non-insulin-dependent diabetes, its mode of action remains unclear. Here we provide evidence that its primary site of action is through a direct inhibition of complex 1 of the respiratory chain. Metformin(50 microM) inhibited mitochondrial oxidation of glutamate+malate in hepatoma cells by 13 and 30% after 24 and 60 h exposure respectively, but succinate oxidation was unaffected. Metformin also caused time-dependent inhibition of complex 1 in isolated mitochondria, whereas in sub-mitochondrial particles inhibition was immediate but required very high metformin concentrations (K(0.5),79 mM). These data are compatible with the slow membrane-potential-driven accumulation of the positively charged drug within the mitochondrial matrix leading to inhibition of complex 1. Metformin inhibition of gluconeogenesis from L-lactate in isolated rat hepatocytes was also time- and concentration-dependent, and accompanied by changes in metabolite levels similar to those induced by other inhibitors of gluconeogenesis acting on complex 1. Freeze-clamped livers from metformin-treated rats exhibited similar changes in metabolite concentrations. We conclude that the drug's pharmacological effects are mediated, at least in part, through a time-dependent, self-limiting inhibition of the respiratory chain that restrains hepatic gluconeogenesis while increasing glucose utilization in peripheral tissues. Lactic acidosis, an occasional side effect, canal so be explained in this way.
Tuning On–Off Current Ratio and Field-Effect Mobility in a MoS2–Graphene Heterostructure via Schottky Barrier Modulation (2014)

Field-effect transistor (FET) devices composed of a MoS2-graphene heterostructure can combine the advantages of high carrier mobility in graphene with the permanent band gap of MoS2 for digital applications. Herein, we investigate the electron transfer, photoluminescence, and gate-controlled carrier transport in such a heterostructure. We show that the junction is a Schottky barrier, whose height can be artificially controlled by gating or doping graphene. When the applied gate voltage (or the doping level) is zero, the photoexcited electron-hole pairs in monolayer MoS2 can be split by the heterojunction, significantly reducing the photoluminescence. By applying negative gate voltage (or p-doping) in graphene, the interlayer impedance formed between MoS2 and graphene exhibits an 100-fold increase. For the first time, we show that the gate-controlled interlayer Schottky impedance can be utilized to modulate carrier transport in graphene, significantly depleting the hole transport, but preserving the electron transport. Accordingly, we demonstrate a new type of FET device, which enables a controllable transition from NMOS digital to bipolar characteristics. In the NMOS digital regime, we report a very high room temperature on/off current ratio (ION/IOFF ∼ 36) in comparison to graphene-based FET devices without sacrificing the field-effect electron mobilities in graphene. By engineering the source/drain contact area, we further estimate that a higher value of ION/IOFF up to 100 can be obtained in the device architecture considered. The device architecture presented here may enable semiconducting behavior in graphene for digital and analogue electronics.
Galactosamine-induced sensitization to the lethal effects of endotoxin. (1979)

Treatment of rabbits, rats, and mice with D-galactosamine increased their sensitivity to the lethal effects of lipopolysaccharide several thousand fold. The susceptibility of the animals was highest when the lipopolysaccharide was injected together with galactosamine and decreased successively when injection was carried out 1, 2, and 3 hr later. Sensitization was absent when the lipopolysaccharide was administered 1 hr before or 4 hr after galactosamine. The onset of lethality after treatment with galactosamine and lipopolysaccharide occurred faster than with lipopolysaccharide alone; usually all animals died 5-9 hr later. The galactosamine-induced sensitization to lipopolysaccharide could be reversed by uridine which is known to inhibit the early biochemical alterations induced by the amino sugar in the hepatocytes. Although galactosamine is known to exhibit hepatotoxic activity inducing ultimate necrosis of the hepatocytes, the data so far suggests that the sensitization to lipopolysaccharide is related only to the early metabolic effects of the hexosamine.
Intracellular Reactive Oxygen Species Mediate the Therapeutic Effect of Induced Pluripotent Stem Cells for Acute Kidney Injury (2020)

We intravenously injected isogenic iPSCs into mice 2 h after renal ischemia-reperfusion injury (IRI). The cells were selectively trafficked to ischemia/reperfusion-injured kidney where they decreased kidney ROS and inflammatory cytokines and improved kidney function and morphology. Pretreating the cells with ROS inhibitors before administration decreased iPSC engraftment and abolished the protective effect of iPSCs. In contrast, pretreating iPSCs with hydrogen peroxide increased iPSC engraftment and therapeutic effect. Although the intravenously administered iPSCs trafficked to the IRI kidney, the cells did not differentiate into proximal or distal tubular epithelial cells. <i>In vitro</i>, the capabilities of the iPSC-released substances to promote proliferation and decrease apoptosis of renal epithelial cells were increased by ROS pretreatment of iPSCs. Moreover, pretreatment of the iPSCs with ROS inhibitor had the opposite effect. Similarly, moderate concentrations of ROS increased while ROS inhibitors decreased iPSC mobility, adhesion to the extracellular matrix, and mitochondrial metabolism. <i>Innovation and Conclusion</i>. iPSCs decreased renal ischemia/reperfusion injury mainly through iPSC-released substances. The therapeutic effect, mitochondrial metabolism, mobility, and kidney trafficking of iPSCs were ROS dependent.
Double-Cantilever Cleavage Mode of Crack Propagation (1964)

The quantitative cleavage method for determining specific surface energies of solids is subject to several possible sources of error. Some of these are investigated analytically in this study, and a general expression for the surface energy is derived from beam theory for a linearly elastic material. The exact equation of motion for the propagating crack is derived but not solved. Errors associated with each term of the general expression are assessed. The ratio of shear to bending strain energy is small if the initial crack length is long compared with the specimen depth. The term arising from strains in the specimen past the tip of the crack is not developed, but is estimated; and a procedure is outlined for determining this term experimentally. Comparison of simple beam theory with more exact elasticity theory shows that in the main spans the difference is small because it involves only the shear strain energy. Also, restriction of anticlastic curvature near the crack tip is unimportant if the initial crack length is long compared with the specimen width. Elastic anisotropy is unimportant when shear can be neglected, provided the appropriate modulus is used. For nonlinear elastic material, as the crack propagates a small amount, the work increment is either zero or double the strain energy increment. A surface energy expression is developed in terms of Timoshenko's ``reduced modulus,'' and upper and lower bounds are fixed. For plastic materials the analysis is based on pseudoinstantaneous plastic response. Justification of this assumption is difficult to defend or deny. Therefore, an important conclusion is that whenever possible specimens should be designed to remain grossly within the elastic limit of the material. Superposition of large axial forces is a potential source of large errors in surface energy determinations, and possible eccentricities in the application of such forces makes even the sign of these errors difficult to determine. Hence, this method for stabilizing the crack plane is not recommended.
Well-Defined Silica-Supported Olefin Metathesis Catalysts (2009)

Two triethoxysilyl-functionalized N-heterocyclic carbene ligands have been synthesized and used to prepare the corresponding second-generation ruthenium olefin metathesis catalysts. These complexes were then grafted onto silica gel, and the resulting materials were efficient heterogeneous catalysts for a number of metathesis reactions. The solid-supported catalysts were shown to be recyclable over a number of reaction cycles, and no detectable levels of ruthenium were observed in reaction filtrates (ruthenium concentration of filtrate <5 ppb).
Using video-oriented instructions to speed up sequence comparison (1997)

Benchmarks on an ULTRA SPARC running at 167 MHz show a speed-up factor of two compared to the same algorithm implemented with integer instructions on the same machine. Performance reaches over 18 million matrix cells per second on a single processor, giving to our knowledge the fastest implementation of the Smith-Waterman algorithm on a workstation. The accelerated procedure was introduced in LASSAP--a LArge Scale Sequence compArison Package software developed at INRIA--which handles parallelism at higher level. On a SUN Enterprise 6000 server with 12 processors, a speed of nearly 200 million matrix cells per second has been obtained. A sequence of length 300 amino acids is scanned against SWISSPROT R33 (1,8531,385 residues) in 29 s. This procedure is not restricted to databank scanning. It applies to all cases handled by LASSAP (intra- and inter-bank comparisons, Z-score computation, etc.
Rheological Properties of Cement Spacer: Mixture Effects (2008)

Cement spacers serve various functions including eroding mud deposition and displacement of drilling fluids before cementing the well. The efficacy of a spacer system is largely dependent on the rheological properties of both the fluid being displaced and the spacer itself. A spacer fluid is commonly a mixture of (1) a solid compound (such as barite), (2) water, and (3) a rheological modification agent. The proportions of these components in a spacer system will control the rheological properties of the final mixture, and thus, performance of the spacer. Therefore, if the spacer system could be modified to yield the rheological properties needed, it would be extremely beneficial. Such a “rheology modifying” spacer system has been developed. This system can be modified to yield the desired properties needed for the spacer to perform a particular function. The parameters needed to make this system work are based on findings from an extensive and systematic laboratory study in which component ratios were changed into numerous combinations and the results compared. This paper describes these tests and also how different flow regimes impact hole cleaning and fluid displacement. The paper then describes the spacer system that was successfully developed as well as its testing. The tests indicate that the rheology modification results in significant improvement in spacer performance.
Inhibition of constitutive STAT3 activity sensitizes resistant non-Hodgkin's lymphoma and multiple myeloma to chemotherapeutic drug-mediated apoptosis. (2003)

Hematopoietic malignancies have been shown to depend on cytokine growth factor autocrine/paracrine loops for growth and differentiation. This results in the constitutive activation of cytokine-mediated transcription factors like signal transducer and activators of transcription (STAT) 3 in non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Recent evidence demonstrates that cytokines also contribute to a drug-resistant phenotype in many tumor cell types. We hypothesized that inhibitors of the STAT3 pathway would sensitize drug-resistant and endogenous cytokine-dependent NHL and MM tumor cells to the cytotoxic effects of chemotherapeutic drugs. We examined an AIDS-related NHL cell line, 2F7, known to be dependent on interleukin (IL)-10 for survival and an MM cell line, U266, known to be dependent on IL-6 for survival. IL-10 and IL-6 signal the cells through the activation of Janus kinase (JAK)1 and JAK2, respectively. Thus, we investigated the effect of two chemical STAT3 pathway inhibitors, namely, piceatannol (JAK1/STAT3 inhibitor) and tyrphostin AG490 (JAK2/STAT3 inhibitor), on the tumor cells for sensitization to therapeutic drugs. We demonstrate by phosphoprotein immunoblotting analysis and electrophoretic mobility shift analysis that piceatannol and AG490 inhibit the constitutive activity of STAT3 in 2F7 and U266, respectively. Furthermore, piceatannol and AG490 sensitize 2F7 and U266 cells, respectively, to apoptosis by a range of therapeutic drugs including cisplatin, fludarabine, Adriamycin, and vinblastine. The specificity of the inhibitors was corroborated in experiments showing that piceatannol had no effect on U266 and, likewise, AG490 has no effect on 2F7. The sensitization observed by these inhibitors correlated with the inhibition of Bcl-2 expression in 2F7 and Bcl-xL expression in U266. Altogether, these results demonstrate that STAT3 pathway inhibitors are a novel class of chemotherapeutic sensitizing agents capable of reversing the drug-resistant phenotype of cytokine-dependent tumor cells.
Lipid-hydrogel nanoparticles: Synthesis methods and characterization (2009)

This dissertation focuses on the directed self-assembly of nanoscale soft matter particles using methods based on liposome-templating. Nanoscale liposomes, nano-sized hydrogel particles ("nanogels"), and hybrids of the two have enormous potential as carriers in drug delivery and nanotoxicity studies, and as nanovials for enzyme encapsulation and single molecule studies. Our goal is to develop assembly methods that produce stable nanogels or hybrid lipid-polymer nanoparticles, using liposomes as size and shape templates. First we describe a bulk method that employs liposomes to template relatively monodisperse nanogels composed of the biopolymer, alginate, which is a favorable material for nanogel formation because it uses a gentle ionic crosslinking mechanism that is suitable for the encapsulation of cells and biomolecules. Liposomes encapsulating sodium alginate are suspended in aqueous buffer containing calcium chloride, and thermal permeabilization of the lipid membrane facilitates transmembrane diffusion of Ca2+ ions from the surrounding buffer into the intraliposomal space, ionically crosslinking the liposome core. Subsequent lipid removal results in bare calcium alginate nanogels with a size distribution consistent with that of their liposome template. The second part of our study investigates the potential for microfluidic-directed formation of lipid-alginate hybrid nanoparticles by adapting the above bulk self-assembly procedure within a microfluidic device. Specifically we investigated the size control of alginate nanogel self-assembly under different flow conditions and concentrations. Finally, we investigate the microfluidic directed self-assembly of lipid-polymer hybrid nanoparticles, using phospholipids and an N-isopropylacrylamide monomer as the liposome and hydrogel precursors, respectively. Microfluidic hydrodynamic focusing is used to control the convective-diffusive mixing of the two miscible nanoparticle precursor solutions to form nanoscale vesicles with encapsulated hydrogel precursor. The encapsulated hydrogel precursor is polymerized off-chip and the resultant hybrid nanoparticle size distributions are highly monodisperse and precisely controlled across a broad range relevant to the targeted delivery and controlled release of encapsulated therapeutic agents. Given the ability to modify liposome size and surface properties by altering the lipid components and the many polymers of current interest for nanoparticle synthesis, this approach could be adapted for a variety of hybrid nanoparticle systems.
α 1 -Antitrypsin Portland, a bioengineered serpin highly selective for furin: Application as an antipathogenic agent (1998)

The important role of furin in the proteolytic activation of many pathogenic molecules has made this endoprotease a target for the development of potent and selective antiproteolytic agents. Here, we demonstrate the utility of the protein-based inhibitor alpha1-antitrypsin Portland (alpha1-PDX) as an antipathogenic agent that can be used prophylactically to block furin-dependent cell killing by Pseudomonas exotoxin A. Biochemical analysis of the specificity of a bacterially expressed His- and FLAG-tagged alpha1-PDX (alpha1-PDX/hf) revealed the selectivity of the alpha1-PDX/hf reactive site loop for furin (Ki, 600 pM) but not for other proprotein convertase family members or other unrelated endoproteases. Kinetic studies show that alpha1-PDX/hf inhibits furin by a slow tight-binding mechanism characteristic of serpin molecules and functions as a suicide substrate inhibitor. Once bound to furin's active site, alpha1-PDX/hf partitions with equal probability to undergo proteolysis by furin at the C-terminal side of the reactive center -Arg355-Ile-Pro-Arg358- downward arrow or to form a kinetically trapped SDS-stable complex with the enzyme. This partitioning between the complex-forming and proteolytic pathways contributes to the ability of alpha1-PDX/hf to differentially inhibit members of the proprotein convertase family. Finally, we propose a structural model of the alpha1-PDX-reactive site loop that explains the high degree of enzyme selectivity of this serpin and which can be used to generate small molecule furin inhibitors.
Human liver fatty acid binding protein cDNA and amino acid sequence. Functional and evolutionary implications. (1985)

Human liver fatty acid binding protein (L-FABP) cDNA clones were identified in a liver cDNA library. The two longest clones were completely sequenced. The nucleotide sequence predicts a protein of 127 amino acid residues. Identity of the clones was confirmed by limited amino acid sequence analysis of purified human L-FABP peptides and Edman degradation of radiolabeled in vitro translated FABP. Statistical analysis of the amino acid and mRNA sequences of human L-FABP, rat L-FABP, rat intestinal (I-) FABP, and mouse 422 protein indicates that the human and rat L-FABPs are highly homologous and that L-FABP and I-FABP diverged a long time ago (approximately 650-690 million years ago), although they are more closely related to each other than either of them is to 422 protein. Secondary structure predictions from the primary sequence of human and rat L-FABP reveal a region (residues 12-30) that might be the putative fatty acid binding domain of the two L-FABPs. Knowledge of the primary amino acid sequence of L-FABP and possible functional domains will be pivotal in further defining and understanding the mechanism of ligand binding and transfer by this protein.
An ultra wide dynamic range CMOS image sensor with a linear response (2006)

An ultra wide dynamic range (WDR) CMOS image sensor (CIS) and the details of evaluation are presented. The proposed signal readout technique of extremely short accumulation (ESA) enables the dynamic range of image sensor to be expanded up to 146dB. Including the ESA signals, total of 4 different accumulation time signals are read out in one frame period based on burst readout technique. To achieve the high-speed signal readout required for the multiple exposure signals, column parallel A/D converters are integrated at the upper and lower sides of pixel arrays. The improved 12-bits cyclic ADCs with a built-in correlated double sampling (CDS) circuit has the differential non-linearity (DNL) of ±0.3<i>LSB</i>.