gebhart/patrepeval huggingface dataset:
Endotoxin, TNF, and IL-1 decrease cholesterol 7 alpha-hydroxylase mRNA levels and activity (1996)

Endotoxin (LPS) and cytokines increase cholesterol synthesis and the secretion of lipoproteins by the liver in rodents resulting in hypercholesterolemia. Cholesterol 7 alpha-hydroxylase (CAH) is the rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver, the major regulated pathway by which cholesterol is eliminated from the body. Decreases in CAH would increase the quantity of cholesterol available for lipoprotein production. In the present study, we demonstrate that LPS, TNF, or IL-1 administration to Syrian hamsters produces a marked decrease in the levels of CAH mRNA in the liver. This marked decrease occurred even when the basal level of CAH expression was increased by feeding the bile acid sequestrant, colestipol. Additionally, a marked decrease was also observed when the animals were fed a cholesterol-enriched diet. Moreover, the decrease in CAH mRNA occurred very rapidly (decreased 66% by 90 min after LPS administration) and required relatively small doses of LPS (100 ng/100 g body weight). Lastly, the decrease in mRNA levels was accompanied by a decrease in CAH activity. This decrease in CAH could contribute to the increase in hepatic lipoprotein production induced by LPS and cytokines. CAH can be added to the growing list of proteins that regulate lipid metabolism and that are altered during the acute phase response.
Organosilicone surfactants as adjuvants for agrochemicals (1993)

Abstract The literature has been reviewed and 160 references are presented to provide an overview of organosilicones as adjuvants for agrochemicals. Early studies (1973–1981) elucidated the special properties of these compounds, notably their extreme spreading and, by virtue of the exceptionally low surface tensions of their aqueous solutions, the ability to induce infiltration of spray formulations into foliage via stomata. Subsequent research at the New Zealand Forest Research Institute explored these and other properties in‐depth, and demonstrated that they enabled the herbicide glyphosate to be used as a cost‐effective alternative to 2,4,5‐T for the control of forest scrubweeds. As a result, in 1985, ‚Silwet’︁ L‐77 was the first organosilicone adjuvant to be commercialised, and various other products have subsequently been introduced. The chemistry and synthesis of these organosilicones have been detailed. A mechanistic approach has been adopted to consider the effects of the distinctive properties of organosilicones in each of the processes involved in spray application of agrochemicals. Commencing with spray formulation, the topics of foaming, hydrolytic stability and interactions with coformulants are discussed. Progressing to spray application, consideration is given to the effects of organosilicones on atomisation and impaction (wetting, adhesion/reflection, spreading, retention/run‐off), and the resultant influences on the activity of protectant agrochemicals. An assessment of the use of organosilicones with systemic agrochemicals includes examination of effects on foliar uptake, via both cuticular and stomatal pathways, and the rainfastness which the latter provides. Also considered is the physiological behaviour of organosilicones, specifically phytotoxicity and effects on translocation of active ingredients. The current and potential future use of organosilicones with herbicides, foliar nutrients, growth regulators, insecticides and fungicides is discussed, as is the specificity of their effects. Additionally, the potential application of organosilicone chemistry to adjuvant classes other than the spreader/penetrant type investigated to date is considered. Finally, the issues of registration, handling hazards, both toxicological and chemical, and environmental impact are discussed. The literature reviewed demonstrates the sound science base on which this novel class of organosilicone adjuvant chemistry rests.
Performance analysis of the CONFIDANT protocol (2002)

Mobile ad-hoc networking works properly only if the participating nodes cooperate in routing and forwarding. However,it may be advantageous for individual nodes not to cooperate. We propose a protocol, called CONFIDANT, for making misbehavior unattractive; it is based on selective altruism and utilitarianism. It aims at detecting and isolating misbehaving nodes, thus making it unattractive to deny cooperation. Trust relationships and routing decisions are based on experienced, observed, or reported routing and forwarding behavior of other nodes. The detailed implementation of CONFIDANT in this paper assumes that the network layer is based on the Dynamic Source Routing (DSR) protocol. We present a performance analysis of DSR fortified by CONFIDANT and compare it to regular defenseless DSR. It shows that a network with CONFIDANT and up to 60% of misbehaving nodes behaves almost as well as a benign network, in sharp contrast to a defenseless network. All simulations have been implemented and performed in GloMoSim.
Lmb, a Protein with Similarities to the LraI Adhesin Family, Mediates Attachment of Streptococcus agalactiae to Human Laminin (1999)

Streptococcus agalactiae is a leading cause of neonatal sepsis and meningitis. Adherence to extracellular matrix proteins is considered an important factor in the pathogenesis of infection, but the genetic determinants of this process remain largely unknown. We identified and sequenced a gene which codes for a putative lipoprotein that exhibits significant homology to the streptococcal LraI protein family. Mutants of this locus were demonstrated to have substantially reduced adherence to immobilized human laminin. The nucleotide sequence of the gene was subsequently designated lmb (laminin binding) and shown to be present in all of the common serotypes of S. agalactiae. To determine the role of Lmb in the adhesion of S. agalactiae wild-type strains to laminin, a recombinant Lmb protein harboring six consecutive histidine residues at the C terminus was cloned, expressed, and purified from Escherichia coli. Preincubation of immobilized laminin with recombinant Lmb significantly reduced adherence of the wild-type strain O90R to laminin. These results indicate that Lmb mediates the attachment of S. agalactiae to human laminin, which may be essential for the bacterial colonization of damaged epithelium and translocation of bacteria into the bloodstream.
Cloning and expression of immunologically active recombinant Amb a V allergen of short ragweed (Ambrosia artemisiifolia) pollen (1993)

We have cloned and sequenced Amb a V, an Ambrosia artemisiifolia (short ragweed) pollen allergen that has proved to be particularly useful in the genetic analysis of human immune responsiveness. The amino acid sequence deduced from the cloned cDNA sequence corresponds to the published sequence of the protein, except that the cDNA sequence encodes an extra 10 amino acids at the C-terminus. The expressed 55-residue protein is then presumably cleaved enzymatically at the C-terminal lysine found in the 45-residue protein isolated from the pollen. The cloning and sequencing of Amb a V genomic DNA confirmed the cDNA sequence and showed that the Amb a V gene has no introns. Recombinant Amb a V allergen, expressed in Escherichia coli, bound to IgG and IgE antibodies in all Amb a V-allergic individuals tested and inhibition studies demonstrated that the recombinant protein contains a subset of the antigenic epitopes found on native Amb a V. In addition, recombinant Amb a V released histamine efficiently from basophils from Amb a V-allergic patients. The recombinant Amb a V allergen and mutants of Amb a V should, therefore, be useful in studies of allergen epitopes in humans, as well as providing a diagnostic tool.
The System and Procedures of Percutaneous Intradiscal Laser Nucleotomy (1990)

Since 1986, percutaneous intradiscal laser nucleotomy (PILN) has been studied in the authors' laser laboratory. The purpose of this report is to develop PILN as an alternative to chemonucleolysis and percutaneous discectomy, which are currently applied, and to establish a safe, easy, accurate and short-time therapy method for lumbar disc herniation. After laser irradiation, intradiscal pressures (IDP) decreased and the nucleus pulposus was gradually replaced with cartilaginous fibrous tissue. The evaluation of heat distribution with thermocouples and thermography was done to determine safe optimum irradiating conditions and to develop a new double-lumen needle and a bare quartz fiber. Neodymium-yttrium-aluminum-garnet (Nd-YAG) laser devices have been improved for easy and safe use, and a new tip type pressure transducer has been made for improved therapeutic results using this new method.
Fast volume rendering using a shear-warp factorization of the viewing transformation (1994)

Several existing volume rendering algorithms operate by factoring the viewing transformation into a 3D shear parallel to the data slices, a projection to form an intermediate but distorted image, and a 2D warp to form an undistorted final image. We extend this class of algorithms in three ways. First, we describe a new object-order rendering algorithm based on the factorization that is significantly faster than published algorithms with minimal loss of image quality. Shear-warp factorizations have the property that rows of voxels in the volume are aligned with rows of pixels in the intermediate image. We use this fact to construct a scanline-based algorithm that traverses the volume and the intermediate image in synchrony, taking advantage of the spatial coherence present in both. We use spatial data structures based on run-length encoding for both the volume and the intermediate image. Our implementation running on an SGI Indigo workstation renders a 2563 voxel medical data set in one second. Our second extension is a shear-warp factorization for perspective viewing transformations, and we show how our rendering algorithm can support this extension. Third, we introduce a data structure for encoding spatial coherence in unclassified volumes (i.e. scalar fields with no precomputed opacity). When combined with our shear-warp rendering algorithm this data structure allows us to classify and render a 2563 voxel volume in three seconds. The method extends to support mixed volumes and geometry and is parallelizable.
Abstract execution: A technique for efficiently tracing programs (1990)

Abstract Many areas of computer performance analysis require detailed traces of events that occur during a program's execution. Collecting traces is expensive. The additional code required to record events greatly slows a program's execution. In addition, the resulting trace files can grow unmanageably large. This paper describes a technique called abstract execution that alleviates both problems. Abstract execution records a small set of events during the traced program's execution. These events serve as input to an abstract version of the program that generates a full trace by re‐executing selected portions of the original program. This process greatly reduces both the cost of tracing the original program and the size of the trace files. The cost of regenerating a trace is insignificant in comparison to the cost of applications that use it. This paper also describes a system called AE that implements Abstract Execution. The paper contains measurements that demonstrate that AE can efficiently trace large programs.
Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas (2005)

The hedgehog pathway plays a critical role in the development of the foregut. Recent studies indicate that the hedgehog pathway activation occurs in the stomach and other gastrointestinal cancers. However, the association of hedgehog pathway activation with tumor stage, differentiation and tumor subtype is not well documented. Here, we report our findings that the elevated expression of hedgehog target genes human patched gene 1 (PTCH1) or Gli1 occurs in 63 of the 99 primary gastric cancers. Activation of the hedgehog pathway is associated with poorly differentiated and more aggressive tumors. The sonic hedgehog (Shh) transcript is localized to the cancer tissue, whereas expression of Gli1 and PTCH1 is observed both in the cancer and in the surrounding stroma. Treatment of gastric cancer cells with KAAD-cyclopamine, a hedgehog signaling inhibitor, decreases expression of Gli1 and PTCH1, resulting in cell growth inhibition and apoptosis. Overexpression of Gli1 under the control of the cytomegalovirus (CMV) promoter renders these cells resistant to cyclopamine-induced apoptosis. Thus, our analysis of in vivo tissues indicates that the hedgehog pathway is frequently activated in advanced gastric adenocarcinomas; our in vitro studies suggest that hedgehog signaling contributes to gastric cancer cell growth. These data predict that targeted inhibition of the hedgehog pathway may be effective in the prevention and treatment of advanced gastric adenocarcinomas.
GROWTH RETARDANTS: Effects on Gibberellin Biosynthesis and Other Metabolic Pathways (2000)

Plant growth retardants are applied in agronomic and horticultural crops to reduce unwanted longitudinal shoot growth without lowering plant productivity. Most growth retardants act by inhibiting gibberellin (GA) biosynthesis. To date, four different types of such inhibitors are known: (a) Onium compounds, such as chlormequat chloride, mepiquat chloride, chlorphonium, and AMO-1618, which block the cyclases copalyl-diphosphate synthase and ent-kaurene synthase involved in the early steps of GA metabolism. (b) Compounds with an N-containing heterocycle, e.g. ancymidol, flurprimidol, tetcyclacis, paclobutrazol, uniconazole-P, and inabenfide. These retardants block cytochrome P450-dependent monooxygenases, thereby inhibiting oxidation of ent-kaurene into ent-kaurenoic acid. (c) Structural mimics of 2-oxoglutaric acid, which is the co-substrate of dioxygenases that catalyze late steps of GA formation. Acylcyclohexanediones, e.g. prohexadione-Ca and trinexapac-ethyl and daminozide, block particularly 3ss-hydroxylation, thereby inhibiting the formation of highly active GAs from inactive precursors, and (d) 16,17-Dihydro-GA5 and related structures act most likely by mimicking the GA precursor substrate of the same dioxygenases. Enzymes, similar to the ones involved in GA biosynthesis, are also of importance in the formation of abscisic acid, ethylene, sterols, flavonoids, and other plant constituents. Changes in the levels of these compounds found after treatment with growth retardants can mostly be explained by side activities on such enzymes.
Biofilm formation by the anaerobic pathogen Clostridium difficile (2014)

Clostridium difficile is an obligate anaerobic, Gram-positive, endospore-forming bacterium. Although an opportunistic pathogen, it is one of the important causes of healthcare-associated infections. While toxins TcdA and TcdB are the main virulence factors of C. difficile, the factors or processes involved in gut colonization during infection remain unclear. The biofilm-forming ability of bacterial pathogens has been associated with increased antibiotic resistance and chronic recurrent infections. Little is known about biofilm formation by anaerobic gut species. Biofilm formation by C. difficile could play a role in virulence and persistence of C. difficile, as seen for other intestinal pathogens. We demonstrate that C. difficile clinical strains, 630, and the strain isolated in the outbreak, R20291, form structured biofilms in vitro. Biofilm matrix is made of proteins, DNA and polysaccharide. Strain R20291 accumulates substantially more biofilm. Employing isogenic mutants, we show that virulence-associated proteins, Cwp84, flagella and a putative quorum sensing regulator, LuxS, Spo0A, are required for maximal biofilm formation by C. difficile. Moreover we demonstrate that bacteria in C. difficile biofilms are more resistant to high concentrations of vancomycin, a drug commonly used for treatment of CDI, and that inhibitory and sub-inhibitory concentrations of the same antibiotic induce biofilm formation. Surprisingly, clinical C. difficile strains from the same out-break, but from different origin, show differences in biofilm formation. Genome sequence analysis of these strains showed presence of a single nucleoide polymorphism (SNP) in the anti-σ factor RsbW, which regulates the stress-induced alternative sigma factor B (σB). We further demonstrate that RsbW, a negative regulator of alternative sigma factor B, has a role in biofilm formation and sporulation of C. difficile. Our data suggest that biofilm formation by C. difficile is a complex multifactorial process and may be a crucial mechanism for clostridial persistence in the host.
Ferroelectric Field Effect Transistor Based on Epitaxial Perovskite Heterostructures (1997)

Ferroelectric field effect devices offer the possibility of nonvolatile active memory elements. Doped rare-earth manganates, which are usually associated with colossal magnetoresistive properties, have been used as the semiconductor channel material of a prototypical epitaxial field effect device. The carrier concentration of the semiconductor channel can be "tuned" by varying the manganate stochiometry. A device with La0.7Ca0.3MnO3 as the semiconductor and PbZr0.2Ti0.8O3 as the ferroelectric gate exhibited a modulation in channel conductance of at least a factor of 3 and a retention loss of 3 percent after 45 minutes without power.
Bioluminescent coelenterazine derivatives with imidazopyrazinone C-6 extended substitution (2014)

Three novel coelenterazine (CTZ) derivatives with extension at the C-6 position of the imidazopyrazinone structure show significant bioluminescence emission with known renilla luciferase variants, indicating a promising method to develop CTZ derivatives with superior optical properties compared to hitherto reported compounds.
Preparation of 3-Substituted-1-Isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines as RET Kinase Inhibitors (2012)

A series of 3-substituted-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines have been designed, synthesized, and evaluated as RET protein kinase inhibitors. On the basis of docking results, a small library of pyrazolopyrimidine compounds with an extended hydrophobic side arm was synthesized. The most promising of the compounds (7a) displayed efficient inhibition in vitro and good selectivity when tested on a panel of kinases. Furthermore, 7a inhibited GDNF-induced RET phosphorylation of ERK1/2 in MCF-7 breast cancer cells at concentrations as low as 100 nM.
Adeno-Associated Viral Vector Mediated Gene Transfer for Hemophilia B (2011)

Abstract Abstract 5 Background: Hemophilia B (HB), an X-linked bleeding disorder, is ideally suited for gene therapy. We investigated a novel approach using peripheral vein infusion of a single dose of a serotype-8 pseudotyped self-complementary adeno-associated virus (AAV) vector expressing a codon-optimized coagulation factor IX (FIX) transgene (scAAV2/8-LP1-hFIXco). Methods: Six severe HB subjects (FIX ≤1%) were enrolled sequentially into one of three dose cohorts with two subjects in each group. Vector was administered without immunosuppression. The subjects were followed for 6–16 months post treatment. Results: AAV-mediated expression of FIX at 2–11% of normal was observed in all subjects. Four of the six have discontinued prophylaxis and remain free of spontaneous hemorrhage. The other two have increased the interval between FIX prophylaxes. A high-dose subject developed asymptomatic, transient elevation of serum transaminases associated with detection of AAV8 capsid specific T cells in peripheral blood. The second high-dose subject experienced a slight increase of liver enzymes, of less clear etiology. Treatment of each with a short course of steroids led to rapid normalization of the transaminases and maintenance of FIX levels in the 3–11% range. Conclusion: Peripheral vein administration of scAAV2/8-LP1-hFIXco was well tolerated and resulted in FIX transgene expression at levels sufficient to improve the bleeding phenotype. Immune-mediated clearance of AAV-transduced hepatocytes remains a concern but our data suggest that this process may be controlled with a short course of steroids without loss of transgene expression. Hence, our novel approach shows promise for gene therapy of HB and other protein deficiencies. (ClinicalTrials.gov number, NCT00979238) Disclosures: Nathwani: Amsterdam Molecular Therapeutics: Patents &amp; Royalties. Gray:Amsterdam Molecular Therapeutics: Patents &amp; Royalties. Davidoff:Amsterdam Molecular Therapeutics: Patents &amp; Royalties.
Efficient Full-Reference Assessment of Image and Video Quality (2007)

Automatic quality assessment of digital pictures is a crucial issue in several image and video processing applications including broadcasting, archiving, or restoration. The visibility of impairments related to digital image processing systems is subject to the spatio-temporal properties of the given image or video content. As quality assessment using subjective tests carried out by humans is very costly, time consuming, and not compatible with real-time constraints, objective measures are required that can predict the perceptual judgment of human viewers. In this paper, a top-down quality assessment tool that mimics a selection of prominent human visual system properties is presented. Quality evaluation is conducted based on perceptually salient feature points in our approach. It is shown that the proposed method, although featuring a significantly lower complexity than standardized quality measures, performs as well as these for block-based hybrid video coding.
A combined physical and genetic map of Pseudomonas aeruginosa PAO (1990)

A combined physical and genetic map of Pseudomonas aeruginosa PAO was constructed by pulsed-field gel electrophoresis and Southern hybridization using cosmid clones from a genomic library carrying known genes. A total of 37 SpeI restriction fragments have been mapped on the 5862 kb genome, and fragment contiguity demonstrated by hybridization with clones from a SpeI junction fragment library and fragments obtained by partial SpeI digestion, both derived from the P. aeruginosa PAO chromosome.
Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations (1994)

The emergence of multidrug-resistant strains of Mycobacterium tuberculosis has resulted in increased interest in the fluoroquinolones (FQs) as antituberculosis agents. To investigate the frequency and mechanisms of FQ resistance in M. tuberculosis, we cloned and sequenced the wild-type gyrA and gyrB genes, which encode the A and B subunits of the DNA gyrase, respectively; DNA gyrase is the main target of the FQs. On the basis of the sequence information, we performed DNA amplification for sequencing and single-strand conformation polymorphism analysis to examine the presumed quinolone resistance regions of gyrA and gyrB from reference strains (n = 4) and clinical isolates (n = 55). Mutations in codons of gyrA analogous to those described in other FQ-resistant bacteria were identified in all isolates (n = 14) for which the ciprofloxacin MIC was > 2 micrograms/ml. In addition, we selected ciprofloxacin-resistant mutants of Mycobacterium bovis BCG and M. tuberculosis Erdman and H37ra. Spontaneously resistant mutants developed at a frequency of 1 in 10(7) to 10(8) at ciprofloxacin concentrations of 2 micrograms/ml, but no primary resistant colonies were selected at higher ciprofloxacin concentrations. Replating of those first-step mutants selected for mutants with high levels of resistance which harbored gyrA mutations similar to those found among clinical FQ-resistant isolates. The gyrA and gyrB sequence information will facilitate analysis of the mechanisms of resistance to drugs which target the gyrase and the implementation of rapid strategies for the estimation of FQ susceptibility in clinical M. tuberculosis isolates.