gebhart/patrepeval huggingface dataset:
Accelerated Wound Healing of Alkali-Burned Corneas in MRL Mice Is Associated with a Reduced Inflammatory Signature (2005)

Alkali-burned corneas heal faster and more completely in MRL mice than in B6 mice, by means of rapid reepithelialization, reduced inflammation, and reduced fibrosis. Reduced inflammation, including decreased neutrophil infiltrates and the lack of a robust proinflammatory gene expression signature correlates with the rapid healing. However, the rapid-healing phenotype is not intrinsic to MRL hematopoietic progenitor cells.
Fishes of North America Endangered, Threatened, or of Special Concern: 1989 (1989)

The American Fisheries Society herein provides an update of their now decade-old list of rare North American fishes. The 1989 list adds 139 new taxa to the list developed by Deacon et al. (1979) of 251 fishes and removes 26 for a total of 364 fishes in Canada, United States, and Mexico that warrant protection because of their rarity. The 26 taxa removed from the 1979 list include 16 removed because of better information on their taxonomy or status and 10 because they have become extinct. Not a single fish warranted removal from the list because of successful recovery efforts. In addition, 49 fishes have changed in status but remain on the list: 7 have improved in status, 24 have declined, and 18 have been reclassified because new information revealed that they were either more common or rarer than was earlier believed and, therefore, were incorrectly classified in 1979. Comparison of the 1979 and 1989 lists indicates that recovery efforts have been locally effective for some species, but are clearly lagging behind deterioration of the overall fish fauna. The health of aquatic habitats in North America continues to decay. A major commitment to conservation of entire ecosystems, rather than the inconsistent recovery efforts for individual species, is needed to reverse this trend.
Specificity of nucleotide sequence in DNA cleavage induced by D-glucosamine and D-glucosamine-6-phosphate in the presence of Cu2+. (1990)

32P-End-labeled restriction fragments derived from pBR322 and pUC9 DNAs were reacted with D-glucosamine or D-glucosamine-6-phosphate in the presence of Cu2+, and, after being heated at 90 degrees C in aqueous piperidine, the DNA products were analyzed on polyacrylamide gels for the sequence-specificity of alkali-labile cleavaged sites. The intensity of oligonucleotide bands of cleavaged sites was directly proportional to the concentration of aminosugars, indicating that the DNA cleavage was caused by the action of aminosugars themselves. The preferred DNA cleavage sites induced by these aminosugars were identical, both at pyrimidine-purine (5'----3') sequences, especially at thymineguanine ones, and to some extent at pyrimidine-pyrimidine (5'----3') sequences. The 6-phosphate moiety of D-glucosamine did not affect the specificity of DNA cleavage.
Coordinate regulation of enzyme markers for inflammation and for protection against oxidants and electrophiles (2008)

An elaborate network of highly inducible phase 2 proteins protects aerobic cells against the cumulative damaging effects of reactive oxygen intermediates and toxic electrophiles, which are the major causes of malignancy and chronic degenerative diseases. Many chemical and phytochemical agents, all of which react with thiol groups, induce the phase 2 response through their reactivity with critical cysteine thiols of Keap1. We recently found that the anti-inflammatory potencies (suppression of iNOS and COX-2 expression) of a series of triterpenoids with Michael reaction centers were closely correlated with the potencies of these agents to induce the phase 2 response. We now report that representatives of seven recognized chemical classes of inducers, including isothiocyanates, bisbenzylidenes, arsenicals, heavy metals, and vicinal dithiols, showed highly correlated inducer and anti-inflammatory potencies spanning more than six orders of magnitude of concentrations in established cells and in primary mouse peritoneal macrophages. Potency measurements were expressed as the D(m) values (median effect concentration) by use of the Median Effect Equation. Whereas the phase 2 induction required the functional integrity of both the repressor Keap1 and the transcription factor Nrf2, the effectiveness of inducers in blocking the up-regulation of iNOS by inflammatory cytokines was related to the nature of the cytokine and the inducer concentration. These studies identify suppression of inflammation as a consistent property of inducers of the phase 2 response and strongly suggest that this property is a central aspect of their chemoprotective actions.
Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease (2004)

The focus of this review is to provide an overview of the current state of knowledge of molecular mechanisms/processes that control differentiation of vascular smooth muscle cells (SMC) during normal development and maturation of the vasculature, as well as how these mechanisms/processes are altered in vascular injury or disease. A major challenge in understanding differentiation of the vascular SMC is that this cell can exhibit a wide range of different phenotypes at different stages of development, and even in adult organisms the cell is not terminally differentiated. Indeed, the SMC is capable of major changes in its phenotype in response to changes in local environmental cues including growth factors/inhibitors, mechanical influences, cell-cell and cell-matrix interactions, and various inflammatory mediators. There has been much progress in recent years to identify mechanisms that control expression of the repertoire of genes that are specific or selective for the vascular SMC and required for its differentiated function. One of the most exciting recent discoveries was the identification of the serum response factor (SRF) coactivator gene myocardin that appears to be required for expression of many SMC differentiation marker genes, and for initial differentiation of SMC during development. However, it is critical to recognize that overall control of SMC differentiation/maturation, and regulation of its responses to changing environmental cues, is extremely complex and involves the cooperative interaction of many factors and signaling pathways that are just beginning to be understood. There is also relatively recent evidence that circulating stem cell populations can give rise to smooth muscle-like cells in association with vascular injury and atherosclerotic lesion development, although the exact role and properties of these cells remain to be clearly elucidated. The goal of this review is to summarize the current state of our knowledge in this area and to attempt to identify some of the key unresolved challenges and questions that require further study.
A Short‐Term Evaluation of Nd:YAG Laser as an Adjunct to Scaling and Root Planing in the Treatment of Periodontal Inflammation (2010)

In the short-term, SRP in combination with a single application of a water-cooled Nd:YAG laser significantly improves clinical signs associated with periodontal inflammation compared to treatment with SRP alone.
An Abstract Semantics and Concrete Language for Continuous Queries over Streams and Relations (2002)

Despite the recent surge of research in query processing over data streams, little attention has been devoted to defining precise semantics for continuous semantics based on several building blocks: formal definitions for streams and relations, mappings among them, and any relational query language. From these basics we define a precise interpretation for continuous queries over streams and relations. We then propose a concrete language, CQL (for Continuous Query Language), which instantiates the abstract semantics using SQL as the relational query language and window specifications derived from SQL-99 to map from streams to relations. We identify some equivalences that can be used to rewrite CQL queries for optimization, and we discuss some additional implementation issues arising from the language and its semantics. We have implemented a substantial fraction of CQL in a Data Stream Management System at Stanford, and we have developed a public repository of data stream applications that includes a wide variety of queries expressed in CQL. 1
Tetrahydrobiopterin biosynthetic activities in human macrophages, fibroblasts, THP-1, and T 24 cells. GTP-cyclohydrolase I is stimulated by interferon-gamma, and 6-pyruvoyl tetrahydropterin synthase and sepiapterin reductase are constitutively present. (1990)

Interferon-gamma induces tetrahydrobiopterin biosynthesis in human cells and cell lines. Macrophages are peculiar in the formation of large amounts of neopterin derivatives as compared to tetrahydrobiopterin (Werner, E. R., Werner-Felmayer, G., Fuchs, D., Hausen, A., Reibnegger, G., and Wachter, H. (1989) Biochem J. 262, 861-866). Here we compare the impact of interferon-gamma treatment on activities of GTP-cyclohydrolase I (EC 3.5.4.16), 6-pyruvoyl tetrahydropterin synthase, and sepiapterin reductase (EC 1.1.1.153) in human peripheral blood-derived macrophages, normal dermal fibroblasts, THP-1 myelomonocytic cells, and the T 24 bladder transitional-cell carcinoma line. Upon interferon-gamma treatment, GTP-cyclohydrolase I activity is increased 7- to 40-fold, whereas 6-pyruvoyl tetrahydropterin synthase and sepiapterin reductase activities, which are constitutively present in all four investigated cells, remain unchanged. In fibroblasts and T 24 cells GTP cyclohydrolase I activity is the rate-limiting step of tetrahydrobiopterin biosynthesis. In macrophages and in THP-1 cells, however, the induced GTP cyclohydrolase I activity is higher than the 6-pyruvoyl tetrahydropterin synthase activity, leading to the accumulation of neopterin and neopterin phosphates.
Folding, interaction with GRP78-BiP, assembly, and transport of the human immunodeficiency virus type 1 envelope protein (1991)

A detailed kinetic and quantitative analysis of the early and late biosynthetic events undergone by the human immunodeficiency virus type 1 envelope protein expressed by a recombinant vaccinia virus was performed. Early folding events that occurred in the endoplasmic reticulum included disulfide bond formation (t1/2 approximately 10 min), folding of envelope protein into a form competent to bind CD4 (t1/2 approximately 15 min), and specific and transient association and dissociation with GRP78-BiP (t1/2 approximately 25 min). After initial folding, envelope protein monomers formed noncovalently associated dimers with high efficiency (t1/2 approximately 30 min). Studies with brefeldin A, a compound that inhibits endoplasmic reticulum-to-Golgi transport, suggested that assembly occurred in the endoplasmic reticulum while cleavage of gp160 into gp120/gp41 subunits occurred in a post-endoplasmic reticulum compartment. Transport to the Golgi was monitored by modification of N-linked sugars to forms partially resistant to endoglycosidase H. The kinetics of endoglycosidase H resistance were nearly identical to the kinetics of gp160 cleavage (t1/2 approximately 80 min). Cleavage efficiency was strongly cell type dependent, ranging from 13 to 70%. By contrast, approximately 50% of the gp120 generated by the cleavage event was shed (t1/2 approximately 120 min) regardless of the cell type used. The results are discussed in terms of the overall biosynthetic pathway of the envelope protein and provide a framework with which to assess the effects of mutations on structure and function.
Inhibition of High-Mobility Group Box 1 Protein (HMGB1) Enhances Bacterial Clearance and Protects against Pseudomonas Aeruginosa Pneumonia in Cystic Fibrosis (2012)

Pulmonary infection with Pseudomonas aeruginosa and neutrophilic lung inflammation significantly contribute to morbidity and mortality in cystic fibrosis (CF). High-mobility group box 1 protein (HMGB1), a ubiquitous DNA binding protein that promotes inflammatory tissue injury, is significantly elevated in CF sputum. However, its mechanistic and potential therapeutic implications in CF were previously unknown. We found that HMGB1 levels were significantly elevated in bronchoalveolar lavage fluids (BALs) of CF patients and cystic fibrosis transmembrane conductance regulator (CFTR )(-/-) mice. Neutralizing anti-HMGB1 monoclonal antibody (mAb) conferred significant protection against P. aeruginosa-induced neutrophil recruitment, lung injury and bacterial infection in both CFTR(-/-) and wild-type mice. Alveolar macrophages isolated from mice treated with anti-HMGB1 mAb had improved phagocytic activity, which was suppressed by direct exposure to HMGB1. In addition, BAL from CF patients significantly impaired macrophage phagocytotic function, and this impairment was attenuated by HMGB1-neutralizing antibodies. The HMGB1-mediated suppression of bacterial phagocytosis was attenuated in macrophages lacking toll-like receptor (TLR)-4, suggesting a critical role for TLR4 in signaling HMGB1-mediated macrophage dysfunction. These studies demonstrate that the elevated levels of HMGB1 in CF airways are critical for neutrophil recruitment and persistent presence of P. aeruginosa in the lung. Thus, HMGB1 may provide a therapeutic target for reducing bacterial infection and lung inflammation in CF.
Phosphorylating DNA with DNA (1999)

Nearly 50 individual DNAs with polynucleotide kinase-like activity were isolated from a random-sequence pool by using in vitro selection. Each self-phosphorylating deoxyribozyme makes use of one or more of the eight standard NTPs or dNTPs as a source of activated phosphate. Although most prototypic deoxyribozymes poorly differentiate between the ribose and deoxyribose moieties, further optimization by in vitro selection produced variants that display up to 100-fold discrimination between related NTP and dNTP substrates. An optimized ATP-dependent deoxyribozyme uses ATP >40,000-fold more efficiently than CTP, GTP, or UTP. This enzyme operates with a rate enhancement of nearly one billion-fold over the uncatalyzed rate of ATP hydrolysis. A bimolecular version of the ATP-dependent deoxyribozyme was further engineered to phosphorylate specific target DNAs with multiple turnover. The substrate-recognition patterns and rate enhancements intrinsic to these DNAs are characteristic of naturally occurring RNA and protein enzymes, supporting the hypothesis that DNA has sufficient catalytic potential to function as an enzyme in biological systems.
Defining Pathways for Development of Disease-Modifying Therapies in Children With Type 1 Diabetes: A Consensus Report (2015)

Emerging data suggest that type 1 diabetes is a more aggressive disease in children than in adults, with important differences in pathophysiology and clinical course. Therefore, the efficacy of disease-modifying therapies may be different in the two populations. Understanding the developmental and regulatory pathways for type 1 diabetes-modifying therapies in children will enable industry, academia, funders, advocacy groups, and regulators to translate new science to clinical care. This consensus report characterizes the fundamental differences in type 1 diabetes between children and adults and proposes a thoughtful approach to better understand the development and regulatory pathways for type 1 diabetes therapies.
A novel image‐guided surgery of hepatocellular carcinoma by indocyanine green fluorescence imaging navigation (2009)

This novel technique is simple and safe, and is therefore considered to be a promising tool for routine intraoperative imaging during a hepatic resection and further clinical exploration for HCC.
Mechanically induced Si layer transfer in hydrogen-implanted Si wafers (2000)

Mechanically induced layer transfer of single-crystal silicon by hydrogen ion implantation, low-temperature wafer bonding, and subsequent mechanical splitting of the implanted wafer has been investigated. The bond strength measurements using the crack opening method in room environment yield a surface energy of ⩾2000 mJ/m2 after exposure to oxygen plasma and subsequent hydrophilic silicon/silicon dioxide bonding at 200 °C. Mechanically induced layer transfer was carried out for silicon wafers implanted to a dose of 5×1016 H2/cm2 at 100 keV and annealed for 2 h at 200 °C. No feature was observed by atomic force microscopy (AFM) measurements on the unbonded free surface after this heat treatment. For lower doses of implantation, annealing at higher temperatures is required to enable the mechanical transfer. AFM measurements on the split silicon surface indicate that low-temperature wafer bonding and mechanical transfer yield a root mean square surface roughness of 4 nm which is less than in the standard Smart-Cut® process.
Lung Cancer Cell Lines as Tools for Biomedical Discovery and Research (2010)

Lung cancer cell lines have made a substantial contribution to lung cancer translational research and biomedical discovery. A systematic approach to initiating and characterizing cell lines from small cell and non-small cell lung carcinomas has led to the current collection of more than 200 lung cancer cell lines, a number that exceeds those for other common epithelial cancers combined. The ready availability and widespread dissemination of the lines to investigators worldwide have resulted in more than 9000 citations, including multiple examples of important biomedical discoveries. The high (but not perfect) genomic similarities between lung cancer cell lines and the lung tumor type from which they were derived provide evidence of the relevance of their use. However, major problems including misidentification or cell line contamination remain. Ongoing studies and new approaches are expected to reveal the full potential of the lung cancer cell line panel.
Discovery of Novel Small-Molecule Inhibitors of BRD4 Using Structure-Based Virtual Screening (2013)

Bromodomains (BRDs) are epigenetic readers that recognize acetylated-lysine (KAc) on proteins and are implicated in a number of diseases. We describe a virtual screening approach to identify BRD inhibitors. Key elements of this approach are the extensive design and use of substructure queries to compile a set of commercially available compounds featuring novel putative KAc mimetics and docking this set for final compound selection. We describe the validation of this approach by applying it to the first BRD of BRD4. The selection and testing of 143 compounds lead to the discovery of six novel hits, including four unprecedented KAc mimetics. We solved the crystal structure of four hits, determined their binding mode, and improved their potency through synthesis and the purchase of derivatives. This work provides a validated virtual screening approach that is applicable to other BRDs and describes novel KAc mimetics that can be further explored to design more potent inhibitors.
The BST1 Gene of Saccharomyces cerevisiaeIs the Sphingosine-1-phosphate Lyase (1997)

Sphingolipids elicit a wide variety of eukaryotic cellular responses, most involving regulation of cell growth, differentiation, and apoptosis. Sphingosine 1-phosphate, a sphingolipid catabolite, is mitogenic in fibroblasts and inhibits the chemotactic mobility and invasiveness of human tumor cells. Sphingosine 1-phosphate degradation requires cleavage at the C2-3 carbon bond by sphingosine phosphate lyase. A yeast genetic approach was used to clone the first sphingosine phosphate lyase gene, BST1. BST1 overexpression conferred resistance to sphingosine in yeast. BST1 deletion produced sensitivity to exogenous D-erythro-sphingosine and phytosphingosine and intracellular accumulation of sphingosine 1-phosphate upon exposure to exogenous sphingosine. This study confirms that sphingoid base metabolism is similar in all eukaryotes and suggests that yeast genetics may be useful in the isolation and identification of other genes involved in sphingolipid signaling and metabolism.
Convolutional Neural Network Based Metal Artifact Reduction in X-Ray Computed Tomography (2018)

In the presence of metal implants, metal artifacts are introduced to x-ray computed tomography CT images. Although a large number of metal artifact reduction (MAR) methods have been proposed in the past decades, MAR is still one of the major problems in clinical x-ray CT. In this paper, we develop a convolutional neural network (CNN)-based open MAR framework, which fuses the information from the original and corrected images to suppress artifacts. The proposed approach consists of two phases. In the CNN training phase, we build a database consisting of metal-free, metal-inserted and pre-corrected CT images, and image patches are extracted and used for CNN training. In the MAR phase, the uncorrected and pre-corrected images are used as the input of the trained CNN to generate a CNN image with reduced artifacts. To further reduce the remaining artifacts, water equivalent tissues in a CNN image are set to a uniform value to yield a CNN prior, whose forward projections are used to replace the metal-affected projections, followed by the FBP reconstruction. The effectiveness of the proposed method is validated on both simulated and real data. Experimental results demonstrate the superior MAR capability of the proposed method to its competitors in terms of artifact suppression and preservation of anatomical structures in the vicinity of metal implants.
The adjuvant effect of stearyl tyrosine on a recombinant subunit hepatitis B surface antigen. (1990)

We describe the enhancement of the antibody response against hepatitis B surface Ag by octadecyl L-tyrosine, a synthetic adjuvant designed to exert its adjuvant effect in a manner similar to that of alum because it binds soluble Ag and releases it slowly from the site of injection. Our data demonstrate that octadecyl L-tyrosine showed a significant enhancement of the antihepatitis B surface Ag response compared to that of alum in the secondary response. The most striking difference between octadecyl L-tyrosine and alum in the antihepatitis B surface Ag antibody response was the absence of IgE-specific antibodies subsequent to immunization of the Ag in octadecyl L-tyrosine. Both the optical isomers of the octadecyl esters of tyrosine were adjuvant active, however, the racemic mixture showed a significantly lowe adjuvant activity. This adjuvant has great potential to be used in humans because it is devoid of side effects as assessed by the lack of acute and chronic toxicity in mice and rats, pyrogenicity in rabbits, formation of granuloma in cats, and adjuvant arthritis in rats.
Reconstitution of High Affinity Leukaemia Inhibitory Factor (LIF) Receptors in Haemopoietic Cells Transfected with the Cloned Human LIF Receptor (2007)

cDNA clones encoding the human leukaemia inhibitory factor (hLIF) receptor were isolated by screening a placental cDNA expression library in COS-7 cells with 125I-hLIF. The cloned LIF receptor is a member of the haemopoietin receptor family and comprises a signal sequence (44 amino acids), an extracellular region of two haemopoietin receptor domains and three fibronectin type III domains (789 amino acids), a transmembrane domain (26 amino acids) and a cytoplasmic domain (238 amino acids). The LIF receptor is expressed in COS-7 cells as a 190 kDa glycoprotein that specifically binds human LIF with low affinity, but does not bind mouse LIF. Clones encoding a soluble form of the homologous mouse LIF receptor have been isolated, suggesting complex interactions between the various forms of LIF ligand and receptor in vivo. The LIF receptor is most related to the gp130 signal-transducing component of the IL-6 receptor, a feature that may provide a molecular basis for the intertwined biologies of LIF and IL-6 in the absence of obvious structural similarly between the ligands. Mouse B9 plasmacytoma cells transfected with the human LIF receptor display novel high affinity LIF receptors that are presumed to consist of transfected receptors in association with endogenous mouse high affinity-converting subunits. Unlike the low affinity human LIF receptor, the mixed species high affinity receptor is capable of binding mouse LIF.