gebhart/patrepeval huggingface dataset:
Molecular Mechanisms of Bacterial Virulence: Type III Secretion and Pathogenicity Islands (1996)

Recently, two novel but widespread themes have emerged in the field of bacterial virulence: type III secretion systems and pathogenicity islands. Type III secretion systems, which are found in various gram-negative organisms, are specialized for the export of virulence factors delivered directly to host cells. These factors subvert normal host cell functions in ways that seem beneficial to invading bacteria. The genes encoding several type III secretion systems reside on pathogenicity islands, which are inserted DNA segments within the chromosome that confer upon the host bacterium a variety of virulence traits, such as the ability to acquire iron and to adhere to or enter host cells. Many of these segments of DNA appear to have been acquired in a single step from a foreign source. The ability to obtain complex virulence traits in one genetic event, rather than by undergoing natural selection for many generations, provides a mechanism for sudden radical changes in bacterial-host interactions. Type III secretion systems and pathogenicity islands must have played critical roles in the evolution of known pathogens and are likely to lead to the emergence of novel infectious diseases in the future.
The Antihyperglycemic Drug α-Lipoic Acid Stimulates Glucose Uptake via Both GLUT4 Translocation and GLUT4 Activation (2001)

The cofactor of mitochondrial dehydrogenase complexes and potent antioxidant alpha-lipoic acid has been shown to lower blood glucose in diabetic animals. alpha-Lipoic acid enhances glucose uptake and GLUT1 and GLUT4 translocation in 3T3-L1 adipocytes and L6 myotubes, mimicking insulin action. In both cell types, insulin-stimulated glucose uptake is reduced by inhibitors of p38 mitogen-activated protein kinase (MAPK). Here we explore the effect of alpha-lipoic acid on p38 MAPK, phosphatidylinositol (PI) 3-kinase, and Akt1 in L6 myotubes. alpha-Lipoic acid (2.5 mmol/l) increased PI 3-kinase activity (31-fold) and Akt1 (4.9-fold). Both activities were inhibited by 100 nmol/l wortmannin. alpha-Lipoic acid also stimulated p38 MAPK phosphorylation by twofold within 10 min. The phosphorylation persisted for at least 30 min. Like insulin, alpha-lipoic acid increased the kinase activity of the alpha (2.8-fold) and beta (2.1-fold) isoforms of p38 MAPK, measured by an in vitro kinase assay. Treating cells with 10 micromol/l of the p38 MAPK inhibitors SB202190 or SB203580 reduced the alpha-lipoic acid-induced stimulation of glucose uptake by 66 and 55%, respectively. In contrast, SB202474, a structural analog that does not inhibit p38 MAPK, was without effect on glucose uptake. In contrast to 2-deoxyglucose uptake, translocation of GLUT4myc to the cell surface by either alpha-lipoic acid or insulin was unaffected by 20 micromol/l of SB202190 or SB203580. The results suggest that inhibition of 2-deoxyglucose uptake in response to alpha-lipoic acid by inhibitors of p38 MAPK is independent of an effect on GLUT4 translocation. Instead, it is likely that regulation of transporter activity is sensitive to these inhibitors.
Dissociation of [35S]t‐Butylbicyclophosphorothionate Binding Differentiates Convulsant and Depressant Drugs that Modulate GABAergic Transmission (1985)

The dissociation of [35S]t-butylbicyclophosphorothionate ([35S]TBPT) from binding sites on membranes from rat cerebral cortex, after addition of saturating concentrations of convulsant and depressant drugs, was studied. The addition of unlabeled TBPT, picrotoxinin, or pentamethylenetetrazol resulted in dissociation patterns that were monophasic and not distinguishable, suggesting that these convulsants bind competitively to the same (convulsant) sites. In contrast, gamma-aminobutyric acid (GABA) greatly facilitated [35S]TBPT dissociation by binding allosterically to the GABA recognition site of the receptor-ionophore complex. TBPT dissociation was similarly accelerated by the depressants etazolate, (+)-etomidate, and barbiturates. The convulsant and depressant S(+) and R(-) stereoisomers of N-methyl-5-phenyl-5-propyl-barbituric acid displayed large stereoselectivity in the acceleration of TBPT dissociation. These results suggest that depressants bind to sites different from the convulsant sites of the allosteric GABA receptor complex, or the binding of depressants to the same population of sites elicits negative cooperativity and dissociates the convulsants.
Size-Selective Capillary Electrophoresis (SSCE) Separation of DNA Fragments (1992)

Abstract A capillary electrophoretic separation of DNA fragment standards in the range of 50 to 105 base pairs was achieved using methylcellulose as a size-selective agent. All 23 fragments in a 1 kb DNA ladder can be resolved in under 25 minutes. Capillary wall deactivation, using a siloxane-bonded polyacrylamide, greatly improved resolution and reproducibility. The concentration effect of the size-selective agent and the applied electric field strength on DNA fragment separation was determined. Instability of the wall coating limits capillary lifetimes to approximately 30 runs. Considerations in using SSCE for the analysis of DNA fragments produced by the PCR technique are discussed.
Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation (2016)

Despite advances in supportive therapy to prevent complications of sickle cell disease (SCD), access to care is not universal. Hematopoietic cell transplantation is, to date, the only curative therapy for SCD, but its application is limited by availability of a suitable HLA-matched donor and lack of awareness of the benefits of transplant. Included in this study are 1000 recipients of HLA-identical sibling transplants performed between 1986 and 2013 and reported to the European Society for Blood and Marrow Transplantation, Eurocord, and the Center for International Blood and Marrow Transplant Research. The primary endpoint was event-free survival, defined as being alive without graft failure; risk factors were studied using a Cox regression models. The median age at transplantation was 9 years, and the median follow-up was longer than 5 years. Most patients received a myeloablative conditioning regimen (n = 873; 87%); the remainder received reduced-intensity conditioning regimens (n = 125; 13%). Bone marrow was the predominant stem cell source (n = 839; 84%); peripheral blood and cord blood progenitors were used in 73 (7%) and 88 (9%) patients, respectively. The 5-year event-free survival and overall survival were 91.4% (95% confidence interval, 89.6%-93.3%) and 92.9% (95% confidence interval, 91.1%-94.6%), respectively. Event-free survival was lower with increasing age at transplantation (hazard ratio [HR], 1.09; <i>P</i> < .001) and higher for transplantations performed after 2006 (HR, 0.95; <i>P</i> = .013). Twenty-three patients experienced graft failure, and 70 patients (7%) died, with the most common cause of death being infection. The excellent outcome of a cohort transplanted over the course of 3 decades confirms the role of HLA-identical sibling transplantation for children and adults with SCD.
Herpes simplex virus (HSV)-specific proliferative and cytotoxic T-cell responses in humans immunized with an HSV type 2 glycoprotein subunit vaccine (1988)

Studies were undertaken to determine whether immunization of humans with a herpes simplex virus type 2 (HSV-2) glycoprotein-subunit vaccine would result in the priming of both HSV-specific proliferating cells and cytotoxic T cells. Peripheral blood lymphocytes (PBL) from all eight vaccines studied responded by proliferating after stimulation with HSV-2, HSV-1, and glycoprotein gB-1. The PBL of five of these eight vaccines proliferated following stimulation with gD-2, whereas stimulation with gD-1 resulted in relatively low or no proliferative responses. T-cell clones were generated from HSV-2-stimulated PBL of three vaccinees who demonstrated strong proliferative responses to HSV-1 and HSV-2. Of 12 clones studied in lymphoproliferative assays, 9 were found to be cross-reactive for HSV-1 and HSV-2. Of the approximately 90 T-cell clones isolated, 14 demonstrated HSV-specific cytotoxic activity. Radioimmunoprecipitation-polyacrylamide gel electrophoresis analyses confirmed that the vaccinees had antibodies only to HSV glycoproteins, not to proteins which are absent in the subunit vaccine, indicating that these vaccinees had not become infected with HSV. Immunization of humans with an HSV-2 glycoprotein-subunit vaccine thus results in the priming of T cells that proliferate in response to stimulation with HSV and its glycoproteins and T cells that have cytotoxic activity against HSV-infected cells. Such HSV-specific memory T cells were detected as late as 2 years following the last boost with the subunit vaccine.
Synthesis of congeners and prodrugs. 3. Water-soluble prodrugs of taxol with potent antitumor activity (1989)

Taxol has shown good in vivo antitumor activity in a number of test systems. The formulation of taxol for antitumor testing has been difficult. Esterification at either C-2' or C-7 resulted in loss of in vitro tubulin assembly activity but not cytotoxicity. These observations suggested that esters at C-2' and/or C-7, which would tend to promote water solubility, might serve as useful prodrugs of taxol. The reaction of taxol with either succinic anhydride or glutaric anhydride in pyridine solution at room temperature gave the crystalline mono 2'-adducts 1b and 1f, respectively. Salts of these acids (1b, 1f, 1i) were formed by the addition of 1 equiv of the corresponding base, followed by evaporation and/or freeze-drying of the solvent(s). The salts had improved antitumor activity as compared to the free acids. The triethanolamine and N-methylglucamine salts showed greatly improved aqueous solubility and were more active than the sodium salts. The glutarate series was preferred because of the higher activity and the higher yields obtained. 2'-Glutaryltaxol (1f) was coupled with 3-(dimethylamino)-1-propylamine, using CDI, to form in excellent yield the amino amide 1o. The hydrochloride salt (1p) showed good solubility and was extremely potent and active. At 10 mg/kg, in the B16 screen, 1p gave a T/C of 352 with 5 out of 10 cures. In the MX-1 breast xenograft assay, this prodrug gave values of -100 at doses of 40 and 20 mg/kg, with all live animals being tumor free.
Board Forum Crawling: A Web Crawling Method for Web Forum (2006)

We present a new method of board forum crawling to crawl Web forum. This method exploits the organized characteristics of the Web forum sites and simulates human behavior of visiting Web forums. The method starts crawling from the homepage, and then enters each board of the site, and then crawls all the posts of the site directly. Board forum crawling can crawl most meaningful information of a Web forum site efficiently and simply. We experimentally evaluated the effectiveness of the method on real Web forum sites by comparing with the traditional breadth-first crawling. We also used this method in a real project, and 12000 Web forum sites have been crawled successfully. These results show the effectiveness of our method
Canola and mustard response to short periods of temperature and water stress at different developmental stages (2004)

Seed yield of Brassica crops in semiarid environments can be increased by minimizing the crops’ exposure to high temperature and water stress that often occurs during the growing season. A growth chamber study was conducted to determine the effect of short periods of high temperature and water stress at different developmental stages on seed yield and yield components of Brassica crops. Two canola-quality Brassica juncea ‘PC98-44’ and ‘PC98-45’, a Brassica napus canola ‘Quantum’, and a B. juncea oriental mustard ‘Cutlass’ were grown under 20/18°C day/night temperatures with photoperiod of 16/8 h light/dark. High (35/18°C) and moderate (28/18°C) temperature stress was imposed for 10 d during bud formation, flowering, and pod development. Low (90% available water) and high (50% available water) water stress was imposed in combination with the temperature treatments. On average, the 35/18°C stress reduced main stem pods by 75%, seeds pod -1 25%, and seed weight 22% from the control. Seed yield per plant was reduced by 15% when plants were severely (35/18°C) stressed during bud formation, 58% when stressed during flowering, and 77% when stressed during pod development. Plants stressed at earlier growth stages exhibited recovery, whereas stress during pod development severely reduced most of the yield components. Effect of water stress on seed yield was minimal regardless of crop developmental stage. The four Brassica cultivars responded similarly to water stress. In response to temperature stress, B. juncea produced greater number of pods per plant but had a great rate of pod infertility than B. napus. Seed yield of B. juncea in semiarid environments can be increased by improving pod fertility, whereas the seed yield of B. napus can be increased by improving pod pro duction and retention. Key words: Oilseed, yield components, Brassica species, moisture.
Clinical Outcome of Lymphoma Patients After Idiotype Vaccination Is Correlated With Humoral Immune Response and Immunoglobulin G Fc Receptor Genotype (2004)

This study is the first to identify the predictive value of FcgammaR polymorphism on clinical outcome in patients who received active immunotherapy with tumor antigen vaccines. Our results imply that the antibodies induced against a tumor antigen are beneficial and that FcgammaR-bearing cells mediate an antitumor effect by killing antibody-coated tumor cells.
Mask topography simulation for EUV lithography (1999)

This paper introduces a methodology for rigorous computation of electric fields in the neighborhood of reflective masks employed in EUV lithography. Specifically, the media used in this application place stringent requirements on the spatial and temporal grids in order to achieve a stable and accurate Finite-Difference, Time-Domain calculation. An analytical expression for the electric field reflectivity off the multilayer is harnessed to define effective media that can decrease run times by as much as an order of magnitude. This framework is then used to analyze the effect of the absorber thickness on image linewidth and quality.
Purification of human adult and foetal intestinal alkaline phosphatases by monoclonal antibody immunoaffinity chromatography (1984)

We have used the technique of monoclonal antibody immunoaffinity chromatography to purify adult and foetal intestinal alkaline phosphatases. Pure adult intestinal enzyme was obtained from a crude tissue extract with a single immunoaffinity chromatographic step in yields exceeding 95%. An additional ion-exchange chromatographic step was necessary for purification of the foetal enzyme, but yields still exceeded 70%. Experiments to optimize the efficiency of the monoclonal antibody immunoaffinity chromatography procedure suggest that the relative strength of binding of an antibody to its antigen is the most important factor to consider when constructing such columns. A column made from an antibody of too low an avidity will not retain the enzyme, while one of too high an avidity will make elution of enzyme in the active state difficult. A scheme is suggested for the application of this technique to a general approach to enzyme purification.
Genetics of O-Antigen Biosynthesis inPseudomonas aeruginosa (1999)

Pathogenic bacteria produce an elaborate assortment of extracellular and cell-associated bacterial products that enable colonization and establishment of infection within a host. Lipopolysaccharide (LPS) molecules are cell surface factors that are typically known for their protective role against serum-mediated lysis and their endotoxic properties. The most heterogeneous portion of LPS is the O antigen or O polysaccharide, and it is this region which confers serum resistance to the organism. Pseudomonas aeruginosa is capable of concomitantly synthesizing two types of LPS referred to as A band and B band. The A-band LPS contains a conserved O polysaccharide region composed of D-rhamnose (homopolymer), while the B-band O-antigen (heteropolymer) structure varies among the 20 O serotypes of P. aeruginosa. The genes coding for the enzymes that direct the synthesis of these two O antigens are organized into two separate clusters situated at different chromosomal locations. In this review, we summarize the organization of these two gene clusters to discuss how A-band and B-band O antigens are synthesized and assembled by dedicated enzymes. Examples of unique proteins required for both A-band and B-band O-antigen synthesis and for the synthesis of both LPS and alginate are discussed. The recent identification of additional genes within the P. aeruginosa genome that are homologous to those in the A-band and B-band gene clusters are intriguing since some are able to influence O-antigen synthesis. These studies demonstrate that P. aeruginosa represents a unique model system, allowing studies of heteropolymeric and homopolymeric O-antigen synthesis, as well as permitting an examination of the interrelationship of the synthesis of LPS molecules and other virulence determinants.
Anatomic markers of human premalignancy and risk of breast cancer (1990)

Epithelial hyperplasia of the breast carries an increased likelihood of carcinoma development, with most lesions best understood as markers of higher risk. The indication of increased cancer risk for more worrisome or complex histologic patterns has been supported in many studies. About 25% of women who underwent biopsies in the premammographic era had well-developed hyperplastic changes associated with an elevated risk of 1.5 to 2.0 times that of the general population when age and length of time of follow-up were considered. Somewhat fewer than 5% of women had specific patterns of atypical hyperplasia (AH) that approached the criteria of carcinoma in situ (CIS). These women with AH had a risk of cancer four to five times that of the general population, or about one half the risk associated with microscopic CIS. Only ductal CIS should be considered without question to be an intrinsic precancerous lesion because of its regular association with recurrence at the site of its initial diagnosis. Further studies indicated an appreciable interaction between AH and other nonanatomic risk factors, particularly a family history of breast cancer. Also, lower dosage estrogen replacement after menopause does not affect risk in any histologically defined group. The atypical hyperplastic lesions are more common in women undergoing biopsies on the indication of mammographic calcifications than because of palpable masses. The primary therapeutic implications of these premalignant lesions are intensified breast cancer surveillance and screening for these patients.
IC reliability simulation (1992)

The motivation and challenges of IC reliability simulation are discussed. The reliability simulator BERT is used to illustrate the physical models and approaches used to simulate the hot-electron effect, oxide time-dependent breakdown, electromigration, and bipolar transistor gain degradation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Experimental Intra-Abdominal Abscesses in Rats: Quantitative Bacteriology of Infected Animals (1974)

An animal model simulating intra-abdominal sepsis was produced by implanting large bowel contents into the pelvic region of rats. Bacteriological analysis of infected sites showed quantitative differences according to the stage of disease. During the initial, often lethal, peritonitis stage, Escherichia coli (mean concentration, 10(6)/ml), enterococci (10(5)) and Bacterioides fragilis (10(6)) were always present. Blood cultures obtained during this phase were uniformly positive, with E. coli being the principal isolate. Animals that survived this early acute peritonitis stage developed indolent intra-abdominal abscesses. The major isolates in abscess contents were B. fragilis (10(8.7)) and Fusobacterium (10(8.6)); E. coli (10(7.8)) and enterococci (10(5.7)) were also present but in lesser concentrations. Rank order analysis of these four species in peritoneal exudates and abscess pus showed that the two aerobes outranked the two anaerobes during the early stage of the disease, whereas the reverse was true in abscesses. These experiments also illustrated that a major simplification of the original fecal inoculum occurred, even though the subsequent infection remained bacteriologically complex.
Total Synthesis of Oxazole‐ and Cyclopropane‐Containing Epothilone B Analogues by the Macrolactonization Approach (1997)

Abstract In order to probe structure‐activity relationships in the epothilone area, two series of epothilone B analogues have been designed and synthesized. The first series containing an oxazole moiety in place of a thiazole on the side chain was constructed by utilizing key intermediates 7–9 or 10, 12 , and 13 (Scheme 1), whereas the second series containing an ethano group instead of the gem ‐dimethyl group at position 4 was synthesized from fragments 42 and 43 . A Yamaguchi‐type macrolactonization reaction was used to construct the macrocycle from a secoacid, which was assembled, in both cases, by means of a) an aldol reaction, b) an Enders alkylation, and c) a Wittig‐type reaction. This convergent strategy provided access to oxazole analogues 2,4,29–32 and 4,4‐ethano derivatives 3,40,60–63 for biological studies.
Search based reverse engineering (2002)

In this paper we describe a two step process for reverse engineering the software architecture of a system directly from its source code. The first step involves clustering the modules from the source code into abstract structures called subsystems. The second step involves reverse engineering the subsystem-level relations using a formal (and visual) architectural constraint language. We use search techniques to accomplish both of these steps, and have implemented a suite of integrated tools to support the reverse engineering process. Through a case study, we demonstrate how our tools can be used to extract the software architecture of an open-source software package from its source code without having any a priori knowledge about its design.
Segmentation by grouping junctions (2002)

We propose a method for segmenting gray-value images. By segmentation, we mean a map from the set of pixels to a small set of levels such that each connected component of the set of pixels with the same level forms a relatively large and "meaningful" region. The method finds a set of levels with associated gray values by first finding junctions in the image and then seeking a minimum set of threshold values that preserves the junctions. Then it finds a segmentation map that maps each pixel to the level with the closest gray value to the pixel data, within a smoothness constraint. For a convex smoothing penalty, we show the global optimal solution for an energy function that fits the data can be obtained in a polynomial time, by a novel use of the maximum-flow algorithm. Our approach is in contrast to a view in computer vision where segmentation is driven by intensity, gradient, usually not yielding closed boundaries.