gebhart/patrepeval huggingface dataset:
Multiple sequence alignment with user-defined constraints (2004)

Abstract: In many situations, automated multi-alignment programs are not able to correctly align families of nucleic acid or protein sequences. Distantly related sequences are generally hard to align, and sequence duplications may present additional challenges to standard alignment algorithms. In the present paper, we describe a semiautomatic approach to multiple sequence alignment. The user can specify parts of the sequences that are thought to be related to each other; our software program will use these sites as anchor points and create a multiple alignment respecting these userdefined constraints. By using functionally, structurally or evolutionarily related positions of the input sequences as anchor points, the proposed method can produce alignments that are biologically more meaningful than alignments produced by fully automated procedures. We apply our approach to genomic sequences around the Hox gene cluster. As a by-product, we obtain useful insights for the further development of alignment algorithms. The described alignment approach has been integrated into the tracker software system.
BRCA1 Downregulation Leads to Premature Inactivation of Spindle Checkpoint and Confers Paclitaxel Resistance (2006)

BRCA1 germline mutations predispose women to early onset, familial breast and ovarian cancer. BRCA1 has been recently implicated in the cellular response to agents that disrupt the mitotic spindle. In this report, we studied BRCA1 contribution to paclitaxel response in MCF-7 breast cancer cells. We show that MCF-7 cells transfected with BRCA1 siRNA display a significant increase in resistance to paclitaxel compared with the control cells. We next demonstrate that downregulation of BRCA1 reduces the mitotic index and triggers premature cyclin B1 degradation and decrease in Cdk1 activity following paclitaxel treatment, suggesting that BRCA1 downregulation results in precocious inactivation of the spindle checkpoint. These findings were confirmed by showing that BRCA1 downregulation induces premature sister-chromatids separation in MCF-7 cells following spindle damage. Furthermore, we show that BRCA1 up-regulates the expression of the protein kinase BubR1, essential component of the functional spindle checkpoint, whose downregulation is known to result in paclitaxel resistance in MCF-7 cells. Altogether, our findings support the notion that downregulation of BRCA1 expression mediates paclitaxel resistance through premature inactivation of spindle checkpoint in MCF-7 breast cancer cells. They link BRCA1 to the mitotic checkpoint that plays an essential role in the maintenance of chromosomal stability.
Sodium Butyrate Stimulates Expression of Fibroblast Growth Factor 21 in Liver by Inhibition of Histone Deacetylase 3 (2012)

Fibroblast growth factor 21 (FGF21) stimulates fatty acid oxidation and ketone body production in animals. In this study, we investigated the role of FGF21 in the metabolic activity of sodium butyrate, a dietary histone deacetylase (HDAC) inhibitor. FGF21 expression was examined in serum and liver after injection of sodium butyrate into dietary obese C57BL/6J mice. The role of FGF21 was determined using antibody neutralization or knockout mice. FGF21 transcription was investigated in liver and HepG2 hepatocytes. Trichostatin A (TSA) was used in the control as an HDAC inhibitor. Butyrate was compared with bezafibrate and fenofibrate in the induction of FGF21 expression. Butyrate induced FGF21 in the serum, enhanced fatty acid oxidation in mice, and stimulated ketone body production in liver. The butyrate activity was significantly reduced by the FGF21 antibody or gene knockout. Butyrate induced FGF21 gene expression in liver and hepatocytes by inhibiting HDAC3, which suppresses peroxisome proliferator-activated receptor-α function. Butyrate enhanced bezafibrate activity in the induction of FGF21. TSA exhibited a similar set of activities to butyrate. FGF21 mediates the butyrate activity to increase fatty acid use and ketogenesis. Butyrate induces FGF21 transcription by inhibition of HDAC3.
Modeling content identification from document images (1994)

A new technique to locate content-representing words for a given document image using abstract representation of character shapes is described. A character shape code representation defined by the location of a character in a text line has been developed. Character shape code generation avoids the computational expense of conventional optical character recognition (OCR). Because character shape codes are an abstraction of standard character code (e.g., ASCII), the mapping is ambiguous. In this paper, the ambiguity is shown to be practically limited to an acceptable level. It is illustrated that: first, punctuation marks are clearly distinguished from the other characters; second, stop words are generally distinguishable from other words, because the permutations of character shape codes in function words are characteristically different from those in content words; and third, numerals and acronyms in capital letters are distinguishable from other words. With these clAssifications, potential content-representing words are identified, and an analysis of their distribution yields their rank. Consequently, introducing character shape codes makes it possible to inexpensively and robustly bridge the gap between electronic documents and hard-copy documents for the purpose of content identification.
Outcomes after Total versus Subtotal Abdominal Hysterectomy (2002)

Neither subtotal nor total abdominal hysterectomy adversely affects pelvic organ function at 12 months. Subtotal abdominal hysterectomy results in more rapid recovery and fewer short-term complications but infrequently causes cyclical bleeding or cervical prolapse.
<i>ARGONAUTE4</i> Control of Locus-Specific siRNA Accumulation and DNA and Histone Methylation (2003)

Proteins of the ARGONAUTE family are important in diverse posttranscriptional RNA-mediated gene-silencing systems as well as in transcriptional gene silencing in Drosophila and fission yeast and in programmed DNA elimination in Tetrahymena. We cloned ARGONAUTE4 (AGO4) from a screen for mutants that suppress silencing of the Arabidopsis SUPERMAN (SUP) gene. The ago4-1 mutant reactivated silent SUP alleles and decreased CpNpG and asymmetric DNA methylation as well as histone H3 lysine-9 methylation. In addition, ago4-1 blocked histone and DNA methylation and the accumulation of 25-nucleotide small interfering RNAs (siRNAs) that correspond to the retroelement AtSN1. These results suggest that AGO4 and long siRNAs direct chromatin modifications, including histone methylation and non-CpG DNA methylation.
Modeling drug exposure data in electronic medical records: an application to warfarin. (2011)

Identification of patients' drug exposure information is critical to drug-related research that is based on electronic medical records (EMRs). Drug information is often embedded in clinical narratives and drug regimens change frequently because of various reasons like intolerance or insurance issues, making accurate modeling challenging. Here, we developed an informatics framework to determine patient drug exposure histories from EMRs by combining natural language processing (NLP) and machine learning (ML) technologies. Our framework consists of three phases: 1) drug entity recognition - identifying drug mentions; 2) drug event detection - labeling drug mentions with a status (e.g., "on" or "stop"); and 3) drug exposure modeling - predicting if a patient is taking a drug at a given time using the status and temporal information associated with the mentions. We applied the framework to determine patient warfarin exposure at hospital admissions and achieved 87% precision, 79% recall, and an area under the receiver-operator characteristic curve of 0.93.
A BODIPY dye as a reactive chromophoric/fluorogenic probe for selective and quick detection of vapors of secondary amines (2013)

A new reaction based fluorescence turn-off strategy for detection of secondary amines was developed. The probe shows fast response and high selectivity to secondary amines in solution/film at sub-ppm levels through chromogenic and fluorescent dual-mode signal changes.
Shaping of Bulk Semiconductor Samples by Photolithography and Chemical Etching (1981)

Semiconductor bulk samples, suitable for characterization of electronic properties, have been made by simultaneous deep patterned mesa etching from opposing faces of polished wafers. Outlines of the samples to be produced were delineated by areas of hard‐baked photoresist on those faces, with mirror‐image masks aligned for the two opposing faces. Sample outlines thus created included the well‐known "bridge‐shaped" and "clover‐shaped" forms used for electrical characterization. The etching action was quenched when canyons etched from the two faces met, releasing individual sample shapes. An etch was used in making samples, from polished wafers of (100), (110), (111), and (211) orientations; wafers of thickness in the range 0.2–0.5 mm could be used without excessive undercutting. Preliminary results are reported for silicon samples made by this method, using an etch.
Effects of Composition, Orientation and Temperature on the O<sub>2</sub> Permeability of Model Polymer/Clay Nanocomposites (2010)

Studies of the barrier properties of polymer/layered silicate nanocomposites have traditionally focused on systems with low organoclay contents, with very little work comparing theory and experiment over broad composition ranges. As a result, in spite of many reports of promising enhancements in barrier properties, the envelope of applicability nanocomposite barrier models is generally unknown, making predictive modeling and materials design difficult if not impossible. In this work, model polystyrene (PS)/dimethyl ditallow modified montmorillonite (DMDT-MMT) nanocomposites are produced via a novel spray casting technique capable of creating homogeneous, free-standing nanocomposite films. This approach provides a single experimental methodology for producing films of pure polymer, pure organoclay, or any intermediate composition, with consistently high levels of layer orientation in all cases. The results of oxygen permeation analysis (OPA) performed on these model materials (0−100 vol % organoclay in 10% increments) are compared to the results from all models commonly used for nanocomposite barrier properties modeling, both before and after the addition of a correction factor for actual layer orientation as measured by 2D wide-angle X-ray diffraction (WAXD), and with fitting parameters limited to physically meaningful values. We report substantial improvements in barrier properties in spite of the absence of exfoliation, with the model fits implying that the permeating species remain sensitive to the aspect ratio of individual platelets at all organoclay contents. While all models match our experimental data at low organoclay contents, significant differentiation occurs as organoclay content is increased. Finally, we confirm that the permeability of these materials follows an Arrhenius relation vs temperature, albeit scaled to lower values as a function of inorganic content.
An In-Plant Evaluation of Froth Washing on Conventional Flotation Cells for Coal (2001)

Column flotation cells have become increasingly popular in the coal industry due to their ability to improve flotation selectivity. The improvement can be largely attributed to the use of froth washing, which minimizes the nonselective entrainment of ultrafine minerals matter into the froth product. Unfortunately, the practice of adding wash water in conventional flotation machines has been largely unsuccessful in industrial trials. In order to better understand the causes of these failures, a detailed in-plant test program was undertaken to evaluate the use of froth washing at an operating coal preparation plant. The tests included detailed circuit audits (solid and liquid mass balances), salt tracer studies, and release analyses. The data collected from these tests have been used to develop criteria that describe when and how froth washing may be successfully applied in industrial flotation circuits. A second series of tests was developed to look at other alternatives to froth washing and their effectiveness. This involved two-staged flotation circuitry. A two-staged approach was developed because the existing flotation cells did not have enough residence time to support froth washing. The process owner wanted to evaluate possible alternatives to column cell flotation. The testing included release analysis testing as well as a detailed series of tests with percent solids control to the secondary flotation unit. II
Definitions of Managed Objects for the Fabric Element in Fibre Channel Standard (2000)

This memo defines an extension to the Management Information Base (MIB) for use with network management protocols in TCP/IP-based internets. In particular, it defines the objects for managing the operations of the Fabric Element portion of the Fibre Channel Standards.
Targeting redox homeostasis in rhabdomyosarcoma cells: GSH-depleting agents enhance auranofin-induced cell death (2017)

Rhabdomyosarcoma (RMS) cells have recently been reported to be sensitive to oxidative stress. Therefore, we investigated whether concomitant inhibition of the two main antioxidant defense pathways, that is, the thioredoxin (TRX) and the glutathione (GSH) systems, presents a new strategy to trigger cell death in RMS. In this study, we discover that GSH-depleting agents, i.e. γ-glutamylcysteine synthetase inhibitor, buthionine sulfoximine (BSO) or the cystine/glutamate antiporter inhibitor erastin (ERA), synergize with thioredoxin reductase (TrxR) inhibitor auranofin (AUR) to induce cell death in RMS cells. Interestingly, AUR causes accumulation of ubiquitinated proteins when combined with BSO or ERA, in line with recent reports showing that AUR inhibits the proteasome besides TrxR. Consistently, AUR/BSO or AUR/ERA cotreatment increases ubiquitination and expression of the short-lived proteins NOXA and MCL-1, accompanied by increased binding of NOXA to MCL-1. Notably, NOXA knockdown significantly rescues RMS cells from AUR/BSO- or AUR/ERA-induced cell death. In addition, AUR acts together with BSO or ERA to stimulate BAX/BAK and caspase activation. Of note, BSO or ERA abolish the AUR-stimulated increase in GSH levels, leading to reduced GSH levels upon cotreatment. Although AUR/BSO or AUR/ERA cotreatment enhances reactive oxygen species (ROS) production, only thiol-containing antioxidants (i.e., N-acetylcysteine (NAC), GSH), but not the non-thiol-containing ROS scavenger α-Tocopherol consistently suppress AUR/BSO- and AUR/ERA-stimulated cell death in both cell lines. Importantly, re-supply of GSH or its precursor NAC completely prevents AUR/ERA- and AUR/BSO-induced accumulation of ubiquitinated proteins, NOXA upregulation and cell death, indicating that GSH depletion rather than ROS production is critical for AUR/BSO- or AUR/ERA-mediated cell death. Thus, by demonstrating that GSH-depleting agents enhance the antitumor activity of AUR, we highlight new treatment options for RMS by targeting the redox homeostasis.
Surfactant-Polymer EOR from Laboratory to the Pilot (2018)

Abstract Central element of MOL Hungarian Oil and Gas Plc. (MOL) US strategy is to increase the hydrocarbon production at Hungarian oil and gas fields using technologies that are more efficient. The main goals of this activity are to increase the recovery factor in fields depleted with extensive water flooding, improving efficiency of recovery technologies. For this purpose, new materials and technologies should be developed and applied at both Hungarian and foreign matured oil fields. That is the biggest challenge of the research and development (R&D) activity of the MOL Upstream. The R&D project began more than ten years ago to meet these challenges and increase the oil recovery factor of the Algyo field, which is the largest Hungarian oil field. This paper describes how a countless number of surfactants, co-surfactants and their mixtures were synthetized, developed and tested in the laboratory to achieve the objective, developing a combined surfactant-polymer (SP) flooding technology. The most important properties of these complex fluids were the thermal stability at reservoir conditions (98°C and 170 bar), the colloid chemical stability in electrolyte medium (formation water) and the compatibility with reservoir rock and pore filling fluids. The primary findings of this job show that several surfactants were effective at high temperature; low salinity reservoir conditions and have good solubilisation and displacement effect and low interfacial tension and low reversible adsorption on reservoir rock. Synergetic effect was observed between surfactants and polymers therefore surfactant-polymer mixtures were produced and tested in core flooding tests. Based on numerous displacement tests on reservoir core plugs it can be stated that the calculated recovery factor was 20-25% using the developed SP mixtures. The successful laboratory displacement tests were also reproduced by numerical simulation on numerical core samples as well as the injectivity test on the new 3D reservoir model that was carried out to see the effect of developed SP mixture under real reservoir conditions. This paper will present the results of several years of research and development work for SP formulation targeting SP flooding in high pressure and high temperature reservoir. The field implementation through an injectivity test will also be presented demonstrating that injection of 2,000 m3 SP solution has huge effect on oil production even 3 years later. Based on the outstanding field results a SP flooding pilot was started in 2016.
CFD Modeling of Heat Recovery Steam Generator and its Components Using Fluent (2005)

Combined Cycle power plants have recently become a serious alternative for standard coal- and oil-fired power plants because of their high thermal efficiency, environmentally friendly operation, and short time to construct. The combined cycle plant is an integration of the gas turbine and the steam turbine, combining many of the advantages of both thermodynamic cycles using a single fuel. By recovering the heat energy in the gas turbine exhaust and using it to generate steam, the combined cycle leverages the conversion of the fuel energy at a very high efficiency. The heat recovery steam generator forms the backbone of combined cycle plants, providing the link between the gas turbine and the steam turbine. The design of HRSG has historically largely been completed using thermodynamic principles related to the steam path, without much regard to the gas-side of the system. An effort has been made using resources at both UK and Vogt Power International to use computational fluid dynamics (CFD) analysis of the gas-side flow path of the HRSG as an integral tool in the design process. This thesis focuses on how CFD analysis can be used to assess the impact of the gas-side flow on the HRSG performance and identify design modifications to improve the performance. An effort is also made to explore the software capabilities to make the simulation an efficient and accurate.
A Novel EGFRvIII T-Cell Bispecific Antibody for the Treatment of Glioblastoma (2022)

T-cell bispecific antibodies (TCB) are engineered molecules that bind both the T-cell receptor and tumor-specific antigens. Epidermal growth factor receptor variant III (EGFRvIII) mutation is a common event in glioblastoma (GBM) and is characterized by the deletion of exons 2-7, resulting in a constitutively active receptor that promotes cell proliferation, angiogenesis, and invasion. EGFRvIII is expressed on the surface of tumor cells and is not expressed in normal tissues, making EGFRvIII an ideal neoantigen target for TCBs. We designed and developed a novel 2+1 EGFRvIII-TCB with optimal pharmacologic characteristics and potent antitumor activity. EGFRvIII-TCB showed specificity for EGFRvIII and promoted tumor cell killing as well as T-cell activation and cytokine secretion only in patient-derived models expressing EGFRvIII. Moreover, EGFRvIII-TCB promoted T-cell recruitment into intracranial tumors. EGFRvIII-TCB induced tumor regression in GBM animal models, including humanized orthotopic GBM patient-derived xenograft models. Our results warrant the clinical testing of EGFRvIII-TCB for the treatment of EGFRvIII-expressing GBMs.
PKC-δ inhibitors sustain self-renewal of mouse embryonic stem cells under hypoxia<i>in vitro</i> (2010)

Under hypoxia, mouse embryonic stem cells (mESCs) lose their self-renewal activity and display an early differentiated morphology mediated by the hypoxia-inducible factor-1 alpha (HIF-1 alpha). Previous studies have demonstrated that PKC-delta is activated by hypoxia and increases the protein stability and transcriptional activity of HIF-1 alpha in human cancer cells. Furthermore, activation of PKC-delta mediates cardiac differentiation of ESCs and hematopoietic stem cells. However, the role of PKC-delta in hypoxia-induced early differentiation of mESCs remains largely unknown. Here, we show the inhibition of PKC-delta activity prevents the early differentiation of mESCs under hypoxia using PKC-delta inhibitors, GF 109203X and rottlerin. Reduction of PKC-delta activity under hypoxia effectively decreased HIF-1 alpha protein levels and substantially recovered the expression of LIF-specific receptor (LIFR) and phosphorylated-STAT3 in mESCs. Furthermore, PKC-delta inhibitors aid to sustain the expression of self-renewal markers and suppress the expression of early differentiation markers in mESCs under hypoxia. Taken together, these results suggest that PKC-delta inhibitors block the early differentiation of mESCs via destabilization of HIF-1 alpha under hypoxia.
A Shared Promoter Element Regulates the Expression of Three Steridogenic Enzymes (1991)

The adrenal cortex of the mouse coordinately expresses three cytochrome P450 enzymes that are required for the biosynthesis of corticosteroids: cholesterol side-chain cleavage enzyme (SCC), steroid 21-hydroxylase (21-OHase), and steroid 11 beta-hydroxylase (11 beta-OHase). Within their 5'-flanking regions, we previously identified six elements containing variations of an AGGTC motif that regulated expression in mouse Y1 adrenocortical cells: 21-OHase elements at -210, -140, and -65; SCC elements at -70 and -40; and an 11 beta-OHase element at -310. We demonstrate here that all six elements interact with the same, or closely related, DNA-binding protein(s). First, these elements all formed complexes of similar mobility in gel shift assays, suggesting that they interacted with protein(s) of similar size. Additional larger complexes were seen with those probes containing exact AGGTCA sequences. Second, competition experiments confirmed that the factor(s) interacting with different elements had closely related or identical recognition specificities. Finally, indistinguishable profiles of shift activities were seen upon fractionation of nuclear proteins over sequential chromatographic columns. Collectively, these results suggest that related elements interact with a shared protein to regulate three essential steroidogenic enzymes. An AGGTCA sequence motif comprises the response element for several members of the nuclear hormone receptor family. Oligonucleotide competitions and specific effects of antisera in gel shift assays implicated chicken ovalbumin upstream promoter-transcription factor in the formation of the larger complexes seen with the elements containing exact AGGTCA sequences. Therefore, this member of the nuclear hormone receptor family also may regulate the expression of the adrenal steroidogenic enzymes.