gebhart/patrepeval huggingface dataset:
New Synthetic Inhibitors of Fatty Acid Synthase with Anticancer Activity (2012)

Fatty acid synthase (FASN) is a lipogenic enzyme that is highly expressed in different human cancers. Here we report the development of a new series of polyphenolic compounds 5-30 that have been evaluated for their cytotoxic capacity in SK-Br3 cells, a human breast cancer cell line with high FASN expression. The compounds with an IC(50) < 50 μM have been tested for their ability to inhibit FASN activity. Among them, derivative 30 blocks the 90% of FASN activity at low concentration (4 μM), is highly cytotoxic in a broad panel of tumor cells, induces apoptosis, and blocks the activation of HER2, AKT, and ERK pathways. Remarkably, 30 does not activate carnitine palmitoyltransferase-1 (CPT-1) nor induces in mice weight loss, which are the main drawbacks of other previously described FASN inhibitors. Thus, FASN inhibitor 30 may aid the validation of this enzyme as a therapeutic target for the treatment of cancer.
Resistance of human immunodeficiency virus type 1 to acyclic 6-phenylselenenyl- and 6-phenylthiopyrimidines (1994)

Acyclic 6-phenylselenenyl- and 6-phenylthiopyrimidine derivatives are potent and specific inhibitors of human immunodeficiency virus type 1 (HIV-1). The development of in vitro resistance to two derivatives, 5-ethyl-1-(ethoxymethyl)-(6-phenylthio)-uracil (E-EPU), was evaluated by serial passage of HIV-1 in increasing concentrations of inhibitor. HIV-1 variants exhibiting > 500-fold resistance to E-EPSeU and E-EPU were isolated after sequential passage in 1, 5, and 10 microM inhibitor. The resistant variants exhibited coresistance to related acyclic 6-substituted pyrimidines and the HIV-1-specific inhibitors (+)-(5S)-4,5,6,7-tetrahydro-5- pyrimidines and the HIV-1-specific inhibitors (+)-(5S)-4,5,6,7-tetrahydro-5- methyl-6-(3-methyl-2-butenyl)imidazo[4,5,1-jk]benzodiazepin-2(1H)- thione (TIBO R82150) and nevirapine, but remained susceptible to 3'-azido-3'-deoxythymidine, 2',3'-dideoxycytidine, 2',3'-dideoxyinosine, and phosphonoformic acid. DNA sequence analysis of reverse transcriptase (RT) derived from E-EPSeU-resistant virus identified a Tyr (TAT)-to-Cys (TGT) mutation at either codon 188 (Cys-188; 9 of 15 clones) or codon 181 (Cys-181; 5 of 15 clones). The same amino acid changes were found in RT from E-EPU-resistant virus, but the Cys-181 mutation was more common (9 of 10 clones) than the Cys-188 mutation (1 of 10 clones). Site-specific mutagenesis and production of mutant recombinant viruses demonstrated that both the Cys-181 and Cys-188 mutations cause resistance to E-EPSeU and E-EPU. Of the two mutations, the Cys-188 substitution produced greater E-EPSeU and E-EPU resistance. The predominance of the Cys-188 mutation in E-EPSeU-resistant variants has not been noted for other classes of HIV-1 specific RT inhibitors. HIV-1 resistance is likely to limit the therapeutic efficacy of acyclic 6-substituted pyrimidines if they are used as monotherapy.
The Role of Fourier Transform Ion Cyclotron Resonance Mass Spectrometry in Biological Research — New Developments and Applications (1996)

The symbiotic relationship between advances in ionization methods and the improved performance of mass spectrometric instrumentation and its computer control has been key to the growth of mass spectrometry. The new capabilities for the ionization of large molecules introduced in 1988 have, in effect, resulted in a situation where the demands for improved sensitivity, resolution, effective tandem MS capabilities for structural studies, and the online combination with separation methods, are greater than ever and effectively open-ended. This situation coincides with a period in which mass spectrometric hardware has begun a transition from a dominance by quadrupole and sector mass analyzer technologies to other technologies that previously were rarely used for “real world” bioanalytical applications (i. e., time-of-flight mass spectrometers and ion trapping methods).
Mapping the Collagen-binding Site in the von Willebrand Factor-A3 Domain (2003)

The multimeric glycoprotein von Willebrand factor (VWF) mediates platelet adhesion to collagen at sites of vascular damage. The binding site for collagen types I and III is located in the VWF-A3 domain. Recently, we showed that His(1023), located near the edge between the "front" and "bottom" faces of A3, is critical for collagen binding (Romijn, R. A., Bouma, B., Wuyster, W., Gros, P., Kroon, J., Sixma, J. J., and Huizinga, E. G. (2001) J. Biol. Chem. 276, 9985-9991). To map the binding site in detail, we introduced 22 point mutations in the front and bottom faces of A3. The mutants were expressed as multimeric VWF, and binding to collagen type III was evaluated in a solid-state binding assay and by surface plasmon resonance. Mutation of residues Asp(979), Ser(1020), and His(1023) nearly abolished collagen binding, whereas mutation of residues Ile(975), Thr(977), Val(997), and Glu(1001) reduced binding affinity about 10-fold. Together, these residues define a flat and rather hydrophobic collagen-binding site located at the front face of the A3 domain. The collagen-binding site of VWF-A3 is distinctly different from that of the homologous integrin alpha(2) I domain, which has a hydrophilic binding site located at the top face of the domain. Based on the surface characteristics of the collagen-binding site of A3, we propose that it interacts with collagen sequences containing positively charged and hydrophobic residues. Docking of a collagen triple helix on the binding site suggests a range of possible engagements and predicts that at most eight consecutive residues in a collagen triple helix interact with A3.
A practical EMG-based human-computer interface for users with motor disabilities. (2000)

In line with the mission of the Assistive Technology Act of 1998 (ATA), this study proposes an integrated assistive real-time system which "affirms that technology is a valuable tool that can be used to improve the lives of people with disabilities." An assistive technology device is defined by the ATA as "any item, piece of equipment, or product system, whether acquired commercially, modified, or customized, that is used to increase, maintain, or improve the functional capabilities of individuals with disabilities." The purpose of this study is to design and develop an alternate input device that can be used even by individuals with severe motor disabilities. This real-time system design utilizes electromyographic (EMG) biosignals from cranial muscles and electroencephalographic (EEG) biosignals from the cerebrum's occipital lobe, which are transformed into controls for two-dimensional (2-D) cursor movement, the left-click (Enter) command, and an ON/OFF switch for the cursor-control functions. This HCI system classifies biosignals into "mouse" functions by applying amplitude thresholds and performing power spectral density (PSD) estimations on discrete windows of data. Spectral power summations are aggregated over several frequency bands between 8 and 500 Hz and then compared to produce the correct classification. The result is an affordable DSP-based system that, when combined with an on-screen keyboard, enables the user to fully operate a computer without using any extremities.
Wireless Implantable Microsystems: High-Density Electronic Interfaces to the Nervous System (2004)

This paper describes the development of a high-density electronic interface to the central nervous system. Silicon micromachined electrode arrays now permit the long-term monitoring of neural activity in vivo as well as the insertion of electronic signals into neural networks at the cellular level. Efforts to understand and engineer the biology of the implant/tissue interface are also underway. These electrode arrays are facilitating significant advances in our understanding of the nervous system, and merged with on-chip circuitry, signal processing, microfluidics, and wireless interfaces, they are forming the basis for a family of neural prostheses for the possible treatment of disorders such as blindness, deafness, paralysis, severe epilepsy, and Parkinson's disease.
Prevention and Management of NSAID-Induced Gastropathy (2000)

Nonsteroidal antiinflammatory drugs (NSAIDs) are the most frequently prescribed medication for chronic pain. Gastrointestinal complications from NSAID treatment are a major cause of morbidity and mortality. In the majority of patients, NSAID induced gastropathy is superficial and self-limiting. However, peptic ulcers develop in some patients and may lead to hemorrhage, perforation, or death. NSAIDs can cause gastrointestinal damage via topical injury of the mucosal barrier, systemic inhibition of prostaglandin synthesis or a combination of both. Risk factors for NSAID related complications include age >s 60 years, history of ulcer disease, concomitant corticosteroid or anticoagulant use, high dose therapy, and multiple NSAID use. Identifying high-risk patients is critical in order to minimize risk. Factors suggested to predict the safety of NSAIDs include selective COX-2 inhibition, absence of enterohepatic circulation, shorter half-life, and nonacidic pro-drug formulations. The COX-2 selective NSAIDs, celecoxib and rofecoxib, have been recently marketed and appear to have less GI toxicity. Long-term studies and post marketing surveillance are needed to confirm the safety of the COX-2 inhibitors. Proton pump inhibitors and misoprostol are the only agents proven beneficial in preventing GI adverse effects from NSAIDs.
Induction Of Tolerance To FVIII Using Nanoparticles In a Murine Model Of Hemophilia A (2013)

Abstract Anti-FVIII inhibitor development is currently considered the most serious side effect in the treatment of hemophilia A patients. In this study, we sought to address this problem by determining the efficacy of a novel tolerogenic protocol utilizing nanoparticle formulations provided by Selecta Biosciences. Thus, hemophilia A mice (FVIII KO, n = 6-8) were treated weekly for five weeks through intravenous route with 1 µg recombinant human FVIII (rFVIII), plus immune modulating agent coupled nanoparticles or control nanoparticles (coded F1 or F2 or F3). An additional control group was included, in which the mice were treated on the same schedule with high dose IVIG + rFVIII. As expected, all the mice in the control group (later revealed to be F3) developed high levels anti-FVIII IgG after the five treatments, with the average levels at 21.2 ± 4.4 µg/ml. Both the F1 and F2 nanoparticle treatments effectively prevented the anti-FVIII inhibitory antibody development throughout the course of the 5-week treatment. One week after the final treatment, the majority (5/7) of both F1 and F2 groups remained undetectable for anti-FVIII IgG antibodies. Consistent with this pattern, the anti-FVIII inhibitor titers for the F1, F2, F3 and IVIG groups were 42.3 ± 9.9, 14.3 ± 7.2, 92.9 ± 2.5, and 30.3 ± 5.6 Bethesda Units (BU)/ml, respectively after another 7 days (p &lt; 0.01 for F1 and F2 vs. F3). To determine the duration of the FVIII-tolerance, the mice were challenged twice with rFVIII (1µg) 29 and 53 days after the final nanoparticle treatment. After the first FVIII challenge, the inhibitor titers for the F1, F2, F3 and IVIG groups were 81.3 ± 10.8, 33.1 ± 13.2, 84.1 ± 2.2 (p = 0.41 for F1 vs. F3; and p &lt; 0.01 for F2 vs. F3), and 50.6 ± 9.7 BU/ml, respectively. Remarkably, the FVIII-tolerance in F2 group was sustained even after additional FVIII challenges ∼ 2 months later, when the effect in IVIG group was completely lost. A therapeutic protocol using mice pre-immunized with FVIII also led to substantial reductions in anti-FVIII titers. In conclusion, the concomitant Selecta F2 nanoparticle treatments not only significantly prevented the anti-FVIII inhibitory antibody development during the treatments, but also resulted in long-term FVIII-tolerance, suggesting a potential clinical application. (Supported in part by a grant-in-aid from Selecta Bioscience and by HL061883) Disclosures: Griset: Selecta Biosciences: Employment, Equity Ownership. Maldonado:Selecta Biosciences: Employment, Equity Ownership. Kishimoto:Selecta Biosciences: Employment, Equity Ownership. Scott:Selecta Biosciences: Research Funding.
Opinion Mining on Newspaper Quotations (2009)

Opinion mining is the task of extracting from a set of documents opinions expressed by a source on a specified target. This article presents a comparative study on the methods and resources that can be employed for mining opinions from quotations (reported speech) in newspaper articles. We show the difficulty of this task, motivated by the presence of different possible targets and the large variety of affect phenomena that quotes contain. We evaluate our approaches using annotated quotations extracted from news provided by the EMM news gathering engine. We conclude that a generic opinion mining system requires both the use of large lexicons, as well as specialised training and testing data.
Effect of the 1-(2'-deoxy-beta-D-ribofuranosyl)-3-nitropyrrole residue on the stability of DNA duplexes and triplexes (1997)

3-Nitropyrrole (M) was introduced as a non-discriminating 'universal' base in nucleic acid duplexes by virtue of small size and a presumed tendency to stack but not hydrogen bond with canonical bases. However, the absence of thermally-induced hyperchromic changes by single-stranded deoxyoligomers in which M alternates with A or C residues shows that M does not stack strongly with A or C nearest neighbors. Yet, the insertion of a centrally located M opposite any canonical base in a duplex is sometimes even less destabilizing than that of some mismatches, and the variation in duplex stability is small. In triplexes, on the other hand, an M residue centrally located in the third strand reduces triplex stability drastically even when the X.Y target base pair is A.T or G. C in a homopurine. homopyrimidine segment. But, when the target duplex opposition is M-T and the third strand residue is T, the presence of M in the test triplet has little effect on triplex stability. Therefore, a lack of hydrogen bonding in an otherwise helix-compatible test triplet cannot be responsible for triplex destabilization when M is the third strand residue. Thus, M is non-discriminating and none-too-destabilizing in a duplex, but in a triplex it is extremely destabilizing when in the third strand.
MEROPS: the peptidase database (2007)

Peptidases (proteolytic enzymes or proteases), their substrates and inhibitors are of great relevance to biology, medicine and biotechnology. The MEROPS database (http://merops.sanger.ac.uk) aims to fulfil the need for an integrated source of information about these. The organizational principle of the database is a hierarchical classification in which homologous sets of peptidases and protein inhibitors are grouped into protein species, which are grouped into families and in turn grouped into clans. Important additions to the database include newly written, concise text annotations for peptidase clans and the small molecule inhibitors that are outside the scope of the standard classification; displays to show peptidase specificity compiled from our collection of known substrate cleavages; tables of peptidase-inhibitor interactions; and dynamically generated alignments of representatives of each protein species at the family level. New ways to compare peptidase and inhibitor complements between any two organisms whose genomes have been completely sequenced, or between different strains or subspecies of the same organism, have been devised.
MAJOR DEPRESSIVE DISORDER SUBTYPES TO PREDICT LONG-TERM COURSE (2014)

Despite being based on retrospective reports, results suggest that useful MDD subtyping distinctions can be made using data mining methods. Further studies are needed to test and expand these results with prospective data.
Hydrodynamic studies of adsorbed diblock copolymers in porous membranes (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydrodynamic studies of adsorbed diblock copolymers in porous membranesRichard M. Webber, John L. Anderson, and Myung S. JhonCite this: Macromolecules 1990, 23, 4, 1026–1034Publication Date (Print):February 1, 1990Publication History Published online1 May 2002Published inissue 1 February 1990https://pubs.acs.org/doi/10.1021/ma00206a020https://doi.org/10.1021/ma00206a020research-articleACS PublicationsRequest reuse permissionsArticle Views99Altmetric-Citations37LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Simple Pulses for Elimination of Leakage in Weakly Nonlinear Qubits (2009)

In realizations of quantum computing, a two-level system (qubit) is often singled out from the many levels of an anharmonic oscillator. In these cases, simple qubit control fails on short time scales because of coupling to leakage levels. We provide an easy to implement analytic formula that inhibits this leakage from any single-control analog or pixelated pulse. It is based on adding a second control that is proportional to the time derivative of the first. For realistic parameters of superconducting qubits, this strategy reduces the error by an order of magnitude relative to the state of the art, all based on smooth and feasible pulse shapes. These results show that even weak anharmonicity is sufficient and in general not a limiting factor for implementing quantum gates.
Efectividad de siete productos antimancha contra ceratocystis sp. en madera de hevea brasiliensis muell arg. (hule) (2002)

El presente trabajo se realizó con el objeto de conocer la eficacia de siete productos antimancha que se comercializan en México, contra el hongo manchador Ceratocystis sp. en madera aserrada de Hevea brasiliensis (hule), mediante el método de los discos, conjuntamente con la norma ASTM D 4445-91. Los productos están elaborados a partir de pentaclorofenato de sodio, tres de ellos, siendo Osmotox, Pentatox y Biotox; tres más están hechos a base de metil bistiocianato y 2-tiocianometiltio benzotiazol y son Busan 1009, Busan 1450 y Busan 1071, y el séptimo solamente contiene 2-tiocianometiltio benzotiazol, siendo el Busan 1118. La concentración mínima observada para evitar el manchado de la madera (crecimiento cero) en un tiempo de 4 semanas, para cada uno de los productos ensayados se obtuvo para Osmotox de 4.68 %, para Pentatox de 2.82 %, para Biotox de 3.24 %, para Busan 1118 de 2.00 % y para Busan 1009, Busan 1450 y Busan 1071 una concentración menor a 0.25%. Tomando en cuenta los precios comerciales de cada producto y de acuerdo con las concentraciones mínimas efectivas para crecimiento cero obtenidas, el tratamiento con Busan 1071 es el más económico y más efectivo.
COBAS AMPLICOR: fully automated RNA and DNA amplification and detection system for routine diagnostic PCR (1996)

The COBAS AMPLICOR system automates amplification and detection of target nucleic acids, making diagnostic PCR routine for a variety of infectious diseases. The system contains a single thermal cycler with two independently regulated heating/cooling blocks, an incubator, a magnetic particle washer, a pipettor, and a photometer. Amplified products are captured on oligonucleotide-coated paramagnetic microparticles and detected with use of an avidin-horseradish peroxidase (HRP) conjugate. Concentrated solutions of amplicon or HRP were pipetted without detectable carryover. Amplified DNA was detected with an intraassay CV of < 4.5%; the combined intraassay CV for amplification and detection was < 15%. No cross-reactivity was observed when three different target nucleic acids were amplified in a single reaction and detected with three target-specific capture probes. The initial COBAS AMPLICOR menu includes qualitative tests for diagnosing infections with Chlamydia trachomatis, Neisseria gonorrhoeae, Mycobacterium tuberculosis, and hepatitis C virus. All tests include an optional Internal Control to provide assurance that specimens are successfully amplified and detected.
Binocular eye tracking in virtual reality for inspection training (2000)

This paper describes the development of a binocular eye tracking Virtual Reality system for aircraft inspection training. The aesthetic appearance of the environment is driven by standard graphical techniques augmented by realistic texture maps of the physical environment. A "virtual flashlight" is provided to simulate a tool used by inspectors. The user's gaze direction, as well as head position and orientation, are tracked to allow recording of the user's gaze locations within
THE ELECTRONIC SWITCHING SPHERICAL ARRAY (ESSA) ANTENNA FOR THE EARTH RADIATION BUDGET SPACECRAFT (ERBS) (1982)

International Telemetering Conference Proceedings / September 28-30, 1982 / Sheraton Harbor Island Hotel and Convention Center, San Diego, California
Essential Role of Ferritin Pfr in Helicobacter pylori Iron Metabolism and Gastric Colonization (2002)

The reactivity of the essential element iron necessitates a concerted expression of ferritins, which mediate iron storage in a nonreactive state. Here we have further established the role of the Helicobacter pylori ferritin Pfr in iron metabolism and gastric colonization. Iron stored in Pfr enabled H. pylori to multiply under severe iron starvation and protected the bacteria from acid-amplified iron toxicity, as inactivation of the pfr gene restricted growth of H. pylori under these conditions. The lowered total iron content in the pfr mutant, which is probably caused by decreased iron uptake rates, was also reflected by an increased resistance to superoxide stress. Iron induction of Pfr synthesis was clearly diminished in an H. pylori feoB mutant, which lacked high-affinity ferrous iron transport, confirming that Pfr expression is mediated by changes in the cytoplasmic iron pool and not by extracellular iron. This is well in agreement with the recent discovery that iron induces Pfr synthesis by abolishing Fur-mediated repression of pfr transcription, which was further confirmed here by the observation that iron inhibited the in vitro binding of recombinant H. pylori Fur to the pfr promoter region. The functions of H. pylori Pfr in iron metabolism are essential for survival in the gastric mucosa, as the pfr mutant was unable to colonize in a Mongolian gerbil-based animal model. In summary, the pfr phenotypes observed give new insights into prokaryotic ferritin functions and indicate that iron storage and homeostasis are of extraordinary importance for H. pylori to survive in its hostile natural environment.