gebhart/patrepeval huggingface dataset:
Genome sequencing of lymphoid malignancies (2013)

Our understanding of the pathogenesis of lymphoid malignancies has been transformed by next-generation sequencing. The studies in this review have used whole-genome, exome, and transcriptome sequencing to identify recurring structural genetic alterations and sequence mutations that target key cellular pathways in acute lymphoblastic leukemia (ALL) and the lymphomas. Although each tumor type is characterized by a unique genomic landscape, several cellular pathways are mutated in multiple tumor types-transcriptional regulation of differentiation, antigen receptor signaling, tyrosine kinase and Ras signaling, and epigenetic modifications-and individual genes are mutated in multiple tumors, notably TCF3, NOTCH1, MYD88, and BRAF. In addition to providing fundamental insights into tumorigenesis, these studies have also identified potential new markers for diagnosis, risk stratification, and therapeutic intervention. Several genetic alterations are intuitively "druggable" with existing agents, for example, kinase-activating lesions in high-risk B-cell ALL, NOTCH1 in both leukemia and lymphoma, and BRAF in hairy cell leukemia. Future sequencing efforts are required to comprehensively define the genetic basis of all lymphoid malignancies, examine the relative roles of germline and somatic variation, dissect the genetic basis of clonal heterogeneity, and chart a course for clinical sequencing and translation to improved therapeutic outcomes.
Computer-Aided Drug Design: Methods and Applications (1989)

Recent advances in the mechanistic approach to discovery new drugs. The methods section includes chapters on computer graphics, molecular mechanics and dynamics, x-ray crystallography, NMR, and enzyme kinetics. The applications section discusses several specific drugs and drug groups, such as variou
Asymmetric Synthesis of (−)-Aurantioclavine via Palladium-Catalyzed Intramolecular Allylic Amination (2014)

The total synthesis of (-)-aurantioclavine (1) was accomplished based on an intramolecular asymmetric amination of allyl carbonate 3 containing a p-tosylamide group. The reaction using tris(dibenzylideneacetone)dipalladium(0), tBu-phosphinooxazoline, and Bu4NCl in CH2Cl2 gave azepane 2 in 77% yield with 95% enantiomeric excess. The obtained azepane 2 was also converted to a substructure of communesin F.
High-Throughput Screening of Enantioselective Catalysts by Immunoassay (2002)

More than 1000 yields and ee determinations are possible per day using an immunoassay. This highly efficient screening method is based on the remarkable binding specificity of antibodies. It has been employed in the development of straightforward procedures for the direct conversion of α-keto acids into chiral α-hydroxy acids, for which the enantioselective reduction of benzoyl formic acid to mandelic acid serves as a model reaction (see scheme). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2002/z17920_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Treatment of Autoimmune Neuroinflammation with a Synthetic Tryptophan Metabolite (2005)

Local catabolism of the amino acid tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is considered an important mechanism of regulating T cell immunity. We show that IDO transcription was increased when myelin-specific T cells were stimulated with tolerogenic altered self-peptides. Catabolites of Trp suppressed proliferation of myelin-specific T cells and inhibited production of proinflammatory T helper-1 (T(H)1) cytokines. N-(3,4,-Dimethoxycinnamoyl) anthranilic acid (3,4-DAA), an orally active synthetic derivative of the Trp metabolite anthranilic acid, reversed paralysis in mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis (MS). Trp catabolites and their derivatives offer a new strategy for treating T(H)1-mediated autoimmune diseases such as MS.
Synthesis and in vitro degradations of low‐molecular‐weight copolyesters composed of L‐lactic acid and aromatic hydroxy acids (1990)

Abstract L ‐lactic acid (LA) was copolycondensed with various aromatic hydroxy acids such as p ‐hydroxybenzoic acid (HBA), p ‐hydroxyphenylacetic acid (HPAA), and p ‐3‐(hydroxyphenyl)propionic acid (HPPA) in the absence of catalysts, in order to investigate the copolymerizability and in vitro degradation. The results of 1 H NMR spectroscopy and gel permeation chromatography (GPC) showed that the reaction proceeds quantitatively, but the molecular weight of the copolyesters is relatively low. The in vitro degradation pattern of copoly(LA/HPPA) was changed into an S‐type from a parabolic‐type with increasing HPPA content in the copolyester, in contrast to only parabolic‐type for both copoly(LA/HBA) and copoly(LA/HPAA).
Integration and Transcription of Human Papillomavirus Type 16 and 18 Sequences in Cell Lines Derived from Cervical Carcinomas (1987)

Five cell lines, SKG-I, SKG-II, SKG-IIIb, QG-U and QG-H derived from cervical carcinomas of Japanese patients, were examined for the presence of human papillomavirus (HPV) DNA and the expression of viral mRNA. The DNA of HPV type 16 was shown to be linked covalently with SKG-IIb, QG-U and QG-H cell DNA, and HPV 18 DNA with SKG-I and SKG-II cell DNA. Although different regions of the HPV genome were integrated in these cell lines, the non-coding region and an early region including the E6 and E7 open reading frames (ORFs) were conserved in all cell lines. The complete genome of HPV 16 was found in QG-H cells by digestion of the DNA with a single-cut restriction enzyme. The other early region ORFs E1, E2, E4 and E5 were interrupted by flanking host cell DNA, suggesting that the integration into host cell DNA occurs preferentially in this region. HPV-specific mRNA species were detected in all five cell lines. In the three cell lines containing the HPV 16 genome, mRNAs hybridized with the early region of the genome, covering the entire E6 and E7 ORFs and a minor part of the E1 ORF, although the amount and size of the major mRNAs varied in these cell lines. These mRNAs did not hybridize with the late region of the HPV genome containing the L1 and L2 ORFs. In SKG-II, SKG-IIIb and QG-H cells we also detected c-myc and c-Ha-ras mRNA expression at about nine times the level of that in normal cells.
The Adhesion Molecule L1CAM as a Novel Therapeutic Target for Treatment of Pancreatic Cancer Patients? (2012)

The Adhesion Molecule L1CAM as a Novel Therapeutic Target for Treatment of Pancreatic Cancer Patients?
Regulation of fatty acid degradation in Escherichia coli: isolation and characterization of strains bearing insertion and temperature-sensitive mutations in gene fadR (1980)

Transposon Tn10 was used to mutagenize the fadR gene in Escherichia coli. Mutants bearing fadR:Tn10 insertion mutations were found to (i) utilize the noninducing fatty acid decanoate as sole carbon source, (ii) beta-oxidize fatty acids at constitutive rates, and (iii) contain constitutive levels of the five key beta-oxidative enzymes. These characteristics were identical to those observed in spontaneous fadR mutants. The constitutive phenotype presented by the fadR:Tn10 mutants was shown to be genetically linked to the associated transposon-encoded drug resistance. These results suggest that the fadR gene product exerts negative control over the fatty acid degradative regulon. The fadR gene of E. coli has been mapped through the use of transposon-mediated fadR insertion mutations. The fadR locus is at 25.5 min on the revised map and cotransduces with purB, hemA, and trp. Three-factor conjugational and transductional crosses indicate that the order of loci in this region of the chromosome is purB-fadR-hemA-trp. Spontaneous fadR mutants were found to map at the same location. Strains that exhibit alterations in the control of the fad regulon in response to changes in temperature were also isolated and characterized. These fadR(Ts) mutants were constitutive for the fad enzymes at elevated temperatures and inducible for these activities at low temperatures. The fadR(Ts) mutations also map at the fadR locus. These results strongly suggest that the fadR gene product is a repressor protein.
Delineation by Fluorescence in Situ Hybridization of a Single Hemizygous Chromosomal Region Associated With Aposporous Embryo Sac Formation in Pennisetum squamulatum and Cenchrus ciliaris (2003)

Apomixis is a means of asexual reproduction by which plants produce embryos without meiosis and fertilization; thus the embryo is of clonal, maternal origin. We previously reported molecular markers showing no recombination with the trait for aposporous embryo sac development in Pennisetum squamulatum and Cenchrus ciliaris, and the collective single-dose alleles defined an apospory-specific genomic region (ASGR). Fluorescence in situ hybridization (FISH) was used to confirm that the ASGR is a hemizygous genomic region and to determine its chromosomal position with respect to rDNA loci and centromere repeats. We also documented chromosome transmission from P. squamulatum in several backcrosses (BCs) with P. glaucum using genomic in situ hybridization (GISH). One to three complete P. squamulatum chromosomes were detected in BC(6), but only one of the three hybridized with the ASGR-linked markers. In P. squamulatum and in all BCs examined, the apospory-linked markers were located in the distal region of the short arm of a single chromosome. All alien chromosomes behaved as univalents during meiosis and segregated randomly in BC(3) and later BC generations, but presence of the ASGR-carrier chromosome alone was sufficient to confer apospory. FISH results support our hypotheses that hemizygosity, proximity to centromeric sequences, and chromosome structure may all play a role in low recombination in the ASGR.
California bonanza? Providers and insurers cheer mandatory health insurance law, but business interests look at legal challenge to newly signed bill. (2003)

Consider it Gov. Gray Davis' going-away present to the state's hospitals, insurers and physician groups. The California Health Insurance Act of 2003 could mean increased revenue for hospitals. Doctors like Brian Johnston, left, say the bill has been a long time coming and are pleased with the legislation, but others are concerned about what effects the mandatory insurance law will have on small businesses.
Crystal structure of the human T cell receptor CD3εγ heterodimer complexed to the therapeutic mAb OKT3 (2004)

The CD3 epsilon gamma heterodimer is essential for expression and function of the T cell receptor. The crystal structure of the human CD3 epsilon gamma heterodimer is described to 2.1-A resolution complexed with OKT3, a therapeutic mAb that not only activates and tolerizes mature T cells but also induces regulatory T cells. The mode of CD3 epsilon gamma dimerization provides a general structural basis for CD3 assembly and maps candidate T cell antigen receptor docking sites, including a duplicated linear region rich in acidic residues that is unique to human CD3 epsilon. OKT3 binds to an atypically small area of CD3 epsilon and has a low affinity for the isolated CD3 epsilon gamma heterodimer. The structure of the OKT3/CD3 epsilon gamma complex has implications for T cell signaling and therapeutic design.
Electronic properties of silole-based organic semiconductors (2004)

We report on a detailed quantum-chemical study of the geometric structure and electronic properties of 2,5-bis(6(')-(2('),2(")-bipyridyl))-1,1-dimethyl-3,4-diphenylsilole (PyPySPyPy) and 2,5-di- (3-biphenyl)-1,1-dimethyl-3,4-diphenylsilole (PPSPP). These molecular systems are attractive candidates for application as electron-transport materials in organic light-emitting devices. Density Functional Theory (DFT), time-dependent DFT, and correlated semiempirical (ZINDO/CIS) calculations are carried out in order to evaluate parameters determining electron-transport and optical characteristics. Experimental data show that PyPySPyPy possesses an electron-transport mobility that is significantly greater than PPSPP, while PPSPP has a significantly larger photoluminescence quantum yield; however, the theoretical results indicate that the two systems undergo similar geometric transformations upon reduction and have comparable molecular orbital structures and energies. This suggests that intermolecular interactions (solid-state packing, electronic coupling) play significant roles in the contrasting performance of these two molecular systems.
MEG Phase Follows Conscious Perception during Binocular Rivalry Induced by Visual Stream Segregation (2005)

We have investigated an unusual form of binocular rivalry between two images that are flickered one to each eye, but are never presented simultaneously to the observer. The images were presented in alternation, with a brief dark period between the images. When the flicker frequency was < 5 Hz, the subjects primarily experienced a unitary flicker that alternated between the two images. When the flicker frequency was > 5 Hz, the subjects primarily experienced two single-image flickers that rival. We investigated magnetoencephalography (MEG) responses at the flicker frequency of the rival stimuli. We found that at some recording locations responses are phase-locked to the flicker that is consciously being perceived. At each flicker rate that induced rivalry, phase shifts following the conscious percept were found consistently at MEG sensors over midline frontal lobe. Most of these sensors show higher magnitude responses when two rivaling flickers are perceived than when a unitary alternating color flicker is perceived. At sensors over occipital lobe, the sensor locations that phase-locked to the perceived flicker depended on the color, orientation, and frequency of flicker. By contrast, sensors over parietal cortex respond preferentially to one flicker, even as the conscious percept changes. Apparently, a large-scale network of cell assemblies in occipital and frontal cortex, responds preferentially to the perceived stimulus during rivalry, and is sensitive to the timing of the flicker driving the conscious percept.
The Biochemistry and Physiology of S-Nitrosothiols (2002)

S-nitrosothiols are biological metabolites of nitric oxide. It has often been suggested that they represent a more stable metabolite of nitric oxide that can either be stored, or transported, although the evidence for this is sparse. There are many unanswered questions concerning how S-nitrosothiols are formed, how they are metabolized and how they elicit biological responses. These questions are highlighted by the fact that the known chemistry of nitric oxide, thiols, and S-nitrosothiols cannot serve to explain their proposed biological activities. This review attempts to highlight the gulf between our chemical understanding of S-nitrosothiols and the proposed biological activities of these compounds with respect to guanylyl cyclase-independent nitric oxide bioactivity and also the control of vascular tone.
Adhesive Polyurethane Liners for Anterior Restorations (1968)

Polyurethane-type compositions were developed as adhesive liners for poly(methyl methacrylate) restorations. Several polyglycol-diisocyanate mixtures had excellent adhesion to human dentin when applied to moist teeth in vitro. Conventional acrylic restorations became durably bonded when applied on top of these urethane liners within 15 to 30 minutes.
Interstitial Doppler optical coherence tomography (2005)

Doppler optical coherence tomography (OCT) can image tissue structure and blood flow at micrometer-scale resolution but has limited imaging depth. We report a novel, linear-scanning, needle-based Doppler OCT system using angle-polished gradient-index or ball-lensed fibers. A prototype system with a 19-guage (diameter of approximately 0.9 mm) echogenic needle is constructed and demonstrates in vivo imaging of bidirectional blood flow in rat leg and abdominal cavity. To our knowledge, this is the first demonstration of Doppler OCT through a needle probe in interstitial applications to visualize deeply situated microcirculation.
Raman Spectra of Amino Acids and Related Compounds. XI. The Ionization of Cysteine1-3 (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRaman Spectra of Amino Acids and Related Compounds. XI. The Ionization of Cysteine1-3David Garfinkel and John T. EdsallCite this: J. Am. Chem. Soc. 1958, 80, 15, 3823–3826Publication Date (Print):August 1, 1958Publication History Published online1 May 2002Published inissue 1 August 1958https://pubs.acs.org/doi/10.1021/ja01548a004https://doi.org/10.1021/ja01548a004research-articleACS PublicationsRequest reuse permissionsArticle Views182Altmetric-Citations41LEARN 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
Ozone Exposure and Mortality (2005)

These findings, coupled with a greater relative risk of ozone in the summer versus the winter, demonstrate that geographic and seasonal heterogeneity in ozone relative risk should be anticipated, but that the observed relationship between ozone and mortality should be considered for future regulatory impact analyses.
A tutorial discussion of the oversampling method for A/D and D/A conversion (2002)

Oversampling A/D and D/A conversion is discussed with emphasis on sigma-delta structures. Oversampling A/D converters modulate their analog inputs into short digital words at a very high sampling rate. Decimation filters resample this code at the Nyquist rate of the signal and increase the word length to maintain resolution. At the D/A, interpolating filters increase the word rate of the digital code by more than an order of magnitude. This code is demodulated to analog form at high speed using very few levels.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Studies on 5'-Nucleotidase-Lacking Mutants Derived from Bacillus Subtilis (1965)

Two 5'-nucleotidase-lacking mutants, R-42 and A-1, were derived from an adenine-requiring mutant, B. subtilis 1145-2-83, which has productivity of both inosine and hypoxanthine. Strain A-1 accumulated 5'-IMP as well as inosine and hypoxanthine, and strain R-42 accumulated 5'-IMP and 5'-GMP as well as inosine and hypoxanthine in their culture fluids. These mutants responded to either adenine or adenosine, but did not to 5'-AMP. This fact suggests that adenine or adenosine may be incorporated into the cells, but 5'-AMP may neither be incorporated into the cells nor be degraded during culture. 5'-GMP was converted to 5'-IMP, and 5'-AMP was phosphrylated to ADP in the growing culture of strain A-1.
Stress Concentration and Material Failure During Coiling of Ultra-Thin TRAC Booms (2018)

Ultra-thin TRAC booms are a promising technology for large deployable structures for space applications.A manufacturing process producing composites TRAC booms with flange thickness as low as 53 μm is proposed.Coiling behavior around hub with radii ranging from 19.1 mm to 31.8 mm is studied both experimentally and through finite element simulations.Due to the thinness of the TRAC boom, a buckle appears in the inner flange, in the transition region from the fully deployed to the coiled configurations.Material failure is observed at this location, and this correlates well with stresses computed in simulation, coupled with the fiber microbuckling failure criterion.Reducing the thickness, either by changing the laminate or by improving the manufacturing process, is shown to reduce stresses, allowing coiling around smaller hubs without material failure.
App store strategies for service providers (2010)

Apple App Store has introduced a substantially different model for digital good distribution to mobile users. Following Apple's spectacular success other smartphone and mobile OS vendors have started similar services. Mobile operators who invest hundreds of millions in 2,5G, 3G and now 4G technologies have a right to participate in the digital economy they enable. Can they quickly bite into the app store business and turn it to their advantage or they will be out of game again? This paper will try to answer these important questions by analysing the app store market and investigating potential app store strategies and scenarios for mobile operators.
Trousseau's syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features. (1977)

Analysis of 182 patients with chronic disseminated intravascular coagulopathy and malignancy shows common features. Migratory thrombophlebitis occurred in 96 patients while at least a single episode of thrombophlebitis was noted in 113. Seventy-five of the patients bled and 45 had arterial emboli in various organs. Twelve patients had the triad of thrombophlebitis, hemorrhage, and arterial emboli, often sequentially. Hematologic data showed derangements associated with intravascular coagulation, the most prominent of which were hypofibrinogenemia and thrombocytopenia. Other abnormalities included prolonged prothrombin time, increased fibrinogen-fibrin degradation products, decreased levels of factors V and VIII, cryofibrinogenemia, and microangiopathic hemolytic anemia. Forty-one patients had lesions of non-bacterial thrombotic endocarditis at autopsy; 31 of these had arterial emboli during life. None of the lesions were infected. Mitral and aortic valves were most frequently involved. No single mechanism that causes the disseminated intravascular coagulopathy has been identified. However, cell products--secretions and enzymes--and the cells themselves have been proposed as the procoagulant(s) responsible for the syndrome. In addition to treatment of the underlying neoplasm, symptomatic disseminated intravascular coagulopathy should be controlled. Heparin is the drug of choice for treatment of this problem, very little benefit having been observed with warfarin therapy. Long-term use of anticoagulants is potentially feasible for control of chronic disseminated intravascular coagulopathy, but without effective control of the underlying tumor ultimately will be unsuccessful.
Product commonality in multiple-period, make-to-stock systems (1999)

It is well known that replacing several products by a single common product can reduce required safety stock levels due to the benefits of risk pooling. Recent research utilizing single-period models has investigated the cost savings (or losses) from doing so. This paper uses a very general multiple-period model, with general demand distributions, any number of products, and the objective of minimizing production, holding, and shortage costs. Two scenarios are considered—one that utilizes a common product and one that does not. Prior results utilizing single-period models indicate that even if the common product is more expensive than the products it replaces, there are many circumstances under which it is still worthwhile to employ. Surprisingly, this paper will show that this is almost never the case in a multiple-period model. © 1999 John Wiley & Sons, Inc. Naval Research Logistics 46: 737–751, 1999