gebhart/patrepeval huggingface dataset:
Evolution of the H3 influenza virus hemagglutinin from human and nonhuman hosts (1992)

The nucleotide and amino acid sequences of 40 influenza virus hemagglutinin genes of the H3 serotype from mammalian and avian species and 9 genes of the H4 serotype were compared, and their evolutionary relationships were evaluated. From these relationships, the differences in the mutational characteristics of the viral hemagglutinin in different hosts were examined and the RNA sequence changes that occurred during the generation of the progenitor of the 1968 human pandemic strain were examined. Three major lineages were defined: one containing only equine virus isolates; one containing only avian virus isolates; and one containing avian, swine, and human virus isolates. The human pandemic strain of 1968 was derived from an avian virus most similar to those isolated from ducks in Asia, and the transfer of this virus to humans probably occurred in 1965. Since then, the human viruses have diverged from this progenitor, with the accumulation of approximately 7.9 nucleotide and 3.4 amino acid substitutions per year. Reconstruction of the sequence of the hypothetical ancestral strain at the avian-human transition indicated that only 6 amino acids in the mature hemagglutinin molecule were changed during the transition between an avian virus strain and a human pandemic strain. All of these changes are located in regions of the molecule known to affect receptor binding and antigenicity. Unlike the human H3 influenza virus strains, the equine virus isolates have no close relatives in other species and appear to have diverged from the avian viruses much earlier than did the human virus strains. Mutations were estimated to have accumulated in the equine virus lineage at approximately 3.1 nucleotides and 0.8 amino acids per year. Four swine virus isolates in the analysis each appeared to have been introduced into pigs independently, with two derived from human viruses and two from avian viruses. A comparison of the coding and noncoding mutations in the mammalian and avian lineages showed a significantly lower ratio of coding to total nucleotide changes in the avian viruses. Additionally, the avian virus lineages of both the H3 and H4 serotypes, but not the mammalian virus lineages, showed significantly greater conservation of amino acid sequence in the internal branches of the phylogenetic tree than in the terminal branches. The small number of amino acid differences between the avian viruses and the progenitor of the 1968 pandemic strain and the great phenotypic stability of the avian viruses suggest that strains similar to the progenitor strain will continue to circulate in birds and will be available for reintroduction into humans.
Precipitation Variation in the Upper and Middle Yellow River Basin, China (2011)

The Yellow River is the second longest river in China which supports 12% of the Chinese population. As a result, describing and understanding the precipitation variations under global climate change are of importance. The present study investigates the daily series of precipitation in the upper and middle Yellow River Basin (YRB) from 67 meteorological stations since 1950s.By using the rotated empirical orthogonal function method, the upper and middle YRB is divided into 7 regions. The Mann-Kendall method was adopted to detect gradual change of precipitation. Results indicate in the source area of YRB, the annual precipitation has increased significantly (p<0.05). However in the middle reach, the annual precipitation and rainstorm of some areas have decreased significantly, which would be one reason of the decrease of water and sediment load in recent years in the YRB. Moreover, the spectrum analysis method was applied to analyze the spatial heterogeneity of precipitation. The frequency information gives the evidence identifying different areas which impact the runoff in the Lower Yellow River.
Clinical application of multiplex quantitative fluorescent polymerase chain reaction (QF-PCR) for the rapid prenatal detection of common chromosome aneuploidies (2001)

The clinical application of quantitative fluorescent polymerase chain reaction (QF-PCR) for rapid prenatal detection of chromosome aneuploidies has been limited in most studies to the detection of autosomal trisomies. Recently it has been shown that a newly identified highly polymorphic marker, termed X22, which maps to the Xq/Yq pseudoautosomal region of the sex chromosomes, used together with the X-linked short tandem repeat (STR) HPRT, allows the accurate detection of gonosome aneuploidies. We have developed a rapid assay, which includes these STR markers together with a sequence of the amelogenin region of the sex chromosomes and selected highly polymorphic autosomal STR. Two more X chromosome markers, as yet not used in previous QF-PCR applications, were also included in the assay. The molecular test was then used in a clinical trial on 551 uncultured amniotic fluid samples, allowing the assessment of copy number for chromosomes X, Y and 21 in 100% of cases. In the course of this study, two fetuses with Turner's syndrome and one with Klinefelter's syndrome were identified along with 17 autosomal trisomies. The assay proved to be so efficient and reliable that in most aneuploidy cases, in which ultrasound findings were in agreement with the molecular result, therapeutical interventions were possible without waiting for the result of cytogenetic analysis.
Structure of Saccharomyces cerevisiae alg3, sec18 mutant oligosaccharides. (1991)

Asparagine-linked oligosaccharides are synthesized by transfer of Glc3Man9GlcNAc2 from dolichol pyrophosphate to nascent polypeptides. Assembly of the precursor proceeds by highly ordered sequential addition of mannose and glucose to form Glc3Man9GlcNAc2-P-P-dolichol. Yeast mutants in asparagine-linked glycosylation (alg), generated by an 3H-Man suicide technique, were assigned to eight complementation groups which define steps in oligosaccharide-lipid synthesis (Huffaker, T.C., and Robbins, P.W. (1982) J. Biol. Chem. 257, 3203-3210). Alg3 invertase oligosaccharides are resistant to endo-beta-N-acetylglucosaminidase H, and the lipid-oligosaccharide pool yields Man5Glc-NAc2, suggesting its structure may be that from mammalian cells lacking Man-P-dolichol (Chapman, A., et al. (1980) J. Biol. Chem. 255, 4441-4446). To test this supposition, the endoplasmic reticulum form of invertase derepressed in alg3,sec18 yeast at 37 degrees C was isolated as a source of oligosaccharides whose processing beyond glucose and/or mannose trimming, if involved, would be prevented. Man8GlcNAc2 and Man5GlcNAc2 were released by peptide-N-glycosidase F from alg3,sec18 invertase in a 1:5 molar ratio. 1H NMR spectroscopy revealed Man8GlcNAc2 to be the alpha 1,2-mannosidase-trimming product described earlier (Byrd, J. C., Tarentino, A. L., Maley, F., Atkinson, P. H., and Trimble, R. B. (1982) J. Biol. Chem. 257, 14657-14666), while Man5GlcNAc2 was Man alpha 1, 2Man alpha 1,2Man alpha 1,3(Man alpha 1,6)Man beta 1,4GlcNAc beta 1, 4GlcNAc. This provides a structural proof for the lipid-linked Man5GlcNAc2 originally proposed from enzymatic and chemical analyses of the radiolabeled mammalian precursor. Experimental evidence indicates that, unlike the mammalian cell mutants which are unable to synthesize Man-P-dolichol, alg3 yeast accumulate Man5GlcNAc2-P-P-dolichol due to a defective alpha 1,3-mannosyltransferase required for the next step in oligosaccharide-lipid elongation.
Identification and order of sequential mutations in beta-actin genes isolated from increasingly tumorigenic human fibroblast strains. (1985)

We have sequenced the mutant beta-actin gene of a tumorigenic human fibroblast cell line (HuT-14T) and found that it carries three mutations that alter the amino acids at positions 36, 83, and 244 as well as a 22-base-pair "insertion" sequence, in the 5' intron, not present in a wild-type gene. The less tumorigenic cell line HuT-14, a progenitor of HuT-14T, has the same codon-244 mutation and the insertion sequence but not the other two mutations. A nontumorigenic cell line that is related to HuT-14 but that has no beta-actin mutations does carry the intron-length polymorphism. We conclude that the mutation at codon 244 occurred first in a beta-actin allele already bearing the 22-base-pair intron insert and that mutations at codons 36 and 83 arose subsequently during the selection for the HuT-14T phenotype. Rat-2 cells synthesize the appropriate charge-variant species of mutant actin protein when transfected with either the singly or the triply mutated beta-actin gene.
The Role of Plasma Protein Binding in Drug Discovery (2007)

Understanding of the molecular properties that control binding is of fundamental importance in the drug discovery process. The extent of plasma protein binding of a candidate drug molecule has an influence on a number of critical areas listed below, and many of these areas will be reviewed in this article, i.e.: • determination of margins in safety assessment/toxicology studies • the efficacy of a drug • drug metabolism and pharmacokinetics • drug–drug interactions • blood–brain barrier penetration
The Pediatric Neurotransmitter Disorders (2007)

The pediatric neurotransmitter disorders represent an enlarging group of neurological syndromes characterized by abnormalities of neurotransmitter synthesis and breakdown. The disorders of dopamine and serotonin synthesis are aromatic amino acid decarboxylase deficiency, tyrosine hydroxylase deficiency, and disorders of tetrahydrobiopterin synthesis. Amino acid decarboxylase, tyrosine hydroxylase, sepiapterin reductase, and guanosine triphosphate cyclohydrolase (Segawa disease) deficiencies do not feature elevated serum phenylalanine and require cerebrospinal fluid analysis for diagnosis. Segawa disease is characterized by dramatic and lifelong responsiveness to levodopa. Glycine encephalopathy is typically manifested by refractory neonatal seizures secondary to a defect of the glycine degradative pathway. gamma-amino butyric acid (GABA) metabolism is associated with several disorders, including glutamic acid decarboxylase deficiency with nonsyndromic cleft lip/ palate, GABA-transaminase deficiency, and succinic semialdehyde dehydrogenase deficiency. The latter is characterized by elevated gamma-hydroxybutyric acid and includes a wide range of neuropsychiatric symptoms as well as epilepsy. Pyridoxine-dependent seizures have now been associated with deficiency of alpha-aminoadipic semialdehyde dehydrogenase, as well as a new variant requiring therapy with pyridoxal-5-phosphate, the biologically active form of pyridoxine.
Effect of pressure on the mechanical properties of polymers. 2. Expansivity and compressibility measurements (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffect of pressure on the mechanical properties of polymers. 2. Expansivity and compressibility measurementsW. K. Moonan and N. W. TschoeglCite this: Macromolecules 1983, 16, 1, 55–59Publication Date (Print):January 1, 1983Publication History Published online1 May 2002Published inissue 1 January 1983https://pubs.acs.org/doi/10.1021/ma00235a011https://doi.org/10.1021/ma00235a011research-articleACS PublicationsRequest reuse permissionsArticle Views273Altmetric-Citations29LEARN 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
The Protooncogene c-Maf Is an Essential Transcription Factor for IL-10 Gene Expression in Macrophages (2005)

IL-10 is an important immunoregulatory factor. However, our understanding of IL-10 gene regulation remains very limited. In this study, following up on our previous novel finding that the protooncogene c-Maf of the basic leucine zipper family of transcription factors is expressed in monocytes and macrophages, we investigate the role of c-Maf in the transcriptional regulation of IL-10 and the underlying molecular mechanism in macrophages. c-Maf-null macrophages exhibit strongly impaired IL-10 protein production and mRNA expression upon LPS stimulation. Ectopic expression of c-Maf stimulates not only exogenously transfected IL-10 promoter-driven luciferase activity in a dose-dependent manner but also enhances endogenous IL-10 gene expression stimulated by LPS. Both in vitro and in vivo experiments identify a c-Maf response element localized to nucleotides -196/-184 relative to the transcription initiation site in the IL-10 promoter. This site represents an atypical 12-O-tetradecanoate-13-acetate-responsive element for musculoaponeurotic fibrosarcoma recognition and functions as an enhancer element in a heterologous and orientation-independent manner. Furthermore, c-Maf is expressed constitutively in resting monocytes/macrophages. IL-4 can up-regulate c-Maf expression, its binding to IL-10 promoter, and dose dependently enhance IL-10 production induced by LPS; moreover, IL-4 failed to enhance LPS-induced IL-10 production in c-Maf-null macrophages. Taken together, these data demonstrate that c-Maf is an indispensable yet constitutive transcription factor for IL-10 gene expression in LPS-activated macrophages, and IL-4 modulates IL-10 production in inflammatory macrophages likely via its ability to induce c-Maf expression. Thus, this study uncovers a novel and important function of c-Maf in macrophages and elucidates its transcriptional mechanism in the regulation of IL-10 gene expression.
High-output-power, single-wavelength silicon hybrid laser using precise flip-chip bonding technology (2012)

An Si/III-V hybrid laser oscillating at a single wavelength was developed for use in a large-scale Si optical I/O chip. The laser had an InP-based reflective semiconductor optical amplifier (SOA) chip integrated with an Si wavelength-selection-mirror chip in a flip-chip configuration. A low coupling loss of 1.55 dB at the Si-SOA interface was accomplished by both mode-field-matching between Si-SOA waveguides and accurately controlling the bonding position. The fabricated Si hybrid laser exhibited a very low threshold current of 9.4 mA, a high output power of 15.0 mW, and a high wall-plug efficiency of 7.6% at 20 °C. Moreover, the device maintained a high output power of >10 mW up to 60°C due to the high thermal conductance between the SOA chip and Si substrate. The short cavity length of the flip-chip bonded laser expanded the longitudinal mode spacing. This resulted in temperature-stable single longitudinal mode lasing and a low RIN level of <-130 dB/Hz.
A surface-emitting laser array with backside guiding holes for passive alignment to parallel optical fibers (1996)

A simple method of coupling parallel fibers to a surface-emitting laser (SEL) array is proposed and demonstrated. The SEL chip has guiding holes on the backside which are aligned precisely to the SEL mesas on the front side. Optical coupling can be achieved by simply inserting fibers to the guiding holes. A 4/spl times/3 array of common-anode SELs with guiding holes is fabricated and assembled in a face-down manner. Three fiber tapes each of which includes four fibers are coupled to the array. The average of measured coupling efficiencies to multimode fibers is 35.0% and further improvement can be expected.
Reversal of established autoimmune diabetes by restoration of endogenous β cell function (2001)

In NOD (nonobese diabetic) mice, a model of autoimmune diabetes, various immunomodulatory interventions prevent progression to diabetes. However, after hyperglycemia is established, such interventions rarely alter the course of disease or allow sustained engraftment of islet transplants. A proteasome defect in lymphoid cells of NOD mice impairs the presentation of self antigens and increases the susceptibility of these cells to TNF-alpha-induced apoptosis. Here, we examine the hypothesis that induction of TNF-alpha expression combined with reeducation of newly emerging T cells with self antigens can interrupt autoimmunity. Hyperglycemic NOD mice were treated with CFA to induce TNF-alpha expression and were exposed to functional complexes of MHC class I molecules and antigenic peptides either by repeated injection of MHC class I matched splenocytes or by transplantation of islets from nonautoimmune donors. Hyperglycemia was controlled in animals injected with splenocytes by administration of insulin or, more effectively, by implantation of encapsulated islets. These interventions reversed the established beta cell-directed autoimmunity and restored endogenous pancreatic islet function to such an extent that normoglycemia was maintained in up to 75% of animals after discontinuation of treatment and removal of islet transplants. A therapy aimed at the selective elimination of autoreactive cells and the reeducation of T cells, when combined with control of glycemia, is thus able to effect an apparent cure of established type 1 diabetes in the NOD mouse.
Hyaluronan:  Preparation, Structure, Properties, and Applications (1998)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHyaluronan: Preparation, Structure, Properties, and Applications†Lubomír Lapčík, Lubomír Lapčík, Stefaan De Smedt, Joseph Demeester, and Peter ChabrečekView Author Information Faculty of Chemistry, Technical University of Brno, Purkyňova 118, CZ-612 00 Brno, Czech Republic Faculty of Pharmacy, University of Ghent, Harelbekestraat 72, B-9000 Ghent, Belgium Central Research Laboratories, Ciba-Geigy, A.G., Postfach, CH-4002 Basel, Switzerland Cite this: Chem. Rev. 1998, 98, 8, 2663–2684Publication Date (Web):November 26, 1998Publication History Received28 April 1997Revised3 September 1998Published online26 November 1998Published inissue 17 December 1998https://pubs.acs.org/doi/10.1021/cr941199zhttps://doi.org/10.1021/cr941199zresearch-articleACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views4814Altmetric-Citations605LEARN 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 SUBJECTS:Degradation,Organic compounds,Pharmaceuticals,Polymers,Viscosity Get e-Alerts
Chemical Screens Identify Drugs that Enhance or Mitigate Cellular Responses to Antibody-Toxin Fusion Proteins (2016)

The intersection of small molecular weight drugs and antibody-based therapeutics is rarely studied in large scale. Both types of agents are currently part of the cancer armamentarium. However, very little is known about how to combine them in optimal ways. Immunotoxins are antibody-toxin gene fusion proteins engineered to target cancer cells via antibody binding to surface antigens. For fusion proteins derived from Pseudomonas exotoxin (PE), potency relies on the enzymatic domain of the toxin which catalyzes the ADP-ribosylation of EF2 causing inhibition of protein synthesis leading to cell death. Candidate immunotoxins have demonstrated clear value in clinical trials but generally have not been curative as single agents. Therefore we undertook three screens to discover effective combinations that could act synergistically. From the MIPE-3 library of compounds we identified various enhancers of immunotoxin action and at least one major class of inhibitor. Follow-up experiments confirmed the screening data and suggested that immunotoxins when administered with everolimus or nilotinib exhibit favorable combinatory activity and would be candidates for preclinical development. Mechanistic studies revealed that everolimus-immunotoxin combinations acted synergistically on elements of the protein synthetic machinery, including S61 kinase and 4E-BP1 of the mTORC1 pathway. Conversely, PARP inhibitors antagonized immunotoxins and also blocked the toxicity due to native ADP-ribosylating toxins. Thus, our goal of investigating a chemical library was justified based on the identification of several approved compounds that could be developed preclinically as 'enhancers' and at least one class of mitigator to be avoided.
Data Mining Approaches for Intrusion Detection (2000)

In this paper we discuss our research in developing general and systematic methods for intrusion detection. The key ideas are to use data mining techniques to discover consistent and useful patterns of system features that describe program and user behavior, and use the set of relevant system features to compute (inductively learned) classifiers that can recognize anomalies and known intrusions. Using experiments on the sendmail system call data and the network tcpdump data, we demonstrate that we can construct concise and accurate classifiers to detect anomalies. We provide an overview on two general data mining algorithms that we have implemented: the association rules algorithm and the frequent episodes algorithm. These algorithms can be used to compute the intra- and inter- audit record patterns, which are essential in describing program or user behavior. The discovered patterns can guide the audit data gathering process and facilitate feature selection. To meet the challenges of both efficient learning (mining) and real-time detection, we propose an agent-based architecture for intrusion detection systems where the learning agents continuously compute and provide the updated (detection) models to the detection agents.
[Phenotypical analysis of effector cells on nonspecific cancer cell therapy]. (2003)

In the present study, we examined the contributions of lymphocyte subpopulations in lymphokine activated killer (LAK) activity. LAK cells prepared from peripheral blood mononuclear cells (PBMC) of healthy donors showed highly cytotoxic activities against target tumor cells. When CD16 and CD56 positive cells in LAK cells were depleted by magnetic cell sorting, their cytotoxic activities were dramatically decreased. In contrast, little change was observed by the depletion of CD3 positive cells, suggesting that CD16 and/or CD56 positive populations, but not CD3 positive populations, including natural killer (NK) cells are the major cell types involved in LAK activity. Indeed, NK-enriched LAK cells prepared by culturing PBMC with IL-2 and OK-432 showed a more potent LAK activity than conventional LAK cells and CD3-activated T cells. These results suggest that selective expansion and activation of CD16 and CD56 positive cells in LAK cells is a useful strategies to improve their anti-tumor potential in nonspecific immunotherapy, and possibly in combination therapy with other target immunotherapies as well.