gebhart/patrepeval huggingface dataset:
Functional Complementation of Yeast ste6 by a Mammalian Multidrug Resistance mdr Gene (1992)

Multidrug resistance in mammalian tumor cells is associated with the overexpression of mdr genes encoding P-glycoproteins, which function as drug efflux pumps. A yeast homolog of mdr, STE6, mediates export of a-factor mating peptide. Yeast MATa cells carrying a ste6 deletion produce no extracellular a-factor and therefore are defective in mating. Expression of a complementary DNA for the mouse mdr3 gene in a yeast ste6 deletion strain restored ability to export a-factor and to mate. A mutation (a serine to phenylalanine substitution at amino acid 939) known to affect the activity of the mdr3 gene product abolished its ability to complement the yeast ste6 deletion. Thus, functions of P-glycoproteins in normal mammalian cells may include the transmembrane export of endogenous peptides.
Improvement of Collateral Perfusion and Regional Function by Implantation of Peripheral Blood Mononuclear Cells Into Ischemic Hibernating Myocardium (2002)

Catheter-based implantation of PB-MNCs can effectively improve collateral perfusion and regional function in hibernating ischemic myocardium by its ability to mainly supply angiogenic factors and cytokines.
Optimizing illumina next-generation sequencing library preparation for extremely at-biased genomes (2012)

We have developed a robust and optimized Next-Generation Sequencing library amplification method suitable for extremely AT-rich genomes. The new amplification conditions significantly reduce bias and retain the complexity of either extremes of base composition. This development will greatly benefit sequencing clinical samples that often require amplification due to low mass of DNA starting material.
Human macrophage colony‐stimulating factor inhibits bone resorption by osteoclasts disaggregated from rat bone (1988)

Colony stimulating factors (CSFs) regulate the survival, proliferation and differentiation of haemopoietic progenitor cells, as well as the functional activity of mature cells. Because the osteoclast is derived from haemopoietic tissue, and because osteoblastic cells produce CSFs, we tested the effects of several CSFs on bone resorption by osteoclasts disaggregated from neonatal rat long bone. We found that recombinant macrophage (M)-CSF was a potent inhibitor of bone resorption, causing significant inhibition at concentrations similar to those required to support the growth of macrophage colonies in agar. Unlike other inhibitors of osteoclastic resorption, M-CSF did not alter cytoplasmic motility in time-lapse recordings, suggesting that M-CSF may inhibit osteoclasts through a different transduction mechanism. None of the remaining cytokines tested (granulocyte-macrophage CSF, interleukin 3, interleukin 6, or interferon gamma) influenced bone resorption. M-CSF production may be a mechanism by which osteoblastic cells, which produce M-CSF, may regulate osteoclastic function. Alternatively, inhibition of osteoclastic resorption by a CSF that is responsible for amplification of the macrophage compartment may reflect a close lineage relationship between mononuclear phagocytes, in which M-CSF induces a diversion of lineage resources away from osteoclastic function.
Cellular and Molecular Characterization of a Major Soybean Allergen (1998)

Soybean proteins share a large number of cross-reacting allergens with other members of the legume family; however, soy-allergic patients rarely react clinically to other members of the legume family. Gly m Bd 30K, an IgE-binding protein with a molecular weight of 30 kD, was identified in soybean extracts by Western IgE-immunoblot analysis. This monomeric allergen was shown to have an N-terminal amino acid sequence and amino acid composition identical to that of the seed 34-kD protein, P34, a thiol protease of the papain family. Electron-microscopic immunolocalization of P34 monoclonal antibodies and IgE binding to sections of soybean seeds showed dense staining throughout the vacuolar bodies, localizing the allergens in protein storage vacuoles of seed cotyledons. We used pooled serum from soybean-sensitive patients to determine the linear IgE-specific epitopes in the 34-kD allergen amino acid sequence. B-cell epitope mapping revealed 10 regions of IgE-binding activity using an overlapping peptide strategy of 15-mers offset by 8 amino acids throughout the P34 sequence. Smaller overlapping peptides, 10-mers offset by 2 amino acids, revealed 16 distinct linear epitopes, 9 of which were mapped to the mature protein. No obvious amino acid sequence motifs could be identified by the smaller IgE-binding epitopes. Using individual patient serum, 5 immunodominant epitopes were identified in this allergen.
Molecular Epidemiology of the Foot-and-Mouth Disease Virus Outbreak in the United Kingdom in 2001 (2006)

The objective of this study was to quantify the extent to which the genetic diversity of foot-and-mouth disease virus (FMDV) arising over the course of infection of an individual animal becomes fixed, is transmitted to other animals, and thereby accumulates over the course of an outbreak. Complete consensus sequences of 23 genomes (each of 8,200 nucleotides) of FMDV were recovered directly from epithelium tissue acquired from 21 farms infected over a nearly 7-month period during the 2001 FMDV outbreak in the United Kingdom. An analysis of these consensus sequences revealed very few apparently ambiguous sites but clear evidence of 197 nucleotide substitutions at 191 different sites. We estimated the rate of nucleotide substitution to be 2.26 x 10(-5) per site per day (95% confidence interval [CI], 1.75 x 10(-5) to 2.80 x 10(-5)) and nucleotide substitutions to accrue in the consensus sequence at an average rate of 1.5 substitutions per farm infection. This is a sufficiently high rate showing that detailed histories of the transmission pathways can be reliably reconstructed. Coalescent methods indicated that the date at which FMDV first infected livestock in the United Kingdom was 7 February 2001 (95% CI, 20 January to 19 February 2001), which was identical to estimates obtained on the basis of purely clinical evidence. Nucleotide changes appeared to have occurred evenly across the genome, and within the open reading frame, the ratio of nonsynonymous-to-synonymous change was 0.09. The ability to recover particular transmission pathways of acutely acting RNA pathogens from genetic data will help resolve uncertainties about how virus is spread and could help in the control of future epidemics.
Gene structure and expression of the Corynebacterium flavum N13 ask-asd operon (1993)

Two promoters required for expression of the ask-asd genes, encoding aspartokinase (AK) and aspartate-semialdehyde dehydrogenase (ASD), in Corynebacterium flavum N13, askP1 and askP2, have been identified by deletion analysis and S1 nuclease mapping. Transcription from askP1 initiates 35 and 38 bp upstream of the ask structural gene. A second promoter, askP2, lies within the ask coding region, upstream of the translation start site of the AK beta subunit and can direct the expression of AK beta and ASD. Western immunoblot analysis and heterologous expression in Escherichia coli demonstrate that two separate polypeptides, a 44.8-kDa alpha subunit and an 18.5-kDa beta subunit, are expressed from the C. flavum N13 ask gene from distinct, in-frame translation initiation sites. A second AK mutation, G345D, which reduces the sensitivity of AK to concerted feedback inhibition by threonine plus lysine, was identified.
Understanding Sydney as a global city (2005)

There is an ascendant academic argument that key economic processes are increasingly built at the scale of the city and, in turn, that successful urban economies are increasingly detached from their traditional hinterlands. Cities, in this city-centric global economy, are argued to be immersed in and driven by globalised networks and connections. The process of a city becoming global, then, means that traditional territorial networks and linkages are variously dislodged, transformed and abandoned. While this argument is intuitively persuasive, it has tended to be underpinned by generalised analyses that are thin on their treatment of change drivers and on the new ways that cities now function. The temptation is for the emergence of a post-national metro-centric global economy to be assumed and for this assumption to direct the nature of urban economy inquiry. Drawing on the example of Sydney, in this paper we argue for the need to develop more grounded theoretical understandings of what drives contemporary accumulation and distribution processes in a global city. We sketch what might be learned-theoretically and empirically-from tracing the 'reach' of Sydney's economy through changing patterns of materials, information and financial flows to produce a spatialised political economy of the city. We argue that this grounded understanding will leave us better positioned, first, to understand Sydney's connection to a global urban hierarchy, second, to critically assess claims regarding the nature of that hierarchy and, third, to devise management strategies aimed to produce more efficient, equitable and sustainable urban outcomes.
An overview of clinically significant drug interactions between medications used to treat psychiatric and medical conditions (2014)

Prescription rates and polypharmacy are increasing, resulting in a greater potential for drug interactions. Psychiatric patients frequently have co-morbid medical conditions, which further increases the risk of polypharmacy and drug interactions. Drug interactions that affect drugs with narrow therapeutic windowsare of particular concern. This review presents some of these drug interactions and provides strategies for identifying and resolving them.
Increased coverage of protein families with the Blocks Database servers (2000)

The Blocks Database WWW (http://blocks.fhcrc.org ) and Email (blocks@blocks.fhcrc.org ) servers provide tools to search DNA and protein queries against the Blocks+ Database of multiple alignments, which represent conserved protein regions. Blocks+ nearly doubles the number of protein families included in the database by adding families from the Pfam-A, ProDom and Domo databases to those from PROSITE and PRINTS. Other new features include improved Block Searcher statistics, searching with NCBI's IMPALA program and 3D display of blocks on PDB structures.
Enantioselectivity in environmental safety of current chiral insecticides (2005)

Chiral pesticides currently constitute about 25% of all pesticides used, and this ratio is increasing as more complex structures are introduced. Chirality occurs widely in synthetic pyrethroids and organophosphates, which are the mainstay of modern insecticides. Despite the great public concerns associated with the use of insecticides, the environmental significance of chirality in currently used insecticides is poorly understood. In this study, we resolved enantiomers of a number of synthetic pyrethroid and organophosphate insecticides on chiral selective columns and evaluated the occurrence of enantioselectivity in aquatic toxicity and biodegradation. Dramatic differences between enantiomers were observed in their acute toxicity to the freshwater invertebrates Ceriodaphnia dubia and Daphnia magna, suggesting that the aquatic toxicity is primarily attributable to a specific enantiomer in the racemate. In field sediments, the (-)enantiomer of cis-bifenthrin or cis-permethrin was preferentially degraded, resulting in relative enrichment of the (+)enantiomer. Enantioselective degradation was also observed during incubation of sediments under laboratory conditions. Enantioselectivity in these processes is expected to result in ecotoxicological effects that cannot be predicted from our existing knowledge and must be considered in future risk assessment and regulatory decisions.
Biological activity of 1,25-dihydroxyvitamin D2 in the chick (1976)

1,25-Dihydroxyvitamin D2 has been prepared from 25-hydroxyvitamin D2 using rachitic chick kidney mitochondria. This metabolite was highly purified by Sephadex LH-20 chromatography and by preparative high-pressure liquid chromatography. Its purity was assessed by analytical high-pressure liquid chromatography which revealed no other 254-nm absorbing material and by mass spectrometry. The concentration of dilute solutions of 1,25-dihydroxyvitamin D2 was determined by high-pressure liquid chromatography and deflection of the 254-nm column monitor. The 1,25-dihydroxyvitamin D2 was then shown to be 1/5 to 1/10 as active as 1,25-dihydroxyvitamin D3 in the chick while it had previously been shown to be equal in activity in the rat. Thus, discrimination against the vitamin D2 side chain by the chick persists in the metabolically active 1,25-dihydroxyvitamin D compounds.
Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis (2008)

There is wide interpatient variability of RBC MTXGlu1-5 accumulation and elimination in adults with RA. These data also suggest that after a dose change, >6 months are required for RBC MTXGlu1-5 to reach steady state. Such delays in achieving steady state suggest that more rapid dose escalation or subcutaneous administration from the outset should be considered.
Synthesis of Human Interferon β1 in Escherichia coliInfected by a Lambda Phage Recombinant containing a Human Genomic Fragment (1981)

DNA from a human adult was fragmented by partial digestion with restriction endonuclease EcoRI and cloned in lambda Charon 4A. Clone C15, with a human DNA insert of 17 X 10(3) bases, was identified as containing a gene for the fibroblast interferon, interferon beta 1. Restriction mapping shows that this gene, located on a 1840-base EcoRI fragment, is not interrupted by introns. Moreover, we show that this human genomic DNA fragment is able to direct the synthesis of active human interferon beta 1 in Escherichia coli. Interferon activity of up to 7 X 10(6) U/l was recovered from phage lysates by chromatography on Cibacron blue--Sepharose, and had the same immunological properties and species specificity as interferon produced by human fibroblasts.
THE INTRINSIC EXTREME ULTRAVIOLET FLUXES OF F5 V TO M5 V STARS (2013)

Extreme ultraviolet (EUV) radiations (10--117 nm) from host stars play important roles in the ionization, heating, and mass loss from exoplanet atmospheres. Together with the host star's Lyman-alpha and far-UV (117--170 nm) radiation, EUV radiation photodissociates important molecules, thereby changing the chemistry in exoplanet atmospheres. Since stellar EUV fluxes cannot now be measured and interstellar neutral hydrogen completely obscures stellar radiation between 40 and 91.2 nm, even for the nearest stars, we must estimate the unobservable EUV flux by indirect methods. New non-LTE semiempirical models of the solar chromosphere and corona and solar irradiance measurements show that the ratio of EUV flux in a variety of wavelength bands to the Lyman-alpha flux varies slowly with the Lyman-alpha flux and thus with the magnetic heating rate. This suggests and we confirm that solar EUV/Lyman-alpha flux ratios based on the models and observations are similar to the available 10--40 nm flux ratios observed with the EUVE satellite and the 91.2--117 nm flux observed with the FUSE satellite for F5 V--M5 V stars. We provide formulae for predicting EUV flux ratios based on the EUVE and FUSE stellar data and on the solar models, which are essential input for modelling the atmospheres of exoplanets.
Mannose receptor-mediated uptake of ricin toxin and ricin A chain by macrophages. Multiple intracellular pathways for a chain translocation. (1986)

The role of the high mannose carbohydrate chains in the mechanism of action of ricin toxin was investigated. Ricin is taken up by two routes in macrophages, by binding to cell surface mannose receptors, or by binding of the ricin galactose receptor to cell surface glycoproteins. Removal of carbohydrate from ricin by periodate oxidation led to a large loss in toxicity via both routes of uptake by an effect on the B chain not due to a loss of galactose binding affinity. These data suggest that the carbohydrate chains of ricin B chain may be required for full toxicity. The pathway of uptake of ricin by the macrophage mannose receptor was found to differ in several respects from uptake via the galactose-specific pathway. Analysis of intoxication of macrophages by ricin in the presence of ammonium chloride suggested that mannose receptor bound ligand passes through acidic vesicles prior to translocation, unlike galactose bound ligand. Intoxication by ricin via galactose-specific uptake was potentiated by swainsonine but not by castanospermine, suggesting that ricin may be attacked by an endogenous mannosidase within the cell, and that ricin passes through either a lysosomal or a Golgi compartment prior to translocation.
Rotation Invariant Neural Network-Based Face Detection (2005)

In this paper, we present a neural network-based face detection system. Unlike similar systems which are limited to detecting upright, frontal faces, this system detects faces at any degree of rotation in the image plane. The system employs multiple networks; a router network first processes each input window to determine its orientation and then uses this information to prepare the window for one or more detector networks. We present the training methods for both types of networks. We also perform sensitivity analysis on the networks, and present empirical results on a large test set. Finally, we present preliminary results for detecting faces rotated out of the image plane, such as profiles and semi-profiles.
Cationic ring-opening polymerization of 2-phenyl-1,3,2-dioxaphosphepane, a seven-membered cyclic phosphonite (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCationic ring-opening polymerization of 2-phenyl-1,3,2-dioxaphosphepane, a seven-membered cyclic phosphoniteShiro Kobayashi, Masazumi Tokunoh, and Takeo SaegusaCite this: Macromolecules 1986, 19, 2, 466–469Publication Date (Print):February 1, 1986Publication History Published online1 May 2002Published inissue 1 February 1986https://pubs.acs.org/doi/10.1021/ma00156a040https://doi.org/10.1021/ma00156a040research-articleACS PublicationsRequest reuse permissionsArticle Views113Altmetric-Citations8LEARN 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
Metal ions, Alzheimer's disease and chelation therapy (2011)

In the last few years, various studies have been providing evidence that metal ions are critically involved in the pathogenesis of major neurological diseases (Alzheimer, Parkinson). Metal ion chelators have been suggested as potential therapies for diseases involving metal ion imbalance. Neurodegeneration is an excellent target for exploiting the metal chelator approach to therapeutics. In contrast to the direct chelation approach in metal ion overload disorders, in neurodegeneration the goal seems to be a better and subtle modulation of metal ion homeostasis, aimed at restoring ionic balance. Thus, moderate chelators able to coordinate deleterious metals without disturbing metal homeostasis are needed. To date, several chelating agents have been investigated for their potential to treat neurodegeneration, and a series of 8-hydroxyquinoline analogues showed the greatest potential for the treatment of neurodegenerative diseases.
Optimized Diazo Scaffold for Protein Esterification (2015)

The O-alkylation of carboxylic acids with diazo compounds provides a means to esterify carboxylic acids in aqueous solution. A Hammett analysis of the reactivity of diazo compounds derived from phenylglycinamide revealed that the (p-methylphenyl)glycinamide scaffold has an especially high reaction rate and ester/alcohol product ratio and esterifies protein carboxyl groups more efficiently than any known reagent.
Biomarkers in Nonalcoholic Fatty Liver Disease (2014)

The present review attempts to provide a comprehensive analysis of the emerging risk biomarkers of NAFLD and NASH, and to use the clinical significance and analytical considerations of each biomarker pointing out sentinel features of disease progression.
Herbicide-resistant forms of Arabidopsis thaliana acetohydroxyacid synthase: characterization of the catalytic properties and sensitivity to inhibitors of four defined mutants (1998)

Acetohydroxyacid synthase (AHAS) catalyses the first step in the synthesis of the branched-chain amino acids and is the target of several classes of herbicides. Four mutants (A122V, W574S, W574L and S653N) of the AHAS gene from Arabidopsis thaliana were constructed, expressed in Escherichia coli, and the enzymes were purified. Each mutant form and wild-type was characterized with respect to its catalytic properties and sensitivity to nine herbicides. Each enzyme had a pH optimum near 7.5. The specific activity varied from 13% (A122V) to 131% (W574L) of the wild-type and the Km for pyruvate of the mutants was similar to the wild-type, except for W574L where it was five-fold higher. The activation by cofactors (FAD, Mg2+ and thiamine diphosphate) was examined. A122V showed reduced affinity for all three cofactors, whereas S653N bound FAD more strongly than wild-type AHAS. Six sulphonylurea herbicides inhibited A122V to a similar degree as the wild-type but S653N showed a somewhat greater reduction in sensitivity to these compounds. In contrast, the W574 mutants were insensitive to these sulphonylureas, with increases in the Kiapp (apparent inhibition constant) of several hundred fold. All four mutants were resistant to three imidazolinone herbicides with decreases in sensitivity ranging from 100-fold to more than 1000-fold.
Self-timed rings and their application to division (1992)

Self-timed systems avoid the problems associated with the global clocks of synchronous systems. This thesis introduces a new type of structure called a self-timed ring that can pass data multiple times through the same function blocks without requiring any external control signals or clocking. The latency and throughput of self-timed rings are analyzed by a method that also determines the performance of asynchronous pipelines as a special case. By meeting certain constraints suggested by this analysis, a self-timed ring can completely hide its control logic delays and achieve operation with zero overhead. If, in addition, the ring is composed of a proposed domino stage configuration without latches, then the ring achieves, in much less area, the same minimal-latency operation as an unrolled combinational array implementing the same function.
A prime example of a problem for which a self-timed ring implementation achieves high performance is the iterative computation of the arithmetic function of division. This thesis compares two self-timed divider chips: a preliminary design and an improved one that adheres to the constraints determined by this research. Measurements showed that design techniques increased performance by a factor of 2.2 due to architecture alone. The self-timed ring of the new divider occupies 7mm$\sp2$ in a 1.2$\mu$ CMOS process and computes quotient bits in 2.9nS, requiring a total latency of 45nS to 160nS for a full 54-bit result, depending on the data operands.