gebhart/patrepeval huggingface dataset:
Inhibition of human papilloma virus E2 DNA binding protein by covalently linked polyamides (2003)

Polyamides are a class of heterocyclic small molecules with the potential of controlling gene expression by binding to the minor groove of DNA in a sequence-specific manner. To evaluate the feasibility of this class of compounds as antiviral therapeutics, molecules were designed to essential sequence elements occurring numerous times in the HPV genome. This sequence element is bound by a virus-encoded transcription and replication factor E2, which binds to a 12 bp recognition site as a homodimeric protein. Here, we take advantage of polyamide:DNA and E2:DNA co-crystal structural information and advances in polyamide synthetic chemistry to design tandem hairpin polyamides that are capable of displacing the major groove-binding E2 homodimer from its DNA binding site. The binding of tandem hairpin polyamides and the E2 DNA binding protein to the DNA site is mutually exclusive even though the two ligands occupy opposite faces of the DNA double helix. We show with circular permutation studies that the tandem hairpin polyamide prevents the intrinsic bending of the E2 DNA site important for binding of the protein. Taken together, these results illustrate the feasibility of inhibiting the binding of homodimeric, major groove-binding transcription factors by altering the local DNA geometry using minor groove-binding tandem hairpin polyamides.
ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, shows antimetastatic activity using a hepatocellular carcinoma model. (2003)

The epidermal growth factor receptor (EGFR) is highly expressed in many human tumors and provides a new target for anticancer drug development. EGFR-targeted agents have shown promising antitumor activity in preclinical and clinical trials. However, little is yet known about the effect of these new agents on tumor metastasis. Here, we investigate the effects of ZD1839 (Iressa), a selective EGFR tyrosine kinase inhibitor, on the metastatic properties of murine hepatocellular carcinoma CBO140C12. ZD1839 inhibited not only cell growth but also epidermal growth factor-induced chemotactic migration and production of active matrix metalloproteinase-9 in vitro. In mice, orthotopic implantation of a fragment of CBO140C12 tumor into the liver resulted in the formation of a solitary tumor nodule and intrahepatic metastasis. ZD1839, given p.o., inhibited growth of the implanted tumor and intrahepatic metastasis by approximately 50%. These results indicate that EGFR signaling plays an important role in tumor metastasis and that ZD1839 is effective at inhibiting intrahepatic metastasis.
In Vitro Mutagenesis of PH‐20 Hyaluronidase from Human Sperm (1997)

The cDNA encoding PH-20 hyaluronidase from human sperm has been mutated at five positions by in vitro mutagenesis. We have changed three acidic amino acids and two arginine residues that are conserved in the sequence of mammalian PH-20 polypeptides as well as in the hyaluronidases from bee and hornet venom. Of the former, the mutants [Gln113]PH-20 and [Gln249]PH-20 had no detectable enzymatic activity; the mutant [Asn111]PH-20 had about 3% activity. The mutant [Thr252]PH-20 was also inactive, while [Gly176]PH-20 had only about 1% activity. This indicates that the PH-20 hyaluronidases, like numerous enzymes that hydrolyze glycosidic bonds, have acidic amino acids in their active site. Moreover, for the binding of the substrate, the polyanion hyaluronan, arginine residues appear to be essential.
Changes in Human Immunodeficiency Virus Type 1 Fitness and Genetic Diversity during Disease Progression (2005)

This study examined the relationship between ex vivo human immunodeficiency virus type 1 (HIV-1) fitness and viral genetic diversity during the course of HIV-1 disease. Primary HIV-1 isolates from 10 patients at different time points were competed against control HIV-1 strains in peripheral blood mononuclear cell (PBMC) cultures to determine relative fitness values. Patient HIV-1 isolates sequentially gained fitness during disease at a significant rate that directly correlated with viral load and HIV-1 env C2V3 diversity. A loss in both fitness and viral diversity was observed upon the initiation of antiretroviral therapy. A possible relationship between genotype and phenotype (virus replication efficiency) is supported by the parallel increases in ex vivo fitness and viral diversity during disease, of which the correlation is largely based on specific V3 sequences. Syncytium-inducing, CXCR4-tropic HIV-1 isolates did have higher relative fitness values than non-syncytium-inducing, CCR5-tropic HIV-1 isolates, as determined by dual virus competitions in PBMC, but increases in fitness during disease were not solely powered by a gradual switch in coreceptor usage. These data provide in vivo evidence that increasing HIV-1 replication efficiency may be related to a concomitant increase in HIV-1 diversity, which in turn may be a determining factor in disease progression.
Restricted Use of Cationic Germline VH Gene Segments in Human Rh(D) Red Cell Antibodies (1997)

The human red cell Rh(D) antigen elicits the production of high-affinity IgG antibodies, which can prevent blood transfusion and cause hemolytic disease of the newborn. It has been known for 20 years that Rh(D) antibodies are among the most positively charged human serum IgGs. Analysis by IEF of 9 human anti-Rh(D) monoclonal antibodies showed that their isoelectric points (pI) (8.3 to 8.6) were also significantly higher than the average pI of serum IgGs (7.0 to 8.5). Sequencing of the anti-Rh(D) H and L chains cDNAs showed a preferential use of V(H)1, V(H)3, J(H)6, and V(kappa)1 gene segments. The high pIs in IEF were correlated with a higher number of cationic amino acid residues in the H chain V regions without clustering in the complementary determining region. Computer analysis indicated that the germline V(H) used in anti-Rh(D) was selected among the most cationic segments available in the human V(H) repertoire or expressed in normal B cells. These results indicate that the selection of cationic V(H) segments may be an important early step in the formation of clinically relevant anti-Rh(D) and other red cell antibodies, possibly to facilitate epitope binding in the negatively charged red cell membrane environment.
Review article: gastroparesis (2008)

Despite a significant progress in the past decade, further controlled trials are required into the therapeutic options available for treating this intriguing condition.
Suitability of MDCK cells grown in a serum-free medium for influenza virus production. (1999)

MDCK cells have been adapted to grow in a serum-free environment using Ultra-MDCK medium (BioWHITTAKER). The growth of adapted U-MDCK cells was maintained for over a year without any reduction in growth rate or modification of cell karyotype; cells were scaled up to spinner culture using several microcarriers. The cells were shown to be a very good host for influenza A and B virus replication in both the presence and absence of trypsin in the infection medium. Trypsin-independent viruses replicated to high titres (10(7)-10(8) TCID50/ml) in U-MDCK cells, after selection through serial passages without trypsin. This virus progeny exhibited uncleaved and antigenically modified haemagglutinin compared with standard viruses grown with trypsin. Finally, large amounts of influenza A and B viruses were produced in U-MDCK cells grown on microcarriers under rod-stirred conditions using selected trypsin-independent variants.
Cas9-chromatin binding information enables more accurate CRISPR off-target prediction (2015)

The CRISPR system has become a powerful biological tool with a wide range of applications. However, improving targeting specificity and accurately predicting potential off-targets remains a significant goal. Here, we introduce a web-based CR: ISPR/Cas9 O: ff-target P: rediction and I: dentification T: ool (CROP-IT) that performs improved off-target binding and cleavage site predictions. Unlike existing prediction programs that solely use DNA sequence information; CROP-IT integrates whole genome level biological information from existing Cas9 binding and cleavage data sets. Utilizing whole-genome chromatin state information from 125 human cell types further enhances its computational prediction power. Comparative analyses on experimentally validated datasets show that CROP-IT outperforms existing computational algorithms in predicting both Cas9 binding as well as cleavage sites. With a user-friendly web-interface, CROP-IT outputs scored and ranked list of potential off-targets that enables improved guide RNA design and more accurate prediction of Cas9 binding or cleavage sites.
Automatic time series modeling,intervention analysis, and effective forecasting (1989)

The purpose of this study is to investigate the forecasting efficiency of an expert system, an automatic time series modeling system, when applied to a quarterly earnings per share series. The Bethlehem steel quarterly earnings series has a severe outlier problem and the intervention analysis which specifically models the outlier may enhance forecasting efficiency. The purpose of this study is to re-examine the intervention analysis of Bethlehem Steel's quarterly earnings per share series behaviour previously analyzed in Hopwood and McKeown (1986). The very large $1 billion loss of Bethlehm Steel in 1982 created an outlier in the quartely earnings series that may distort the autocorrelation and partial autocorrelation function estimates such that traditional time series models may not be appropriate [Box and Tiao (1975)]. The intervention analysis model reported in Hopwood and McKeown is substantiated in this analysis; however, the intervention modeling effort is expanded by using the intervention model in forecasting earnings. The automatic time series model, estimated by an expert system, is superioir in forecasting efficiency relative to the traditional random walk with drift model.
Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells (2004)

Recent studies have shown inflammatory markers in affected neural tissues of amyotrophic lateral sclerosis (ALS) patients. We examined immunocytochemically spinal cord tissues of six patients with ALS, two with corticospinal tract degeneration secondary to cerebral infarcts and three control subjects without neuropathologic abnormalities. ALS spinal cords had dense macrophage infiltration (one log greater than control spinal cords) involving the white and gray matter, with heaviest infiltration of lateral and ventral columns and, in one patient, prefrontal gyrus and the occipital lobes of the brain. Macrophages in ALS spinal cord showed strong expression of cyclooxygenase-2 (COX-2) (one log greater than control tissues) and inducible nitric oxide synthase. In the gray matter, macrophages surrounded and appeared to phagocytize neurons (NeuN-positive) that appeared to be dying. Vessels showed damage to the tight junction protein ZO-1 in relation to perivascular CD40 receptor-positive macrophages and CD40 ligand-positive T lymphocytes. ALS spinal cords, but not control cords, were sparsely infiltrated with mast cells. In control cases with corticospinal tract degeneration following hemispheric cerebral infarction, macrophage infiltration of the white matter was COX-2-negative and restricted to lateral and anterior corticospinal tracts. Our data suggest that inflammation in ALS spinal cord and cortex is based on innate immune responses by macrophages and mast cells and adaptive immune responses by T cells.
EMPLOYEE PERFORMANCE REVIEW IN ORGANISATION AND INDUSTRIES (2018)

Every Employees are assets for organization because all other sources of organization employee i.e., humans are liveable persons which machines and others can’t understand. Hence for any organization employees are real assets. This study highlights factors influencing job satisfaction which in turn linked with organization success. The major objective of the study is to find out the influencing factors effecting employee job satisfaction and also to find out is there any association between employee job satisfaction with their designation and work experience at big bazaar. The results finds that work experience has a significant association between employee job satisfaction and work experience where as designation doesn’t play a signification in finding association between employee job satisfaction and designation of employee.
Protein folding (1990)

Research Article| August 15 1990 Protein folding T E Creighton T E Creighton 1MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1990) 270 (1): 1–16. https://doi.org/10.1042/bj2700001 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation T E Creighton; Protein folding. Biochem J 15 August 1990; 270 (1): 1–16. doi: https://doi.org/10.1042/bj2700001 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1990 London: The Biochemical Society1990 Article PDF first page preview Close Modal You do not currently have access to this content.
Feature Space Optimization for Semantic Video Segmentation (2016)

We present an approach to long-range spatio-temporal regularization in semantic video segmentation. Temporal regularization in video is challenging because both the camera and the scene may be in motion. Thus Euclidean distance in the space-time volume is not a good proxy for correspondence. We optimize the mapping of pixels to a Euclidean feature space so as to minimize distances between corresponding points. Structured prediction is performed by a dense CRF that operates on the optimized features. Experimental results demonstrate that the presented approach increases the accuracy and temporal consistency of semantic video segmentation.
Asymmetric synthesis of (S)- and (R)-malic acid from ketene and chloral (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAsymmetric synthesis of (S)- and (R)-malic acid from ketene and chloralHans Wynberg and Emiel G. J. StaringCite this: J. Am. Chem. Soc. 1982, 104, 1, 166–168Publication Date (Print):January 1, 1982Publication History Published online1 May 2002Published inissue 1 January 1982https://pubs.acs.org/doi/10.1021/ja00365a030https://doi.org/10.1021/ja00365a030research-articleACS PublicationsRequest reuse permissionsArticle Views2710Altmetric-Citations285LEARN 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
Spatial Frequency Columns in Primary Visual Cortex (1981)

Using the activity-dependent 2-[14C]deoxy-D-glucose technique, we have demonstrated a columnar organization of spatial frequency--specific sensitivity in striate cortex. Cats viewing patterns containing a single spatial frequency presented at all orientations show columns of increased deoxyglucose uptake extending through all cortical layers. A control stimulus containing all spatial frequencies presented at all orientations produces no columnar density differences within the striate cortex.
The Glycine1Residue in Cyclic Lactam Analogues of Galanin(1−16)-NH2Is Important for Stabilizing an N-Terminal Helix (1999)

The neuropeptide galanin is a 29- or 30-residue peptide whose physiological functions are mediated by G-protein-coupled receptors. Galanin's agonist activity has been shown to be associated with the N-terminal sequence, galanin(1-16). Conformational investigations previously carried out on full-length galanin have, furthermore, indicated the presence of a helical conformation in the neuropeptide's N-terminal domain. Several cyclic lactam analogues of galanin(1-16)-NH2 were prepared in an attempt to stabilize an N-terminal helix in the peptide. Here we describe and compare the solution conformational properties of these analogues in the presence of SDS micelles as determined by NMR, CD, and fluorescence spectroscopy. Differences in CD spectral profiles were observed among the compounds that were studied. Both c[D4, K8]Gal(1-16)-NH2 and c[D4,K8]Gal(1-12)-NH2 adopted stable helical conformations in the micelle solution. On the basis of the analyses of their respective alpha H chemical shifts and NOE patterns, this helix was localized to the first 10 residues. The distance between the aromatic rings of Trp2 and Tyr9 in c[D4, K8]Gal(1-16)-NH2 was determined to be 10.8 +/- 3 A from fluorescence resonance energy transfer measurements. This interchromophore spacing was found to be more consistent with a helical structure than an extended one. Removal of the Gly1 residue in compounds c[D4,K8]Gal(1-16)-NH2 and c[D4, K8]Gal(1-12)-NH2 resulted in a loss of helical conformation and a concomitant reduction in binding potency at the GalR1 receptor but not at the GalR2 receptor. The nuclear Overhauser enhancements obtained for the Gly1 deficient analogues did, however, reveal the presence of nascent helical structures within the N-terminal sequence. Decreasing the ring structure size in c[D4, K8]Gal(1-16)-NH2 by replacing Lys8 with an ornithine residue or by changing the position of the single lysine residue from eight to seven was accompanied by a complete loss of helical structure and dramatically reduced receptor affinity. It is concluded from the data obtained for the series of cyclic galanin(1-16)-NH2 analogues that both the ring structure size and the presence of an N-terminal glycine residue are important for stabilizing an N-terminal helix in these compounds. However, although an N-terminal helix constitutes a predominant portion of the conformational ensemble for compounds c[D4,K8]Gal(1-16)-NH2 and c[D4, K8]Gal(1-12)-NH2, these peptides nevertheless are able to adopt other conformations in solution. Consequently, the correlation between the ability of the cyclic galanin analogues to adopt an N-terminal helix and bind to the GalR1 receptor may be considered as a working hypothesis.
Nonmathematical Concepts of Selection, Evolutionary Energy, and Levels of Evolution (1972)

The place of mathematics in hypotheticodeductive processes and in biological research is discussed. (Natural) Selection is defined and described as differential elimination of performed sets at any level. Sets and acting sets are groups of units (themselves sets of smaller units) at any level that may or do interact. A pseudomathematical equation describes directional change (evolution) in sets at any level. Selection is the ram of evolution; it cannot generate, but can only direct, evolutionary energy. The energy of evolution is derived from molecular or chemical levels, is transmitted upwards through the increasingly complex sets of sets that form living systems, and is turned in directions determined by the sum of selective processes, at different levels, which may either supplement or oppose each other. All evolutionary processes conform to the pseudomathematical equation referred to above, use energy as described above, and have a P/OE (ratio of programming to open-endedness) that cannot be measured, but can be related to other P/OE values. Phylogeny and ontogeny are compared as processes af directional change with set selection. Stages in the evolution of multi-cellular individuals are suggested, and are essentially the same as stages in the evolution of some multi-individual insect societies. Thinking is considered as a part of ontogeny involving an irreversible, nonrepetitive process of set selection in the brain.
Ultrasound Examination of Peripheral Nerves in the Forearm (2007)

Nerves in the forearm are consistently located using ultrasound. Further confirmation in clinical practice is required.
QTL: their place in engineering tolerance of rice to salinity (2000)

Secondary salinization and its relationship to irrigation are strong incentives to improve the tolerance of crops to salinity and to drought. Achieving this through the pyramiding of physiological traits (phenotypic selection without knowledge of genotype) is feasible. However, wide application of this approach is limited by the practicalities of assessing not only the parents, but also large numbers of individuals and families in segregating generations. Genotypic information is required in the form of markers for any quantitative trait loci involved (marker-assisted selection) or of direct knowledge of the genes. In the absence of adequate candidate genes for salt tolerance, a quantitative trait locus/marker-assisted selection approach has been used here. Putative markers for ion transport and selectivity, identified from analysis of amplified fragment length polymorphism, had been discovered within a custom-made mapping population of rice. Here it is reported that none of these markers showed any association with similar traits in a closely related population of recombinant inbred lines or in selections of a cultivar. Whilst markers will be of value in using élite lines from the mapping population in backcrossing, this has to be considered alongside the effort required to develop and map any given population. This result cautions against any expectation of a general applicability of markers for physiological traits. It is concluded that direct knowledge of the genes involved is needed. This cannot be achieved at present by positional cloning. The elucidation of candidate genes is required. Here the problem lies not in the analysis of gene expression but in devising protocols in which only those genes of interest are differentially affected by the experimental treatments.
Complex Behavior at Scale: An Experimental Study of Low-Power Wireless Sensor Networks (2002)

A new class of networked systems is emerging that involve very large numbers of small, low-power, wireless devices. We present findings from a large scale empirical study involving over 150 such nodes operated at various transmission power settings. The instrumentation in our experiments permits us to separate effects at the various layers of the protocol stack. At the link layer, we present statistics on packet reception, effective communication range and link asymmetry; at the MAC layer, we measure contention, collision and latency; and at the application layer, we analyze the structure of trees constructed using flooding. The study reveals that even a simple protocol, flooding, can exhibit surprising complexity at scale. The data and analysis lay a foundation for a much wider set of algorithmic studies in this space.
Monodisperse Magnetic Single‐Crystal Ferrite Microspheres (2005)

Particularly uniform: Monodisperse ferrite microspheres can be synthesized to have diameters of about 200–800 nm (TEM image, left). High-resolution TEM analysis (image, right and inset) shows that each microsphere is a single crystal. Their hydrophilic and magnetic properties impart to the microparticles many potential uses in electronics and biomedicine.