gebhart/patrepeval huggingface dataset:
Interaction of polypyrimidine tract-binding protein with the 5' noncoding region of the hepatitis C virus RNA genome and its functional requirement in internal initiation of translation (1995)

Initiation of translation of the human hepatitis C virus (HCV) RNA genome occurs by internal ribosome entry into the 5' noncoding region (5'NCR) in a cap-independent manner. The internal ribosome entry site of the HCV 5'NCR has been previously defined to encompass almost the entire 5'NCR. Here we report the interaction of polypyrimidine tract-binding protein (PTB) at three distinct regions within the 5'NCR by UV cross-linking assays. All three regions contain a consensus polypyrimidine tract motif. The evidence for the interaction of recombinant PTB at multiple sites within the 5'NCR is based on the use of 5'NCR mutants as competitors and by direct UV cross-linking of the mutant RNAs. Furthermore, the PTB isomers from HeLa nuclear extracts interact with the HCV 5'NCR, as shown by immunoprecipitation of a UV cross-linked complex with anti-PTB serum. Immunodepletion of PTB from translation lysates suggested the functional requirement for PTB during translation initiation of the HCV RNA. Addition of purified PTB to immunodepleted lysates did not restore translation mediated by the HCV 5'NCR, indicating the requirement of PTB-associated factors that were removed during immunodepletion.
Multivariate Analysis in Metabolomics (2012)

Metabolomics aims to provide a global snapshot of all small-molecule metabolites in cells and biological fluids, free of observational biases inherent to more focused studies of metabolism. However, the staggeringly high information content of such global analyses introduces a challenge of its own; efficiently forming biologically relevant conclusions from any given metabolomics dataset indeed requires specialized forms of data analysis. One approach to finding meaning in metabolomics datasets involves multivariate analysis (MVA) methods such as principal component analysis (PCA) and partial least squares projection to latent structures (PLS), where spectral features contributing most to variation or separation are identified for further analysis. However, as with any mathematical treatment, these methods are not a panacea; this review discusses the use of multivariate analysis for metabolomics, as well as common pitfalls and misconceptions.
Conformational effects of 1,3-syn-diaxial repulsion and 1,2-gauche attraction between hydroxy groups in monomolecular N-octyl-D-hexonamide solutions. A13C and1H NMR spectroscopic study (1994)

Homo- and hetero-nuclear NMR-techniques were used to assign signals and coupling constants to vicinal CH and CH–OH protons in N-octyl-D-hexonamides 1–5(galacton, mannon, glucon, talon and gulon) dissolved in DMSO. Analysis of the data showed (i) quite uniform conformations for all hexonamides and a particular rigidity about the central C-3–C-4 bond, (ii) a dominating attractive gauche-interaction between neighbouring hydroxy groups, (iii) strong repulsion between syn-diaxial 1,3-hydroxy groups and (iv) no internal hydrogen bonds. All conformations found experimentally in solution result from the interaction of both effects, but neither the attractive nor the repulsive intramolecular interactions are of importance in supramolecular assemblies or crystals.
Clinical Uses of Botulinum Neurotoxins: Current Indications, Limitations and Future Developments (2012)

Botulinum neurotoxins (BoNTs) cause flaccid paralysis by interfering with vesicle fusion and neurotransmitter release in the neuronal cells. BoNTs are the most widely used therapeutic proteins. BoNT/A was approved by the U.S. FDA to treat strabismus, blepharospam, and hemificial spasm as early as 1989 and then for treatment of cervical dystonia, glabellar facial lines, axillary hyperhidrosis, chronic migraine and for cosmetic use. Due to its high efficacy, longevity of action and satisfactory safety profile, it has been used empirically in a variety of ophthalmological, gastrointestinal, urological, orthopedic, dermatological, secretory, and painful disorders. Currently available BoNT therapies are limited to neuronal indications with the requirement of periodic injections resulting in immune-resistance for some indications. Recent understanding of the structure-function relationship of BoNTs prompted the engineering of novel BoNTs to extend therapeutic interventions in non-neuronal systems and to overcome the immune-resistance issue. Much research still needs to be done to improve and extend the medical uses of BoNTs.
High-voltage regulation and process considerations for high-density 5 V-only E/sup 2/PROM's (1983)

A high density 5-V-only HMOS 1 FLOTOX E/SUP 2/PROM technology has been developed using stepper lithography and dry etching techniques. A 1.5-/spl mu/m minimum feature size and 0.5-/spl mu/m registration result in a FLOTOX cell with an area of 270 /spl mu/m/SUP 2/. This represents a 50% reduction of the original cell size. Equivalent endurance (10K cycles) and data retention (10 years) have been obtained. Improved critical dimension control has increased the uniformity of the new cell within the array. Junction leakage has been reduced by using an extended low-temperature anneal cycle. Circuit techniques have been developed to ensure full temperature range (-55-125/spl deg/C) operation. A capacitive voltage divider in a feedback loop, an E/SUP 2/ trimmable voltage reference, and a switched-capacitor RC network are employed to produce a temperature-stable programming pulse with a rising edge time constant of ~ 600 /spl mu/s. The programming voltage can be trimmed with an accuracy of /spl plusmn/ 0.5 V over a typical range of 19-24 V in order to match the requirements of the array. 16K and 64K 5-V-only E/SUP 2/PROMs with die sizes of 128 /spl times/ 182 mil and 223 X 278 mil have been fabricated.
Helix capping propensities in peptides parallel those in proteins. (1993)

Helix content of peptides with various uncharged nonaromatic amino acids at either the N-terminal or C-terminal position has been determined. The choice of N-terminal amino acid has a major effect on helix stability: asparagine is the best, glycine is very good, and glutamine is the worst helix-stabilizing amino acid at this position. The rank order of helix stabilization parallels the frequencies of these amino acids at the N-terminal boundary (N-cap) position of helices in proteins found by Richardson and Richardson [Richardson, J. S. & Richardson, D. C. (1988) Science 240, 1648-1652], and the N-terminal amino acid in a peptide composed of helix-forming amino acids may be considered as the N-cap residue. The choice of C-terminal amino acid has only a minor effect on helix stability. N-capping interactions may be responsible for the asymmetric distribution of helix content within a given peptide found by various workers. An acetyl group on the N-terminal alpha-amino function cancels the N-cap effect and the acetyl group is equivalent to N-terminal asparagine in an unacetylated peptide. Our results demonstrate a close relationship between the mechanisms of alpha-helix formation in peptides and in proteins.
Automatic annotation of matrix‐assisted laser desorption/ionization N‐glycan spectra (2005)

Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) is the pre-eminent technique for mass mapping of glycans. In order to make this technique practical for high-throughput screening, reliable automatic methods of annotating peaks must be devised. We describe an algorithm called Cartoonist that labels peaks in MALDI spectra of permethylated N-glycans with cartoons which represent the most plausible glycans consistent with the peak masses and the types of glycans being analyzed. There are three main parts to Cartoonist. (i) It selects annotations from a library of biosynthetically plausible cartoons. The library we currently use has about 2800 cartoons, but was constructed using only about 300 archetype cartoons entered by hand. (ii) It determines the precision and calibration of the machine used to generate the spectrum. It does this automatically based on the spectrum itself. (iii) It assigns a confidence score to each annotation. In particular, rather than making a binary yes/no decision when annotating a peak, it makes all plausible annotations and associates them with scores indicating the probability that they are correct.
Computed circular dichroism spectra for the evaluation of protein conformation (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComputed circular dichroism spectra for the evaluation of protein conformationNorma J. Greenfield and Gerald D. FasmanCite this: Biochemistry 1969, 8, 10, 4108–4116Publication Date (Print):October 1, 1969Publication History Published online1 May 2002Published inissue 1 October 1969https://pubs.acs.org/doi/10.1021/bi00838a031https://doi.org/10.1021/bi00838a031research-articleACS PublicationsRequest reuse permissionsArticle Views10472Altmetric-Citations2992LEARN 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
Role of the ferric uptake regulator of Pseudomonas aeruginosa in the regulation of siderophores and exotoxin A expression: purification and activity on iron-regulated promoters (1995)

The cloned Pseudomonas aeruginosa fur (ferric uptake regulator) gene was overexpressed in P. aeruginosa by using a T7 expression system, and the Fur protein (PA-Fur) was purified by using a combination of ion-exchange chromatography and metal affinity chromatography. The DNA binding activity of the PA-Fur protein was confirmed by gel mobility shift assays and DNase I footprints of the synthetic DNA fragment GATAAT GATAATCATTATC, representing a perfect "Fur box". In addition, it was shown that PA-Fur is capable of binding to promoter and operator determinants of the tightly iron-regulated Escherichia coli fepA-fes enterobactin gene system. The activity of PA-Fur on the promoters of iron-regulated genes involved in the production of two siderophores, pyochelin and pyoverdin, and in the expression of exotoxin A was investigated. Data indicating that the promoters of the pchR gene, encoding a transcriptional activator for pyochelin synthesis, and of the pvdS gene, encoding a positive regulator for pyoverdin production, are specifically recognized by Fur-Fe(II) are presented, suggesting that PA-Fur represses expression of pchR and pvdS during growth in an iron-replete environment. However, neither the promoter region of the gene encoding exotoxin A (toxA) nor the promoters of the regAB operon, required for toxA expression, interacted with high concentrations of purified PA-Fur. These data indicate that iron regulation of exotoxin A production involves additional factors which may ultimately be under the control of PA-Fur.
Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function (2003)

The first step in metabolism of glucose (Glc) is usually phosphorylation, catalyzed by hexokinase. However, the Glc-6-P produced can then enter one or more of several alternative pathways. Selective expression of isozymic forms of hexokinase, differing in catalytic and regulatory properties as well as subcellular localization, is likely to be an important factor in determining the pattern of Glc metabolism in mammalian tissues/cells. Despite their overall structural similarity, the Type I, Type II and Type III isozymes differ in important respects. All three isozymes are inhibited by the product, Glc-6-P, but with the Type I isozyme, this inhibition is antagonized by P(I), whereas with the Type II and Type III isozymes, P(i) actually causes additional inhibition. Reciprocal changes in intracellular levels of Glc-6-P and P(i) are closely associated with cellular energy status, and it is proposed that the response of the Type I isozyme to these effectors adapts it for catabolic function, introducing Glc into glycolytic metabolism for energy production. In contrast, the Type II, and probably the Type III, isozymes are suggested to serve primarily anabolic functions, e.g. to provide Glc-6-P for glycogen synthesis or metabolism via the pentose phosphate pathway for lipid synthesis. Type I hexokinase binds to mitochondria through interaction with porin, the protein that forms channels through which metabolites traverse the outer mitochondrial membrane. Several experimental approaches have led to the conclusion that the Type I isozyme, bound to actively phosphorylating mitochondria, selectively uses intramitochondrial ATP as substrate. Such interactions are thought to facilitate coordination of the introduction of Glc into glycolysis, via the hexokinase reaction, with the terminal oxidative stages of Glc metabolism occurring in the mitochondria, thus ensuring an overall rate of Glc metabolism commensurate with cellular energy demands and avoiding excessive production of lactate. The Type II isozyme also binds to mitochondria. Whether such coupling occurs with mitochondrially bound Type II hexokinase in normal tissues, and how it might be related to the proposed anabolic role of this isozyme, remain to be determined. The Type III isozyme lacks the hydrophobic N-terminal sequence known to be critical for binding of the Type I and Type II isozymes to mitochondria. Immunolocalization studies have indicated that, in many cell types, the Type III has a perinuclear localization, the possible metabolic consequences of which remain unclear.
Cellular and molecular mechanisms of intestinal fibrosis (2012)

Fibrosis is a chronic and progressive process characterized by an excessive accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring of the involved tissue. Intestinal fibrosis may develop in several different enteropathies, including inflammatory bowel disease. It develops through complex cell, extracellular matrix, cytokine and growth factor interactions. Distinct cell types are involved in intestinal fibrosis, such as resident mesenchymal cells (fibroblasts, myofibroblasts and smooth muscle cells) but also ECM-producing cells derived from epithelial and endothelial cells (through a process termed epithelial- and endothelial-mesenchymal transition), stellate cells, pericytes, local or bone marrow-derived stem cells. The most important soluble factors that regulate the activation of these cells include cytokines, chemokines, growth factors, components of the renin-angiotensin system, angiogenic factors, peroxisome proliferator-activated receptors, mammalian target of rapamycin, and products of oxidative stress. It soon becomes clear that although inflammation is responsible for triggering the onset of the fibrotic process, it only plays a minor role in the progression of this condition, as fibrosis may advance in a self-perpetuating fashion. Definition of the cellular and molecular mechanisms involved in intestinal fibrosis may provide the key to developing new therapeutic approaches.
Adolescent Pregnancy Prevention by Health Education Computer Games: Computer-Assisted Instruction of Knowledge and Attitudes (1989)

Adolescents enjoy animated-action computer games that capture and hold attention. In this study, the use of computer-assisted instruction in improving knowledge and attitudes in favor of decreased teenage pregnancy is evaluated. Computer-assisted health education is an interactive process and simulates reality. Teenagers explore alternatives and outcomes, and experience consequences of behavioral choices. Two games were designed to promote understanding of the impact and cost of sexual behaviors and parenthood, as well as provide sexual survival skills. Educational evaluation in high schools showed improvements in knowledge and attitudes in these sensitive areas. Test instruments based on the content of each game were developed to assess the impact of the two interventions. Half of the 718 teenagers used the educational programs, and half served as matched control subjects who did not use computer games. Players rated the games highly and evaluated them positively. Measures of 19 factual and psychologic factors associated with pregnancy and parenting were separately made for control and experimental groups. Teenagers who played the games gained knowledge and positive attitude changes to a significantly greater extent than did the comparison group. "The Baby Game!" users increased their knowledge of costs of birth and of costs in money and time of child rearing. "Romance!" users would seek more professional help, had a better understanding of risk of pregnancy, learned more effective means of contraception, and had greater acceptance of oral contraceptives. Teachers and teenagers found the computer games acceptable and fun, and the games reduced counseling time in physician's offices. Computer-assisted instruction is a useful means of providing health education and a promising intervention for adolescent pregnancy.
A Locus for Autosomal Recessive Pseudoxanthoma Elasticum, with Penetrance of Vascular Symptoms in Carriers, Maps to Chromosome 16p13.1 (1997)

Pseudoxanthoma elasticum (PXE) is a heritable systemic disorder characterized by calcification of the elastic fibers of the connective tissue. Symptoms are predominantly noted in the eye, the skin, and the cardiovascular system, resulting in visual loss, skin lesions, and life-threatening vascular disease. In the study we combined homozygosity mapping and genome scanning with 374 markers in affected individuals from a PXE family from a genetically isolated population in The Netherlands. Initial homozygosity in two or three patients was found with up to 20 markers, among which D16S292 located in 16p13.1. Upon refined and more extensive family screening of the latter region, close linkage without recombination was found with the marker D16S764 (Zmax = 6.27). Despite clear autosomal recessive inheritance of the ocular symptoms in PXE, vascular symptoms appear in 40%-50% of the heterozygotes.
Highly efficient pure blue electroluminescence from polyfluorene: Influence of the molecular weight distribution on the aggregation tendency (2000)

A dependency between the molecular weight distribution of polyfluorene (PFO) and its aggregation tendency on operation in organic light-emitting devices (OLED) is described. As a result of these findings, low molecular parts of the polymer could be made responsible for the aggregation in liquid crystalline PFO. Consequently, a procedure was developed which leads to PFO-based OLEDs which do not show aggregation on operation anymore but exhibit highly efficient and stable blue electroluminescence.
Primary structure of a proteinase inhibitor II gene from potato (Solanum tuberosum) (1986)

The isolation and characterization of a genomic clone encoding proteinase inhibitor II of potato (Solanum tuberosum) is described. The structure of this gene was determined by sequencing a genomic fragment of about 2 kb containing the entire RNA coding as well as about 900 nucleotides of the 5'-upstream and 250 nucleotides of the 3'-downstream region. The transcription start site was determined by RNase protection experiments. The comparison of the genomic sequence with cDNA sequences reveals the presence of one intron with a length of 117 nucleotides. The genomic clone contains an open reading frame of 462 nucleotides allowing for a protein of 154 amino acids. The proteinase inhibitor II gene displays typical features of eucaryotic genes. The sequence TATAAA is found 26 nucleotides upstream of the transcription initiation site and the sequence CAAAT at position--103. In the 3'-region the sequence AATAA is found 33 nucleotides in front of the poly-A addition site.
Intramuscular Therapeutic Vaccination Targeting HPV16 Induces T Cell Responses That Localize in Mucosal Lesions (2014)

About 25% of high-grade cervical intraepithelial neoplasias (CIN2/3) caused by human papillomavirus serotype 16 (HPV16) undergo complete spontaneous regression. However, to date, therapeutic vaccination strategies for HPV disease have yielded limited success when measured by their ability to induce robust peripheral blood T cell responses to vaccine antigen. We report marked immunologic changes in the target lesion microenvironment after intramuscular therapeutic vaccination targeting HPV16 E6/E7 antigens, in subjects with CIN2/3 who had modest detectable responses in circulating T lymphocytes. Histologic and molecular changes, including markedly (average threefold) increased intensity of CD8(+) T cell infiltrates in both the stromal and epithelial compartments, suggest an effector response to vaccination. Postvaccination cervical tissue immune infiltrates included organized tertiary lymphoid-like structures in the stroma subjacent to residual intraepithelial lesions and, unlike infiltrates in unvaccinated lesions, showed evidence of proliferation induced by recognition of cognate antigen. At a molecular level, these histologic changes in the stroma were characterized by increased expression of genes associated with immune activation (CXCR3) and effector function (Tbet and IFNβ), and were also associated with an immunologic signature in the overlying dysplastic epithelium. High-throughput T cell receptor sequencing of unmanipulated specimens identified clonal expansions in the tissue that were not readily detectable in peripheral blood. Together, these findings indicate that peripheral therapeutic vaccination to HPV antigens can induce a robust tissue-localized effector immune response, and that analyses of immune responses at sites of antigen are likely to be much more informative than analyses of cells that remain in the circulation.
Study on the Li[sup +] Insertion/Extraction for Silicon Nanosized Silver Composite Electrode (2007)

Nanosized silver particle was highly dispersed on the surface of silicon particle by electroless deposition on the basis of a stirred silver mirror reaction. Ex situ X-ray diffraction and discharge/charge cycling measurements indicated that silver, as well as silicon, participated in the insertion/extraction process of and played a positive role in the complete extraction of from silicon host. Furthermore, ordered structure of silicon can be obtained after the extraction of with the help of silver additives, which indicates the effect of silver additives in promoting the recrystallization of amorphous -extracted silicon.
Current applications of molecular cytogenetic technologies. (1997)

This review discusses select current applications of fluorescent in situ hybridization (FISH) which may be of utility for the average clinical cytogenetic laboratory. Owing to the large number of men and women affected, the applications chosen to illustrate the use of FISH technology in cancer focus on two diseases: breast cancer and prostate cancer. The applicability of FISH to detect common aneuploidies, such as trisomy 21, trisomy 18, trisomy 13 and the sex chromosome aneuploidies in prenatal diagnosis, is discussed, as well as FISH for the detection of microdeletions and microduplications. Quality assurance/quality control issues and standards and guidelines relating to laboratory practices in molecular cytogenetic testing are reviewed.