gebhart/patrepeval huggingface dataset:
Targeting of HIV-1 Antigens for Rapid Intracellular Degradation Enhances Cytotoxic T Lymphocyte (CTL) Recognition and the Induction of De Novo CTL Responses In Vivo After Immunization (1997)

CD8+ cytotoxic T lymphocytes (CTLs) have the ability to recognize and eliminate virally infected cells before new virions are produced within that cell. Therefore, a rapid and vigorous CD8+ CTL response, induced by vaccination, can, in principle, prevent disseminated infection in vaccinated individuals who are exposed to the relevant virus. There has thus been interest in novel vaccine strategies that will enhance the induction of CD8+ CTLs. In this study, we have tested the hypothesis that targeting an antigen to undergo more efficient processing by the class I processing pathway will elicit a more vigorous CD8+ CTL response against that antigen. Targeting a type I transmembrane protein, the HIV-1 envelope (env) protein, for expression in the cytoplasm, rather than allowing its normal co-translational translocation into the endoplasmic reticulum, sensitized target cells expressing this mutant more rapidly for lysis by an env-specific CTL clone. Additionally, a greatly enhanced de novo env-specific CTL response was induced in vivo after immunization of mice with recombinant vaccinia vectors expressing the cytoplasmic env mutant. Similarly, targeting a cytoplasmic protein, HIV-1 nef, to undergo rapid cytoplasmic degradation induced a greatly enhanced de novo nef-specific CD8+ CTL response in vivo after immunization of mice with either recombinant vaccinia vectors or DNA expression plasmids expressing the degradation targeted nef mutant. The targeting of viral antigens for rapid cytoplasmic degradation represents a novel and highly effective vaccine strategy for the induction of enhanced de novo CTL responses in vivo.
Computing with Nucleic Acids (2005)

This chapter contains sections titled: Introduction Massively Parallel Approaches The Seeman–Winfree Paradigm: Molecular Self-assembly The Rothemund–Shapiro Paradigm: Simulating State Machines Nucleic Acid Catalysts in Computation Conclusion
The production of pharmaceutical proteins from the milk of transgenic animals (1995)

The preparation of recombinant proteins of pharmaceutical interest from the milk of transgenic animals is becoming a reality. No protein has reached the market yet but several have been prepared in large quantities not only from laboratory animals but also from ruminants (goat and sheep) and pigs. Rabbit appears more and more to be an intermediate animal well adapted for the preparation of limited amounts of proteins. Several problems remain to be solved to optimize the method. The expression level of genes of interest associated with milk protein gene control regions is usually unpredictable. The recombinant proteins secreted in milk are not always in a satisfactory biochemical form. Cleavage and glycosylation are not always carried out correctly. The problem of the possible presence of agents pathogenic for humans in proteins extracted from milk is not completely solved. Prions have not been found in mammary glands and other milk pathogens may be controlled using good practice in breeding.
Molecular characterization of upper urinary tract tumours (2009)

Our data suggest that bladder cancer and UTUC share some characteristics, but have differences in gene expression. None of BIRC5, FGFR3, IGF2, KRT20, UPK2, EBF1, CDH1, FXYD3, HTERT, TP53, AGR2, HER2 and VEGF were correlated either tumour progression or survival.
Pharmacokinetic Profiling of Conjugated Therapeutic Oligonucleotides: A High-Throughput Method Based Upon Serial Blood Microsampling Coupled to Peptide Nucleic Acid Hybridization Assay (2017)

Therapeutic oligonucleotides, such as small interfering RNAs (siRNAs), hold great promise for the treatment of incurable genetically defined disorders by targeting cognate toxic gene products for degradation. To achieve meaningful tissue distribution and efficacy in vivo, siRNAs must be conjugated or formulated. Clear understanding of the pharmacokinetic (PK)/pharmacodynamic behavior of these compounds is necessary to optimize and characterize the performance of therapeutic oligonucleotides in vivo. In this study, we describe a simple and reproducible methodology for the evaluation of in vivo blood/plasma PK profiles and tissue distribution of oligonucleotides. The method is based on serial blood microsampling from the saphenous vein, coupled to peptide nucleic acid hybridization assay for quantification of guide strands. Performed with minimal number of animals, this method allowed unequivocal detection and sensitive quantification without the need for amplification, or further modification of the oligonucleotides. Using this methodology, we compared plasma clearances and tissue distribution profiles of two different hydrophobically modified siRNAs (hsiRNAs). Notably, cholesterol-hsiRNA presented slow plasma clearances and mainly accumulated in the liver, whereas, phosphocholine-docosahexaenoic acid-hsiRNA was rapidly cleared from the plasma and preferably accumulated in the kidney. These data suggest that the PK/biodistribution profiles of modified hsiRNAs are determined by the chemical nature of the conjugate. Importantly, the method described in this study constitutes a simple platform to conduct pilot assessments of the basic clearance and tissue distribution profiles, which can be broadly applied for evaluation of new chemical variants of siRNAs and micro-RNAs.
pl Bl5: A cDNA Clone of the Rat mRNA Encoding Cyclophilin (1988)

We present the complete nucleotide sequence of a cDNA encoding rat cyclophilin. The 743-nucleotide sequence contains a 42-nucleotide 5' noncoding region, a 492 nucleotide open reading frame corresponding to a translation product of 164 amino acids with a molecular weight of 17,874, and a 3' noncoding region of 209 nucleotides. Primer extension studies reveal the presence of one minor and two major transcription start sites. Southern blot analyses are consistent with as many as 20 copies of the cyclophilin gene and possible pseudogenes. Cyclophilin mRNA is expressed in virtually all types of tissues of rat and monkey and appears to have been highly conserved during mammalian evolution.
Use of Ionic Liquids for Liquid-Phase Microextraction of Polycyclic Aromatic Hydrocarbons (2003)

This paper demonstrates, for the first time, that ionic liquids (IL) such as 1-octyl-3-methylimidazolium hexafluorophosphate ([C(8)MIM][PF(6)]) are excellent extraction solvents in liquid-phase microextraction (LPME). The unique properties of nonvolatility and adequate viscosity allow IL to be conveniently adopted as extraction solvents in both direct-immersion and headspace LPME. Model compounds, polycyclic aromatic hydrocarbons (PAHs), are conveniently and rapidly enriched in a 3-microL drop of [C(8)MIM][PF(6)] suspended on the tip of a microsyringe followed by liquid chromatographic determination. Compared to 1-octanol, a larger volume drop of [C(8)MIM][PF(6)] can be formed and survive for a longer extraction time; therefore, a much higher enrichment factor for PAHs can be reached. For low-volatility PAHs, direct-immersion LPME provides higher enrichment factors than that of headspace LPME. However, the enrichment factor obtained by headspace LPME was almost 3-fold of that by direct-immersion LPME in a 30-min extraction of the most volatile PAH, naphthalene. For 30-min direction-immersion LPME of EPA priority PAHs, the enrichment factor, correlation coefficient (R(2)), and reproducibility (RSD, n = 5) were in the range of 42-166, 0.9169-0.9976, and 2.8-12%, respectively. Considering that IL can be easily prepared from relatively inexpensive materials and tuned by combination of different anions and cations for task-specific extraction of analytes from various solvent media, this proposed method should have great potentiality in sample preparation. Furthermore, the nonvolatility of IL makes it potentially useful for headspace LPME of volatile analytes.
Pathway of p-Coumaric Acid Incorporation into Maize Lignin As Revealed by NMR (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPathway of p-Coumaric Acid Incorporation into Maize Lignin As Revealed by NMRJohn Ralph, Ronald D. Hatfield, Stephane Quideau, Richard F. Helm, John H. Grabber, and Hans-Joachim G. JungCite this: J. Am. Chem. Soc. 1994, 116, 21, 9448–9456Publication Date (Print):October 1, 1994Publication History Published online1 May 2002Published inissue 1 October 1994https://pubs.acs.org/doi/10.1021/ja00100a006https://doi.org/10.1021/ja00100a006research-articleACS PublicationsRequest reuse permissionsArticle Views2267Altmetric-Citations351LEARN 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
Transmission of Microwave Through Perforated Flat Plates of Finite Thickness (1973)

Transmission characteristics of a thick conducting plate perforated with either circular or rectangular holes are presented. Simple explicit formulas for predicting energy leakage through a reflector surface are derived.
cDNA Cloning of Mouse and Human Cholesterol 25-Hydroxylases, Polytopic Membrane Proteins That Synthesize a Potent Oxysterol Regulator of Lipid Metabolism (1998)

Oxysterols regulate the expression of genes involved in cholesterol and lipid metabolism and serve as intermediates in cholesterol catabolism. Among the most potent of regulatory oxysterols is 25-hydroxycholesterol, whose biosynthetic enzyme has not yet been isolated. Here, we report the cloning of cholesterol 25-hydroxylase cDNAs from the mouse and human. The encoded enzymes are polytopic membrane proteins of 298 and 272 amino acids, respectively, which contain clusters of histidine residues that are essential for catalytic activity. Unlike most other sterol hydroxylases, cholesterol 25-hydroxylase is not a cytochrome P450, but rather it is a member of a small family of enzymes that utilize diiron cofactors to catalyze the hydroxylation of hydrophobic substrates. The cholesterol 25-hydroxylase gene lacks introns, and in the human it is located on chromosome 10q23. The murine gene is expressed at low levels in multiple tissues. Expression of cholesterol 25-hydroxylase in transfected cells reduces the biosynthesis of cholesterol from acetate and suppresses the cleavage of sterol regulatory element binding protein-1 and -2. The data suggest that cholesterol 25-hydroxylase has the capacity to play an important role in regulating lipid metabolism by synthesizing a co-repressor that blocks sterol regulatory element binding protein processing and ultimately leads to inhibition of gene transcription.
A Microfluidic Platform Using Molecular Beacon-Based Temperature Calibration for Thermal Dehybridization of Surface-Bound DNA (2004)

This work presents a simple microfluidic device with an integrated thin-film heater for studies of DNA hybridization kinetics and double-stranded DNA melting temperature measurements. The heating characteristics of the device were evaluated with a novel, noninvasive indirect technique using molecular beacons as temperature probes inside reaction chambers. This is the first microfluidic device in which thermal dehybridization of surface-bound oligonucleotides was performed for measurement of double-stranded DNA melting temperatures with +/- 1 degrees C precision. Surface modification and oligonucleotide immobilization were performed by continuously flowing reagents through the microchannels. The resulting reproducibility of oligonucleotide surface densities, at 9% RSD, was better than for the same modification chemistries on glass slides in unstirred reagent solutions (RSD=20%). Moreover, the surface density of immobilized DNA probe molecules could be varied controllably by changing the concentration of the reagent solution used for immobilization. Thus, excellent control of surface characteristics was made possible, something which is often difficult to achieve with larger devices. Solid-phase hybridization reactions, a fundamental aspect of microarray technologies often taking several hours in conventional systems, were reduced to minutes in this device. It was also possible to determine forward rate constants for hybridization, k. These varied from 820,000 to 72,000 M(-1) s(-1), decreasing as surface densities increased. Surface densities could therefore be optimized to obtain rapid hybridization using such an approach. Taken together, this combined microfluidic/small-volume heating approach represents a powerful tool for surface-based DNA analysis.
Dynamic modeling and control of doubly fed induction generators driven by wind turbines (2009)

Two different models are presented and developed in PSCAD/EMTDC to represent a variable-speed wind turbine equipped with a doubly fed induction generator (DFIG). One is the most detailed switching-level (SL) model. The other is a simplified fundamental-frequency (FF) model. The effect of different shaft system representations on the dynamic behavior of the wind turbine generator (WTG) system and the issue of damping low-frequency torsional oscillations are investigated. Dynamic and transient simulation studies are carried out to compare two models with different shaft system representations. Results show that the FF model is sufficient while the lumped- mass shaft model is insufficient to represent the dynamic behavior of the WTG. The FF model with the two-mass shaft representation is therefore recommended to represent the DFIG wind turbines for power system dynamic and transient studies.
R2oDNA Designer: Computational Design of Biologically Neutral Synthetic DNA Sequences (2014)

R2oDNA Designer is a web application that stochastically generates orthogonal sets of synthetic DNA sequences designed to be biologically neutral. Biologically neutral sequences may be used for directing efficient DNA assembly by overlap-directed methods, as a negative control for functional DNA, as barcodes, or potentially as spacer regions to insulate biological parts from local context. The software creates optimized sequences using a Monte Carlo simulated annealing approach followed by the elimination of sequences homologous to host genomes and commonly used biological parts. An orthogonal set is finally determined by using a network elimination algorithm. Design constraints can be defined using either a web-based graphical user interface (GUI) or uploading a file containing a set of text commands.
Myc activates telomerase (1998)

Telomere maintenance has been proposed as an essential prerequisite to human tumor development. The telomerase enzyme is itself a marker for tumor cells, but the genetic alterations that activate the enzyme during neoplastic transformation have remained a mystery. Here, we show that Myc induces telomerase in both normal human mammary epithelial cells (HMECs) and normal human diploid fibroblasts. Myc increases expression of hEST2 (hTRT/TP2), the limiting subunit of telomerase, and both Myc and hEST2 can extend the life span of HMECs. The ability of Myc to activate telomerase may contribute to its ability to promote tumor formation.
The filamentous haemagglutinin, a multifaceted adhesin produced by virulent Bordetella spp. (1993)

Filamentous haemagglutinin (FHA) is the major attachment factor produced by virulent Bordetella spp. Similar to the other virulence factors, its production is tightly regulated by a two-component system in response to environmental changes. Although of impressive size (c. 220 kDa), it is very efficiently released into the culture supernatant of Bordetella pertussis. Its biogenesis involves complex processing of a larger precursor with a calculated molecular mass of 370 kDa. Export of FHA into the culture medium depends on an outer membrane protein homologous to haemolysin accessory proteins. Purified extracellular FHA is able to increase the adherence of other pathogens to the host, which may contribute to super-infection in whooping cough. Although FHA- mutants colonize lungs as efficiently as the wild-type parent strains, immune responses against FHA appear to protect against colonization. Unlike many other adhesins, FHA expresses at least three different attachment activities, one specific for the CR3 integrins of macrophages, one involving a carbohydrate-binding site, specific for interactions with cilia, and a heparin-binding activity that may be important for interaction of B. pertussis with epithelial cells or extracellular matrices.
Regulation of Expression of the Fructan Hydrolase Gene of Streptococcus mutans GS-5 by Induction and Carbon Catabolite Repression (1999)

The polymers of fructose, levan and inulin, as well as sucrose and raffinose, are substrates for the product of the fruA gene of Streptococcus mutans GS-5. The purpose of this study was to characterize the DNA immediately flanking fruA, to explore the regulation of expression of fruA by the carbohydrate source, and to begin to elucidate the molecular basis for differential expression of the gene. Located 3' to fruA was an open reading frame (ORF) with similarity to beta-fructosidases which was cotranscribed with fruA. A transcriptional initiation site, located an appropriate distance from an extended -10-like promoter, was mapped at 165 bp 5' to the fruA structural gene. By the use of computer algorithms, two overlapping, stable stem-loop sequences with the potential to function as rho-independent terminators were found in the 5' untranslated region. Catabolite response elements (CREs), which have been shown to govern carbon catabolite repression (CCR) by functioning as negative cis elements in gram-positive bacteria, were located close to the promoter. The levels of production of fruA mRNA and FruA were elevated in cells growing on levan, inulin, or sucrose as the sole carbohydrate source, and repression was observed when cells were grown on readily metabolizable hexoses. Deletion derivatives containing fusions of fruA promoter regions, lacking sequences 5' or 3' to the promoter, and a promoterless chloramphenicol acetyltransferase gene were used (i) to demonstrate the functionality of the promoter mapped by primer extension, (ii) to demonstrate that CCR of the fru operon requires the CRE that is located 3' to the promoter region, and (iii) to provide preliminary evidence that supports the involvement of an antitermination mechanism in fruA induction.
Molecular heterogeneity of human serum cholinesterase. (1971)

The evidence is described that serum cholinesterases are a group of discrete isoenzymes, differing primarily in molecular size but also kinetically. A number of genetically determined variants have been described which probably differ by virtue of structural modifications. The clinical importance of the measurement of serum cholinesterase activity is discussed.
Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study (2010)

Eliglustat tartrate is an investigational oral substrate reduction therapy for Gaucher disease type 1 that is pharmacologically distinct from intravenous enzyme replacement therapy. Eliglustat tartrate improved clinical manifestations in patients who received 50 or 100 mg twice daily for 1 year during an open-label phase 2 study (Blood. 2010;116(6):893-899). We report further improvements after 2 years of treatment in 20 patients (11 females, 9 males; mean age, 33 years) with baseline splenomegaly and thrombocytopenia and/or anemia. Statistically significant (P < .001) percentage improvements from baseline occurred in platelet count (mean ± SD, 81% ± 56%), hemoglobin level (20% ± 15%), spleen volume (-52% ± 11%), and liver volume (-24% ± 13%). Mean platelet count increased ∼ 50 000/mm(3). Mean hemoglobin level increased 2.1 g/dL overall and 3.1 g/dL in 10 patients with baseline anemia. Organ volume reductions were greatest in patients with severe baseline organomegaly. Seventeen (85%) patients met established therapeutic goals for ≥ 3 of the 4 parameters. Lumbar spine bone mineral density increased 7.8% ± 10.6% (P = .01) and T-score 0.6 ± 0.8 (P = .012), with major gains in osteoporotic and osteopenic patients. Magnetic resonance imaging assessment showed that bone marrow infiltration by Gaucher cells was decreased (8/18 patients) or stable (10/18 patients). No safety-related trends emerged during 2 years of treatment. This multisite, open-label, single-arm phase 2 study is registered at www.clinicaltrials.gov as NCT00358150.
Glial cell line-derived neurotrophic factor/neurturin-induced differentiation and its enhancement by retinoic acid in primary human neuroblastomas expressing c-Ret, GFR alpha-1, and GFR alpha-2. (1998)

Neuroblastomas often undergo spontaneous differentiation and/or regression in vivo, which is at least partly regulated by the signals through neurotrophins and their receptors. Recently, glial cell line-derived neurotrophic factor (GDNF) and a second family member, neurturin (NTN), have been found to mediate their signals by binding to a heterotetrameric complex of c-Ret tyrosine kinase receptors and glycosylphosphatidylinositol-linked proteins, GFR alpha-1 (GDNFR-alpha) or GFR alpha-2 (TrnR2/GDNFR-beta/NTNR-alpha/RETL2). Here, we studied the effect of GDNF and NTN on human neuroblastomas in the short-term primary culture system, as well as the expression of c-Ret, GFR alpha-1, GFR alpha-2, GDNF, and NTN. GDNF (1-100 ng/ml) induced morphological differentiation in 34 of 38 primary neuroblastomas and an accompanying increase in c-Fos induction. These effects were markedly enhanced by treatment with 5 microM all-trans-retinoic acid. Although GDNF alone induced a rather weak differentiation independent of the disease stages, the enhancement of neurite outgrowth induced by treatment with both GDNF and all-trans-retinoic acid was significantly correlated with younger age (less than 1 year; P = 0.0039), non-stage 4 diseases (P = 0.0023), a single copy of N-myc (P = 0.027), and high levels of TRK-A expression (P = 0.0062). To examine the expression levels of GFR alpha-1, we cloned a short form of the human GFR alpha-1 gene with a 15-bp deletion by screening a human adult substantia nigra cDNA library. Many primary neuroblastomas expressed c-Ret, GFR alpha-1, and GFR alpha-2 as well as their ligands, GDNF and NTN, suggesting the presence of a paracrine or autocrine signaling system within the tumor tissue. The effect of NTN on primary culture cells of neuroblastoma was similar to that of GDNF. These imply that the GDNF(NTN)/c-Ret/GFR alpha-1(GFR alpha-2) signaling may have an important role in regulating the growth, differentiation, and cell death of neuroblastomas.