gebhart/patrepeval huggingface dataset:
Real-Time Virus Trapping and Fluorescent Imaging in Microfluidic Devices (2003)

We have used dielectrophoretic filters within microfluidic biochips to capture from a flow and image virus particles in real-time. The verification of capture was performed by fluorescently labeling the particles using dual or triple labeling. These nonmechanical filters can be very valuable in the sample preparation, purification, and concentration of viral particles from a mixed sample. The described imaging methodology can be used for real-time imaging of nanometer scale virus particles for analysis of capture, detection, and characterization of these particles within micro and nanoscale sensors.
IL-17 cytokine/receptor families: emerging targets for the modulation of inflammatory responses (2003)

IL-17 was identified a decade ago as a pro-inflammatory cytokine produced by activated T cells that stimulates the secretion of other cytokines from various non-lymphoid cells by acting through a unique cell surface receptor, IL17R. Evidence that IL-17 may contribute to several immune-mediated diseases, such as rheumatoid arthritis and airway inflammation, prompted much interest in this cytokine. Recently, the large-scale analysis of expressed sequence tags (EST) led to the discovery of novel genes dispersed in the human genome that encode at least five additional cytokines structurally related to IL-17. Screening of EST databases also uncovered at least four novel genes encoding Type I transmembrane proteins with significant homology to IL-17R, thereby forming a family of receptors whose cognate ligands are likely to belong to the IL-17 cytokine family. Initial characterisation of some of these cytokines and one IL-17R homologue demonstrated their involvement in regulating inflammatory responses in a manner similar to, albeit distinct from, that of prototypic IL-17. The IL-17 cytokine/receptor families appear therefore to represent unique signalling systems within the cytokine network that might offer innovative approaches to manipulate immune and inflammatory responses. The prospect of targeting these molecules for therapeutic purposes has generated a substantial volume of patent literature that will be reviewed here.
EmtA, a rRNA methyltransferase conferring high‐level evernimicin resistance (2001)

Enterococcus faecium strain 9631355 was isolated from animal sources on the basis of its resistance to the growth promotant avilamycin. The strain also exhibited high-level resistance to evernimicin, a drug undergoing evaluation as a therapeutic agent in humans. Ribosomes from strain 9631355 exhibited a dramatic reduction in evernimicin binding, shown by both cell-free translation assays and direct-binding assays. The resistance determinant was cloned from strain 9631355; sequence alignments suggested it was a methyltransferase and therefore it was designated emtA for evernimicin methyltransferase. Evernimicin resistance was transmissible and emtA was localized to a plasmid-borne insertion element. Purified EmtA methylated 50S subunits from an evernimicin-sensitive strain 30-fold more efficiently than those from a resistant strain. Reverse transcription identified a pause site that was unique to the 23S rRNA extracted from resistant ribosomes. The pause corresponded to methylation of residue G2470 (Escherichia coli numbering). RNA footprinting revealed that G2470 is located within the evernimicin-binding site on the ribosome, thus providing an explanation for the reduced binding of the drug to methylated ribosomes.
The Neglected Market (1987)

The purpose of this article is to focus on the market for tangible assets, a market which has often been overlooked in the literature on macroeconomic models. For some macroeconomic problems, the addition of this "neglected market" has little bearing. However, when people change their asset preferences between financial assets (bonds) and tangible assets (previously-produced goods), there are dramatic implications for interest rates and macroeconomic variables generally. Accordingly, this article amends the standard IS-LM model to include a market for tangible assets.
New Nitrogen-Fixing Microorganisms Detected in Oligotrophic Oceans by Amplification of Nitrogenase ( nifH ) Genes (1998)

ABSTRACT Oligotrophic oceanic waters of the central ocean gyres typically have extremely low dissolved fixed inorganic nitrogen concentrations, but few nitrogen-fixing microorganisms from the oceanic environment have been cultivated. Nitrogenase gene ( nifH ) sequences amplified directly from oceanic waters showed that the open ocean contains more diverse diazotrophic microbial populations and more diverse habitats for nitrogen fixers than previously observed by classical microbiological techniques. Nitrogenase genes derived from unicellular and filamentous cyanobacteria, as well as from the α and γ subdivisions of the class Proteobacteria , were found in both the Atlantic and Pacific oceans. nifH sequences that cluster phylogenetically with sequences from sulfate reducers or clostridia were found associated with planktonic crustaceans. Nitrogenase sequence types obtained from invertebrates represented phylotypes distinct from the phylotypes detected in the picoplankton size fraction. The results indicate that there are in the oceanic environment several distinct potentially nitrogen-fixing microbial assemblages that include representatives of diverse phylotypes.
Eukaryotic MCM Proteins: Beyond Replication Initiation (2004)

The minichromosome maintenance (or MCM) protein family is composed of six related proteins that are conserved in all eukaryotes. They were first identified by genetic screens in yeast and subsequently analyzed in other experimental systems using molecular and biochemical methods. Early data led to the identification of MCMs as central players in the initiation of DNA replication. More recent studies have shown that MCM proteins also function in replication elongation, probably as a DNA helicase. This is consistent with structural analysis showing that the proteins interact together in a heterohexameric ring. However, MCMs are strikingly abundant and far exceed the stoichiometry of replication origins; they are widely distributed on unreplicated chromatin. Analysis of mcm mutant phenotypes and interactions with other factors have now implicated the MCM proteins in other chromosome transactions including damage response, transcription, and chromatin structure. These experiments indicate that the MCMs are central players in many aspects of genome stability.
Decreased Diversity of the Fecal Microbiome in RecurrentClostridium difficile–Associated Diarrhea (2008)

Antibiotic-associated diarrhea due to Clostridium difficile (CDAD) is thought to reflect colonization of a disrupted microbial community by the pathogen. We profiled the fecal microbiota of patients with CDAD (both initial and recurrent episodes) by culture-independent phylogenetic analysis of 16S rRNA-encoding gene sequences. Compared with those from control subjects and patients with an initial episode, the fecal communities in patients with recurrent CDAD were highly variable in bacterial composition and were characterized by markedly decreased diversity. Preservation and restoration of the microbial diversity could represent novel strategies for prevention and treatment of recurrent CDAD, which is often recalcitrant to existing therapies.
Cytotoxic T cells from ovarian malignant tumors can recognize polymorphic epithelial mucin core peptides. (1993)

CTL isolated from tumor infiltrating lymphocytes/tumor associated lymphocytes (TAL) infiltrating ovarian tumors have been demonstrated to mediate lysis of tumor targets after in vitro culture. These effector cells are of particular interest as cellular probes to detect and define human tumor Ag and epitopes that stimulate cellular immunity to human tumors. Polymorphic epithelial mucin (PEM) core peptides are potential candidates as tumor specific Ag because of their preferential expression on epithelial tumors. We report here that ovarian CTL-TAL can recognize mucin (Muc-1) core peptide of PEM. Several ovarian CTL-TAL lines were developed that recognized in a non-MHC restricted fashion an Muc-1+ ovarian tumor, but not Muc-1-tumor. To define the specificity of these CTL-TAL and exclude cross-reactivity with other potential Ag, cytotoxicity experiments were performed using as targets EBV-transformed cell lines with an expression construct containing the Muc.1 cDNA. These ovarian CTL-TAL lysed mucin core-peptide transfected cells but not targets transfected with an expression construct containing a mucin frame-shift mutant cDNA as control. In addition, targets pulsed with short synthetic peptides composed of amino acids 1-14 of the Muc 1 core peptide repeat were also lysed by the same CTL-TAL. This lysis was inhibited by the mAb SM3 that recognize an epitope on the mucin core peptide. These results, which are a demonstration of a specific Ag recognized by ovarian CTL-TAL, may be of interest for specific immunotherapy of ovarian cancer.
A monoclonal antibody to the IL-1 beta peptide 163-171 blocks adjuvanticity but not pyrogenicity of IL-1 beta in vivo (1989)

The synthetic fragment VQGEESNDK, corresponding to the amino acid sequence in position 163-171 of human IL-1 beta, possesses the immunostimulatory but not the pyrogenic activity of the mature IL-1 beta polypeptide in vivo. To assess the relevance of this domain of IL-1 beta for its biologic activities, a mAb was raised against the synthetic peptide 163-171. The mAb Vhp20 could effectively recognize human rIL-1 beta in RIA and immunoblotting. In vivo, the mAb Vhp20 was able to selectively inhibit the immunostimulatory activity of IL-1 beta, but it could not affect the fever-inducing capacity of IL-1 beta. It is proposed that functional domains could be identified in the human IL-1 beta protein and that the fragment in position 163-171 is of major importance for the adjuvant capacity of the entire molecule, but irrelevant to its pyrogenic activity.
LRP1 Controls cPLA2 Phosphorylation, ABCA1 Expression and Cellular Cholesterol Export (2009)

LRP1 regulates LXR-mediated gene transcription and participates in reverse cholesterol transport by controlling cPLA(2) activation and ABCA1 expression. LRP1 thus functions as a physiological integrator of cellular lipid homeostasis with signals that regulate cellular proliferation and vascular wall integrity.
The large-scale cultivation of VERO cells in micro-carrier culture for virus vaccine production. Preliminary results for killed poliovirus vaccine. (1981)

As the increasing shortage of monkeys is a reality, the application of an alternative cell substrate for large-scale production of Killed Poliomyelitis Vaccine (KPV) was studied. Through progress of scientific knowledge the non-tumorigenic VERO cell line was considered to be a suitable alternative cell substrate for this purpose. The Master-Cell-Bank and Working-Cell-Banks prepared by us are giving a practically inexhaustible cell source. Using micro-carrier culture, weekly more than 400 billions of cells at a concentration of 10(6) cells per ml could be obtained for virus inoculation. The virus yield per cell was at least as high as for primary monkey kidney cells. Processing of virus harvests could be performed according to the methods used at the production on primary monkey kidney cells. From a technological view-point large-scale production of KPV on VERO cells appears to be possible economically. More research on the safety control might be necessary.
Characterization of PDC6, a third structural gene for pyruvate decarboxylase in Saccharomyces cerevisiae (1991)

Pyruvate decarboxylase is the key enzyme in alcoholic fermentation in yeast. Two structural genes, PDC1 and PDC5 have been characterized. Deletion of either of these genes has little or no effect on the specific pyruvate decarboxylase activity, but enzyme activity is undetectable in mutants lacking both PDC1 and PDC5 (S. Hohmann and H. Cederberg, Eur. J. Biochem. 188:615-621, 1990). Here I describe PDC6, a gene structurally closely related to PDC1 and PDC5. The product of PDC6 does not seem to be required for wild-type pyruvate decarboxylase activity in glucose medium; delta pdc6 mutants have no reduced specific enzyme activity, and the PDC6 deletion did not change the phenotype or the specific enzyme activity of mutants lacking either or both of the other two structural genes. However, in cells grown in ethanol medium the PDC6 deletion caused a reduction of pyruvate decarboxylase activity. Northern (RNA) blot analysis showed that PDC6 is weakly expressed, and expression seemed to be higher during growth in ethanol medium. This behavior remained obscure since pyruvate decarboxylase catalyzes an irreversible reaction. Characterization of all combinations of PDC structural gene deletion mutants, which produce different amounts of pyruvate decarboxylase activity, showed that the enzyme is also needed for normal growth in galactose and ethanol medium and in particular for proper growth initiation of spores germinating on ethanol medium.
Oxopyrido[2,3-d]pyrimidines as Covalent L858R/T790M Mutant Selective Epidermal Growth Factor Receptor (EGFR) Inhibitors (2015)

In nonsmall cell lung cancer (NSCLC), the threonine(790)-methionine(790) (T790M) point mutation of EGFR kinase is one of the leading causes of acquired resistance to the first generation tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. Herein, we describe the optimization of a series of 7-oxopyrido[2,3-d]pyrimidinyl-derived irreversible inhibitors of EGFR kinase. This led to the discovery of compound 24 which potently inhibits gefitinib-resistant EGFR(L858R,T790M) with 100-fold selectivity over wild-type EGFR. Compound 24 displays strong antiproliferative activity against the H1975 nonsmall cell lung cancer cell line, the first line mutant HCC827 cell line, and promising antitumor activity in an EGFR(L858R,T790M) driven H1975 xenograft model sparing the side effects associated with the inhibition of wild-type EGFR.
Screening of 38 Genes Identifies Mutations in 62% of Families with Nonsyndromic Deafness in Turkey (2010)

More than 60% of prelingual deafness is genetic in origin, and of these up to 95% are monogenic autosomal recessive traits. Causal mutations have been identified in 1 of 38 different genes in a subset of patients with nonsyndromic autosomal recessive deafness. In this study, we screened 49 unrelated Turkish families with at least three affected children born to consanguineous parents. Probands from all families were negative for mutations in the GJB2 gene, two large deletions in the GJB6 gene, and the 1555A>G substitution in the mitochondrial DNA MTRNR1 gene. Each family was subsequently screened via autozygosity mapping with genomewide single-nucleotide polymorphism arrays. If the phenotype cosegregated with a haplotype flanking one of the 38 genes, mutation analysis of the gene was performed. We identified 22 different autozygous mutations in 11 genes, other than GJB2, in 26 of 49 families, which overall explains deafness in 62% of families. Relative frequencies of genes following GJB2 were MYO15A (9.9%), TMIE (6.6%), TMC1 (6.6%), OTOF (5.0%), CDH23 (3.3%), MYO7A (3.3%), SLC26A4 (1.7%), PCDH15 (1.7%), LRTOMT (1.7%), SERPINB6 (1.7%), and TMPRSS3 (1.7%). Nineteen of 22 mutations are reported for the first time in this study. Unknown rare genes for deafness appear to be present in the remaining 23 families.
A Nonfluoroscopic Catheter‐Based Mapping Technique to Ablate Focal Ventricular Tachycardia (1998)

The recent introduction of a nonfluoroscopic electroanatomical cardiac mapping system (CARTO) is an exciting development in catheter ablation treatment of cardiac arrhythmias. The system uses ultralow magnetic fields to locate a sensor positioned near the tip of a regular mapping and ablation catheter. The catheter location and electrograms are recorded and reconstructed in real-time and presented as a three-dimensional geometrical mapped color coded with the electrophysiological information. The CARTO represents an important tool to guide the ablation of patients who have focal tachycardia (e.g., right ventricular outflow tract [RVOT] tachycardia and idiopathic left ventricular [ILV] tachycardia). This study describes how the CARTO system is useful in mapping and ablating these arrhythmias. Two case illustrations, one patient with RVOT tachycardia and another with ILV tachycardia, are described in this article. The tachycardia was mapped and ablated using the new electromagnetic catheter technology creating an electroanatomical map of the arrhythmia focus for each tachycardia without fluoroscopy; both tachycardias were successfully ablated, terminated, and rendered noninducible. The CARTO system is useful in mapping and guiding the ablation of focal tachycardia and merits further study.
Development of Cell Lines Capable of Complementing E1, E4, and Protein IX Defective Adenovirus Type 5 Mutants (1995)

The cloning capacity of currently available E1- and E3-deleted adenovirus (Ad) vectors does not exceed 8 kb. To increase capacity and improve vector safety further, we have explored the possibility that Early Region 4 (E4) and the gene encoding protein IX (pIX) might also be deleted. To generate cell lines expressing sufficient levels of E4 and pIX proteins in trans in addition to E1-encoded proteins to complement mutations in these genes, we transformed 293 cells with constructs containing the E4 transcription unit and pIX coding sequences under the control of inducible mouse mammary tumor virus (MMTV) and metallothionein promoters, respectively. We obtained two lines, VK2-20 and VK10-9, that express both E4 and pIX proteins as well as E1. The lines could be efficiently transfected with DNA, and allowed the rescue and propagation of an adenovirus; recombinant, Ad5dlE3,4, containing a 2.7-kb E3 deletion and a 2.8-kb E4 deletion in addition to an insertion of plasmid DNA sequences in E1A. Because the E4 sequences within VK2-20 and VK10-9 cells do not overlap with the DNA sequence of Ad5dlE3,E4, the probability of regeneration of the wild-type E4 during virus propagation should be very low. Using the cell lines described in this study, it should be possible to generate Ad vectors lacking E1, pIX, E3, and E4. This would not only increase capacity over that of currently available vectors (to approximately 11 kb) but would also result in more severely attenuated vectors than those with deletions only of E1 or of E1 and E3 and, hence, safer for use in gene therapy protocols.
High confidence visual recognition of persons by a test of statistical independence (1993)

A method for rapid visual recognition of personal identity is described, based on the failure of a statistical test of independence. The most unique phenotypic feature visible in a person's face is the detailed texture of each eye's iris. The visible texture of a person's iris in a real-time video image is encoded into a compact sequence of multi-scale quadrature 2-D Gabor wavelet coefficients, whose most-significant bits comprise a 256-byte "iris code". Statistical decision theory generates identification decisions from Exclusive-OR comparisons of complete iris codes at the rate of 4000 per second, including calculation of decision confidence levels. The distributions observed empirically in such comparisons imply a theoretical "cross-over" error rate of one in 131000 when a decision criterion is adopted that would equalize the false accept and false reject error rates. In the typical recognition case, given the mean observed degree of iris code agreement, the decision confidence levels correspond formally to a conditional false accept probability of one in about 10/sup 31/.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
<title>86-mm magneto-optical disk drive with a compact and fast-seek-time optical head</title> (1990)

An average seek time less than 20 msec was achieved using a head with a 6 gr moving part with an 86 mm diameter magneto-optical disk drive.© (1990) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Campylobacter mustelae, a New Species Resulting from the Elevation of Campylobacter pylori subsp. mustelae to Species Status (1989)

The name Campylobacter pylori subsp. mustelae was recently proposed for strains belonging to the genus Campylobacter that were isolated from the gastric mucosa of ferrets because of the high levels of deoxyribonucleic acid relatedness (85 to 100%) of these strains to the type strain of Campylobacter pylori. Subsequent deoxyribonucleic acid relatedness studies done independently in three laboratories by three different methods indicate that the original results were in error. Strains isolated from ferrets in the United States, England, and Australia are members of a single species that is substantially different from C. pylori (10 to 20% relatedness at 50°C and 3 to 10% relatedness at 65°C as determined by the hydroxyapatite method; less than 10% relatedness at 65°C as determined by the nylon membrane blot method; and 30 to 49% relatedness at 66 to 68°C as determined by the spectrophotometric method). The strains isolated from ferrets also differ from human C. pylori strains in their ability to reduce nitrates, their negative leucine arylamidase reaction, their susceptibility to nalidixic acid, and their resistance to cephalothin. The strains from ferrets possess both polar and lateral flagella, whereas only polar flagella have been demonstrated in human C. pylori strains. Thus, the strains isolated from ferrets are members of a species that is distinct from C. pylon, and we propose elevating C. pylori subsp. mustelae to species status as Campylobacter mustelae sp. nov.
Dapoxetine Has No Pharmacokinetic or Cognitive Interactions With Ethanol in Healthy Male Volunteers (2007)

Dapoxetine is being investigated for the treatment of premature ejaculation. This study evaluated the potential pharmacokinetic and cognitive interactions of dapoxetine 60 mg with ethanol 0.5 g/kg in a single-center, double-blind, randomized, placebo-controlled crossover study in healthy adult male participants (n = 24). Dapoxetine was rapidly absorbed and eliminated; peak concentrations were noted 1.47 hours after administration and decreased with an alpha half-life of 1.33 hours and a terminal half-life of 15.6 hours. Pharmacokinetic parameters (C(max), AUC(infinity), t((1/2)), and t(max)) of dapoxetine were not altered with concurrent ethanol consumption. Furthermore, coadministration of dapoxetine did not affect the pharmacokinetics of ethanol or potentiate the cognitive and subjective effects of ethanol.