gebhart/patrepeval huggingface dataset:
Sequence analysis and molecular characterization of genes required for the biosynthesis of type 1 capsular polysaccharide in Staphylococcus aureus (1994)

We previously cloned a 19.4-kb DNA region containing a cluster of genes affecting type 1 capsule production from Staphylococcus aureus M. Subcloning experiments showed that these capsule (cap) genes are localized in a 14.6-kb region. Sequencing analysis of the 14.6-kb fragment revealed 13 open reading frames (ORFs). Using complementation tests, we have mapped a collection of Cap- mutations in 10 of the 13 ORFs, indicating that these 10 genes are involved in capsule biosynthesis. The requirement for the remaining three ORFs in the synthesis of the capsule was demonstrated by constructing site-specific mutations corresponding to each of the three ORFs. Using an Escherichia coli S30 in vitro transcription-translation system, we clearly identified 7 of the 13 proteins predicted from the ORFs. Homology search between the predicted proteins and those in the data bank showed very high homology (52.3% identity) between capL and vipA, moderate homology (29% identity) between capI and vipB, and limited homology (21.8% identity) between capM and vipC. The vipA, vipB, and vipC genes have been shown to be involved in the biosynthesis of Salmonella typhi Vi antigen, a homopolymer polysaccharide consisting of N-acetylgalactosamino uronic acid, which is also one of the components of the staphylococcal type 1 capsule. The homology between these sets of genes therefore suggests that capL, capI, and capM may be involved in the biosynthesis of amino sugar, N-acetylgalactosamino uronic acid. In addition, the search showed that CapG aligned well with the consensus sequence of a family of acetyltransferases from various prokaryotic organisms, suggesting that CapG may be an acetyltransferase. Using the isogenic Cap- and Cap+ strains constructed in this study, we have confirmed that type 1 capsule is an important virulence factor in a mouse lethality test.
Comparative Genetics of Nucleotide Binding Site-Leucine Rich Repeat Resistance Gene Homologues in the Genomes of Two Dicotyledons: Tomato and Arabidopsis (2000)

The presence of a single resistance (R) gene allele can determine plant disease resistance. The protein products of such genes may act as receptors that specifically interact with pathogen-derived factors. Most functionally defined R-genes are of the nucleotide binding site-leucine rich repeat (NBS-LRR) supergene family and are present as large multigene families. The specificity of R-gene interactions together with the robustness of plant-pathogen interactions raises the question of their gene number and diversity in the genome. Genomic sequences from tomato showing significant homology to genes conferring race-specific resistance to pathogens were identified by systematically "scanning" the genome using a variety of primer pairs based on ubiquitous NBS motifs. Over 70 sequences were isolated and 10% are putative pseudogenes. Mapping of the amplified sequences on the tomato genetic map revealed their organization as mixed clusters of R-gene homologues that showed in many cases linkage to genetically characterized tomato resistance loci. Interspecific examination within Lycopersicon showed the existence of a null allele. Consideration of the tomato and potato comparative genetic maps unveiled conserved syntenic positions of R-gene homologues. Phylogenetic clustering of R-gene homologues within tomato and other Solanaceae family members was observed but not with R-gene homologues from Arabidopsis thaliana. Our data indicate remarkably rapid evolution of R-gene homologues during diversification of plant families.
An Improvement of theN-Arylation of Amides; Application to the Synthesis of Substituted 3-(N-Acetyl-N-phenylamino)-pyridines (1989)

In the presence of catalytic quantities of tris(3,6-dioxaheptyl)amine (TDA-1) and of copper(I) chloride, with azeotropic separation of the reaction water, the N-arylation of carboxamides has been simplified and can now be performed under rather mild conditions, using substituted bromobenzenes as arylating agents in quasi-stoichiometric quantities in boiling xylene, or using chlorobenzenes as arylating agents and as reaction solvents at reflux. The general applicability of the reaction to the preparation of various diarylamines is demonstrated.
The role of the beta 4‐subunit in determining the kinetic properties of rat neuronal nicotinic acetylcholine alpha 3‐receptors. (1991)

1. Single-channel currents were recorded from Xenopus oocytes which had been injected with complementary RNAs (cRNAs) for the neuronal nicotinic acetylcholine receptor subunits alpha 3 and beta 4. The co-expression of alpha 3 and beta 4 gave rise to three different channel types with conductances of 22, 18 and 13 pS. 2. The activity arising from the expression of these two subunits was compared with that observed when the alpha 3 subunit was co-expressed with an alternative beta-subunit, beta 2. The alpha 3 beta 4-receptors differed from alpha 3 beta 2-receptors in conductance, open times and most notably, in burst kinetics. The association of the beta 4-subunit with the alpha 3-subunit results in receptors which have a high probability of re-opening after closing, yielding protracted bursts of activity not observed when the alpha 3-subunit is associated with the beta 2-subunit. 3. All three alpha 3 beta 4-channel types had similar burst kinetics. However, the 13 pS conductance channels showed an additional long-lived open state to varying degrees when clusters of activity within an individual record were examined.
The acute effects of a loading dose of phenylalanine in unipolar depressed patients with and without tardive dyskinesia. (1992)

The effects of a loading dose of 100 mg/kg phenylalanine (PHE) were assessed in three groups of DSM-III-R diagnosed unipolar depressed patients: patients with tardive dyskinesia (TD) (n = 11); patients exposed to neuroleptics (NLs) but without TD (n = 10); and patients never exposed to NLs (n = 10). No significant differences were obtained in fasting and 2 hour postloading PHE plasma levels between the groups. A statistically significant correlation was found between Abnormal Involuntary Movements Scale total scores and postloading PHE plasma levels (p less than .05). Three TD patients showed unusually large increases in PHE plasma levels and PHE:large neutral amino acid ratios. Abnormalities in PHE metabolism may contribute to the development and severity of TD in some NL-treated unipolar depressed patients.
Automated Fabrication: Improving Productivity in Manufacturing (1993)

Technologies currently available for the monitoring of electrical stimulation (ES) in promoting blood circulation and tissue oxygenation are limited. This study integrated a muscle stimulator with a diffuse correlation spectroscopy (DCS) flow-oximeter to noninvasively quantify muscle blood flow and oxygenation responses during ES. Ten healthy subjects were tested using the integrated system. The muscle stimulator delivered biphasic electrical current to right leg quadriceps muscle, and a custom-made DCS flow-oximeter was used for simultaneous measurements of muscle blood flow and oxygenation in both legs. To minimize motion artifact of muscle fibers during ES, a novel gating algorithm was developed for data acquisition at the time when the muscle was relaxed. ES at 2, 10, and 50 Hz were applied for 20 min on each subject in three days sequentially. Results demonstrate that the 20-min ES at all frequencies promoted muscle blood flow significantly. However, only the ES at 10 Hz resulted in significant and persistent increases in oxy-hemoglobin concentration during and post ES. This pilot study supports the application of the integrated system to quantify tissue hemodynamic improvements for the optimization of ES treatment in patients suffering from diseases caused by poor blood circulation and low tissue oxygenation (e.g., pressure ulcer).
Monoclonal Antibody Inducing Human Sperm Agglutination (1983)

A mouse fused splenic cell line producing antibody that induces agglutination of human sperm was cultivated. The antibody was localized to the midpiece and tail of human spermatozoa by an indirect immunofluorescence method. The interacting antigen was identified in a sperm membrane protein preparation by SDS gel/protein blot immunofluorescence method. The molecular weight of the antigen was in the vicinity of 84 Kdaltons.
Cetuximab (C), oxaliplatin (Ox) and fluoropyrimidine (Fp): Toxicity during the first 12 weeks of treatment for the first 804 patients entered into the MRC COIN (CR10) trial (2007)

4070 Background: COIN is a 3-arm trial comparing continuous chemotherapy (CT) plus C or intermittent CT with standard continuous CT (OxFp) in the first-line treatment of advanced colorectal cancer (ACRC). Methods: Eligible patients have measurable, inoperable ACRC; no prior CT for metastases; PS 0–2; GFR &gt;50; ALP &lt;5 xULN; bili &lt;1.25 xULN. Patients and/or clinicians choose the OxFp regimen, either FOLFOX (Braun,M BJC 89:1155f, 2003) or capecitabine (Cap) with Ox. Thereafter, randomization is 1:1:1 between: (A) OxFp; (B) OxFp plus weekly C; or (C) Intermittent OxFp. In Arms A and B treatment is given until progression, cumulative toxicity or patient choice, in Arm C it is stopped at 12 wks in stable/responding patients and reintroduced following progression off treatment. Primary endpoint is Overall Survival (OS). The trial aims to recruit 2,421 patients over 3.5 years. Release of this preliminary toxicity data has been approved by the independent Data Monitoring Committee (DMC). Results: 804 patients were randomised between 03/05 and 07/06 and 12 week toxicity is available on approx. 85% of patients. 62% of patients received Ox + cap and 38% received FOLFOX. Grade 3 /4 toxicities (%) in the first 12 weeks by regimen are reported below. Conclusions: The addition of cetuximab to OxFp combinations results in increased grade 3/4 toxicities overall and specifically in GI, skin rash and lethargy. Cap combination is associated with more GI toxicity but less neutropenia. Unexpectedly, no hypersensitivity reactions have yet been seen on FOLFOX (with or without C). [Table: see text] [Table: see text]
Gene expression of PPARγ and PGC-1α in human omental and subcutaneous adipose tissues is related to insulin resistance markers and mediates beneficial effects of physical training (2009)

Gene expression of PPARgamma and PGC-1alpha in human adipose tissue is related to markers of insulin resistance and cardiovascular risk. Increased muscle and adipose tissue PPARgamma and PGC-1alpha expression in response to physical training may mediate the beneficial effects of exercise on insulin sensitivity.
Radioimmunoassay for Cyclic Nucleotides (1972)

Abstract Sensitive and specific radioimmunoassays have been developed for cyclic adenosine 3',5'-monophosphate (cAMP), cyclic guanosine 3',5'-monophosphate (cGMP), cyclic inosine 3',5'-monophosphate (cIMP), and cyclic uridine 3',5'-monophosphate (cUMP). These assays are based upon competition of the cyclic nucleotide with isotopically labeled cyclic nucleotide derivatives for binding sites on specific antibody. Antibodies to the cyclic nucleotides were obtained by immunizing rabbits with an antigen prepared by conjugating the 2'-O-succinyl derivative of the cyclic nucleotide with protein (human serum albumin or keyhole limpet hemocyanin). High specific activity derivatives of the cyclic nucleotides (g150 Ci per mmole) were prepared by iodinating (125I) the tyrosine methyl ester derivative of the succinylated cyclic nucleotide. Free and bound 125I-labeled cyclic nucleotides were separated by either the second antibody precipitation technique or (NH4)2SO4 fractionation. Binding equilibrium was reached in 24 hours, but sensitive and reproducible assays were obtained after 4 to 6 hours of incubation. The sensitivity and assay range for the various radioimmunoassays are (picomoles per tube): cAMP, 0.01 to 2; cGMP, 0.01 to 1.0; cIMP, 0.12 to 10.0; and cUMP, 0.1 to 10.0. Structurally related purine and pyrimidine nucleotides and nucleosides exhibited ≤0.005% competitive binding in all immunoassays except cIMP which showed 0.35% competitive binding in the cGMP assay, cGMP 1% in the cIMP assay, and cIMP 1% in the cUMP assay.
TLR SIGNALING PATHWAY IN PATIENTS WITH SEPSIS (2008)

The pathogenesis of sepsis involves complex interaction between the host and the infecting microorganism. Bacterial recognition and signaling are essential functions of the cells of innate immune systems and drive a coordinated immune response. One of the more intriguing aspects of sepsis is the fact that the protective and damaging host response are part of the same process, that is, the inflammatory response that is aimed to control the infectious process also underscores many of the pathophysiological events of sepsis. The discovery of Toll-like receptors (TLRs) in humans, and the early recognition of TLR-4 as the receptor that signals LPS bioactivity were major breakthroughs not only in the field of sepsis but also in immunology as a whole. In this article, we aimed to review TLR expression and signaling in the context of sepsis. The results obtained by our group show that TLR and other cellular surface receptors may be differently regulated on mononuclear cells and neutrophils, and that they are dynamically modulated across the stages of sepsis. Toll-like receptor signaling gene expression in mononuclear cells is decreased in more severe forms of the disease. In contrast, up-regulated genes are seen along the clinical spectrum of sepsis in neutrophils.
Regulation of Gene Expression by Internal Ribosome Entry Sites or Cryptic Promoters: the eIF4G Story (2002)

As an alternative to the scanning mechanism of initiation, the direct-internal-initiation mechanism postulates that the translational machinery assembles at the AUG start codon without traversing the entire 5' untranslated region (5'-UTR) of the mRNA. Although the existence of internal ribosome entry sites (IRESs) in viral mRNAs is considered to be well established, the existence of IRESs in cellular mRNAs has recently been challenged, in part because when testing is carried out using a conventional dicistronic vector, Northern blot analyses might not be sensitive enough to detect low levels of monocistronic transcripts derived via a cryptic promoter or splice site. To address this concern, we created a new promoterless dicistronic vector to test the putative IRES derived from the 5'-UTR of an mRNA that encodes the translation initiation factor eIF4G. Our analysis of this 5'-UTR sequence unexpectedly revealed a strong promoter. The activity of the internal promoter relies on the integrity of a polypyrimidine tract (PPT) sequence that had been identified as an essential component of the IRES. The PPT sequence overlaps with a binding site for transcription factor C/EBPbeta. Two other transcription factors, Sp1 and Ets, were also found to bind to and mediate expression from the promoter in the 5'-UTR of eIF4G mRNA. The biological significance of the internal promoter in the eIF4G mRNA might lie in the production of an N-terminally truncated form of the protein. Consistent with the idea that the cryptic promoter we identified underlies the previously reported IRES activity, we found no evidence of IRES function when a dicistronic mRNA containing the eIF4G sequence was translated in vitro or in vivo. Using the promoterless dicistronic vector, we also found promoter activities in the long 5'-UTRs of human Sno and mouse Bad mRNAs although monocistronic transcripts were not detectable on Northern blot analyses. The promoterless dicistronic vector might therefore prove useful in future studies to examine more rigorously the claim that there is IRES activity in cellular mRNAs.
DIFFERENTIATION AND MATURATION OF PORCINE FETAL ISLET CELLS IN VITRO AND AFTER TRANSPLANTATION1 (1999)

Optimal maturation of porcine fetal pancreatic cells is obtained in serum-free medium supplemented with nicotinamide. Butyrate is a potent stimulus for beta cell differentiation but leads to increased apoptotic cell death.
Nonsurgical closure of patent ductus arteriosus: clinical application of the Rashkind PDA Occluder System. (1987)

The first successful application of a transcatheter closure technique for patent ductus arteriosus (PDA) suitable for use in infants and children was performed by us in 1977. Since that time, there has been continued improvement and simplification of the equipment as well as in the implantation technique. Following a Food and Drug Administration protocol, a multicenter study was conducted to test the safety and effectiveness of this interventional method. The clinical results from three major regional test centers (Philadelphia, Houston, and New Haven) are presented. One hundred forty-six patients from a test population of 156 were treated for PDA with use of the Rashkind PDA Occluder Systems. Successful closure was accomplished in 94 (66%) of the total cases. Ten patients (7%) retained residual ductal murmurs despite correct placement of the occlusion devices; five additional patients (3%) were considered failures due to the presence of abnormal Doppler flow patterns after the procedure. Postrelease embo...
Structural characterization of the oligosaccharides formed by depolymerization of heparin with nitrous acid. (1985)

Heparin was cleaved with nitrous acid at pH 1.5 and the products were reduced with Na+ boro[3H]hydride to generate a mixture of di- and tetrasaccharides having anhydro-D-[3H]mannitol (AManR) residues on their reducing terminals. The products were purified to homogeneity by gel filtration and high-performance liquid chromatography. For each oligosaccharide, the proportions of D-glucuronic acid (GlcUA), L-iduronic acid (IdoUA), N-acetyl-D-glucosamine (GlcNAc), and AManR and the monosaccharide sequence were determined by quantification of the products of acid hydrolysis. The tetrasaccharide sequences were determined by comparison of the disaccharide units formed by hydrazinolysis and deamination with previously characterized disaccharides. The following new oligosaccharides were identified: GlcUA(2-SO4)-AManR, GlcUA(2-SO4)-AManR(6-SO4), GlcUA-AManR(3,6-diSO4), GlcUA-GlcNAc-GlcUA-AManR, IdoUA-GlcNAc-GlcUA-AManR, GlcUA-GlcNAc(6-SO4)-GlcUA-AManR, IdoUA(2-SO4)-GlcNAc-GlcUA-AManR, IdoUA-GlcNAc(6-SO4)-GlcUA-AManR, IdoUA(2-SO4)-GlcNAc-GlcUA-AManR(6-SO4), IdoUA-GlcNAc(6-SO4)-GlcUA-AManR(6-SO4), IdoUA-GlcNAc(6-SO4)-GlcUA-AManR(3-SO4), IdoUA-GlcNAc(6-SO4)-GlcUA-AManR(3,6-diSO4), and IdoUA(2-SO4)-GlcNAc(6-SO4)-GlcUA-AManR(6-SO4). Then the disaccharides and the tetrasaccharides were readily resolved by high-performance anion-exchange liquid chromatography and were quantified on the basis of the amount of 3H counts/min in each. The structures are discussed in terms of their implications regarding heparin biosynthesis and anticoagulant activity.
Nicotine Biosynthetic Enzyme Activities in Nicotiana tabacum L. Genotypes with Different Alkaloid Levels (1979)

Young plants of five Nicotiana tabacum L. genotypes were examined for activity of nicotine biosynthetic enzymes. Genotypes near isogenic except at two loci each with two alleles controlling nicotine level were used in a comparison of the four homozygous allelic combinations producing high, high intermediate, low intermediate, and low nicotine levels in a "Burley 21" background. Putrescine N-methyltransferase (EC 2.1.1.53) and quinolinic acid phosphoribosyltransferase (EC 2.4.2.19) activities in root tissue of these four genotypes were proportional to leaf nicotine level, whereas N-methylputrescine oxidase activity in root tissue differed in proportion and ranking. Quinolinic acid phosphoribosyltransferase activities in leaf tissue were lower than in roots, but no differences were found among the four genotypes. The homozygous recessive alleles at either locus affect levels of all three enzyme activities examined in roots. Each locus seems to be involved in regulation of nicotine metabolism, but whether directly as a regulatory locus or indirectly through the metabolic product of a structural locus is not known.No difference was observed between enzymic oxidation of putrescine and N-methylputrescine by leaf and root extracts of Burley 21 (a high nicotine, low nornicotine genotype) and a high nornicotine cultivar, "Robinson Medium Broadleaf." Putrescine was utilized as a substrate to a greater extent than N-methylputrescine by leaf extracts compared with root extracts of both cultivars. It was concluded that genetic differences in levels of nicotine and nornicotine were not due to differences in enzymic oxidation of these two precursors during alkaloid biosynthesis.
Treatment of Port-Wine Stains with the Flashlamp-pumped Pulsed Dye Laser: Extended Clinical Experience in Children and Adults (1994)

Seventy-six patients (51 females, 25 males) with port-wine stains (PWS) were treated with the flashlamp-pumped pulsed dye laser (585 nm, 450 microseconds). The patients ranged in age from 1 month to 71 years (average, 14 yr). Forty-nine percent of all patients under study had a 90% or better (average, 94.6%) lightening response after an average of 9.0 (range, 4-15) laser treatment. Overall, there was a 79% clinical improvement seen after an average of 9.1 (range, 2-19) laser treatments. In contrast to previous studies, the number of treatments necessary to obtain PWS clearing in older children (9-15 yr) and adults (> 16 yr) was not significantly greater than the number required to treat PWS in infants (0-2 yr) and younger children (3-8 yr). In fact, PWS in children aged 3 to 8 years required the greatest number of laser treatments, which may be due to continued abnormal growth of the ectatic blood vessels comprising the lesion during the growth of the child. In addition, there did not appear to be a significant difference in the number of laser treatments necessary to obtain clearing of PWS in different body locations. While the 585 nm pulsed dye laser continues to be the treatment of choice for removal of PWS in children and adults, the number of treatments necessary to obtain lesional clearing in all age groups in greater than previously reported.
Human Immunodeficiency Virus Type 1 Vaccine Development: Recent Advances in the Cytotoxic T-Lymphocyte Platform “Spotty Business” (2007)

For human immunodeficiency virus type 1 (HIV-1) vaccine development, a central focus is developing a vaccine that primarily drives strong and broad CD8 ϩ cytotoxic T lymphocytes (CTLs).This focus is largely due to the difficulty in generating cross-neutralizing antibodies against the diverse array of HIV viral envelopes (9,40,78, 139).The ability of CD8 ϩ T cells to impact or control viral replication is supported by model primate studies and is reiterated by studies of immune control in infected individuals.For example, Cao et al. ( 28) reported that HIV-1-infected long-term nonprogressors exhibited high levels of HIV-specific CTLs.In addition, HIV-1-infected patients with high levels of virus-specific CTLs exhibited lower viral loads, slower CD4 ϩ T-cell declines as measured in peripheral blood, and relatively stable clinical statuses (23,81, 108, 112).Preclinical studies conducted with simian immunodeficiency virus (SIV)-infected monkeys showed that upon their in vivo depletion of CD8 ϩ T cells, a rapid and dramatic increase in viremia was observed (70, 131).While no correlates of immunity for protection against HIV-1 have been concretely established, these data as well as those of others (6, 13, 137) strongly suggest that CD8 ϩ T cells are important in controlling viral infection and may be an important component of an effective HIV-1 vaccine.In this review, we summarize recent advances in HIV vaccine development utilizing various platforms that target the induction of cellular immunity.In particular, we draw inferences, as appropriate, for the induction of cellular immune responses at mucosal as well as systemic sites.