gebhart/patrepeval huggingface dataset:
Nerve growth factor and sensory nerve function (1999)

Nerve growth factor (NGF) was the first described neurotrophic factor and it remains the best studied. This molecule regulates the growth, survival and phenotypic properties of restricted subsets of neurones and these properties have received much experimental examination. There is also currently considerable interest in the potential therapeutic uses of this molecule in two broad areas. The first derives from the hope that NGF in particular and neurotrophic factors in general will prove useful in the treatment of neurodegenerative disorders (see [1] for review). The hope is that since these molecules exert profound survival-promoting effects in the developing animal, they may also be of benefit in arresting or reversing degenerative or atrophic changes associated with disease states. Data from the study of animal models of degenerative diseases are encouraging. Very recently, a phase III clinical trial has started using NGF for the treatment of human diabetic neuropathy or HIV. The results of preceding trials have been published.
INCREASED APOPTOSIS OF IMMUNOREACTIVE HOST CELLS AND AUGMENTED DONOR LEUKOCYTE CHIMERISM, NOT SUSTAINED INHIBITION OF B7 MOLECULE EXPRESSION ARE ASSOCIATED WITH PROLONGED CARDIAC ALLOGRAFT SURVIVAL IN MICE PRECONDITIONED WITH IMMATURE DONOR DENDRITIC CELLS PLUS ANTI-CD40L mAb1,2 (1999)

The donor-specific acceptance of rejection-prone heart allografts by recipients pretreated with immature donor DC and anti-CD40L mAb is not dependent on sustained inhibition of donor DC CM (CD86) expression. Instead, the pretreatment facilitates a tolerogenic cascade similar to that in spontaneously tolerant liver recipients that involves: (1) chimerism-driven immune activation, succeeded by deletion of host immune responder cells by apoptosis in the spleen and allograft that is linked to interleukin-2 deficiency in both locations and (2) persistence of comparatively large numbers of donor-derived leukocytes. These tolerogenic mechanisms are thought to be generic, explaining the tolerance induced by allografts spontaneously, or with the aid of various kinds of immunosuppression.
Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting (2015)

Estimates of the global prevalence and incidence of chlamydia, gonorrhoea, trichomoniasis, and syphilis in adult women and men remain high, with nearly one million new infections with curable STI each day. The estimates highlight the urgent need for the public health community to ensure that well-recognized effective interventions for STI prevention, screening, diagnosis, and treatment are made more widely available. Improved estimation methods are needed to allow use of more varied data and generation of estimates at the national level.
Impaired Expression of Peripheral Blood Apoptotic‐Related Gene Transcripts in Acute Multiple Sclerosis Relapse (2007)

Abstract : Differential expression of apoptotic genes may influence the susceptibility of activated lymphocytes to expand and induce acute relapse and persistent inflammation in patients with relapsing–remitting multiple sclerosis (RRMS). The exact relationship between alterations in apoptotic‐related gene expression and clinical disease activity has not been broadly evaluated. In this study we studied peripheral blood mononuclear cells (PBMCs) expression of pro‐ and antiapoptotic genes in RRMS patients during acute relapse in comparison to patients in remission. Using cDNA Affymetrix microarrays platform (U133A2 microarrays) we analyzed the gene expression profile of PBMC derived from 22 RRMS patients in acute relapse (15 females, mean age 34.6 ± 1.8 years, disease duration 5.6 ± 0.8 years) in comparison to 20 sex‐ and age‐matched RRMS patients in remission. One thousand five hundred seventy‐eight gene transcripts significantly differentiated acute multiple sclerosis (MS) relapse from remission. This characteristic gene expression signature was enriched by an apoptotic‐related pathway. The 1578 gene transcripts that significantly differentiated acute relapse from remission were enriched by 55 apoptotic‐related genes in that reflected different operating pathways during the acute phase of the disease. These genes mainly involved the caspase‐dependent pathway and included overexpression of the negative regulator of FAS‐induced apoptosis (TOSO) and the BCL2 antiapoptotic family members (BCL2, BCL2 AA) as well as downexpression of proapoptotic genes like BAX, apoptotic protease‐activating factor 1 (APAF1) and caspases 1, 2, 8, 9. and 10. An additional group of antiapoptotic genes related to T cell receptor‐mediated apoptosis was also found to be overexpressed in acute relapse and included TCR‐binding CD3E antigen, antiapoptotic serine threonin kinase (AKT), and NFκB‐associated genes like reticuloendotheliosis viral oncogene homolog A (RELA) and human T cell leukemia virus type I‐binding protein (Tax1BP) known to inhibit tumor necrosis factor (TNF)‐induced apoptosis. Our findings demonstrate impaired apoptotic mechanisms in peripheral lymphocytes from RRMS patients during acute relapse. This suggests that the inflammatory process in active disease is targeted by inhibition of proapoptotic and repression of antiapoptotic genes that allow prolonged abnormal immune responses.
The Role of 3′ Poly(A) Tail Metabolism in Tumor Necrosis Factor-α Regulation (1997)

In unstimulated RAW 264.7 macrophage-like cells, tumor necrosis factor-alpha (TNF-alpha) mRNA was transcribed and accumulated in the cytoplasm, but the TNF-alpha transcripts failed to associate with polysomes, and TNF-alpha protein was not detected. Stimulation with lipopolysaccharide (LPS) induced an increase in TNF-alpha transcription, cytoplasmic TNF-alpha mRNA accumulation, polysome association, and secretion of TNF-alpha protein. This process was associated with a 200-nucleotide increase in the apparent length of the TNF-alpha mRNA. The difference in TNF-alpha mRNA size was caused by marked truncation of the 3' poly(A) tail in unstimulated cells. Fully adenylated TNF-alpha mRNA appeared within 15 min of LPS stimulation. We speculate that removal of the poly(A) tail blocks initiation of TNF-alpha translation in unstimulated macrophages. LPS inactivates this process, allowing synthesis of translatable polyadenylated TNF-alpha mRNA.
Construction of a map of chromosome 16 by using radiation hybrids. (1992)

A human-hamster cell hybrid carrying a single copy of chromosome 16 as the only human genetic material was irradiated with a single dose of gamma-rays (7000 rads; 1 rad = 0.01 Gy) and then fused with a thymidine kinase-deficient hamster cell line (RJKM) to generate radiation hybrids retaining unselected fragments of this human chromosome. In two experiments, 223 hybrids were isolated in hypoxanthine/aminopterine/thymidine (HAT) medium and screened with 38 DNA probes, corresponding to anonymous DNA or gene sequences localized on chromosome 16. The most likely order and location of the 38 DNA sequences were established by multiple pairwise analysis and scaled to estimate physical distance in megabases. The order and the distances thus obtained are mostly consistent with available data on genetic and physical mapping of these markers, illustrating the usefulness of radiation hybrids for mapping.
Using Substrate Specificity of Antiplasmin-Cleaving Enzyme for Fibroblast Activation Protein Inhibitor Design (2009)

Circulating antiplasmin-cleaving enzyme (APCE), a prolyl-specific serine proteinase, is essentially identical to membrane-inserted fibroblast activation protein (FAP) that is transiently expressed during epithelial-derived cancer growth. Human precursive alpha(2)-antiplasmin (Met-alpha(2)AP), the only known physiologic substrate for APCE, is cleaved N-terminally to Asn-alpha(2)AP that is rapidly cross-linked to fibrin and protects it from digestion by plasmin. Identifying a specific inhibitor of APCE/FAP continues to be intensely pursued. Recombinant FAP cleavage of peptide libraries of short amino acid sequences surrounding the scissile bond, -Pro(12)-Asn(13)-, indicated that P2 Gly and P1 Pro are required, just as we found for APCE. We examined cleavage of P4-P4' peptides, using 19 amino acid substitutions at each position and selected ones in P8-P5. K(m) values determined for peptide substrates showed that P7 Arg has the highest affinity for APCE. Peptide cleavage rate increased with Arg in P6 rather than P5 or native P7. Placing Arg in P4 or P8 reduced cleavage rates dramatically. Cleavage of substrates with extended peptide sequences before or after the scissile bond showed endopeptidase to be superior to dipeptidase activity for APCE. A substrate analogue inhibitor, Phe-Arg-(8-amino-3,6-dioxaoctanoic acid)-Gly-[r]-fluoropyrrolidide, inhibited APCE with a K(i) of 54 microM but not dipeptidyl peptidase IV even at 2 mM. The inhibitor also blocked cleavage of Met-alpha(2)AP with an IC(50) of 91 microM. Replacing Arg with Gly at the same distance from fluoropyrrolidide as P7 Arg is from P1 Pro reduced its inhibition of APCE approximately 10-fold. Results indicate that Arg at P5, P6, or P7 distances from P1 enhances affinity and efficiency of substrates or inhibitors toward APCE or FAP.
Sequence-Specific Recognition and Cooperative Dimerization of N-Terminal Aromatic Peptides in Aqueous Solution by a Synthetic Host (2006)

This article describes the selective recognition and noncovalent dimerization of N-terminal aromatic peptides in aqueous solution by the synthetic host compound, cucurbit[8]uril (Q8). Q8 is known to bind two aromatic guests simultaneously and, in the presence of methyl viologen, to recognize N-terminal tryptophan over internal and C-terminal sequence isomers. Here, the binding of Q8 to aromatic peptides in the absence of methyl viologen was studied by isothermal titration calorimetry (ITC), (1)H NMR spectroscopy, and X-ray crystallography. The peptides studied were of sequence X-Gly-Gly, Gly-X-Gly, and Gly-Gly-X (X = Trp, Phe, Tyr, and His). Q8 selectively binds and dimerizes Trp-Gly-Gly (1) and Phe-Gly-Gly (4) with high affinity (ternary K = 10(9)-10(11) M(-)(2)); binding constants for the other 10 peptides were too small to be measured by ITC. Both peptides bound in a stepwise manner, and peptide 4 bound with positive cooperativity. Crystal structures of Q8.1 and Q8.4(2) reveal the basis for selective recognition as simultaneous inclusion of the hydrophobic aromatic side chain into the cavity of Q8 and chelation of the proximal N-terminal ammonium group by carbonyl groups of Q8. The peptide sequence selectivity and positively cooperative dimerization reported here are, to the best of our knowledge, unprecedented for synthetic hosts in aqueous solution. Specific peptide recognition and dimerization by synthetic hosts such as Q8 should be important in the study of dimer-mediated biochemical processes and for the separation of peptides and proteins.
Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn's disease involving the ileum (2007)

Intestinal bacteria are implicated increasingly as a pivotal factor in the development of Crohn's disease, but the specific components of the complex polymicrobial enteric environment driving the inflammatory response are unresolved. This study addresses the role of the ileal mucosa-associated microflora in Crohn's disease. A combination of culture-independent analysis of bacterial diversity (16S rDNA library analysis, quantitative PCR and fluorescence in situ hybridization) and molecular characterization of cultured bacteria was used to examine the ileal mucosa-associated flora of patients with Crohn's disease involving the ileum (13), Crohn's disease restricted to the colon (CCD) (8) and healthy individuals (7). Analysis of 16S rDNA libraries constructed from ileal mucosa yielded nine clades that segregated according to their origin (P<0.0001). 16S rDNA libraries of ileitis mucosa were enriched in sequences for Escherichia coli (P<0.001), but relatively depleted in a subset of Clostridiales (P<0.05). PCR of mucosal DNA was negative for Mycobacterium avium subspecies paratuberculosis, Shigella and Listeria. The number of E. coli in situ correlated with the severity of ileal disease (rho 0.621, P<0.001) and invasive E. coli was restricted to inflamed mucosa. E. coli strains isolated from the ileum were predominantly novel in phylogeny, displayed pathogen-like behavior in vitro and harbored chromosomal and episomal elements similar to those described in extraintestinal pathogenic E. coli and pathogenic Enterobacteriaceae. These data establish that dysbiosis of the ileal mucosa-associated flora correlates with an ileal Crohn's disease (ICD) phenotype, and raise the possibility that a selective increase in a novel group of invasive E. coli is involved in the etiopathogenesis to Crohn's disease involving the ileum.
Argon: performance insulation for shared storage servers (2007)

Services that share a storage system should realize the same efficiency, within their share of time, as when they have the system to themselves. The Argon storage server explicitly manages its resources to bound the inefficiency arising from inter-service disk and cache interference in traditional systems. The goal is to provide each ser-vice with at least a configured fraction (e.g., 0.9) of the throughput it achieves when it has the storage server to itself, within its share of the server—a service allocated 1nth of a server should get nearly 1nth (or more) of the throughput it would get alone. Argon uses automatically-configured prefetch/write-back sizes to insulate stream-ing efficiency from disk seeks introduced by competing workloads. It uses explicit disk time quanta to do the same for non-streaming workloads with internal local-ity. It partitions the cache among services, based on their observed access patterns, to insulate the hit rate each achieves from the access patterns of others. Experiments show that, combined, these mechanisms and Argon’s au-tomatic configuration of each achieve the insulation goal. 1
Genomic structure of the murine IL-6 gene. High degree conservation of potential regulatory sequences between mouse and human. (1988)

The genomic clone of mouse IL-6 was isolated and compared with the human IL-6 gene. The comparison revealed that the mouse IL-6 consists of five exons and four introns and that the overall organization is similar to that of the human IL-6 gene although the third intron is about 2 kb longer. The sequence similarity in the coding region is about 60%, whereas the 3'-untranslated region and the first 300-bp sequence of the 5'-flanking region are highly conserved (greater than 80%). Several sequence blocks with high homology are also found in the introns. Furthermore, sequences similar to transcriptional enhancer elements such as the c-fos serum responsive element and the consensus sequences for cAMP induction, activator protein 1 binding, and the glucocorticoid receptor binding are identified within the highly conserved 5'-flanking regions of the genes from the two species. These sequences may play an important role in transcriptional activation of the IL-6 gene.
Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial. (1997)

Caelyx is an active agent in advanced breast cancer with a safety profile that differs markedly from nonliposomal doxorubicin. A regimen of 45 mg/m2 every 4 weeks was well tolerated in this cohort of women with advanced poor-prognosis breast cancer. The mild myelosuppression seen with this regimen would favor its use in combination chemotherapy.
Salt melt synthesis of ceramics, semiconductors and carbon nanostructures (2013)

Materials synthesis in the liquid phase, or wet-chemical synthesis, utilizes a solution medium in which the target materials are generated from a series of chemical and physical transformations. Although this route is central in organic chemistry, for materials synthesis the low operational temperature range of the solvent (usually below 200 °C, in extreme 350 °C) is a serious restriction. Here, salt melt synthesis (SMS) which employs a molten inorganic salt as the medium emerges as an important complementary route to conventional liquid phase synthesis. Depending on the nature of the salt, the operational temperature ranges from near 100 °C to over 1000 °C, thus allowing the access to a broad range of inorganic crystalline materials and carbons. The recent progress in SMS of inorganic materials, including oxide ceramic powders, semiconductors and carbon nanostructures, is reviewed here. We will introduce in general the range of accessible materials by SMS from oxides to non-oxides, and discuss in detail based on selected examples the mechanisms of structural evolution and the influence of synthetic conditions for certain materials. In the later sections we also present the recent developments in SMS for the synthesis of organic solids: covalent frameworks and polymeric semiconductors. Throughout this review, special emphasis is placed on materials with nanostructures generated by SMS, and the possible modulation of materials structures at the nanoscale in the salt melt. The review is finalized with the summary of the current achievements and problems, and suggestions for potential future directions in SMS.
Zinc-blende–wurtzite polytypism in semiconductors (1992)

The zinc-blende (ZB) and wurtzite (W) structures are the most common crystal forms of binary octet semiconductors. In this work we have developed a simple scaling that systematizes the T=0 energy difference \ensuremath{\Delta}${\mathit{E}}_{\mathrm{W}\mathrm{\ensuremath{-}}\mathrm{ZB}}$ between W and ZB for all simple binary semiconductors. We have first calculated the energy difference \ensuremath{\Delta}${\mathit{E}}_{\mathrm{W}\mathrm{\ensuremath{-}}\mathrm{ZB}}^{\mathrm{LDF}}$(AB) for AlN, GaN, InN, AlP, AlAs, GaP, GaAs, ZnS, ZnSe, ZnTe, CdS, C, and Si using a numerically precise implementation of the first-principles local-density formalism (LDF), including structural relaxations. We then find a linear scaling between \ensuremath{\Delta}${\mathit{E}}_{\mathrm{W}\mathrm{\ensuremath{-}}\mathrm{ZB}}^{\mathrm{LDF}}$(AB) and an atomistic orbital-radii coordinate R\ifmmode \tilde{}\else \~{}\fi{}(A,B) that depends only on the properties of the free atoms A and B making up the binary compound AB. Unlike classical structural coordinates (electronegativity, atomic sizes, electron count), R\ifmmode \tilde{}\else \~{}\fi{} is an orbital-dependent quantity; it is calculated from atomic pseudopotentials. The good linear fit found between \ensuremath{\Delta}${\mathit{E}}_{\mathrm{W}\mathrm{\ensuremath{-}}\mathrm{ZB}}$ and R\ifmmode \tilde{}\else \~{}\fi{} (rms error of \ensuremath{\sim}3 meV/atom) permits predictions of the W-ZB energy difference for many more AB compounds than the 13 used in establishing this fit. We use this model to identify chemical trends in \ensuremath{\Delta}${\mathit{E}}_{\mathrm{W}\mathrm{\ensuremath{-}}\mathrm{ZB}}$ in the IV-IV, III-V, II-VI, and I-VII octet compounds as either the anion or the cation are varied. We further find that the ground state of MgTe is the NiAs structure and that CdSe and HgSe are stable in the ZB form. These compounds were previously thought to be stable in the W structures.
Isolation of higher plant developmental mutants. (1991)

A variety of biological restraints limit the number of plant species suitable for genetic and molecular analysis of development. A number of approaches to isolate developmental and physiological mutants are described as well as complications that arise in mutant selection procedures. Examples of mutant types especially in Arabidopsis are presented for a number of processes.
VIMENTIN EXPRESSION IN CERVICAL CARCINOMAS: ASSOCIATION WITH INVASIVE AND MIGRATORY POTENTIAL (1996)

Vimentin is an intermediate filament protein normally expressed in mesenchymal cells, but evidence is accumulating in the literature which suggests that the aberrant expression of vimentin in epithelial cancer cells might be related to local invasiveness and metastatic potential. Vimentin expression has previously been associated with invasive properties in an in vitro model consisting of a set of HPV-33-transformed cervical keratinocyte cell lines. In the present study, in order to emphasize those in vitro findings, the expression of vimentin has been investigated in cervical neoplasms of different grades, using immunohistochemistry. A clear association is reported between vimentin expression and metastatic progression, since vimentin was detected in all invasive carcinomas and lymph node metastases, but not in CIN III lesions. These in vivo results are compared with present and previous data obtained in vitro on cervical keratinocyte cell lines, where vimentin expression also correlated with in vitro invasiveness.
Characterisation and PCR‐based detection of a CYP2A6 gene deletion found at a high frequency in a Chinese population (1999)

Cytochrome P450 2A6 is an important human hepatic P450 which activates pre-carcinogens, oxidises some drugs and constitutes the major nicotine C-oxidase. In fact, results have been presented in the literature which suggested a relationship between the distribution of defective CYP2A6 alleles and smoking behaviour as well as cigarette consumption. In the present report, we describe the structure of a novel CYP2A locus where the whole CYP2A6 gene has been deleted, resulting in an abolished cytochrome P450 2A6-dependent metabolism. The origin of this locus is apparently due to an unequal crossover event between the 3'-flanking region of the CYP2A6 and CYP2A7 genes. A rapid PCR-based method for the detection of the CYP2A6del allele was developed and the allele frequency was 15.1% among 96 Chinese subjects, but only 1.0% in Finns (n=100) and 0.5% in Spaniards (n=100). In the Chinese population, we did not detect any CYP2A6*2 alleles using an improved genotyping procedure, in contrast to the 11-20% previously reported. It is concluded that genotyping for the CYP2A6del allele is of great importance in studies correlating, for example, smoking behaviour, pre-carcinogen activation or drug metabolism to the CYP2A6 genotype, in particular when oriental populations are investigated.
Inhibition of glycine currents by dextromethorphan in neurones dissociated from the guinea‐pig nucleus tractus solitarii (1997)

1. The effect of dextromethorphan (DM) on the current induced by glycine in acutely dissociated nucleus tractus solitarii (NTS) neurones of guinea-pigs was studied by use of the whole-cell patch clamp technique. The effect of DM on gamma-aminobutyric acid (GABA)-induced currents (IGABA) was also examined. 2. DM inhibited 30 microM glycine-induced current (IGly), without affecting the current caused by 30 microM GABA. The action of DM was concentration-dependent, with a maximum effect at 100 microM, and reversible. The half-maximum inhibitory concentration (IC50) of DM was 3.3 microM, about 85 times higher than that of strychnine. 3. DM 3 microM shifted the concentration-response curve for glycine to the right without affecting the maximum value. DM 10 microM shifted the curve even more to the right, although it was not a parallel shift. Strychnine at a concentration of 0.1 microM shifted the curve for glycine in a nearly parallel fashion. 4. The effect of 10 microM DM was slightly weak voltage-dependency, but the lower concentration of DM, 3 microM, inhibited IGly equally at -50 mV and +50 mV. The effect of 3 microM DM on IGly showed no use-dependence. Blockade by strychnine 0.1 microM showed no voltage- or use-dependence. 5. The results indicate that DM inhibits IGly in single neurones of NTS, and further suggest that DM at a low concentration may act on the glycine receptor-ionophore complex, but not on the Cl channel of the complex. However, a relatively high concentration of DM may at least partly affect the Cl- channel of the complex.