gebhart/patrepeval huggingface dataset:
Overexpression of αvβ6 integrin in serous epithelial ovarian cancer regulates extracellular matrix degradation via the plasminogen activation cascade (2002)

Recent evidence suggests that integrins are involved in the multi-step process of tumour metastasis. The biological relevance of alpha(v) integrins and associated beta-subunits in ovarian cancer metastasis was examined by analysing the expression of these cell surface receptors in nine ovarian cancer cell lines and also in the primary human ovarian surface epithelial cell line (HOSE). beta1, beta3 and beta5 subunits were present in all ten ovarian cell lines. beta6 subunit was present at varying levels in eight out of nine cancer cell lines but was absent in the HOSE cell line. Immunohistochemical staining showed that beta6 was present in both non-invasive (borderline) and high-grade ovarian cancer tissues but was absent in benign and normal ovarian tissue. High alpha(v)beta6 integrin expressing ovarian cancer cell lines had high cell surface expression of uPA and uPAR. Ovarian cancer cell lines expressing high to moderate level of alpha(v)beta6 integrin demonstrated ligand-independent enhanced levels of high molecular weight (HMW)-uPA and pro-matrix metalloproteinase 2 and 9 (pro-MMP-2 and pro-MMP-9) expression in the tumour-conditioned medium. High and moderate expression of alpha(v)beta6 integrin correlated with increased plasminogen-dependent degradation of extracellular matrix which could be inhibited by inhibitors of plasmin, uPA and MMPs or by monoclonal antibody against uPA, MMP-9 or alpha(v)beta6 integrin. These results suggest that endogenous de novo expression of alpha(v)beta6 integrin in ovarian cancer cells may contribute to their invasive potential, and that alpha(v)beta6 expression may play a role in ovarian cancer progression and metastasis.
Immunization of Macaca fascicularis against experimental periodontitis using a vaccine containing cysteine proteases purified from Porphyromonas gingivalis (2007)

Immunization using a purified protein antigen from P. gingivalis inhibits alveolar bone destruction in a ligature-induced periodontitis model in M. fascicularis.
Comparative Genomics of NAD Biosynthesis in Cyanobacteria (2006)

Biosynthesis of NAD(P) cofactors is of special importance for cyanobacteria due to their role in photosynthesis and respiration. Despite significant progress in understanding NAD(P) biosynthetic machinery in some model organisms, relatively little is known about its implementation in cyanobacteria. We addressed this problem by a combination of comparative genome analysis with verification experiments in the model system of Synechocystis sp. strain PCC 6803. A detailed reconstruction of the NAD(P) metabolic subsystem using the SEED genomic platform (http://theseed.uchicago.edu/FIG/index.cgi) helped us accurately annotate respective genes in the entire set of 13 cyanobacterial species with completely sequenced genomes available at the time. Comparative analysis of operational variants implemented in this divergent group allowed us to elucidate both conserved (de novo and universal pathways) and variable (recycling and salvage pathways) aspects of this subsystem. Focused genetic and biochemical experiments confirmed several conjectures about the key aspects of this subsystem. (i) The product of the slr1691 gene, a homolog of Escherichia coli gene nadE containing an additional nitrilase-like N-terminal domain, is a NAD synthetase capable of utilizing glutamine as an amide donor in vitro. (ii) The product of the sll1916 gene, a homolog of E. coli gene nadD, is a nicotinic acid mononucleotide-preferring adenylyltransferase. This gene is essential for survival and cannot be compensated for by an alternative nicotinamide mononucleotide (NMN)-preferring adenylyltransferase (slr0787 gene). (iii) The product of the slr0788 gene is a nicotinamide-preferring phosphoribosyltransferase involved in the first step of the two-step non-deamidating utilization of nicotinamide (NMN shunt). (iv) The physiological role of this pathway encoded by a conserved gene cluster, slr0787-slr0788, is likely in the recycling of endogenously generated nicotinamide, as supported by the inability of this organism to utilize exogenously provided niacin. Positional clustering and the co-occurrence profile of the respective genes across a diverse collection of cellular organisms provide evidence of horizontal transfer events in the evolutionary history of this pathway.
A Pilot Clinical Trial of Oral Pentosan Polysulfate And Oral Hydroxyzine in Patients With Interstitial Cystitis (2003)

The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC. This trial demonstrated the feasibility of conducting a multicenter randomized clinical trial in IC using uniform procedures and outcomes. However, slow recruitment underscored the difficulties of evaluating commonly available IC drugs.
Global Vision Impairment Due to Uncorrected Presbyopia (2008)

Uncorrected presbyopia causes widespread, avoidable vision impairment throughout the world. Alleviation of this problem requires a substantial increase in the number of personnel trained to deliver appropriate eye care together with the establishment of sustainable, affordable spectacle delivery systems in developing countries. In addition, given that people with presbyopia are at higher risk for permanently sight-threatening conditions such as glaucoma and diabetic eye disease, primary eye care should include refraction services as well as detection and appropriate referral for these and other such conditions.
The Ubiquitin E3 Ligase MARCH7 is Differentially Regulated by the Deubiquitylating Enzymes USP7 and USP9X (2008)

Protein modification by one or more ubiquitin chains serves a critical signalling function across a wide range of cellular processes. Specificity within this system is conferred by ubiquitin E3 ligases, which target the substrates. Their activity is balanced by deubiquitylating enzymes (DUBs), which remove ubiquitin from both substrates and ligases. The RING-CH ligases were initially identified as viral immunoevasins involved in the downregulation of immunoreceptors. Their cellular orthologues, the Membrane-Associated RING-CH (MARCH) family represent a subgroup of the classical RING genes. Unlike their viral counterparts, the cellular RING-CH proteins appear highly regulated, and one of these in particular, MARCH7, was of interest because of a potential role in neuronal development and lymphocyte proliferation. Difficulties in detection and expression of this orphan ligase lead us to search for cellular cofactors involved in MARCH7 stability. In this study, we show that MARCH7 readily undergoes autoubiquitylation and associates with two deubiquitylating enzymes - ubiquitin-specific protease (USP)9X in the cytosol and USP7 in the nucleus. Exogenous expression and short interfering RNA depletion experiments demonstrate that MARCH7 can be stabilized by both USP9X and USP7, which deubiquitylate MARCH7 in the cytosol and nucleus, respectively. We therefore demonstrate compartment-specific regulation of this E3 ligase through recruitment of site-specific DUBs.
Mechanism of action of oxazolidinones: effects of linezolid and eperezolid on translation reactions (1997)

The oxazolidinones are a new class of synthetic antibiotics with good activity against gram-positive pathogenic bacteria. Experiments with a susceptible Escherichia coli strain, UC6782, demonstrated that in vivo protein synthesis was inhibited by both eperezolid (formerly U-100592) and linezolid (formerly U-100766). Both linezolid and eperezolid were potent inhibitors of cell-free transcription-translation in E. coli, exhibiting 50% inhibitory concentrations (IC50s) of 1.8 and 2.5 microM, respectively. The ability to demonstrate inhibition of in vitro translation directed by phage MS2 RNA was greatly dependent upon the amount of RNA added to the assay. For eperezolid, 128 microg of RNA per ml produced an IC50 of 50 microM whereas a concentration of 32 microg/ml yielded an IC50 of 20 microM. Investigating lower RNA template concentrations in linezolid inhibition experiments revealed that 32 and 8 microg of MS2 phage RNA per ml produced IC50s of 24 and 15 microM, respectively. This phenomenon was shared by the translation initiation inhibitor kasugamycin but not by streptomycin. Neither oxazolidinone inhibited the formation of N-formylmethionyl-tRNA, elongation, or termination reactions of bacterial translation. The oxazolidinones appear to inhibit bacterial translation at the initiation phase of protein synthesis.
Clustering and Enhanced Activity of an Inwardly Rectifying Potassium Channel, Kir4.1, by an Anchoring Protein, PSD-95/SAP90 (1997)

An inwardly rectifying potassium channel predominantly expressed in glial cells, Kir4.1/KAB-2, has a sequence of Ser-Asn-Val in its carboxyl-terminal end, suggesting a possible interaction with an anchoring protein of the PSD-95 family. We examined the effects of PSD-95 on the distribution and function of Kir4.1 in a mammalian cell line. When Kir4.1 was expressed alone, the channel immunoreactivity was distributed homogeneously. In contrast, when co-expressed with PSD-95, prominent clustering of Kir4.1 in the cell membrane occurred. Kir4.1 was co-immunoprecipitated with PSD-95 in the co-expressed cells. Glutathione S-transferase-fusion protein of COOH terminus of Kir4.1 bound to PSD-95. These interactions disappeared when the Ser-Asn-Val motif was deleted. The magnitude of whole-cell Kir4.1 current was increased by 2-fold in cells co-expressing Kir4.1 and PSD-95 compared with cells expressing Kir4. 1 alone. SAP97, another member of the PSD-95 family, showed similar effects on Kir4.1. Furthermore, we found that Kir4.1 as well as SAP97 distributed not diffusely but clustered in retinal glial cells. Therefore, PSD-95 family proteins may be a physiological regulator of the distribution and function of Kir4.1 in glial cells.
Segmentation and intensity estimation for microarray images with saturated pixels (2011)

The presented method adjusts for signal saturation at the segmentation stage that identifies a pixel as part of the foreground, background or other. The cluster membership of a pixel can be altered versus treating saturated values as truly observed. Thus, the resulting spot intensity estimates may be more accurate than those obtained from existing methods that correct for saturation based on already segmented data. As a model-based segmentation method, our procedure is able to identify inner holes, fuzzy edges and blank spots that are common in microarray images. The approach is independent of microarray platform and applicable to both single- and dual-channel microarrays.
Patterns of amino acid efflux from isolated normal and cystinotic human leucocyte lysosomes. (1982)

This study describes the first direct measurements of amino acid efflux from human lysosomes.Isolated leucocyte lysosomes can be loaded with radioactive amino acids by exposure to low concentrations of the corresponding labeled amino acid methyl esters.EffIux of amino acid from the loaded lysosomes can then be determined.Conditions during loading are adjusted for each ester to permit its adequate intralysosomal hydrolysis and subsequent accumulation of the free amino acid.Relative rates of efflux were leucine E phenylalanine 2 methionine > tryptophan > > cystine.Efflux of leucine, tryptophan, or cystine was independent of exogenous cation, ATP, or amino acid concentrations under the conditions tested.Leucine efflux was similar in normal and cystinotic lysosomes, providing strong evidence that isolated cystinotic lysosomes do not manifest a generalized defect in amino acid efflux.In both normal and cystinotic lysosomes, cystine efflux was much slower than efflux of leucine or other amino acids from human or rat liver lysosomes.Significant differences in mean cystine efflux between isolated normal and cystinotic lysosomes were not apparent in the present test system, although the possibility of differences in rates could not be excluded.For both fundamental and practical reasons, it would be highly desirable to have a direct method for measuring amino acid efflux from human lysosomes.For example, in the disease known as cystinosis (cystine storage disease) (1,2) a defective efflux mechanism could play a major role in the process leading to intralysosomal cystine accumulation.The molecular defect responsible for cystine storage is not known.Efforts to identify a faulty enzymatic activity which could account for decreased cystine degradation, reduction, or derivatization in cystinotic cells have so far been unsuccessful.Abnormal cystine accumulation could also he due to defective efflux of cystine itself from lysosomes into the cell cytoplasm (1, 2).This possibility has previously been impossible to assess directly.Until recently, the techniques used to study lysosomal permeability have been indirect and were based on the degree of preservation of lysosomal enzyme latency by high concentrations (-0.25 M) of test compounds ( 3 ) .In 1973 Goldman and Kaplan (4) observed loss of lysosomal latency following exposure of isolated rat liver lysosomes to certain L-amino acid methyl esters (0.5-2 mM).The hypothesis emerged from these experiments that the methyl esters, unlike the come-
Enhanced Optical Imaging of Rat Gliomas and Tumor Margins (1994)

Current intraoperative methods used to maximize the extent of tumor removal are limited to intraoperative biopsies, ultrasound, and stereotactic volumetric resections. A new technique involving the optical imaging of an intravenously injected dye has the potential to localize tumors and their margins with a high degree of accuracy. In a rat glioma model, enhanced optical imaging was performed and indocyanine green was used as the contrast-enhancing agent. In all 22 animals, the peak optical change in the tumor was greater than in the ipsilateral brain around the tumor and the contralateral normal hemisphere. The clearance of the dye was significantly delayed to a greater extent in the tumor than in the brain around the tumor and the normal brain. After attempts were made at complete microscopic resection, enhanced optical imaging of the tumor margins and the histological samples demonstrated a specificity of 93% and a sensitivity of 89.5%. Enhanced optical imaging was capable of outlining the tumor even when the imaging was done through the cranium. The optical imaging of rat gliomas with a contrast-enhancing dye is able to differentiate between normal brain and tumor tissue both at the cortical surface and at the tumor margins. The application of these studies in an intraoperative clinical setting may allow for the more accurate determination of tumor margins and may increase the extent of tumor removal.
Evidence for use of rare codons in the dnaG gene and other regulatory genes of Escherichia coli. (1983)

Amino acid sequence and composition data of Escherichia coli dnaG primase protein and its tryptic peptides have confirmed that the dnaG gene contains an unusually high number of codons that are not frequently used in most E. coli genes. In 25 E. coli proteins analyzed the codons AUA, UCG, CCU, CCC, ACG, CAA, AAT, and AGG are infrequently used, occurring as 4% of the total codons in the reading frame and 11% and 10% in the nonreading frames. In dnaG they occur as 11% in the reading frame and 12% in the nonreading frames. The rpsU and rpoD genes, which flank the dnaG gene [Smiley, B. L., Lupski, J. R., Svec, P. S., McMacken, R. & Godson, G. N. (1982) Proc. Natl. Acad. Sci. USA 79, 4550-4554], however, have normal codon usage. Translational modulation using isoaccepting tRNA availability may therefore be part of the mechanism of keeping the dnaG gene expression low, while expression of the adjacent rpsU and rpoD genes on the same mRNA transcript is high.
Knowledge acquisition for temporal abstraction. (1996)

Temporal abstraction is the task of detecting relevant patterns in data over time. The knowledge-based temporal-abstraction method uses knowledge about a clinical domain's contexts, external events, and parameters to create meaningful interval-based abstractions from raw time-stamped clinical data. In this paper, we describe the acquisition and maintenance of domain-specific temporal-abstraction knowledge. Using the PROTEGE-II framework, we have designed a graphical tool for acquiring temporal knowledge directly from expert physicians, maintaining the knowledge in a sharable form, and converting the knowledge into a suitable format for use by an appropriate problem-solving method. In initial tests, the tool offered significant gains in our ability to rapidly acquire temporal knowledge and to use that knowledge to perform automated temporal reasoning.
Staling in Starch Breads: The Effect of Antistaling α‐Amylase (1997)

Abstract A novel starch bread that contained no gluten was found to firm at a rate comparable to a normal standard bread made from wheat flour. Treatment of both the starch and the standard bread with Novamyl, an antistaling enzyme mix, inhibited firming. 13 C CP/MAS NMR studies showed that the decreased firming of the Novamyl‐treated starch bread was correlated with decreased starch retrogradation. For the Novamyl‐treated bread the increase in retrograded starch over six days following baking was about 11% compared to an increase of over 200% for the untreated bread. These results suggests that starch retrogradation is sufficient to cause bread firming.
Function and therapeutic potential of host defence peptides (2005)

Cationic host defence (antimicrobial) peptides are an important component of the innate immune systems of a wide variety of plants, animals, and bacteria. Although most of these compounds have direct antimicrobial activities under specific conditions, a greater appreciation for the diversity of functions of these molecules is beginning to develop in the field. In addition to their directly antimicrobial activities, they also have a broad spectrum of activity on the host immune system, with both pro-inflammatory and anti-inflammatory effects being invoked. Increasingly sophisticated approaches to understand the role of host defence peptides in modulating innate immunity are already serving to guide the development of novel therapeutics.
Screening for and surveillance of gastric cancer (2014)

Although the prevalence of gastric cancer (GC) progressively decreased during the last decades, due to improved dietary habit, introduction of food refrigeration and recovered socio-economic level, it still accounts for 10% of the total cancer-related deaths. The best strategy to reduce the mortality for GC is to schedule appropriate screening and surveillance programs, that rises many relevant concerns taking into account its worldwide variability, natural history, diagnostic tools, therapeutic strategies, and cost-effectiveness. Intestinal-type, the most frequent GC histotype, develops through a multistep process triggered by Helicobacter pylori (H. pylori) and progressing from gastritis to atrophy, intestinal metaplasia (IM), and dysplasia. However, the majority of patients infected with H. pylori and carrying premalignant lesions do not develop GC. Therefore, it remains unclear who should be screened, when the screening should be started and how the screening should be performed. It seems reasonable that screening programs should target the general population in eastern countries, at high prevalence of GC and the high-risk subjects in western countries, at low prevalence of GC. As far as concern surveillance, currently, we are lacking of standardized international recommendations and many features have to be defined regarding the optimal diagnostic approach, the patients at higher risk, the best timing and the cost-effectiveness. Anyway, patients with corpus atrophic gastritis, extensive incomplete IM and dysplasia should enter a surveillance program. At present, screening and surveillance programs need further studies to draw worldwide reliable recommendations and evaluate the impact on mortality for GC.
Western blot analysis of serological response in Helicobacter pylori in acid peptic diseases. (1997)

A prospective study was undertaken in 70 patients presenting with acid peptic disease with the objective of characterising the serological response to Helicobacter pylori and finding antigens specific for the serodiagnosis of H. pylori infection. H. pylori status was assessed by smear microscopy, rapid urease activity, culture and histopathology of endoscopic gastric antral biopsy specimens. Serological characterisation was carried out by using western blotting of various antigenic components of H. pylori and subsequent enzymatic detection of antibodies against them. Four reactive bands in the molecular weight range of 45-65 kDa were present in all subjects irrespective of H. pylori status. Four to six immunoreactive bands in the molecular weight range of 21-45 kDa were found only in patients with positive H. pylori status and histopathologically proven gastritis. These immunoreactive components may be valuable in specific immunodiagnosis of H. pylori infection.
Repression of c- fos Transcription and an Altered Genetic Program in Senescent Human Fibroblasts (1990)

Normal cells in culture invariably undergo senescence, whereby they cease proliferation after a finite number of doublings. Irreversible changes in gene expression occurred in senescent human fetal lung fibroblasts: a non-cell cycle-regulated mRNA was partially repressed; an unusual polyadenylated histone mRNA was expressed; although serum induced c-H-ras, c-myc, and ornithine decarboxylase mRNA normally, ornithine decarboxylase activity was deficient; and serum did not induce mRNA for a replication-dependent histone and for the c-fos proto-oncogene. The loss of c-fos inducibility was the result of a specific, transcriptional block. The results suggest that senescent fibroblasts were unable to proliferate because of, at least in part, selective repression of c-fos; moreover, the multiple changes in gene expression support the view that cellular senescence is a process of terminal differentiation.
Photochemical and Photophysical Studies within Zeolites (1992)

In this article, we illustrate how one can utilize a zeolite matrix to control the photophysical and photochemical behavior of guest molecules included in them. In the first part, the emphasis is placed on the cation and on a single zeolite, faujasite (X and Y). Photophysical properties of naphthalene and other aromatic guest molecules included in X-type faujasite zeolites (M+X, M = Li, Na, K, Rb, Cs, Tl) have been investigated. As expected for an external heavy-atom-perturbed excited state, both singlet- and triplet-excited-state lifetimes and emission efficiencies depend upon the identity and accessibility of the cation present within the zeolite supercage. The power of the heavy-atom-cation effect in zeolites has been demonstrated by recording phosphorescence from several olefins whose phosphorescence has not previously been recorded. The second section brings out an inherent feature of a field at its infancy-serendipity. Surprisingly, radical ions of organic molecules can be generated and stabilized within zeolites by a simple procedure. This study has been expanded to include oligomers of thiophenes and α,ω-diphenylpolyenes which serve as models for conducting polymers. This is followed by a presentation wherein the importance of the relative size of the host cavity to that of the guest to achieve maximum selectivity in a photoreaction is highlighted. Concepts developed in this section with faujasite and pentasil (ZSM-5 and ZSM-11) as models are believed to be general and applicable to other organized media.