gebhart/patrepeval huggingface dataset:
Infection of Hamsters with Epidemiologically Important Strains ofClostridium difficile (2001)

Five different toxigenic strains of Clostridium difficile of known human epidemiologic importance were tested for virulence in hamsters. Three strains—types B1, J9, and K14—have caused hospital outbreaks. Type Y2 is associated with a high rate of asymptomatic colonization in patients. The fifth strain, type CF2, is a toxin A–negative, toxin B–positive strain implicated in multiple human cases of C. difficile–associated diarrhea. Groups of 10 hamsters per strain were given 1 dose of clindamycin, followed 5 days later with gastric inoculation of 100 cfu of C. difficile. Hamsters given types B1, J9, K14, or Y2 showed 90%–100% colonization (albeit at a slower rate with type Y2) and 100% mortality of colonized animals. Hamsters challenged with type CF2 showed 60% (P=.01) colonization and 30% mortality (P=.0003). The hamster model demonstrated pathogenicity differences between a toxin variant strain and standard toxigenic strains but no significant differences among the standard strains
Ribonucleoprotein SS-B/La belongs to a protein family with consensus sequences for RNA-binding (1989)

Autoantibodies from systemic rheumatic disorders have become useful reagents in molecular biology. SS-B/La, a major target of autoantibodies in lupus and Sjogren's syndrome, has been identified as a 46 kDa protein component of a ribonucleoprotein (RNP) particle implicated in the maturation of RNA polymerase III transcripts. This report describes the complete sequences of human and bovine SS-B/La and the identification of RNA-binding protein consensus sequences RNP1 and RNP2 in the N-terminal region previously shown to be complexed with RNA in UV-crosslinking experiments. Segments of about 95 residues from the RNA-binding domain of SS-B/La and from 29 RNA-binding domains of several other proteins are analysed with respect to the frequency of amino acids and their hydrophobicity at each position. The data suggest that SS-B/La belongs to a large family of RNA-binding proteins which includes heterogeneous nuclear RNPs, nucleolin, mRNA polyadenylate binding protein, and small nuclear RNPs.
Multiple Forms of Mouse Vascular Endothelial Growth Factor-D Are Generated by RNA Splicing and Proteolysis (2001)

The secreted glycoprotein vascular endothelial growth factor-D (VEGF-D) is angiogenic, lymphangiogenic, and promotes metastatic spread of tumor cells via lymphatic vessels. VEGF-D consists of a receptor-binding domain (VEGF homology domain) and N- and C-terminal propeptides. Proteolytic processing produces numerous forms of human VEGF-D, including fully processed derivatives (containing only the VEGF homology domain), partially processed, and unprocessed derivatives. Proteolysis is essential to generate human VEGF-D that binds the angiogenic receptor VEGF receptor-2 (VEGFR-2) and the lymphangiogenic receptor VEGFR-3 with high affinity. Here, we report that alternative use of an RNA splice donor site in exon 6 of the mouse VEGF-D gene produces two different protein isoforms, VEGF-D(358) and VEGF-D(326), with distinct C termini. The two isoforms were both expressed in all adult mouse tissues and embryonic stages of development analyzed. Both isoforms are proteolytically processed in a similar fashion to human VEGF-D to generate a range of secreted derivatives and bind and cross-link VEGFR-3 with similar potency. The isoforms are differently glycosylated when expressed in vitro. This study demonstrates that RNA splicing, protein glycosylation, and proteolysis are mechanisms for generating structural diversity of mouse VEGF-D.
Cloning of cDNA coding for human tissue-type plasminogen activator and its expression in Escherichia coli. (1986)

cDNA clones of the mRNA coding for tissue-type plasminogen activator (t-PA) have been obtained and their nucleotide sequences compared to those reported previously. A gene coding for t-PA has been reconstructed and inserted into vectors for expression in prokaryotic cells. Relatively high levels of t-PA accumulated in inclusion bodies in Escherichia coli containing an optimized expression plasmid, but only a small proportion of the insoluble protein was recovered as active enzyme using a variety of solubilization procedures.
Hyaluronic acid capsule is a virulence factor for mucoid group A streptococci. (1991)

Mucoid strains of group A Streptococcus have been associated with recent outbreaks of acute rheumatic fever. The mucoid colony morphology of these strains is a result of abundant production of capsular polysaccharide, which is composed of hyaluronic acid. To study the role of the hyaluronic acid capsule in virulence, we derived an acapsular mutant from a mucoid strain of group A Streptococcus by transposon mutagenesis. M protein expression was not altered in the mutant strain. The mucoid wild-type strain grew in fresh human blood and was resistant to phagocytic killing in vitro. In contrast, the acapsular mutant failed to grow in fresh human blood and was sensitive to phagocytic killing in vitro. Loss of capsule was associated with a 100-fold reduction in virulence of the organisms in mice. We conclude that the hyaluronic acid capsule protects mucoid group A streptococci from phagocytosis and has an important role in virulence.
Genome-Scale CRISPR-Cas9 Knockout Screening in Human Cells (2013)

The simplicity of programming the CRISPR (clustered regularly interspaced short palindromic repeats)-associated nuclease Cas9 to modify specific genomic loci suggests a new way to interrogate gene function on a genome-wide scale. We show that lentiviral delivery of a genome-scale CRISPR-Cas9 knockout (GeCKO) library targeting 18,080 genes with 64,751 unique guide sequences enables both negative and positive selection screening in human cells. First, we used the GeCKO library to identify genes essential for cell viability in cancer and pluripotent stem cells. Next, in a melanoma model, we screened for genes whose loss is involved in resistance to vemurafenib, a therapeutic RAF inhibitor. Our highest-ranking candidates include previously validated genes NF1 and MED12, as well as novel hits NF2, CUL3, TADA2B, and TADA1. We observe a high level of consistency between independent guide RNAs targeting the same gene and a high rate of hit confirmation, demonstrating the promise of genome-scale screening with Cas9.
Effects of n-3 Polyunsaturated Fatty Acids on Glucose Homeostasis and Blood Pressure in Essential Hypertension (1995)

Fish oil, in doses that reduce blood pressure and lipid levels in hypertensive persons, does not adversely affect glucose metabolism.
Corrosion Inhibitors for Aluminum Films (1988)

Patterned aluminum films are used as conductors for integrated circuits. Unless encapsulated in plastic for protection, these films are easily corroded by moisture, which can result in device failure. In humid environments, this may not fully protect the aluminum, and a means to provide, at low cost, additional protection is needed. In this paper, the properties of aluminum thin films, which have been treated with organic corrosion inhibitors, are reported. To quantify accelerated corrosion testing, a simple optical reflectance technique was developed. In addition, the surface properties of aluminum obtained after treatment were determined by infrared and x‐ray photoelectron spectroscopy. These measurements show that nitrilotris(methylene)triphosphonic acid (NTMP) reacts with the aluminum surface to form a coating which is an effective inhibitor of the reaction of evaporated aluminum thin films on glass or silicon with distilled or deionized water.
Expression of the Elm1 Gene, a Novel Gene of the CCN (Connective Tissue Growth Factor, Cyr61/Cef10, and Neuroblastoma Overexpressed Gene) Family, Suppresses In Vivo Tumor Growth and Metastasis of K-1735 Murine Melanoma Cells (1998)

We previously isolated a partial cDNA fragment of a novel gene, Elm1 (expressed in low-metastatic cells), that is expressed in low-metastatic but not in high-metastatic K-1735 mouse melanoma cells. Here we determined the full-length cDNA structure of Elm1 and investigated the effect of Elm1 expression on growth and metastatic potential of K-1735 cells. The Elm1 gene encodes a predicted protein of 367 amino acids showing approximately 40% amino acid identity with the CCN (connective tissue growth factor [CTGF], Cyr61/Cef10, neuroblastoma overexpressed gene [Nov]) family proteins, which consist of secreted cysteine-rich proteins with growth regulatory functions. Elm1 is also a cysteine-rich protein and contains a signal peptide and four domains conserved in the CCN family proteins. Elm1 was highly conserved, expressed ubiquitously in diverse organs, and mapped to mouse chromosome 15. High-metastatic K-1735 M-2 cells, which did not express Elm1, were transfected with an Elm1 expression vector, and several stable clones with Elm1 expression were established. The in vivo growth rates of cells expressing a high level of Elm1 were remarkably slower than those of cells expressing a low level of Elm1. Metastatic potential of transfectants was reduced in proportion to the level of Elm1 expression. Thus, Elm1 is a novel gene of CCN family that can suppress the in vivo growth and metastatic potential of K-1735 mouse melanoma cells.
Assessment of Suitable Porcine Semen for Freezing, According to the Ejaculate Characteristics in the Iberico × Landrace Breed (2002)

A total of 35 ejaculates were studied in order to assess the suitability of porcine semen for freezing according to the ejaculate characteristics. The effects of the freezing procedure were identified; a decrease in motility and acrosome quality was found after thawing. The best results on motility were linked to the ejaculates with a volume of less than 100 ml of the sperm-rich fraction, a concentration lower than 450 x 10(6) spermatozoa/ml and an agglutination score below 2. However, the best normal apical ridge (NAR) was found when the volume of the sperm-rich fraction was greater than 150 ml. For this reason, an intermediate volume of the sperm-rich fraction of the ejaculate for the best motility and the best NAR, a concentration lower than 450 x 106 spermatozoa/ml and a rate of agglutination below 2 should provide the best quality after freezing. This study also attempted to determine whether a positive effect of ejaculate selection on the overall freezing performance might be expected.
High levels of stromal hyaluronan predict poor disease outcome in epithelial ovarian cancer. (2000)

Several malignant tumors accumulate hyaluronan, a matrix component suggested to promote cancer cell migration and growth. To explore the potential clinical importance of this concept, we assessed the hyaluronan levels in epithelial ovarian cancer. A biotinylated affinity probe specific for hyaluronan was prepared and applied to histological sections of 309 epithelial ovarian cancers and 45 matched metastatic lesions. The staining was scored according to the percentage area of strong hyaluronan signal of total peri- and intratumoral stroma as low (<35%), moderate (35-75%), or high (>75%). Low, moderate, and high levels of stromal hyaluronan were observed in 95, 116, and 98 carcinomas, respectively. The high stromal hyaluronan level was significantly associated with poor differentiation, serous histological type, advanced stage, and large primary residual tumor, whereas it was not correlated with high CD44 expression on cancer cells. The 5-year outlook of the disease deteriorated with increasing stromal hyaluronan levels for both overall (45% versus 39% versus 26%; P = 0.002) and recurrence-free (66% versus 56% versus 40%; P = 0.008) survival. High levels of stromal hyaluronan were more frequent in metastatic lesions than in primary tumors (z = -3.9; P = 0.0001). In Cox's multivariate analyses, high level of stromal hyaluronan was an independent prognostic factor in all patients, as well as in stage-specific subgroups. These results suggest that stromal hyaluronan accumulation may be a powerful enhancer of tumor progression and, as such, provides a novel, independent prognostic marker and a potential target of therapy.
Human Breast Cancer Specimens: Diffraction-enhanced Imaging with Histologic Correlation—Improved Conspicuity of Lesion Detail Compared with Digital Radiography (2000)

Seven breast cancer specimens were examined with diffraction-enhanced imaging at 18 keV with a silicon crystal with use of the silicon 333 reflection in Bragg mode. Images were compared with digital radiographs of the specimen, and regions of increased detail were identified. Six of the seven cases (86%) showed enhanced visibility of surface spiculation that correlated with histopathologic information, including extension of tumor into surrounding tissue.
A Sun-Pumped cw One-Watt Laser (1966)

1 W of w laser output has been obtained at room temperature from a sun-pumped, neodymium-doped YAG crystal. The water-cooled laser rod was pumped with a modified Cassegrain sun-tracking telescope consisting of a 61-cm diam paraboloidal primary mirror collector, a water-cooled hyperbolic-cylindric secondary mirror and a hemicircular cylindric tertiary mirror. The cylindrical image volume was coincident with 24 mm of the 3-mm by 30-mm YAG rod. The spike-free output was obtained for hours at a time with a late October sun at a 42 degrees North latitude. Using the same primary mirror and near-unity numerical aperture refractors, approximately 1.25 W were obtained in 7 msec pulses from an uncooled, sun-pumped, neodymium-doped, glass rod. Further refinements in the telescope and the laser crystal, and a space environment, should allow 1 W of laser output to be generated by using a 30-cm diam collector.
Structural Basis for Parathyroid Hormone-related Protein Binding to the Parathyroid Hormone Receptor and Design of Conformation-selective Peptides (2009)

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are two related peptides that control calcium/phosphate homeostasis and bone development, respectively, through activation of the PTH/PTHrP receptor (PTH1R), a class B G protein-coupled receptor. Both peptides hold clinical interest for their capacities to stimulate bone formation. PTH and PTHrP display different selectivity for two distinct PTH1R conformations, but how their binding to the receptor differs is unclear. The high resolution crystal structure of PTHrP bound to the extracellular domain (ECD) of PTH1R reveals that PTHrP binds as an amphipathic alpha-helix to the same hydrophobic groove in the ECD as occupied by PTH, but in contrast to a straight, continuous PTH helix, the PTHrP helix is gently curved and C-terminally "unwound." The receptor accommodates the altered binding modes by shifting the side chain conformations of two residues within the binding groove: Leu-41 and Ile-115, the former acting as a rotamer toggle switch to accommodate PTH/PTHrP sequence divergence, and the latter adapting to the PTHrP curvature. Binding studies performed with PTH/PTHrP hybrid ligands having reciprocal exchanges of residues involved in different contacts confirmed functional consequences for the altered interactions and enabled the design of altered PTH and PTHrP peptides that adopt the ECD-binding mode of the opposite peptide. Hybrid peptides that bound the ECD poorly were selective for the G protein-coupled PTH1R conformation. These results establish a molecular model for better understanding of how two biologically distinct ligands can act through a single receptor and provide a template for designing better PTH/PTHrP therapeutics.
Enantioselective Total Syntheses of Various Amphilectane and Serrulatane Diterpenoids via Cope Rearrangements (2016)

Ampilectane and serrulatane natural products are structurally and stereochemically complex compounds that display various potent pharmacological activities ranging from anti-inflammatory to antituberculosis. A general synthetic route toward this family of natural products has been developed, which accomplished a number of amphilectane and serrulatane natural products. The key step employed a stereoselective Cope rearrangement either promoted by gold catalysis or thermal conditions, while a regioselective gold-catalyzed 6-endo-dig cyclization was optimized to afford a precursor. The preparation of the chiral β-ketoester as a starting material was established via an optimized asymmetric 1,4-addition followed by trapping with Mander's reagent, and this initially installed stereogenic center provided good control in the subsequent introduction of all the other stereocenters. A rarely investigated one-pot conversion of α-pyrone into phenol was also examined to enable the syntheses. DFT calculations explain the high stereoselectivity of the Cope rearrangement of the intermediate that eventually led to amphilectolide and caribenol A.
Thrombospondin-1 Inhibits TCR-Mediated T Lymphocyte Early Activation (2001)

Biological activities of the matrix glycoprotein thrombospondin-1 (TSP1) are cell type specific and depend on the relative expression or activation of several TSP1 receptors. Although engaging individual TSP1 receptors in T lymphocytes can elicit costimulating signals, in this study we show that intact TSP1 inhibits TCR-mediated T cell activation, assessed globally using cDNA microarrays. TSP1 signaling suppressed expression of several genes induced in Jurkat T cells, including the T cell activation markers CD69, early growth response gene-1 (Egr-1), and phosphatase of activated cells (PAC-1). TCR-stimulated and CD47-costimulated IL-2 secretion and cell surface CD69 expression were also inhibited by TSP1. The specific inhibitory effect of TSP1 was verified in freshly isolated human PBMCs. TSP1 inhibited TCR-mediated but not protein kinase C-mediated T cell activation. Using CD69 expression as a marker, we demonstrated that the inhibitory activity of TSP1 depended on two TSP1 receptors, CD47 and integrin-associated protein heparan sulfate proteoglycans. Signals from these receptors inhibited TCR signaling downstream of ZAP70, but upstream of NF-AT. Therefore, the expression of TSP1 induced during wound repair and in tumor stroma may limit T cell activation at these sites.
The national cancer data base report on non‐hodgkin's lymphoma (1997)

BACKGROUND The National Cancer Data Base (NCDB) has reported on many malignancies occurring in men and women in the U. S. from >1400 contributing hospitals. The current report on non-Hodgkin's lymphoma (NHL) is a companion to an upcoming Patient Care Evaluation study of this relatively common and serious cancer. METHODS This report is comprised of all NHL cases submitted to the NCDB divided into two diagnostic-year groups: 1985-1988 and 1990-1993. Variables routinely collected by hospital cancer registries have been analyzed to report on patterns of diagnosis and treatment. RESULTS High grade NHL cases were more likely to be Stage IV (40.8%) than were low or intermediate grade cases (34.8% and 32.5%, respectively). Patients with NHL arising from lymph node sites tended to present with more advanced disease (55.8% with Stages III and IV disease), whereas patients with NHL arising from extranodal sites and non-lymph node nodal sites presented at an earlier stage (64.7% and 74.0%, respectively, with Stage I or Stage II disease). Approximately 67% of all patients underwent chemotherapy, whereas only 25% underwent surgery or radiation. By histology, 5-year survival was 68.8% for low grade disease, 51.9% for intermediate grade disease, and 45.8% for high grade disease; by stage, survival rates ranged from 73.5% for Stage I to 42.9% for Stage IV disease. CONCLUSIONS To the authors' knowledge, the 91,306 cases in this study represent the largest contemporary sample of NHL patients. The material reported here may serve as a reference with which to compare local patterns with national data. The Working Formulation's ability to stratify patients' survival rates confirms its utility for NHL. Stage according to the American Joint Committee on Cancer also was accurate in predicting survival. Cancer 1997; 80:2311-20. © 1997 American Cancer Society.
Tyrosine phosphatase SHP-2 dephosphorylates the platelet-derived growth factor receptor but enhances its downstream signalling (1999)

SHP-2 is a widely distributed Src homology 2 (SH2) domain-containing tyrosine phosphatase that is recruited to growth factor receptors on stimulation. We have transiently co-expressed several catalytically active and inactive forms of the enzyme with the platelet-derived growth factor (PDGF) receptor in human embryonic kidney 293 cells. The catalytically active forms of SHP-2 decreased the tyrosine phosphorylation of the receptor, whereas the catalytically inactive forms increased the phosphorylation. However, PDGF-induced activation of the mitogen-activated protein (MAP) kinase pathway was enhanced by the active forms of SHP-2 but decreased by the inactive forms. The results suggest that the PDGF receptor is a physiological substrate of SHP-2 and that SHP-2 has a positive role in the PDGF-stimulated activation of MAP kinase. The dissociation of the receptor phosphorylation from the activation of MAP kinase suggests that signalling through growth factor receptors does not depend merely on their tyrosine phosphorylation.
Many chemokines including CCL20/MIP-3α display antimicrobial activity (2003)

Previous studies have demonstrated that beta-defensins exhibit chemotactic activity by sharing the chemokine receptor CCR6 with the CC chemokine ligand CCL20/macrophage-inflammatory protein-3alpha (MIP-3alpha). Structural analysis of CCL20/MIP-3alpha revealed that most of the positively charged residues are concentrated at one area of its topological surface, a characteristic considered to be important for the antimicrobial activity of defensins. Here, we report that similar to defensins, CCL20/MIP-3alpha has antimicrobial effects on Escherichia coli, Pseudomonas aeruginosa, Moraxella catarrhalis, Streptococcus pyogenes, Enterococcus faecium, Staphylococcus aureus, and Candida albicans. Additionally, by screening a total of 30 human chemokines, we have identified an additional 17 human chemokines, which exhibit antimicrobial activity in vitro. Collectively, about two-thirds of the chemokines investigated so far has the capacity to kill microorganisms in vitro, suggesting that antimicrobial activity may be another host-defense function for certain chemokines. Comparison of the structural characteristics between antimicrobial and nonantimicrobial chemokines suggests that topological formation of a large, positively charged electrostatic patch on the surface of the molecule is likely to be a common structural feature of antimicrobial chemokines.