gebhart/patrepeval huggingface dataset:
Platelet thrombospondin modulates endothelial cell adhesion, motility, and growth: a potential angiogenesis regulatory factor. (1990)

Components of the extracellular matrix have been shown to modulate the interaction of endothelial cells with their microenvironment. Here we report that thrombospondin (TSP), an extracellular matrix component, induces adhesion and spreading of murine lung capillary (LE-II) and bovine aortic (BAEC) endothelial cells. This TSP-induced spreading was inhibited by heparin and fucoidan, known to bind the amino-terminal globular domain of the molecule. In addition, endothelial cells were induced to migrate by a gradient of soluble TSP (chemotaxis). The chemotactic response was inhibited by heparin and fucoidan, as well as by the mAb A2.5, which also binds to the amino-terminal domain. These data are in agreement with our previous observation that the TSP aminoterminal heparin binding region is responsible for the induction of tumor cell spreading and chemotactic motility. The inhibition of chemotaxis and spreading by antibodies against the beta 3 but not the beta 1 chain of the integrin receptor points to a role for the integrins in the interaction of endothelial cells with TSP. We also found that TSP modulates endothelial cell growth. When added to quiescent LE-II cells, it inhibited the mitogenic effects of serum and the angiogenic factor bFGF, in a dose-dependent manner. The inhibition of DNA synthesis detected in the mitogenic assay resulted in a true inhibition of BAEC and LE-II cell growth, as assessed by proliferation assay. This work indicates that TSP affects endothelial cell adhesion, spreading, motility and growth. TSP, therefore, has the potential to modulate the angiogenic process.
Structure of the human gamma-fibrinogen gene. Alternate mRNA splicing near the 3' end of the gene produces gamma A and gamma B forms of gamma-fibrinogen. (1984)

The gamma chain of human fibrinogen exists in 2 nonallelic forms, gamma A and gamma B, which differ only in their carboxyl termini. We have found that only one genomic locus exists for gamma-fibrinogen and that the gamma A and gamma B chains arise by alternate mRNA splicing near the 3' end of this gene. In contrast to the rat gamma B mRNA which is produced by alternate splicing with identical polyadenylation sites, human gamma B is produced when the eighth intervening sequence remains unspliced and a polyadenylation signal within this intron is used. The new carboxyl terminus is 16 amino acids longer than the gamma A protein, and although there is only minimal homology between the rat and human carboxyl termini they share a very high proportion of acidic amino acids.
The Development and Survival but Not Function of Follicular B Cells Is Dependent on IL-7Rα Tyr449 Signaling (2014)

IL-7 is a critical cytokine for lymphocyte development. Recent work has highlighted critical roles for IL-7 signaling in mature T cell homeostasis and function, but its role in B cells is less well characterized. Using a knock-in mouse possessing a Tyr to Phe mutation at position 449 (IL-7Rα(449F/449F) mice) within the cytoplasmic SH2-binding motif of IL-7Rα, we evaluated the role of IL-7Rα Y449 motif in spleen B cells. IL-7Rα(449F/449F) mice had reduced numbers and increased death of follicular B cells compared to WT, but had significantly more follicular cells than IL-7Rα(-/-). The death of IL-7Rα(449F/449F) follicular cells was not due to a failure to respond to BAFF or lower levels of BAFF, a critical B cell survival factor. Marginal zone B cells were unaffected by the IL-7Rα(449F/449F) mutation. Any role for TSLP was ruled out, as TSLPR(-/-) mice had an identical B cell phenotype to wild-type mice. Bone marrow chimeras and the absence of IL-7Rα on B cells suggested that IL-7 did not directly regulate mature B cells, but that an IL-7-responsive cell was influencing B cells. IL-7 was also critical at the checkpoint between the T1 and T2 stages in the spleen. IL-7Rα(-/-) mice fail to develop T2 cells, but IL-7Rα(449F/449F) show a reduction compared to WT but not complete absence of T2 cells. We also tested the functional responses of IL-7Rα(449F/449F) to antigens and infection and found no difference in antibody responses to T-dependent or T-independent antigens, or to Influenza/A. IL-7 was important for generation of antibody responses to the intestinal worm H. polygyrus and for naive levels of IgA. Taken together, this suggests that IL-7 regulates follicular B cell numbers and survival in a cell-extrinsic manner, via a bone-marrow derived cell, but is not critical for antibody production outside the gut.
A Feature Level Fusion in Similarity Matching to Content-Based Image Retrieval (2006)

This paper presents a fusion-based similarity matching framework for content-based image retrieval on a combination of global, semi-global and local region specific features at different levels of abstraction. In this framework, an image is represented by global color and edge histogram descriptors, semi-global color and texture descriptors from grid based overlapping sub-images and local color features from a clustering-based segmented regions. As a result, image similarities are obtained through a weighted combination of overall similarity fusing global, semi-global and local region-based image level similarities. This fusing approach decreases the impact of inaccurate segmentation and increases retrieval effectiveness as constituent features are of a complementary nature. The experimental results on a general-purpose image database indicate that the aggregation or fusion-based technique provides an effective and flexible tool for similarity calculation based on a combination of descriptors from different levels of image representation
Resistance to d -Cycloserine in the Tubercle Bacilli: Mutation Rate and Transport of Alanine in Parental Cells and Drug-Resistant Mutants (1971)

A single transport system was found to accumulate l- and d-alanine, glycine and d-serine in Mycobacterium tuberculosis. The results of inhibition experiments suggested that the antibiotics d-cycloserine and O-carbamyl-d-serine were also transported by the alanine-glycine-d-serine system. A d-cycloserine-resistant permease-competent (d-CS(r)/perm(+)) mutant and a d-cycloserine-resistant permease-defective (d-CS(r)/perm(-)) mutant were isolated. The d-CS(r)/perm(-) mutant was not found to be more resistant to the drug than was the d-CS(r)/perm(+) mutant. The data were consistent with the conclusion that resistance to d-cycloserine in the tubercle bacilli is primarily due to mutations in the gene(s) controlling the enzyme d-alanyl-d-alanine synthetase. The mutation rate was calculated to be about 10(-10) mutations per bacterium per generation.
Subgroup analysis by measurable metastatic lesion (ML) number and selected lesion locations (LL) at baseline (BL) in NAPOLI-1: A phase III study of liposomal irinotecan (nal-IRI)±5-fluorouracil/leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. (2018)

460 Background: We report a post hoc, exploratory analysis of pts with BL ML number and LL data who received nal-IRI+5-FU/LV, nal-IRI or 5-FU/LV in NAPOLI-1, a pivotal, phase 3 trial (NCT01494506). nal-IRI+5-FU/LV increased median OS (mOS) vs 5-FU/LV (6.1 vs 4.2 mo [HR=0.67; p=0.012]). Methods: ML (1, 2, 3, &gt;3) and LL were recorded (local investigator) at BL. Pts with &gt;1 LL were counted for each location. Results: 354 of 417 ITT pts had measurable BL ML and 1,080 LL were recorded. There was no clear trend in the percentage of pts with KPS ≥80 in 1- &gt;3 ML (range 87%-95%) or LL (range 89%-94%) subgroups. ML 1 (n=81), 2 (n=65) and 3 (n=24) subgroups were small. nal-IRI+5-FU/LV significantly improved mOS vs. 5-FU/LV in pts with 2/&gt;3 ML (n=184/24); nal-IRI+5-FU/LV had numerically higher mOS vs. 5-FU/LV for all LL (Table). nal-IRI+5-FU/LV had favourable median PFS (mPFS) vs. 5-FU/LV in pts with 1–&gt;3 ML (range 2.0-4.2 vs. 1.4-1.9 mo; HR range 0.35-0.88) and for all LL (range 2.8-4.2 vs. 1.4-2.0 mo; HR range 0.39-0.55). Conclusions: Low pt numbers across groups and repeat counting of pts in LL subgroups preclude firm conclusions on treatment efficacy, pending further analyses. Allowing for these limitations, we detected no clear prognostic effect on outcomes of higher BL ML number or LL in NAPOLI-1 ITT pts. nal-IRI+5-FU/LV improved mOS vs. 5-FU/LV in some ML groups and across LL groups; improvement in mPFS vs. 5-FU/LV in the ITT population was maintained in all subgroups. Clinical trial information: NCT01494506. [Table: see text]
Immigration Detention: Information Gaps and Institutional Barriers to Reform (2013)

This Article examines and critiques the institutional design choices underlying the civil immigration detention system in the United States. The stated objective of this system is to effectuate removal orders and ensure public safety during the removal process by detaining noncitizens who pose a flight risk or danger to the public. The design choices utilized to achieve this objective, however, hinder the effective acquisition and use of information regarding flight risk and danger. Reliance on mandatory detention, evidentiary limitations, and shifting burdens of proof create a presumption of detention. As a result, decision makers lack the means or the incentive to collect and use information to release individuals who do not pose a flight risk or danger— including individuals who may not ultimately be removed from the United States—at significant cost to the administration of the immigration system as a whole.
Expression of tissue factor in tumor stroma correlates with progression to invasive human breast cancer: paracrine regulation by carcinoma cell-derived members of the transforming growth factor beta family. (1996)

Tissue factor (TF), the cellular initiator of the protease blood coagulation cascade, has been shown to be expressed in a variety of solid tumors, particularly those of epithelial origin. However, the mechanisms that mediate TF expression in tumors, as well as the clinical implications of this expression, remain largely unknown. In this study, we examined the cytological distribution of TF in normal human breast tissue and breast carcinomas. Epithelial cells exhibited TF immunoreactivity with little obvious correlation with malignant progression from in situ lesions to invasive cancer. However, there was a strong correlation between progression to invasive cancer and the expression of TF antigen in cellular components of the stroma. TF-positive cells were particularly abundant in close proximity to infiltrating tumor cells and included both macrophages and myofibroblasts, as determined by double-immunofluorescent staining for TF and cell type-specific marker proteins. Double-immunofluorescent staining for TF and transforming growth factor beta (TGF-beta) revealed TGF-beta immunoreactivity both in tumor cells and in the extracellular matrix surrounding TF-positive stromal cells. To test the role of carcinoma cell-derived growth factors in the regulation of stromal cell TF activity, we examined the ability of conditioned media (CM) from breast carcinoma cell lines to stimulate TF activity in myofibroblast-like cells in vitro. Extracts from myofibroblasts exposed to CM displayed strong TF procoagulant activity. However, extracts from cells exposed to unconditioned media or CM pretreated with anti-TGF-beta antibodies did not. The induction of TF activity was also observed upon treatment of indicator cells with recombinant TGF-beta isoforms. Collectively, these data indicate that the recruitment and/or activation of TF-expressing stromal cells is an early event in progression to invasive breast cancer and likely occurs, in part, as a paracrine response to tumor cell-derived members of the TGF-beta family of growth factors.
Derivatives of molecular surface area and volume: Simple and exact analytical formulas (2011)

The computational effort of biomolecular simulations can be significantly reduced by means of implicit solvent models in which the energy generally contains a correction depending on the surface area and/or the volume of the molecule. In this article, we present simple derivation of exact, easy-to-use analytical formulas for these quantities and their derivatives with respect to atomic coordinates. In addition, we provide an efficient, linear-scaling algorithm for the construction of the power diagram required for practical implementation of these formulas. Our approach is implemented in a C++ header-only template library.
Expression and localization of the vascular endothelial growth factor family in ovarian epithelial tumors. (1997)

Vascular endothelial growth factor (VEGF) is an angiogenic factor secreted by various tumors, including epithelial tumors of the ovary, and is involved in tumor progression and maintenance. The significance and function of other members of the VEGF family in the ovary has not yet been elucidated. In the present study, we have defined the expression of mRNA encoding VEGF-B, VEGF-C, and placenta growth factor (PIGF), compared with that of VEGF mRNA, in normal ovary and a range of ovarian epithelial tumors. Analysis by reverse transcription-PCR indicated that mRNA encoding VEGF (isoforms 121 and 165), VEGF-B (isoforms 167 and 186), and VEGF-C, but not PIGF, were present in all ovarian tissues examined. By in situ hybridization, neither VEGF-C nor PIGF transcripts were detected in any of the samples. The expression pattern of VEGF-B mRNA was generally similar to that of VEGF mRNA, in that transcripts were readily detected in the epithelial cells of all histologic types of ovarian carcinoma, but could not be detected in normal or benign tumor epithelium. Specific differences in the expression of the two genes were noted in areas of tumor necrosis, in which the expression of VEGF mRNA, but not VEGF-B mRNA, was further enhanced, and in a sample in which VEGF-B mRNA was strongly expressed in tumor-associated macrophages that did not hybridize with the riboprobe to VEGF mRNA. These results imply that a second member of the VEGF family, VEGF-B, may play a significant role in the angiogenesis, progression, and maintenance of ovarian carcinomas.
Synthesis of 7‐ethyl‐4,7‐dihydro‐4‐oxo‐2‐(4‐pyridinyl)thieno[2,3‐b]pyridine‐5‐carboxylic acid (1991)

Abstract 7‐Ethyl‐4,7‐dihydro‐4‐oxo‐2‐(4‐pyridinyl)thieno[2,3‐ b ]pyridine‐5‐carboxylic acid ( 4 ), an analog of nalidixic acid, was synthesized in seven steps starting from commercially available 4‐methylpyridine. Bacterial susceptibility to compound 4 was tested and the title compound was found to exhibit only weak antibacterial activity against a variety of pathogens including S. Aureus, E. Coli and P. Aeruginosa .
A Two-Dimensional Array Receiver for Reducing Refraction Artifacts in Ultrasonic Computed Tomography of Attenuation (1987)

Abstrucf-Conventional ultrasonic computed tomography (UCT) of attenuation yields images having significant refraction artifacts. A large-aperture two-dimensional receiving array has been fabricated and used to acquire UCT attenuation data. Reconstructed images demonstrate signi6cantly decreased corruption by refraction. The array images exhibit reducededge-enhancement artifacts, although artifacts are still significant in the worst cases. The artifact reduction should allow for reasonably meaningful estimates of attenuation coefficient since, for example, attenuation coefficient from very refraction-dependent single-element UCT has correlated with breast lesion pathology.
Effector Coupling Mechanisms of the Cloned 5-HT1A Receptor (1989)

The signal transduction pathways of the cloned human 5-HT1A receptor have been examined in two mammalian cell lines transiently (COS-7) or permanently (HeLa) expressing this receptor gene. In both systems, 5-hydroxytryptamine (5-HT, serotonin) mediated a marked inhibition of beta 2-adrenergic agonist-stimulated (80% inhibition in COS-7 cells) or forskolin-stimulated cAMP formation (up to 90% inhibition in HeLa cells). This serotonin effect (EC50 = 20 nM) could be competitively antagonized by metitepine and spiperone (Ki = 81 and 31 nM, respectively) and could also be blocked by pretreatment of cells with pertussis toxin. In both cell types, 5-HT failed to stimulate adenylyl cyclase through the expressed receptors. In HeLa cells, 5-HT also stimulated phospholipase C (approximately 40-75% stimulation of formation of inositol phosphates). Again, this effect was inhibited by metitepine. However, the EC50 of 5-HT was considerably higher (approximately 3.2 microM) than that found for inhibition of adenylyl cyclase. Both pathways were demonstrated to be similarly affected by pertussis toxin. These findings indicate that like the M2 and M3 muscarinic cholinergic receptors, the 5-HT1A receptor can couple to multiple transduction pathways with varying efficiencies via pertussis toxin-sensitive G-proteins. The lack of stimulation of cAMP formation by this 5-HT1A receptor may suggest the existence of another pharmacologically closely related receptor.
Contribution of the Chemical Structure of Wheat Starch to Japanese Noodle Quality (1997)

Wheat starch has been completely digested with bacterial α-amylase, and the pattern of oligosaccharides obtained from this digestion varies with starches from different wheat varieties. Wheat varieties of good Japanese noodle-making quality (based on sensory testing) give relatively small amounts of oligosaccharides with a degree of polymerisation (DP) of 5 or greater, while varieties of poor noodle-making quality give much greater amounts of these larger oligosaccharides. There is a significant negative correlation between the amount of DP5 oligosaccharide and noodle eating quality. The correlation between the amount of this oligosaccharide and starch paste viscosity was much smaller. The size of the HPLC peak corresponding to this oligosaccharide may be used as a rapid method of screening for noodle-making quality. Because oligosaccharides of greater than DP4 should have at least one branch point, the results suggest that the structure of the amylopectin in starch of good noodle-making wheats has relatively few branch points close together. Amylose also appeared to be important for noodle quality. The optimum amylose content seemed to be about 22% for good quality noodles, with starch of higher or lower amylose content coming from flour of lower noodle-making quality. Factors other than amylose content must contribute to noodle quality, as some flours of relatively poor noodle quality also contained close to the optimum amount of amylose. © 1997 SCI.
Alternative Splicing and Programmed Cell Death (1999)

Programmed cell death (PCD) is critical for development and homeostasis of multicellular organisms. Genetic and biochemical studies have revealed that PCD is under complex and delicate regulation. An important level of such regulation may be pre-mRNA splicing as suggested by the observation that a number of PCD regulatory genes are expressed as functionally distinct or even antagonistic isoforms as a result of alternative splicing. Studies on alternative splicing of these genes are reviewed here. Expression and function of a large number of genes involved in PCD are regulated by alternative splicing, including death receptors and intracellular components of the death machinery. Alternative splicing affects not only intracellular distribution but also functional activity of these death regulators, providing a fine-tuning mechanism in modulating a presumably tightly controlled process of cell death.
Inhibition of protein kinase C by tamoxifen. (1985)

The antiestrogen drug tamoxifen inhibits rat brain protein kinase C in vitro, whether the enzyme is activated by Ca2+ and phospholipid (50% inhibitory dose, 100 microM), 12-O-tetradecanoylphorbol-13-acetate and phospholipid (50% inhibitory dose, 40 microM), or teleocidin and phospholipid. Tamoxifen does not inhibit the Ca2+- and phospholipid-independent phosphorylation of protamine sulfate by protein kinase C, indicating that the drug does not interact with the active site of the enzyme. The binding of [3H]phorbol dibutyrate to high-affinity membrane receptors of cultured mouse fibroblast cells is inhibited by tamoxifen (50% inhibitory dose, 5 microM). Our findings suggest that the growth-inhibitory and cytotoxic effects of tamoxifen, which have been observed at microM concentrations of the drug, may be in part due to its effects on protein kinase C.
Arginine Binding Motifs: Design and Synthesis of Galactose-Derived Arginine Tweezers as Galectin-3 Inhibitors (2008)

Anionic O2 derivatives of methyl 3-deoxy-3-(4-methylbenzamido)-1-thio-beta-D-galactopyranoside have been synthesized as inhibitors against galectin-3. The sulfate, H-phosphonate, and benzyl phosphate derivatives showed an increased affinity as compared to the parent unsubstituted galactopyranoside. Modeling revealed arginine-144 being pinched by the C3 benzamide and O2 anionic substituents in that the benzamide stacked face-to-face and the anionic O2 substituent ion-paired with the guanidinium moiety.
Ouabain Assembles Signaling Cascades through the Caveolar Na+/K+-ATPase (2004)

Based on the observation that the Na(+)/K(+)-ATPase alpha subunit contains two conserved caveolin-binding motifs, we hypothesized that clustering of the Na(+)/K(+)-ATPase and its partners in caveolae facilitates ouabain-activated signal transduction. Glutathione S-transferase pull-down assay showed that the Na(+)/K(+)-ATPase bound to the N terminus of caveolin-1. Significantly, ouabain regulated the interaction in a time- and dose-dependent manner and stimulated tyrosine phosphorylation of caveolin-1 in LLC-PK1 cells. When added to the isolated membrane fractions, ouabain increased tyrosine phosphorylation of proteins from the isolated caveolae but not other membrane fractions. Consistently, ouabain induced the formation of a Na(+)/K(+)-ATPase-Src-caveolin complex in the isolated caveolae preparations as it did in live cells. Finally, depletion of either cholesterol by methyl beta-cyclodextrin or caveolin-1 by siRNA significantly reduced the caveolar Na(+)/K(+)-ATPase and Src. Concomitantly, cholesterol depletion abolished ouabain-induced recruitment of Src to the Na(+)/K(+)-ATPase signaling complex. Like depletion of caveolin-1, it also blocked the effect of ouabain on ERKs, which was restored after cholesterol repletion. Clearly, the caveolar Na(+)/K(+)-ATPase represents the signaling pool of the pump that interacts with Src and transmits the ouabain signals.
Asymmetric polymerase chain reaction improves streptavidin–biotin based purification of polymerase chain reaction products prior to matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometric analysis (1998)

Asymmetric polymerase chain reaction (PCR) simplifies the application of biotin–streptavidin based purification formats for PCR products in matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis. The use of an excess of non-biotinylated primer improves the turnover of biotinylated primer. Thereby performance deficiencies caused by non-extended biotinylated primer are eliminated. © 1998 John Wiley & Sons, Ltd.
Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants (1993)

An algorithm has been developed for the automatic interpretation of a given set of observed reciprocal-lattice points. It extracts a reduced cell and assigns indices to each reflection by a graph-theoretical implementation of the local indexing method. All possible symmetries of the observed lattice compatible with the metric of the reduced cell are recognized and reported, together with the unit-cell constants and the linear index transformation relating the conventional to the reduced cell. This algorithm has been incorporated into the program XDS [Kabsch (1988). J. Appl. Cryst. 21 , 916–924], which is now able to process single-crystal area-detector data without prior knowledge of the symmetry and the unit-cell constants.