gebhart/patrepeval huggingface dataset:
Type 1 Plasminogen Activator Inhibitor Binds to Fibrin via Vitronectin (2000)

Type 1 plasminogen activator inhibitor (PAI-1), the primary inhibitor of tissue-type plasminogen activator (t-PA), circulates as a complex with the abundant plasma glycoprotein, vitronectin. This interaction stabilizes the inhibitor in its active conformation In this report, the effects of vitronectin on the interactions of PAI-1 with fibrin clots were studied. Confocal microscopic imaging of platelet-poor plasma clots reveals that essentially all fibrin-associated PAI-1 colocalizes with fibrin-bound vitronectin. Moreover, formation of platelet-poor plasma clots in the presence of polyclonal antibodies specific for vitronectin attenuated the inhibitory effects of PAI-1 on t-PA-mediated fibrinolysis. Addition of vitronectin during clot formation markedly potentiates PAI-1-mediated inhibition of lysis of (125)I-labeled fibrin clots by t-PA. This effect is dependent on direct binding interactions of vitronectin with fibrin. There is no significant effect of fibrin-associated vitronectin on fibrinolysis in the absence of PAI-1. The binding of PAI-1 to fibrin clots formed in the absence of vitronectin was characterized by a low affinity (K(d) approximately 3.5 micrometer) and rapid loss of PAI-1 inhibitory activity over time. In contrast, a high affinity and stabilization of PAI-1 activity characterized the cooperative binding of PAI-1 to fibrin formed in the presence of vitronectin. These findings indicate that plasma PAI-1.vitronectin complexes can be localized to the surface of fibrin clots; by this localization, they may modulate fibrinolysis and clot reorganization.
A Load Distribution through Competition for Workstation Clusters (1994)

The aim of this work is to develop a competition driven solution approach for load distribution in distributed computing system (DCS) environments. The subject DCS is composed of a set of workstation clusters. The study deals with concurrent applications, but assumes the existence of the independent tasks executing on individual workstations as well. Akin to conventional load balancing algorithms, the approach considers two phases; the partitioning phase and the mapping phase. Each phase is based on the application and the DCS data which is translated into market data, mainly price. The price is governed by the demand and supply of the traded commodities ( processing and communication capacities) and the competition created between the buyers (tasks) and the sellers (workstations), respectively. The work provides a basis for an elaborate study on realistic concurrent applications and workstation networks. It underlines the development of simple, faster, and flexible solutions to load distribution over clusters of workstations, inspired by the market rules.
Molecular cloning, characterization and analysis of the regulation of the AR02 gene, encoding chorismate synthase, of Saccharomyces cerevisiae (1991)

We describe here the cloning, characterization and analysis of the regulation of the ARO2 gene of Saccharomyces cerevisiae, the first reported study of a eukaryotic gene encoding chorismate synthase (E.C. 4.6.1.4). The gene contains an ORF of 1128 bp, encoding a protein with a calculated molecular mass of 40.8 kDa. ARO2 is regulated under the 'general control system' for amino acid biosynthesis by the transcriptional activator GCN4 which binds in vitro at three sites within the ARO2 promoter. The ARO2 gene product is highly similar to its Escherichia coli counterpart, with a 47% identity distributed over the entire length of the peptide. We therefore suggest that the S. cerevisiae chorismate synthase, in contrast to the Neurospora crassa enzyme, but like other chorismate synthases, is a monofunctional peptide, solely possessing chorismate synthase activity.
Exploration of oligosaccharide‐protein interactions in glycoprotein quality control by synthetic approaches (2006)

High-mannose-type oligosaccharides, which are cotranslationally introduced to nascent polypeptides, play important roles in glycoprotein quality control. This process is highly complex, involving a number of lectins, chaperones, and glycan-processing enzymes. For example, calnexin and calreticulin (CRT) are molecular chaperones that recognize monoglucosylated forms of high-mannose-type glycans. UDP-glucose : glycoprotein glucosyltransferase (UGGT) only glucosylates high-mannose-type glycans attached to partially folded proteins. Fbs1 is a component of ubiquitin ligase that recognizes sugar chains. Although recent studies have clarified the properties of these proteins, most of them used oligosaccharides derived from natural sources, which contain structural heterogeneity. In order to gain a more precise understanding, we started our program to comprehensively synthesize high-mannose-type glycans associated with a protein quality control system. Additionally, investigation of artificial glycoproteins led us to the discovery of the first nonpeptidic substrate of UGGT. These synthetic oligosaccharide probes have allowed us to conduct quantitative evaluations of the activity and specificity of CRT, Fbs1, and UGGT.
Convenient Synthesis of 1,2-Diamines from β-Chloro Amines: Precursors of New Substituted Piperazin-2-ones (2013)

Abstract A practical synthesis of 1,2-diamines from β-chloro amines is reported. The reaction proceeds through the intermediacy of an aziridinium ion opening by amines. The conversion of these diamines into polysubstituted piperazinones is also investigated. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.
Assessing human exposure to phthalates using monoesters and their oxidized metabolites as biomarkers. (2003)

Phthalates are a group of industrial chemicals with many commercial uses, such as solvents, additives, and plasticizers. For example, di-(2-ethylhexyl) phthalate (DEHP) is added in varying amounts to certain plastics, such as polyvinyl chloride, to increase their flexibility. In humans, phthalates are metabolized to their respective monoesters, conjugated, and eliminated. However, despite the high production and use of DEHP, we have recently found that the urinary levels of the DEHP metabolite mono-(2-ethylhexyl) phthalate (MEHP) in 2,541 persons in the United States were lower than we anticipated, especially when compared with urinary metabolite levels of other commonly used phthalates. This finding raised questions about the sensitivity of this biomarker for assessing DEHP exposure. We explored the utility of two other DEHP metabolites, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), as additional DEHP biomarkers. These metabolites are formed by oxidative metabolism of MEHP. In urine from 62 people, both the range and the mean urinary levels of MEOHP and MEHHP were on average 4-fold higher than those of MEHP; the mean of the individual ratios of MEHHP/MEOHP, MEHHP/MEHP, and MEOHP/MEHP were 1.4, 8.2, and 5.9, respectively. These data suggest that MEOHP and MEHHP are more sensitive biomarkers of exposure to DEHP than is MEHP. These findings also suggest a predominant human metabolic route for DEHP hydrolysis to MEHP followed by oxidation of MEHP; they also imply that a similar mechanism may be relevant for other high-molecular-weight phthalates, such as di-n-octyl, di-isononyl, and di-isodecyl phthalates.
Down-regulation of miR-203 induced byHelicobacter pyloriinfection promotes the proliferation and invasion of gastric cancer by targeting CASK (2014)

Several microRNAs (miRNA) have been implicated in H. pylori related gastric cancer (GC). However, the molecular mechanism of miRNAs in GC has not been fully understood. In this study, we reported that miR-203 is significantly down-regulated in H. pylori positive tissues and cells and in tumor tissues with important functional consequences. Ectopic expression of miR-203 dramatically suppressed cell proliferation and invasion. We found that miR-203 strongly reduced the expression of CASK oncogene in GC cells. Similar to the restoring miR-203 expression, CASK down-regulation inhibited cell growth and invasion, whereas CASK over-expression rescued the suppressive effect of miR-203. These results can also be found in nude mice. In clinical specimens, CASK was over-expressed in tumors and H. pylori positive tissues and its mRNA levels were inversely correlated with miR-203 expression. Taken together, our results indicated that miR-203 functions as a growth-suppressive miRNA in H. pylori related GC, and that its suppressive effects are mediated mainly by repressing CASK expression.
Synthesis of Large Areas of Highly Oriented, Very Long Silicon Nanowires (2000)

Nanoscale forms of silicon, a very important electronic material, have interesting properties, but the investigation of Si nanowires, for example, has been hampered by difficulties in producing oriented samples. The authors report here the successful synthesis of large areas of highly oriented, very long (1.5–2 mm) Si nanowires—as shown in the Figure—by thermal evaporation of silicon monoxide.
Inhibition of cholesterol synthesis by cyclopropylamine derivatives of squalene in human hepatoblastoma cells in culture (1992)

Two squalene derivatives, trisnorsqualene cyclopropylamine and trisnorsqualene N-methylcyclopropylamine, were synthesized and tested for inhibition of lanosterol and squalene epoxide formation from squalene in rat hepatic microsomes, and for the inhibition of cholesterol synthesis in human cultured hepatoblastoma (HepG2) cells. Trisnorsqualene cyclopropylamine inhibited [3H]-squalene conversion to [3H]squalene epoxide in microsomes (IC50 = 5.0 microM), indicating that this derivative inhibited squalene mono-oxygenase. Trisnorsqualene N-methylcyclopropylamine inhibited [3H]squalene conversion to [3H]lanosterol (IC50 = 12.0 microM) and caused [3H]-squalene epoxide to accumulate in microsomes, indicating that this derivative inhibited 2,3-oxidosqualene cyclase. Cholesterol biosynthesis from [14C]acetate in HepG2 cells was inhibited by both derivatives (IC50 = 1.0 microM for trisnorsqualene cyclopropylamine; IC50 = 0.5 microM for trisnorsqualene N-methylcyclopropylamine). Cells incubated with trisnorsqualene cyclopropylamine accumulated [14C]squalene, while cells incubated with trisnorsqualene N-methylcyclopropylamine accumulated [14C]squalene epoxide and [14C]squalene diepoxide. The concentration range of inhibitor which caused these intermediates to accumulate coincided with that which inhibited cholesterol synthesis. The results indicate that cyclopropylamine derivatives of squalene are effective inhibitors of cholesterol synthesis, and that substitutions at the nitrogen affect enzyme selectivity and thus the mechanism of action of the compounds.
Inhibition of interleukin‐1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis (2002)

These data support a major role for IL-1, but not TNFalpha, in angiogenesis and suggest that an additional antiarthritic mechanism afforded by IL-1 inhibitors, but not anti-TNF agents, is the suppression of the angiogenic component of pannus.
Lupus anticoagulants: misnomer, paradox, riddle, epiphenomenon. (1988)

Lupus anticoagulants (LA) were originally described in patients with systemic lupus erythematosus (SLE) and clinical bleeding. Following the original description, they were associated with numerous clinical conditions and it was soon appreciated that there was not an increased risk of hemorrhage. Hence the name is a misnomer which has resisted attempts at modification. The paradox of LA is the apparent increased risk of both arterial and venous thromboembolic events. Thus, a laboratory finding which was once associated with bleeding and subsequently was regarded as a nuisance has now acquired new respectability as a marker of a thrombotic predisposition. The riddle of the anticoagulant effect in vivo and the apparent procoagulant effect in vivo remains unsolved. Perhaps it is an epiphenomenon, but more importantly, it may open the door to greater understanding of the delicate regulatory systems which prevent thrombosis. LA exist in virtually every patient population. Therefore, they are no longer a topic of interest limited to hematologists, rather they have achieved multidisciplinary attention. Laboratories are now being asked to prospectively evaluate patients for the presence of LA or antiphospholipid antibodies (APA). The evaluation of LA, both in the research laboratory and clinic, should continue to provide important insights applicable to a variety of specialties.
Both Regulatory T Cells and Antitumor Effector T Cells Are Primed in the Same Draining Lymph Nodes during Tumor Progression (2005)

The peripheral tolerance mechanism prevents effective antitumor immunity, even though tumor cells possess recognizable tumor-associated Ags. Recently, it has been elucidated that regulatory T cells (Treg) play a critical role in maintaining not only self-tolerance, but also tolerance of tumor cells. However, because the Treg that maintain self-tolerance arise naturally in the thymus and are thought to be anergic in peripheral, it is still unclear where and when Treg for tumor cells are generated. In this study we analyze tumor-draining lymph nodes (LNs) and demonstrate that both antitumor effector T cells and Treg capable of abrogating the antitumor reactivity of the effector T cells are primed in the same LNs during tumor progression. The regulatory activity generated in tumor-draining LNs exclusively belonged to the CD4(+) T cell subpopulation that expresses both CD25 and a high level of CD62L. Forkhead/winged helix transcription factor gene expression was detected only in the CD62L(high)CD4(+)CD25(+) T cells. CD62L(high)CD4(+)CD25(+) Treg and CD62L(low)CD4(+)CD25(+) T cells, which possess effector T cell functions, had comparable expression of LFA-1, VLA-4, CTLA-4, lymphocyte activation gene-3, and glucocorticoid-induced TNFR. Thus, only CD62L expression could distinguish regulatory CD4(+)CD25(+) cells from effector CD4(+)CD25(+) cells in draining LNs as a surface marker. The Treg generated in tumor-draining LNs possess the same functional properties as the Treg that arise naturally in the thymus but recognize tumor-associated Ag. CD62L(high)CD4(+)CD25(+) Treg contained a subpopulation that expressed CD86. Blocking experiments revealed that ligation of CTLA-4 on effector T cells by CD86 on Treg plays a pivotal role in regulating CD4(+) effector T cells.
TEAD Transcription Factors Mediate the Function of TAZ in Cell Growth and Epithelial-Mesenchymal Transition (2009)

The TAZ transcription co-activator has been shown to promote cell proliferation and to induce epithelial-mesenchymal transition. Recently we have demonstrated that TAZ is phosphorylated and inhibited by the Hippo tumor suppressor pathway, which is altered in human cancer. The mechanism of TAZ-mediated transcription is unclear. We demonstrate here that TEAD is a key downstream transcription factor mediating the function of TAZ. Disruption of TEAD-TAZ binding or silencing of TEAD expression blocked the function of TAZ to promote cell proliferation and to induce epithelial-mesenchymal transition, demonstrating TEAD as a key downstream effector of TAZ. We also identified CTGF, a gene that regulates cell adhesion, proliferation, and migration, as a direct target of TAZ and TEAD. Our study establishes a functional partnership between TAZ and TEAD under negative regulation by the Hippo signaling pathway.
Protease-Activated Receptor-1 Can Mediate Responses to SFLLRN in Thrombin-Desensitized Cells:  Evidence for a Novel Mechanism for Preventing or Terminating Signaling by PAR1's Tethered Ligand (1999)

The thrombin receptor PAR1 is activated when thrombin cleaves the receptor's amino-terminal exodomain to reveal the new N-terminal sequence SFLLRN which then acts as a tethered peptide ligand. Free SFLLRN activates PAR1 independent of receptor cleavage and has been used to probe PAR1 function in various cells and tissues. PAR1-expressing cells desensitized to thrombin retain responsiveness to SFLLRN. Toward determining the mechanism of such responses, we utilized fibroblasts derived from a PAR1-deficient mouse. These cells were unresponsive to thrombin and SFLLRN and became sensitive to both ligands after transfection with human PAR1 cDNA. Moreover, PAR1-transfected cells responded to SFLLRN after thrombin-desensitization, indicating that signaling of thrombin-desensitized cells to SFLLRN was mediated by PAR1 itself. SFLLRN caused signaling in thrombin-desensitized cells when no uncleaved PAR1 was detectable on the cell surface; however, cleaved PAR1 was present. To determine whether the cleaved receptors could still signal, fibroblasts were transfected with a PAR1 mutant containing a trypsin site/SFLLRN sequence carboxyl terminal to the native thrombin site. These cells retained responsiveness to trypsin after thrombin-desensitization. Conversely, fibroblasts expressing a PAR1 mutant with the trypsin site/SFLLRN sequence amino terminal to the native thrombin site retained responsiveness to thrombin after trypsin-desensitization. This suggests that a population of thrombin-cleaved PAR1 can respond both to exogenous SFLLRN and to a second tethered ligand. In this population, the tethered ligand unmasked by thrombin cleavage must not be functional, suggesting the possibility of a novel mechanism of receptor shutoff involving sequestration or modification of the tethered ligand to prevent or terminate its function.
Photosystem II Peripheral Accessory Chlorophyll Mutants inChlamydomonas reinhardtii. Biochemical Characterization and Sensitivity to Photo-Inhibition, (2001)

In addition to the four chlorophylls (Chls) involved in primary charge separation, the photosystem II (PSII) reaction center polypeptides, D1 and D2, coordinate a pair of symmetry-related, peripheral accessory Chls. These Chls are axially coordinated by the D1-H118 and D2-H117 residues and are in close association with the proximal Chl antennae proteins, CP43 and CP47. To gain insight into the function(s) of each of the peripheral Chls, we generated site-specific mutations of the amino acid residues that coordinate these Chls and characterized their energy and electron transfer properties. Our results demonstrate that D1-H118 and D2-H117 mutants differ with respect to: (a) their relative numbers of functional PSII complexes, (b) their relative ability to stabilize charge-separated states, (c) light-harvesting efficiency, and (d) their sensitivity to photo-inhibition. The D2-H117N and D2-H117Q mutants had reduced levels of functional PSII complexes and oxygen evolution capacity as well as reduced light-harvesting efficiencies relative to wild-type cells. In contrast, the D1-H118Q mutant was capable of near wild-type rates of oxygen evolution at saturating light intensities. The D1-H118Q mutant also was substantially more resistant to photo-inhibition than wild type. This reduced sensitivity to photo-inhibition is presumably associated with a reduced light-harvesting efficiency in this mutant. Finally, it is noted that the PSII peripheral accessory Chls have similarities to a to a pair of Chls also present in the PSI reaction center complex.
Allergy and Immunology (1996)

Developments in our understanding of the regulation of the immune response highlight the past year's progress in the field of allergy and immunology. Three of the important topics include the genetic regulation of IgE production, Fas regulation of immune responses, and the control of TH1 and TH2 immune responses. High total serum IgE levels are known to correlate with allergies, asthma, and bronchial hyperresponsiveness. The observed familial aggregation of allergies and asthma has long supported the existence of an important heritable component to these conditions. As with most complex disorders, however, the allergic and asthmatic phenotypes do not seem to be inherited in simple Mendelian fashion. Furthermore, the clinical expression of these disorders is influenced by age, sex, and exposure to allergens, pollutants, and viral respiratory infections.<sup>1,2</sup>Consequently, the mode(s) of inheritance and the gene(s) responsible for these complex atopic disorders have been incompletely understood. Recent investigations into the
Mouse insulinoma beta TC3 cells express prodynorphin messenger ribonucleic acid and derived peptides: a unique cellular model for the study of prodynorphin biosynthesis and processing (1995)

The tumor cell line beta TC3 has been established from insulinomas derived from transgenic mice carrying a hybrid insulin promoter-simian virus-40 tumor antigen gene. The beta TC3 cells express high steady state levels of proinsulin messenger RNA (mRNA). In this same cell line, we describe in the present study high expression levels of prodynorphin (pro-Dyn) mRNA and its derived peptides. By Northern blot analysis, the screening of 23 cell lines of endocrine (n = 10) and of nonendocrine (n = 13) origin revealed the presence of high levels of the 2.6-kilobase pro-Dyn transcript only in beta TC3 cells. The beta TC3 cells expressed levels of pro-Dyn mRNA comparable to those in rat tissues expressing pro-Dyn. Chromatographic and radioimmunological studies showed that pro-Dyn mRNA was translated and fully processed into opioid peptides with leucine-enkephalin (Leu-Enk)-extended sequences [dynorphin-A-(1-8), dynorphin-B-(1-13), and alpha-neo-endorphin]. The expression of the prohormone convertases was also examined in beta TC3 cells by Northern blot analysis. In addition to the ubiquitously expressed furin, beta TC3 cells have abundant levels of prohormone convertase-1 (PC1) and PC2 mRNAs, but undetectable levels of PACE4 or PC5 mRNAs. Incubation of beta TC3 cells with 8-bromo-cAMP for 24 h stimulated 3-fold both the pro-Dyn mRNA levels and the secretion of opioid peptides. In contrast to pro-Dyn mRNA, furin, PC1, and PC2 mRNA levels were not affected by 8-bromo-cAMP. The beta TC3 cells constitute a unique model to elucidate the biosynthetic pathway of pro-Dyn processing, to identify the proteolytic enzymes responsible for the production of pro-Dyn end products, and to assess the potential role of opioid peptides in the regulation of pancreatic function.
Panoramic Image Mosaics (1998)

This paper presents some techniques for constructing panoramic image mosaics from sequences of images. Our mosaic representation associates a transformation matrix with each input image, rather than explicitly projecting all of the images onto a common surface (e.g., a cylinder). In particular, to construct a full view panorama, we introduce a rotational mosaic representation that associates a rotation matrix (and optionally a focal length) with each input image. A patch-based alignment algorithm is developed to quickly align two images given motion models. Techniques for estimating and refining camera focal lengths are also presented. In order to reduce accumulated registration errors, we apply global alignment (block adjustment) to the whole sequence of images, which results in an optimally registered image mosaic. To compensate for small amounts of motion parallax introduced by translations of the camera and other unmodeled distortions, we develop a local alignment (deghosting) technique which warps each image based on the results of pairwise local image registrations. By combining both global and local alignment, we significantly improve the quality of our image mosaics, thereby enabling the creation of full view panoramic mosaics with hand-held cameras. We also present an inverse texture mapping algorithm for efficiently extracting environment maps from our panoramic image mosaics. By mapping the mosaic onto an arbitrary texture-mapped polyhedron surrounding the origin, we can explore the virtual environment using standard 3D graphics viewers and hardware without requiring special-purpose players. 1