gebhart/patrepeval huggingface dataset:
Inhibition of tumor cell collagenolytic activity by bovine endothelial cells. (1986)

The ability of cellular vascular components including endothelial cells, smooth muscle cells, and fibroblasts to interact with the collagenolytic activity of invasive human tumor cell lines has been investigated. The human HT1080 fibrosarcoma and Bowe melanoma cells, which rapidly digest collagenous proteins in vitro, failed to dissolve them when cocultivated with bovine endothelial cells. This inhibition was not dependent on the ability of endothelial cells to form a monolayer separating the tumor cells from the collagenous substrate. In contrast, little collagenolysis inhibitory activity was detected in bovine vascular smooth muscle cells and human fibroblasts when compared to endothelial cells. Serum-free medium conditioned by endothelial cells inhibited tumor cell-mediated collagenolysis. Our data further suggest that this inhibition was mediated by secreted collagenase inhibitors, since endothelial cell-conditioned medium did not suppress the production of metalloproteinases by the tumor cells but inhibited the activities of collagenases derived from tadpole, rabbit, and human fibroblasts. Treatment of the endothelial cells with cycloheximide suppressed the collagenase inhibitory activity, demonstrating active production of collagenase inhibitors by the cells. Gel filtration chromatography of endothelial cell-conditioned medium allowed the separation of two distinct peaks with inhibitory activities for vertebrate collagenase in the molecular weight range of 70,000 to 75,000 and 30,000 to 35,000, respectively. While the inhibitor with an approximate molecular weight of 30,000 to 35,000 shared many properties with the tissue inhibitor of metalloproteinases, the high-molecular-weight inhibitor demonstrated characteristics not yet described for any collagenase inhibitor. The production and secretion of inhibitors of vertebrate collagenase by bovine endothelial cells may be of importance in the local control of collagen turnover under physiological as well as pathological conditions.
Towards Web/Java-based high performance distributed computing-an evolving virtual machine (1996)

Discusses the emergent World Wide Web-based distributed environments for high-performance computing and communications (HPCC) on the National Information Infrastructure (NII) with the focus on Java as an enabling technology. We start with a review of the past, present and near-term future of the "Java phenomenon", exposed in the background of some related previous approaches towards a distributed interpretative virtual machine architecture. Next, we discuss the anticipated role of Java in building distributed Web-based computing environments. We outline an evolutionary path from the current Web technology "soup" towards "all-Java" systems and we illustrate this process in terms of the Northeast Parallel Architectures Center (NPAC) Web technology prototypes (WebVM, WebFlow, Bridge-based Collaboratory) and selected applications (CareWeb, 3D Visible Human).
Substitutional Reality (2015)

Experiencing Virtual Reality in domestic and other uncontrolled settings is challenging due to the presence of physical objects and furniture that are not usually defined in the Virtual Environment. To address this challenge, we explore the concept of Substitutional Reality in the context of Virtual Reality: a class of Virtual Environments where every physical object surrounding a user is paired, with some degree of discrepancy, to a virtual counterpart. We present a model of potential substitutions and validate it in two user studies. In the first study we investigated factors that affect participants' suspension of disbelief and ease of use. We systematically altered the virtual representation of a physical object and recorded responses from 20 participants. The second study investigated users' levels of engagement as the physical proxy for a virtual object varied. From the results, we derive a set of guidelines for the design of future Substitutional Reality experiences.
Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-β signaling in cooperation with active Kras expression (2006)

Pancreatic ductal adenocarcinoma (PDAC) is an almost uniformly lethal disease in humans. Transforming growth factor-beta (TGF-beta) signaling plays an important role in PDAC progression, as indicated by the fact that Smad4, which encodes a central signal mediator downstream from TGF-beta, is deleted or mutated in 55% and the type II TGF-beta receptor (Tgfbr2) gene is altered in a smaller subset of human PDAC. Pancreas-specific Tgfbr2 knockout mice have been generated, alone or in the context of active Kras (Kras(G12D)) expression, using the Cre-loxP system driven by the endogenous Ptf1a (pancreatic transcription factor-1a) locus. Pancreas-selective Tgfbr2 knockout alone gave no discernable phenotype in 1.5 yr. Pancreas-specific Kras(G12D) activation alone essentially generated only intraepithelial neoplasia within 1 yr. In contrast, the Tgfbr2 knockout combined with Kras(G12D) expression developed well-differentiated PDAC with 100% penetrance and a median survival of 59 d. Heterozygous deletion of Tgfbr2 with Kras(G12D) expression also developed PDAC, which indicated a haploinsufficiency of TGF-beta signaling in this genetic context. The clinical and histopathological manifestations of the combined Kras(G12D) expression and Tgfbr2 knockout mice recapitulated human PDAC. The data show that blockade of TGF-beta signaling and activated Ras signaling cooperate to promote PDAC progression.
In Vitro Reconstitution of the End Replication Problem (2001)

The end replication problem hypothesis proposes that the ends of linear DNA cannot be replicated completely during lagging strand DNA synthesis. Although the idea has been widely accepted for explaining telomere attrition during cell proliferation, it has never been directly demonstrated. In order to take a biochemical approach to understand how linear DNA ends are replicated, we have established a novel in vitro linear simian virus 40 DNA replication system. In this system, terminally biotin-labeled linear DNAs are conjugated to avidin-coated beads and subjected to replication reactions. Linear DNA was efficiently replicated under optimized conditions, and replication products that had replicated using the original DNA templates were specifically analyzed by purifying bead-bound replication products. By exploiting this system, we showed that while the leading strand is completely synthesized to the end, lagging strand synthesis is gradually halted in the terminal approximately 500-bp region, leaving 3' overhangs. This result is consistent with observations in telomerase-negative mammalian cells and formally demonstrates the end replication problem. This study provides a basis for studying the details of telomere replication.
Very-Short-Term Probabilistic Forecasting of Wind Power With Generalized Logit–Normal Distributions (2012)

Summary Very-short-term probabilistic forecasts, which are essential for an optimal management of wind generation, ought to account for the non-linear and double-bounded nature of that stochastic process. They take here the form of discrete–continuous mixtures of generalized logit–normal distributions and probability masses at the bounds. Both auto-regressive and conditional parametric auto-regressive models are considered for the dynamics of their location and scale parameters. Estimation is performed in a recursive least squares framework with exponential forgetting. The superiority of this proposal over classical assumptions about the shape of predictive densities, e.g. normal and beta, is demonstrated on the basis of 10-min-ahead point and probabilistic forecasting at the Horns Rev wind farm in Denmark.
Dpysl4 Is Involved in Tooth Germ Morphogenesis through Growth Regulation, Polarization and Differentiation of Dental Epithelial Cells (2013)

Dihydropyrimidinase-related protein 4 (Dpysl4) is a known regulator of hippocampal neuron development. Here, we report that Dpysl4 is involved in growth regulation, polarization and differentiation of dental epithelial cells during tooth germ morphogenesis. A reduction in Dpysl4 gene expression in the tooth germ produced a loss of ameloblasts, resulting in the decrease of synthesis and secretion of enamel. The inhibition of Dpysl4 gene expression led to promotion of cell proliferation of inner enamel epithelial cells and inhibition of the differentiation of these cells into pre-ameloblasts, which was confirmed by analyzing cell polarization, columnar cell structure formation and the expression of ameloblast marker genes. By contrast, overexpression of Dpysl4 in dental epithelial cells induces inhibition of growth and increases the expression of the inner enamel epithelial cell marker gene, Msx2. These findings suggest that Dpysl4 plays essential roles in tooth germ morphogenesis through the regulation of dental epithelial cell proliferation, cell polarization and differentiation.
Glucose-regulated protein (GRP94 and GRP78) genes share common regulatory domains and are coordinately regulated by common trans-acting factors. (1989)

We isolated the promoter of the human gene encoding the 94,000-dalton glucose-regulated protein (GRP94). The 5'-flanking region important for its expression was identified by deletion analysis. Comparison of the promoters of the genes for GRP78 and GRP94 derived from human, rat, and chicken cells revealed a common domain of 28 base pairs within the putative regulatory regions of both genes. This domain has been shown to interact with protein factors in the promoter of the gene for GRP78. Since the genes for GRP94 and GRP78 are transcriptionally regulated with similar kinetics under a variety of stress conditions, we are interested in examining the possible mechanisms for their coordinated expression. Through in vitro and in vivo competition assays, we found that the protein factors which interact with the promoter of the gene for GRP94 also have affinity for the conserved domain of the promoter of the gene for GRP78. These findings suggest that the genes for GRP94 and GRP78 are coordinately regulated through common trans-acting factors which recognize a common regulatory domain of glucose-regulated protein gene promoters.
Vaccinia virus DNA ligase: specificity, fidelity, and inhibition (1995)

Vaccinia DNA ligase and mammalian DNA ligases II and III comprise a distinct subgroup of structurally homologous enzymes within the eukaryotic DNA ligase family. The specificity and fidelity of the viral enzyme were investigated using purified recombinant ligase and synthetic duplex DNA substrates containing a single strand discontinuity. Vaccinia ligase catalyzed efficient strand joining on nicked DNAs in the presence of magnesium and ATP (Km = 95 microM). dATP, ITP, AMPPCP, 3'dATP, and ATP alpha S could not substitute for ATP; of these, 3'dATP and ATP alpha S were inhibitors of ligation. The vaccinia enzyme was unable to seal strands across a 1 nt (nucleotide) or 2 nt gap. Ligase action at a 1 nt gap resulted in accumulation of high levels of the normally undetectable DNA-adenylate reaction intermediate. In contrast, no DNA-adenylate was formed at a 2 nt gap. A native gel mobility shift assay showed that vaccinia DNA ligase was capable of discriminating between nicked and gapped DNAs at the substrate binding step. The ligase was fairly tolerant of mismatches at a nick involving the 5' phosphate donor terminus but was inhibited strongly by mismatches at the 3' OH acceptor terminus, especially by purine.-purine mispairs. These findings underscore the importance of a proper 3' OH terminus in substrate recognition and reaction chemistry but also raise the possibility that ligase may generate mutations during DNA repair by sealing DNA molecules with mispaired ends. Ligase was inhibited by several DNA binding drugs, including, in order of decreasing potency, distamycin, ethidium bromide, and actinomycin. Strand joining by purified ligase was not affected by etoposide, a drug that inhibits vaccinia virus replication in vivo and which depends on the presence of vaccinia ligase for its antiviral action.
Plant Tissue 2 (1992)

A new five-element electrical model was proposed recently (Zhang, Stout, and Willison, 1990; Zhang and Willison, 1991) to represent plant tissues. In previous studies on the relationship between electrical impedance and cold-hardiness, one of us had analysed data in relation to a simpler three-element electrical model. Here, we have re-analysed these data in relation to the more complex model. F-tests showed that the new model always fitted measured impedance spectra significantly better (P<0·005) than the earlier model. The previously reported increase in intracellular resistance during cold acclimation was found to be related to increased resistance of both the cytoplasm and vacuole In the species trial of birdsfood trefoil and alfalfa, cold acclimation was accompanied by an increase in extracellular resistance and a decrease in capacitances of both the plasma membrane and tonoplast. In the cultivar trial of birdsfoot trefoil, cold acclimation did not affect plasma membrane capacitance in Viking and extracellular resistance in both Leo and Viking. In the species and growth time trial, cold acclimation was accompanied by a decrease in plasma membrane capacitance in alfalfa but not in birdsfoot trefoil
Histone methyltransferase SETDB1 is required for prostate cancer cell proliferation, migration and invasion (2014)

SETDB1 has been established as an oncogene in a number of human carcinomas. The present study was to evaluate the expression of SETDB1 in prostate cancer (PCa) tissues and cells and to preliminarily investigate the role of SETDB1 in prostate tumorigenesis in vitro. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used to detect the expression of SETDB1 in PCa tissues, adjacent normal tissues, benign prostatic hyperplasia (BPH) tissues, PCa cell lines and normal prostate epithelial cells. The results suggested that SETDB1 was upregulated in human PCa tissues compared with normal tissues at the mRNA and protein levels. The role of SETDB1 in proliferation was analyzed with cell counting kit-8, colony-forming efficiency and flow cytometry assays. The results indicated that downregulation of SETDB1 by siRNA inhibited PCa cell growth, and induced G0/G1 cell cycle arrest. The PCa cell migration and invasion decreased by silcencing SETDB1 which were assessed by using in vitro scratch and transwell invasion assay respectively. Our data suggested that SETDB1 is overexpressed in human PCa. Silencing SETDB1 inhibited PCa cell proliferation, migration and invasion.
Leukemogenic MLL Fusion Proteins Bind across a Broad Region of the Hox a9 Locus, Promoting Transcription and Multiple Histone Modifications (2005)

Chromosome translocations involving the mixed lineage leukemia gene MLL are associated with aggressive acute leukemias in both children and adults. Leukemogenic MLL fusion proteins delete the MLL SET domain Lys(4) methyltransferase activity and fuse MLL to 1 of >40 different translocation partners. Some MLL fusion proteins involve nuclear proteins that are transcriptional activators, whereas others have transcriptional activating activity but instead dimerize the truncated MLL molecule. Both types of MLL fusion proteins enforce persistent expression of Hox a9 and Meis1, which is pivotal for leukemogenesis through mechanisms that remain obscure. Here, we show that nuclear and dimerizable forms of MLL bind with a similar pattern to the Hox a9 locus that overlaps the distribution of wild-type MLL and deregulate transcription of three isoforms of Hox a9. Induction of MLL fusion protein activity is associated with increased levels of histone acetylation and Lys(4) methylation at Hox target genes. In addition, the MLL-ENL-ER protein, but not dimerized MLL, also induces dimethylation of histone H3 at Lys(79), suggesting alternative mechanisms for transcriptional activation.
System-level power optimization (2004)

More features and higher bandwidth needed for new mobile services consume more power than battery technology can provide. Higher performance in information processing produces more heat than cooling technology can dissipate. These trends require power aware design methodologies throughout the entire design. The largest impact on the power consumption can be achieved at the system level where the algorithms and the system architecture are defined. In this contribution we present a system-level design flow and respective EDA support tools for low power designs. We analyze the requirements for such a design technology, which shifts more responsibility to the system architect. We exemplify this approach with a design flow for low power systems. The architecture of a power estimation tool is presented, which is capable to guide the designer in system level and architecture level decisions in the pre-implementation phase. The effectiveness of the approach is demonstrated through some use cases.
Heat shock proteins: molecular chaperones of protein biogenesis (1993)

Heat shock proteins (Hsps) were first identified as proteins whose synthesis was enhanced by stresses such as an increase in temperature. Recently, several of the major Hsps have been shown to be intimately involved in protein biogenesis through a direct interaction with a wide variety of proteins. As a reflection of this role, these Hsps have been referred to as molecular chaperones. Hsp70s interact with incompletely folded proteins, such as nascent chains on ribosomes and proteins in the process of translocation from the cytosol into mitochondria and the endoplasmic reticulum. Hsp60 also binds to unfolded proteins, preventing aggregation and facilitating protein folding. Although less well defined, other Hsps such as Hsp90 also play important roles in modulating the activity of a number of proteins. The function of the proteolytic system is intertwined with that of molecular chaperones. Several components of this system, encoded by heat-inducible genes, are responsible for the degradation of abnormal or misfolded proteins. The budding yeast Saccharomyces cerevisiae has proven very useful in the analysis of the role of molecular chaperones in protein maturation, translocation, and degradation. In this review, results of experiments are discussed within the context of experiments with other organisms in an attempt to describe the current state of understanding of these ubiquitous and important proteins.
Increasing Levels of Interleukin (IL)-1Ra and IL-6 During the First 2 Days of Hospitalization in Unstable Angina Are Associated With Increased Risk of In-Hospital Coronary Events (1999)

These findings indicate that although they receive the same medical therapy as patients who do not experience an in-hospital event, patients with unstable angina and with complicated in-hospital courses have higher cytokine levels on admission. A fall in IL-1Ra and IL-6 48 hours after admission was associated with an uneventful course and their increase with a complicated hospital course. These findings may suggest novel therapeutic approaches to patients with unstable angina.
Androgen receptor signaling in prostate cancer development and progression (2011)

The androgen receptor (AR) signaling axis plays a critical role in the development, function and homeostasis of the prostate. The classical action of AR is to regulate gene transcriptional processes via AR nuclear translocation, binding to androgen response elements on target genes and recruitment of, or crosstalk with, transcription factors. Prostate cancer initiation and progression is also uniquely dependent on AR. Androgen deprivation therapy remains the standard of care for treatment of advanced prostate cancer. Despite an initial favorable response, almost all patients invariably progress to a more aggressive, castrate-resistant phenotype. Considerable evidence now supports the concept that development of castrate-resistant prostate cancer (CRPC) is causally related to continued transactivation of AR. Understanding the critical events and complexities of AR signaling in the progression to CRPC is essential in developing successful future therapies. This review provides a synopsis of AR structure and signaling in prostate cancer progression, with a special focus on recent findings on the role of AR in CRPC. Clinical implications of these findings and potential directions for future research are also outlined.
Inhibition of focal adhesion kinase prevents experimental lung fibrosis and myofibroblast formation (2011)

These results implicate FAK as a central mediator of fibrogenesis, and highlight this kinase as a potential therapeutic target in fibrotic diseases.
Application of ultrasound energy for intracardiac ablation of arrhythmias (1995)

Ultrasound is a potential energy source for cardiac ablation. Small ultrasound applicators were tested for their ability to create lesions in cardiac tissue. Ultrasound applicators were designed, constructed and tested in canine cardiac tissue in degassed normal saline, and both in vitro and in vivo, lesions were produced by using transducers with frequencies of about 10 MHz. Lesion depth increased with longer duration of energy delivery from 15-60 s, and there was a linear relationship between increasing power and depth of lesions. Seven in vivo experiments in open-chest dogs were performed, and the ultrasound transducers were mounted on the tip of 7-French angiographic catheters. On the epicardium the maximum lesion depth was 9 mm. When the transducer was inserted into the left ventricle, lesions of 8.7 +/- 2.9 mm (n = 4) were produced. It is concluded that an ultrasound transducer mounted on a cardiac catheter can produce lesions that may be useful for ablation of cardiac arrhythmias.
Differential sensitivity of mouse pronuclei and zygote cytoplasm to Hoechst staining and ultraviolet irradiation (1988)

The exposure of mouse zygotes pre-stained with Hoechst 33342 to u.v. irradiation for 20-30 sec significantly or completely inhibited development to blastocysts in vitro. However, development to the blastocyst stage of enucleated eggs receiving pronuclei from untreated eggs was as good as that of control reconstituted eggs when the cytoplasm originated from eggs exposed to u.v. irradiation for 20-30 sec, but was significantly lower when the cytoplasm was from eggs exposed for 40 sec. The chromosomes at the second metaphase stage could be removed with 15 sec of exposure to u.v. irradiation under a fluorescence microscope. Most eggs enucleated at the second metaphase that received a single inner cell mass nucleus (75%) showed pronuclear formation 6 h after activation; 23% of them developed to morphologically normal 2-cell eggs and 5% developed to blastocysts. These results demonstrate that the cytoplasm of mouse zygotes is more resistant to u.v. irradiation after Hoechst staining. Eggs at the second metaphase, from which chromosomes have been removed under a fluorescence microscope, can therefore be used as cytoplasm recipients for nuclear transplantation of inner cell mass nuclei.