gebhart/patrepeval huggingface dataset:
Identification and characterization of ERAP1 as a novel molecular target for breast cancer therapy (2008)

2357 To discover novel therapeutic targets for breast cancer, we previously analyzed genome-wide expression profiles of 81 breast cancers by using cDNA microarray. Among the transactivated genes, we identified ERAP1 (Estrogen Receptor-Associated Protein1) as a candidate molecule for development of drugs for breast cancer. Semiquantitative RT-PCR and northern analyses confirmed that expression of ERAP1 was up-regulated in the great majority of breast cancer samples. Knockdown of ERAP1 expression with specific small-interfering RNA significantly suppressed the growth of breast cancer cell lines, BT-549 and BT-474 cells. In addition, introduction of ERAP1 into NIH3T3 cells significantly enhanced cell growth at in vitro, suggesting an oncogenic role of ERAP1 for development of breast cancer. Furthermore, we found the interaction of ERAP1 and prohibitin 2/repressor of estrogen receptor activity (PHB2/REA) by co-immunoprecipitation and immunoblotting assays. Interestingly, in an absence of ERAP1 protein, PHB2/REA translocated together with ERα to the nucleus by the stimulation of 17β-estradiol (E2), but in the presence of exogenously expressed ERAP1 protein it remained in cytoplasm. Introduction of ERAP1 protein enhanced of ER transcriptional activity in MCF7 (ERα-positive) cells after E2 treatment, while did not enhance ER transcriptional activity in SK-BR-3 (ERα-negative) cells, implying that ERAP1 is likely to be involved in breast tumorigenesis by the regulation of ERα transcriptional activity through the inhibition of interaction between ERα and PHB2/REA. Taken together, our findings suggest that ERAP1 may play key roles in breast tumor cell growth.
Abdominal adhesions to prosthetic mesh evaluated by laparoscopy and electron microscopy1 (2000)

Intraabdominal adhesions are best studied by sequential laparoscopy. Adhesions develop within 1 day of prosthesis placement. Adhesion-free surfaces are carpeted with mesothelial cells by day 7 and remain free thereafter, for duration of study.
A major calmodulin-binding protein common to various vertebrate tissues. (1982)

A major calmodulin-binding protein (CaM-BP) of Mr 240,000 was demonstrated in various rat tissues by using a 125I-labeled CaM gel overlay technique. This protein (designated p240) was detected in the particulate fraction and to a lesser extent in the cytosol of all tissues studied. Binding of CaM to p240 was completely dependent on Ca2+. A second, exclusively soluble, CaM-BP (Mr115,000) common to several tissues and a number of other CaM-BPs with a more restricted tissue distribution were also observed by using this technique. CaM binding to p240 occurred in high amounts in plasma membranes from avian erythrocytes but was absent from mammalian erythrocyte membranes. Antibodies prepared against turkey erythrocyte p240 (anti-Tp240) crossreacted with p240 in other tissues. Identity between the proteins recognized by anti-Tp240 and CaM was confirmed by demonstrating that 125I-labeled CaM could bind to p240 specifically immunoprecipitated from either rat brain or turkey erythrocytes by anti-Tp240. The p240 may be related to a previously described actin-binding protein and may represent a major site of action of CaM on the cytoskeleton.
Prediction and validation of cell alignment along microvessels as order principle to restore tissue architecture in liver regeneration (2010)

Only little is known about how cells coordinately behave to establish functional tissue structure and restore microarchitecture during regeneration. Research in this field is hampered by a lack of techniques that allow quantification of tissue architecture and its development. To bridge this gap, we have established a procedure based on confocal laser scans, image processing, and three-dimensional tissue reconstruction, as well as quantitative mathematical modeling. As a proof of principle, we reconstructed and modeled liver regeneration in mice after damage by CCl(4), a prototypical inducer of pericentral liver damage. We have chosen the regenerating liver as an example because of the tight link between liver architecture and function: the complex microarchitecture formed by hepatocytes and microvessels, i.e. sinusoids, ensures optimal exchange of metabolites between blood and hepatocytes. Our model captures all hepatocytes and sinusoids of a liver lobule during a 16 days regeneration process. The model unambiguously predicted a so-far unrecognized mechanism as essential for liver regeneration, whereby daughter hepatocytes align along the orientation of the closest sinusoid, a process which we named "hepatocyte-sinusoid alignment" (HSA). The simulated tissue architecture was only in agreement with the experimentally obtained data when HSA was included into the model and, moreover, no other likely mechanism could replace it. In order to experimentally validate the model of prediction of HSA, we analyzed the three-dimensional orientation of daughter hepatocytes in relation to the sinusoids. The results of this analysis clearly confirmed the model prediction. We believe our procedure is widely applicable in the systems biology of tissues.
Effects of GP IIb/IIIa Receptor Monoclonal Antibody (7E3), Heparin, and Aspirin in an Ex Vivo Canine Arteriovenous Shunt Model of Stent Thrombosis (1997)

7E3 produced a dose-dependent inhibition of acute stent thrombosis under high-shear flow conditions. Stent thrombosis was resistant to heparin and aspirin. Thus, 7E3 may be an effective agent for preventing stent thrombosis.
Interindividual variability in the response to oral antiplatelet drugs: a position paper of the Working Group on antiplatelet drugs resistance appointed by the Section of Cardiovascular Interventions of the Polish Cardiac Society, endorsed by the Working Group on Thrombosis of the European Society of Cardiology (2008)

Oral antiplatelet drugs are a cornerstone of modern pharmacotherapy in cardiovascular atherothrombotic diseases. The efficacy of acetylsalicylic acid (ASA, aspirin) and clopidogrel in decreasing the risk of adverse events in coronary heart disease patients has been well established in the past 20 years. Despite chronic oral antiplatelet therapy, a number of atherothombotic events continue to occur. In recent years, a number of reports in the literature have shown possible relationships between residual platelet activity, as measured with a variety of laboratory tests, and clinical outcome, raising the possibility that 'resistance' to oral antiplatelet drugs may underlie many such clinical adverse events. The present position paper, conveyed within a group of clinical cardiologists with expertise in thrombosis appointed by the Section of Cardiovascular Interventions of the Polish Cardiac Society, has been further elaborated and endorsed by the Working Group on Thrombosis of the European Society of Cardiology. It aims at summarizing the main findings in this complex area, issuing opinions in cases of high controversy, and fostering future research in this area to obtain reliable laboratory and clinical data for the resolution of the many problems still open.
Binding of cis- and trans-diamminedichloroplatinum(II) to deoxyribonucleic acid exposes nucleosides as measured immunochemically with anti-nucleoside antibodies (1986)

We report the use of anti-nucleoside antibodies to probe for local denaturation of calf thymus DNA upon binding of the antitumor drug cis-diamminedichloroplatinum(II), cis-DDP, and the biologically inactive analogues trans-diamminedichloroplatinum(II), trans-DDP, and chloro(diethylenetriamine)platinum(II) chloride, [Pt(dien)Cl]Cl. These antibodies specifically recognize each of the four DNA nucleosides. They bind well to denatured DNA, but not to native DNA in which the bases are less accessible owing to Watson-Crick duplex structure. At relatively high levels of modification (D/N approximately 0.1), cis-DDP causes significant disruption of DNA base pairing as reflected by the increased binding of anti-cytidine, anti-adenosine, and anti-thymidine antibodies. At lower levels of platinum adduct formation, however, all four anti-nucleoside antibodies bind more to DNA modified with trans-DDP. This result indicates that adducts formed by trans-DDP disrupt the DNA structure to a greater extent than those formed by cis-DDP at low D/N ratios. Modification of DNA by the monofunctional complex [Pt(dien)Cl]Cl does not affect its recognition by anti-nucleoside antibodies, demonstrating that base pair disruption is a consequence of bifunctional binding. The relative anti-nucleoside antibody recognition of cis-DDP-modified DNA is anti-cytosine greater than anti-adenosine approximately anti-thymidine much greater than anti-guanosine, consistent with the major adduct being an intrastrand d(GpG) cross-link. These results reveal that base pair disruption in a naturally occurring DNA modified by either cis-DDP or trans-DDP is sufficient to be detected by protein (antibody) binding. The relevance of these findings to current ideas about the molecular mechanism of action of cis-DDP is discussed.
Über Einbau und Wirkung von Fremdstoffen in Indiumarsenid (1956)

In der vorliegenden Arbeit ist das Verhalten einer Reihe von Fremdstoffen in der halbleitenden Verbindung Indiumarsenid untersucht. An in der flüssigen Phase dotiertem und mit gerichteter Kristallisation erstarrtem Indiumarsenid sind aus HALL-Effekts- und Leitfähigkeitsmessungen die Verteilungskoeffizienten und Ungleichungen für die Löslichkeiten von Mg, Zn, Cd, Si, Ge, Sn, S, Se und Te ermittelt worden. Ca ist auch bei den kleinsten verwendbaren Konzentrationen nicht löslich. Die Elemente der zweiten und vierten Gruppe substituieren In. Die zweite Gruppe bildet dabei Akzeptoren, die vierte Donatoren. Die Elemente der sechsten Gruppe substituieren As unter Bildung von Donatoren. Bei der Diskussion der gemessenen Verteilungskurven werden besonders die Verhältnisse in der Nähe der Eigenleitung bei einem großen Verhältnis der Elektronen- zur Defektelektronenbeweglichkeit berücksichtigt. Hieraus ergibt sich die Nullstelle des HALL-Koeffizienten bei einem derartigen Verhältnis. Ausdehnung der Messungen auf einen Temperaturbereich von 60 bis 1000° K zeigt, daß die Ionisierungsenergie sämtlicher Störstellen &lt; 0,005 eV ist. Es ergibt sich ein eindeutiger Zusammenhang zwischen den Störstellenkonzentrationen und der Beweglichkeit, unabhängig von dem betrachteten Element. Die Leitfähigkeit durchläuft mit steigender Störstellenkonzentration ein Maximum, jenseits von dem der Beweglichkeitsabfall den Anstieg der Ladungsträgerdichte überkompensiert.
The contourograph (1966)

Utilization of the three-dimensional aspects of the cathode-ray tube-vertical signal deflection, flexible time base, and intensity modulation-makes it possible to organize certain types of data into a meaningful format, greatly simplifying the interpretation of these data. This article describes the basic principles of organizing and displaying data in the contouro-graphic form, indicates several degrees of complexity in providing the instrumentation for this method, and presents a number of contourograms illustrating various applications.
Ras-induced cellular events (2000)

Ras is a crucial regulator of cell growth in eukaryotic cells. Activated Ras can stimulate signal transduction cascades, leading to cell proliferation, differentiation or apoptosis. It is also one of the most commonly mutated genes in both solid tumours and haematologic neoplasias. In leukaemia and tumours, aberrant Ras signalling can be induced directly by Ras mutation or indirectly by altering genes that associate with Ras or its signalling pathways. A requisite for Ras function is localization to the plasma membrane, which is induced by the post-translational modification farnesylation. Molecules that interfere with this Ras modification have been used as antitumour agents. Ras is emerging as a dual regulator of cell functions, playing either positive or negative roles in the control of proliferation or apoptosis. The diversity of Ras-mediated effects may be related in part to the differential involvement of Ras homologues in distinct cellular processes or to the expanding array of Ras effectors.
New Class IV Charge Model for Extracting Accurate Partial Charges from Wave Functions (1998)

We propose a new formalism, Charge Model 2 (CM2), to obtain accurate partial atomic charges from a population analysis of wave functions by a parametrized mapping procedure, so that the resulting charges reproduce highly accurate charge-dependent observables. The new method, which produces class IV charges, is illustrated by developing CM2 mappings of Löwdin charges obtained from semiempirical and ab initio Hartree−Fock theory and density functional theory, in particular AM1, PM3, HF/MIDI!, HF/6-31G*, HF/6-31+G*, BPW91/MIDI!, BPW91/6-31G*, B3LYP/MIDI!, and BPW91/DZVP calculations. The CM2 partial charges reproduce experimental dipole moments with root-mean-square errors that are typically a factor of 7 better than dipole moments computed from Mulliken population analysis, a factor of 3 better than dipole moments computed by Löwdin analysis, and even a factor of 2 better than dipole moments computed from the continuous electron denisty. At the HF/6-31G* and B3LYP/MIDI! levels, the new charge model yields root-mean-square errors of 0.19 and 0.18 D, respectively, for the dipole moments of a set of 211 polar molecules containing a diverse range of structures and organic functional groups and the elements H, C, N, O, F, Si, P, S, Cl, Br, and I. A comparison shows that the new charge model predicts dipole moments more accurately than MP2/cc-pVDZ calculations, which are considerably more expensive. The quality of the results is similarly good for electrostatic potentials and for the other parametrizations as well.
Cutting Edge: Increased Expression of Bcl-2 in Antigen-Specific Memory CD8+ T Cells (2000)

Bcl-2 plays a critical role in regulating cell survival and apoptosis. We examined Bcl-2 expression in virus-specific CD8 T cells during the expansion, death, and memory phases of the T cell response following infection of mice with lymphocytic choriomeningitis virus (LCMV). Naive CD8 T cells expressed a basal level of Bcl-2 that was down-regulated in effector CD8 T cells just before the death phase. Bcl-2 levels remained low during the death phase but surviving memory CD8 T cells expressed higher levels of Bcl-2 than naive cells. These changes were shown to occur in LCMV TCR transgenic cells as well as virus-specific CD8 T cells in C57BL/6 and BALB/c mice identified by MHC class I tetramers. In all instances, memory CD8 T cells expressed higher levels of Bcl-2, suggesting that increased Bcl-2 expression plays a role in the long-term maintenance of memory CD8 T cells in vivo.
Optical interconnection system for arrays of microemitters and detectors: combining printed microlenses and large-diameter GRINs (1998)

We present a high speed compact optical system with a large field of view, dedicated to optically interconnect planes of microemitters and receivers.
Effects of synthetic polycations on leucine incorporation, lactate dehydrogenase release, and morphology of human umbilical vein endothelial cells (1988)

Naturally occurring cationic proteins secreted by human granulocytes have pro-inflammatory effects including induction of increased vascular permeability and oedema, which are likely to be mediated by damage to vascular endothelium. Synthetic cationic polyamino acids have been shown to exert similar inflammatory effects in vivo. We have therefore used a range of synthetic polycationic amino acids to investigate the characteristics required to cause endothelial cell damage, assessed by in vitro inhibition of leucine incorporation into macromolecules by human umbilical vein endothelial cells (HUVEC) in culture. Exposure of HUVEC to 20 nM-2 microM cationic polypeptides of similar Mr(av) (approximately 40,000) in the presence of 20% serum produced a dose-dependent inhibition of [3H]leucine incorporation by polymers of ornithine, arginine or lysine. Similar results were obtained using [3H]thymidine. Neutral or anionic polypeptides of similar Mr were without effect. The molar potency of polylysines increased over the range Mr 40,000-120,000, while polylysines of Mr(av) less than 25,000 had no effect. In the absence of serum, inhibition occurred more rapidly and at lower doses. Inhibition of leucine and thymidine incorporation was time-dependent, e.g. exposure to 800 nM-polylysine, Mr(av) 90,000, led to progressively increasing inhibition that was complete after 24 h exposure, and was irreversible. The effects of polycations could not be blocked by pretreatment of the cells with polyanions. Precoating of the culture surface with polylysines had no effect on leucine incorporation by HUVEC or their subsequent response to polylysines in solution. Exposure to the peptide Arg-Gly-Asp-Ser inhibited incorporation by 30% but did not increase susceptibility to polylysine.(ABSTRACT TRUNCATED AT 250 WORDS)
Monte Carlo simulations of antibody adsorption and orientation on charged surfaces (2004)

Monte Carlo simulations were performed to study the adsorption and orientation of antibodies on charged surfaces based on both colloidal and all-atom models. The colloidal model antibody consists of 12 connected beads representing the 12 domains of an antibody molecule. The structure of the all-atom antibody model was taken from the protein databank. The effects of the surface charge sign and density, the solution pH and ionic strength on the adsorption and orientation of different colloidal model antibodies with different dipole moments were examined. Simulation results show that both the 12-bead and the all-atom models of the antibody, for which the dipole moment points from the Fc to (Fab)2 fragments, tend to have the desired "end-on" orientation on positively charged surfaces and undesired "head-on" orientation on negatively charged surfaces at high surface charge density and low solution ionic strength where electrostatic interactions dominate. At low surface charge density and high solution ionic strength where van der Waals interactions dominate, 12-bead model antibodies tend to have "lying-flat" orientation on surfaces. The orientation of adsorbed antibodies results from the compromise between electrostatic and van der Waals interactions. The dipole moment of an antibody is an important factor for antibody orientation on charged surfaces when electrostatic interactions dominate. This charge-driven protein orientation hypothesis was verified by our simulations results in this work. It was further confirmed by surface plasmon resonance biosensor and time-of-flight secondary ion mass spectrometry experiments reported elsewhere.
CN-CELEB: a challenging Chinese speaker recognition dataset (2019)

Recently, researchers set an ambitious goal of conducting speaker recognition in unconstrained conditions where the variations on ambient, channel and emotion could be arbitrary. However, most publicly available datasets are collected under constrained environments, i.e., with little noise and limited channel variation. These datasets tend to deliver over optimistic performance and do not meet the request of research on speaker recognition in unconstrained conditions. In this paper, we present CN-Celeb, a large-scale speaker recognition dataset collected `in the wild'. This dataset contains more than 130,000 utterances from 1,000 Chinese celebrities, and covers 11 different genres in real world. Experiments conducted with two state-of-the-art speaker recognition approaches (i-vector and x-vector) show that the performance on CN-Celeb is far inferior to the one obtained on VoxCeleb, a widely used speaker recognition dataset. This result demonstrates that in real-life conditions, the performance of existing techniques might be much worse than it was thought. Our database is free for researchers and can be downloaded from http://project.cslt.org.
A review of operational risk in banks and its role in the financial crisis (2013)

The role of operational risk in the 2007/2008 financial crisis is explored. The factors that gave rise to the crisis are examined and it is found that although the event is largely regarded as a credit crisis, operational risk factors played a significant role in fuelling its duration and severity. It is concluded that, from an operational risk perspective, 2008 was the worst on record. Considering the extensive role of operational risk in global financial calamities, suggestions are made to improve the management of this risk type.
Supporting effective common ground construction in Asynchronous Collaborative Visual Analytics (2011)

Asynchronous Collaborative Visual Analytics (ACVA) leverages group sensemaking by releasing the constraints on when, where, and who works collaboratively. A significant task to be addressed before ACVA can reach its full potential is effective common ground construction, namely the process in which users evaluate insights from individual work to develop a shared understanding of insights and collectively pool them. This is challenging due to the lack of instant communication and scale of collaboration in ACVA. We propose a novel visual analytics approach that automatically gathers, organizes, and summarizes insights to form common ground with reduced human effort. The rich set of visualization and interaction techniques provided in our approach allows users to effectively and flexibly control the common ground construction and review, explore, and compare insights in detail. A working prototype of the approach has been implemented. We have conducted a case study and a user study to demonstrate its effectiveness.
KEEP SETTLEMENT OUT OF THE TRANSPORT TRAP (1976)

The author states that if car ownership continues to increase and population densities to fall, the dispersed development pattern which results will require a great deal of energy to service it. If energy supply problems occurred in Britain in the 1990s, the changes in land use could not be reversed quickly and individual hardship would be suffered by people living in areas of low population density. It is suggested that the need to move out of areas of high population density should be minimised, an essential part of such an approach being the support of alternatives /TRRL/
Restricted ketogenic diet enhances the therapeutic action of <i>N</i>‐butyldeoxynojirimycin towards brain GM2 accumulation in adult Sandhoff disease mice (2010)

Sandhoff disease is an autosomal recessive, neurodegenerative disease involving the storage of brain ganglioside GM2 and asialo-GM2. Previous studies showed that caloric restriction, which augments longevity, and N-butyldeoxynojirimycin (NB-DNJ, Miglustat), an imino sugar that hinders the glucosyltransferase catalyzing the first step in glycosphingolipid biosynthesis, both increase longevity and improve motor behavior in the beta-hexosaminidase (Hexb) knockout (-/-) murine model of Sandhoff disease. In this study, we used a restricted ketogenic diet (KD-R) and NB-DNJ to combat ganglioside accumulation. Adult Hexb-/- mice were placed into one of the following groups: (i) a standard diet (SD), (ii) a SD with NB-DNJ (SD + NB-DNJ), (iii) a KD-R, and (iv) a KD-R with NB-DNJ (KD-R + NB-DNJ). Forebrain GM2 content (mug sialic acid/100 mg dry wt) in the four groups was 375 +/- 15, 312 +/- 8, 340 +/- 28, and 279 +/- 26, respectively, indicating an additive interaction between NB-DNJ and the KD-R. Most interestingly, brain NB-DNJ content was 3.5-fold greater in the KD-R + NB-DNJ mice than in the SD + NB-DNJ mice. These data suggest that the KD-R and NB-DNJ may be a potential combinatorial therapy for Sandhoff disease by enhancing NB-DNJ delivery to the brain and may allow lower dosing to achieve the same degree of efficacy as high dose monotherapy.