gebhart/patrepeval huggingface dataset:
Glucocorticoids Inhibit Developmental Stage-specific Osteoblast Cell Cycle (2000)

Unique cell cycle control is instituted in confluent osteoblast cultures, driving growth to high density. The postconfluent dividing cells share features with cells that normally exit the cell cycle; p27(kip1) is increased, p21(waf1/cip1) is decreased, free E2F DNA binding activity is reduced, and E2F4 is primarily nuclear. E2F4-p130 becomes the predominant E2F-pocket complex formed on E2F sites, but, unlike the complex that typifies resting cells, cyclin A and CDK2 are also present. Administration of dexamethasone at this, but not earlier stages, results in reduction of cyclin A and CDK2 levels with a parallel decrease in the associated kinase activity, dissociation of cyclin A-CDK2 from the E2F4-p130 complexes, and inhibition of G(1)/S transition. The glucocorticoid-mediated cell cycle attenuation is also accompanied by, but not attributable to, increased p27(kip1) and decreased p21(waf1/cip1) levels. The attenuation of osteoblast growth to high density by dexamethasone is associated with severe impairment of mineralized extracellular matrix formation, unless treatment commences in cultures that have already grown to high density. Both the antimitotic and the antiphenotypic effects are reversible, and both are antagonized by RU486. Thus, glucocorticoids induce premature attenuation of the osteoblast cell cycle, possibly contributing to the osteoporosis induced by these drugs in vivo.
Resistance to BET Bromodomain Inhibitors Is Mediated by Kinome Reprogramming in Ovarian Cancer (2016)

Small-molecule BET bromodomain inhibitors (BETis) are actively being pursued in clinical trials for the treatment of a variety of cancers, but the mechanisms of resistance to BETis remain poorly understood. Using a mass spectrometry approach that globally measures kinase signaling at the proteomic level, we evaluated the response of the kinome to targeted BETi treatment in a panel of BRD4-dependent ovarian carcinoma (OC) cell lines. Despite initial inhibitory effects of BETi, OC cells acquired resistance following sustained treatment with the BETi JQ1. Through application of multiplexed inhibitor beads (MIBs) and mass spectrometry, we demonstrate that BETi resistance is mediated by adaptive kinome reprogramming, where activation of compensatory pro-survival kinase networks overcomes BET protein inhibition. Furthermore, drug combinations blocking these kinases may prevent or delay the development of drug resistance and enhance the efficacy of BETi therapy.
Inductive Representation Learning in Large Attributed Graphs (2017)

Graphs (networks) are ubiquitous and allow us to model entities (nodes) and the dependencies (edges) between them. Learning a useful feature representation from graph data lies at the heart and success of many machine learning tasks such as classification, anomaly detection, link prediction, among many others. Many existing techniques use random walks as a basis for learning features or estimating the parameters of a graph model for a downstream prediction task. Examples include recent node embedding methods such as DeepWalk, node2vec, as well as graph-based deep learning algorithms. However, the simple random walk used by these methods is fundamentally tied to the identity of the node. This has three main disadvantages. First, these approaches are inherently transductive and do not generalize to unseen nodes and other graphs. Second, they are not space-efficient as a feature vector is learned for each node which is impractical for large graphs. Third, most of these approaches lack support for attributed graphs. To make these methods more generally applicable, we propose a framework for inductive network representation learning based on the notion of attributed random walk that is not tied to node identity and is instead based on learning a function $Φ: \mathrm{\rm \bf x} \rightarrow w$ that maps a node attribute vector $\mathrm{\rm \bf x}$ to a type $w$. This framework serves as a basis for generalizing existing methods such as DeepWalk, node2vec, and many other previous methods that leverage traditional random walks.
Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy (2000)

Lateral resolution that exceeds the classical diffraction limit by a factor of two is achieved by using spatially structured illumination in a wide-field fluorescence microscope. The sample is illuminated with a series of excitation light patterns, which cause normally inaccessible high-resolution information to be encoded into the observed image. The recorded images are linearly processed to extract the new information and produce a reconstruction with twice the normal resolution. Unlike confocal microscopy, the resolution improvement is achieved with no need to discard any of the emission light. The method produces images of strikingly increased clarity compared to both conventional and confocal microscopes.
Study of mechanisms of cold roll welding of aluminium alloy to steel strip (2004)

The mechanisms of cold roll welding of aluminium alloy to steel strip has been assessed based on a study of interfacial behaviour at deformations of up to 60% together with the surface characteristics of peeled Al clad steel strip. The proposed mechanisms are applicable where the contact surfaces are degreased and then scratch brushed before the rolling deformation. According to this mechanisms the scratch-brushed layers are fractured shortly after entering the roll gap at a reduction of approximately 10%, which is about the threshold deformation for the roll bonding of aluminium to steel. The transfer cracks formed then become wider so that the distance between each coherent block increases as the rolling deformation increases through the mill. This process allows the bond to be established between the underlying areas, termed as virgin metal, of base metal, which are extruded between the cracks at the scratch brushed regions.
Discovery of a Potent and Selective Noncovalent Linear Inhibitor of the Hepatitis C Virus NS3 Protease (BI 201335) (2010)

C-Terminal carboxylic acid containing inhibitors of the NS3 protease are reported. A novel series of linear tripeptide inhibitors that are very potent and selective against the NS3 protease are described. A substantial contribution to the potency of these linear inhibitors arises from the introduction of a C8 substituent on the B-ring of the quinoline moiety found on the P2 of these inhibitors. The introduction of a C8 methyl group results not only in a modest increase in the cell-based potency of these inhibitors but more importantly in a much better pharmacokinetic profile in rats as well. Exploration of C8-substitutions led to the identification of the bromo derivative as the best group at this position, resulting in a significant increase in the cell-based potency of this class of inhibitors. Structure-activity studies on the C8-bromo derivatives ultimately led to the discovery of clinical candidate 29 (BI 201335), a very potent and selective inhibitor of genotype1 NS3 protease with a promising PK profile in rats.
Metalorganic deposition of high-J c Ba2YCu3O7−x thin films from trifluoroacetate precursors onto (100) SrTiO3 (1990)

Superconducting thin films of Ba2YCu3O7-x were prepared on (100) SrTiO3 substrates by metalorganic deposition (MOD) of trifluoroacetate precursors. The best electrical transport properties were measured in films annealed at 750 °C in a humid, low PO2 gas mixture followed by slow cooling in oxygen. These specimens had sharp resistive transitions with Tc above 90 K and zero-field critical current densities in excess of 106 A/cm2 at 77 K. Critical current densities of this magnitude have not previously been reported in films produced by MOD. The highest Jc obtained in films fired only in humid oxygen was 3×105 A/cm2. Annealing at high temperature in the low PO2 atmosphere also resulted in a smoother surface morphology than was observed in the oxygen-fired films. Use of the low PO2 furnace gas appeared to suppress the formation of b-axis normal oriented grains in the superconducting films and to strengthen c-axis normal texture. X-ray powder diffraction indicated the presence of a-axis normal textured material in the films, although it was not present as separate microstructural features which could be identified by scanning electron microscopy.
Induction of apoptosis in macrophages by Pseudomonas aeruginosa azurin: tumour‐suppressor protein p53 and reactive oxygen species, but not redox activity, as critical elements in cytotoxicity (2003)

Azurin is a copper-containing protein involved in electron transfer during denitrification. We reported recently that purified azurin demonstrates cytotoxicity to macrophages by forming a complex with the tumour-suppressor protein p53, thereby stabilizing it and enhancing its function as an inducer of proapoptotic activity (Yamada, T., Goto, M., Punj, V., Zaborina, O., Kimbara, K., Das Gupta, T. K., and Chakrabarty, A. M. 2002, Infect Immun70: 7054-7062). It is, however, not known whether the oxidoreductase (redox) activity of azurin or the involvement of copper is important for its cytotoxicity. We have isolated apo-azurin devoid of copper and site-directed mutants that are redox negative because of either replacement of a cysteine residue (Cys-112) involved in co-ordination with copper or mutational replacement of two methionine residues (Met-44 and Met-64) that are present in the hydrophobic patch of azurin and allow interaction of azurin with its redox partner cytochrome c551. We demonstrate that, although the wild type (wt) and the Cys-112 Asp mutant azurin can form complexes with the tumour-suppressor protein p53 and generate high levels of reactive oxygen species (ROS), the redox-negative Met-44LysMet-64Glu mutant azurin is defective in complex formation with p53, generates low levels of ROS and lacks appreciable cytotoxicity towards macrophages. Thus, complex formation with p53 and ROS generation, rather than azurin redox activity, are important in the cytotoxic action of azurin towards macrophages.
An integrated approach to electronic waste (WEEE) recycling (2007)

Purpose This paper aims to present a review carried out under DEFRA‐funded project WRT208, describing: the composition of WEEE, current treatment technologies, emerging technologies and research. Design/methodology/approach This paper summarises the output from the first part of the project. It provides information on the composition of WEEE and an extensive survey of technologies relevant to materials recycling from WEEE. A series of further papers will be published from this research project. Findings WEEE has been identified as one of the fastest growing sources of waste in the EU, and is estimated to be increasing by 16‐28 per cent every five years. Within each sector a complex set of heterogeneous secondary wastes is created. Although treatment requirements are complicated, the sources from any one sector possess many common characteristics. However, there exist huge variations in the nature of electronic wastes between sectors, and treatment regimes appropriate for one cannot be readily transferred to another. Research limitations/implications A very large number of treatment technologies are available, both established and emerging, that singly and in combination could address the specific needs of each sector. However, no single set of treatment methods can be applied universally. Originality/value This paper is the first part of work leading to the development of technical strategies and methodologies for reprocessing WEEE into primary and secondary products, and where possible the recovery of higher added‐value components and materials.
Heterochromatic features of an 11-megabase transgene in brain cells. (1991)

Transgenic mice provide a remarkable experimental setting for the study of nuclear architecture. The three-dimensional localization and fine structure of a foreign DNA within the mouse genome can be conveniently followed by using high-resolution in situ hybridization. Foreign DNAs designed with specific characteristics, such as base bias, sequence motif(s), and size can stably integrate into finite positions on host chromosomes. Thus the relative importance of each of these characteristics in determining the three-dimensional nuclear position and the detailed morphology of the transgene can be evaluated in different cell types. The aim of this study was to evaluate a transgene with sequence characteristics that might contribute to the de novo formation of heterochromatin in interphase nuclei. The structure of a phenotypically silent 11-megabase transgene, containing tandem repeats of beta-globin-pBR sequences integrated into the peritelomeric region of both mouse chromosome 3 homologs, was determined in adult brain cells. Neurons that are largely euchromatic were especially informative in three-dimensional studies of transgene position. The two transgenic loci behaved much like centromeric or paracentromeric A + T-rich satellite DNAs of comparable length from a single chromosome; one or both transgene domains localized together with centromeric satellite DNA on the nucleolus. This is an unusual nuclear position for a telomeric or chromosome arm region that does not contain a substantial amount of constitutively heterochromatic satellite DNA. G + C richness did not prevent these regions from assembling as dense heterochromatic bodies of approximately 1 micron3 in volume. Ultrastructurally, transgenic domains were often intimately connected with constitutive heterochromatin and were highly condensed. Labeled supercoils, formed by a discrete approximately 250-nm-wide fiber, were observed in oblique thin sections through the center of the domain. The structural data were consistent with negligible transcriptional activity detected for this locus, as well as the predicted conformation of constitutive heterochromatin. Interestingly, in transgenic but not control mice, a substantial number of large neurons, including approximately 30% of cerebellar Purkinje cells, showed excessive invaginations of the nuclear membrane.
Neuroinhibition of Xylazine Induced Emesis (1988)

Xylazine produces retching and vomiting presumably by activation of the chemoreceptor trigger zone (CTZ). The purpose of this project was to investigate whether neuroinhibition can prevent xylazine vomiting. Inhibitory neurons in the cervical vagus nerve of cats were stimulated with implanted cuff electrodes. Female cats, weighing from 3 to 4 kg, were anaesthetized with pentobarbital for surgical implantation of electrodes. After full recovery from surgery, animals were tested in weekly sessions. Stimulation was via a pulse generator connected to photon coupled linear isolator supplying constant current. Videotape was used to record observations. The range of effective stimulation was 1-10 ma, 4-100 Hz and 0.3-0.6 msec. Stimulation was initiated thirty sec. after subcutaneous injection of xylazine, 0.66 mg/kg. Stimulation of the inhibitory nerve group of the cervical vagus was effective in preventing vomiting in over 85% of the experimental trials. In addition to preventing emesis during stimulation, the latency of xylazine emesis was increased over control values. Repeated experimental trials of stimulation coupled with xylazine injection could result in the complete absence of emesis.
Review of measures for light-source color rendition and considerations for a two-measure system for characterizing color rendition (2013)

Twenty-two measures of color rendition have been reviewed and summarized. Each measure was computed for 401 illuminants comprising incandescent, light-emitting diode (LED) -phosphor, LED-mixed, fluorescent, high-intensity discharge (HID), and theoretical illuminants. A multidimensional scaling analysis (Matrix Stress = 0.0731, R(2) = 0.976) illustrates that the 22 measures cluster into three neighborhoods in a two-dimensional space, where the dimensions relate to color discrimination and color preference. When just two measures are used to characterize overall color rendition, the most information can be conveyed if one is a reference-based measure that is consistent with the concept of color fidelity or quality (e.g., Q(a)) and the other is a measure of relative gamut (e.g., Q(g)).
Super-channels: DWDM transmission beyond 100 Gb/s (2012)

Super-channels promise high-bandwidth transmission while decoupling channel capacity from baud rate. Photonic Integrated Circuits (PICs) are optimal for delivering super-channels at over 100 Gb/s, with flexibility in modulation format, baud rate, dispersion tolerance, and reach.
Correcting human mitochondrial mutations with targeted RNA import (2012)

Mutations in the human mitochondrial genome are implicated in neuromuscular diseases, metabolic defects, and aging. An efficient and simple mechanism for neutralizing deleterious mitochondrial DNA (mtDNA) alterations has unfortunately remained elusive. Here, we report that a 20-ribonucleotide stem-loop sequence from the H1 RNA, the RNA component of the human RNase P enzyme, appended to a nonimported RNA directs the import of the resultant RNA fusion transcript into human mitochondria. The methodology is effective for both noncoding RNAs, such as tRNAs, and mRNAs. The RNA import component, polynucleotide phosphorylase (PNPASE), facilitates transfer of this hybrid RNA into the mitochondrial matrix. In addition, nucleus-encoded mRNAs for mitochondrial proteins, such as the mRNA of human mitochondrial ribosomal protein S12 (MRPS12), contain regulatory sequences in their 3'-untranslated region (UTR) that confers localization to the mitochondrial outer membrane, which is postulated to aid in protein translocation after translation. We show that for some mitochondrial-encoded transcripts, such as COX2, a 3'-UTR localization sequence is not required for mRNA import, whereas for corrective mitochondrial-encoded tRNAs, appending the 3'-UTR localization sequence was essential for efficient fusion-transcript translocation into mitochondria. In vivo, functional defects in mitochondrial RNA (mtRNA) translation and cell respiration were reversed in two human disease lines. Thus, this study indicates that a wide range of RNAs can be targeted to mitochondria by appending a targeting sequence that interacts with PNPASE, with or without a mitochondrial localization sequence, providing an exciting, general approach for overcoming mitochondrial genetic disorders.
Twelfth annual Pezcoller symposium: signaling cross-talks in cancer cells. (2000)

Signaling as an overall cellular process is a prerequisite for the life of normal and cancer cells and is regulated by a multiplicity of mechanisms including "cross-talks" among pathways. Cross-talk is often critical in determining the decision of a cell to go toward a specific biological direction, such as proliferation, apoptosis, or differentiation. Both signaling pathways and cross-talk among them involve such biochemical processes as protein-to-protein interactions and well-regulated phosphorylation and dephosphorylation processes. This symposium was focused on mechanisms of the regulation of signaling with special emphasis on regulatory cross-talk among pathways and on changes that occur in cancer cells. The phenomena discussed were also considered with reference to opportunities that may be offered toward the development of potential therapeutic intervention.
Recognition of HLA Class I–Restricted β-Cell Epitopes in Type 1 Diabetes (2006)

Type 1 diabetes results from the autoimmune destruction of insulin-producing pancreatic beta-cells by cytotoxic T-lymphocytes (CTLs). In humans, few beta-cell epitopes have been reported, thereby limiting the study of beta-cell-specific CTLs in type 1 diabetes. To identify additional epitopes, HLA class I peptide affinity algorithms were used to identify a panel of peptides derived from the beta-cell proteins islet amyloid polypeptide (IAPP), islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), insulin, insulinoma-associated antigen 2 (IA-2), and phogrin that were predicted to bind HLA-A*0201. Peripheral blood mononuclear cells from 24 HLA-A*0201 recent-onset type 1 diabetic patients and 11 nondiabetic control subjects were evaluated for gamma-interferon secretion in response to peptide stimulation in enzyme-linked immunospot assays. We identified peptides IAPP9-17, IGRP215-223, IGRP152-160, islet IA-2(172-180), and IA-2(482-490) as novel HLA-A*0201-restricted T-cell epitopes in type 1 diabetic patients. Interestingly, we observed a strong inverse correlation between the binding affinity of beta-cell peptides to HLA-A*0201 and CTL responses against those peptides in recent-onset type 1 diabetic patients. In addition, we found that self-reactive CTLs with specificity for an insulin peptide are frequently present in healthy individuals. These data suggest that many beta-cell epitopes are recognized by CTLs in recent-onset type 1 diabetic patients. These epitopes may be important in the pathogenesis of type 1 diabetes.
Erythropoietin improves myocardial performance in doxorubicin-induced cardiomyopathy (2006)

Aims Doxorubicin (Dox) is a potent chemotherapeutic agent associated with severe cardiotoxicity. Erythropoietin (Epo) has recently been shown to exhibit proangiogenic properties related to endothelial progenitor cell (EPC) mobilization. We tested the hypothesis that EPC are compromised in rats with Doxinduced cardiotoxicity and correction of this functional impairment by treatment with Epo could result in attenuation of myocardial dysfunction. Methods and results Wistar rats were either treated with two different doses of Epo (20U or 200U) or PBS (n 40 in each group) for four consecutive weeks, followed by Dox administration. In a second study, EPC obtained from healthy rats were transfused intravenously (n 20/group) prior to induction of Dox cardiomyopathy. EPC from healthy subjects were evaluated for their proliferative and migratory properties in the presence or absence of Dox and Epo pre-treatment. Echocardiography demonstrated an improvement in fractional shortening (FS) in Epo-treated rats. Epo treatment was associated with a reduced mortality in both Epo-treated groups. Circulating EPC numbers were three times higher in Epo-treated compared with non-treated animals. Adhesive properties, migration, and tube formation capacity in matrigel of EPCs from both Epo-treated groups as compared with controls were significantly enhanced. EPC transfer to Dox-treated rats led to functional myocardial improvement equivalent to the protection afforded by treatment with Epo. In EPC obtained from humans, pre-incubation with Epo significantly attenuated the anti-proliferative and anti-migratory effects of treatment with Dox. Conclusion Epo treatment is potentially protective against myocardial dysfunction induced by Dox. These effects are partially mediated by enhancement in the number of EPC and their functional properties.