gebhart/patrepeval huggingface dataset:
Serum-based diagnosis and mouse models for preeclampsia (2009)

The overarching goal of this study is to use serum as a blueprint to establish in vivo and in vitro diagnostic and treatment models for pregnancy disorders such as preeclampsia and intrauterine growth restriction (IUGR). When combined, preeclampsia and IUGR complicate 10–15% of all pregnancies worldwide and are a major cause of maternal, fetal and neonatal mortality and morbidity. Despite intense investigation, these complications have remained enigmatic and the mechanisms that contribute to their emergence are largely unknown. We have recently initiated serum-based studies to establish in vitro and in vivo predictive and mechanistic assays for IUGR/preeclampsia. Our data strongly suggest that serum from preeclampsia/IUGR patients contains an „activity“ that disrupts cross-talk between placental invading trophoblasts and endothelial cells as well as causes preeclampsia and IUGR like symptoms in pregnant mice. The latter phenotype is particularly apparent in interleukin-10 (IL-10) deficient mice. A major task has been to expand these studies using a larger sample of human samples to verify these novel preliminary results and to identify the dysregulated protein component(s) by state of the art proteomic techniques such as mass spectrometry based Surface Enhanced Laser Desorption and Ionization-Time of Flight (SELDI-TOF). Results will be described with a focus on identification and biochemical and physiological properties of a novel protein that is invariably deficient in preeclampsia serum. Supported by the NIH-NCRR grant P20RR018728 and the Rhode Island Research Alliance Collaborative Research Award and STIFT (Foundation for Technology, Innovation and Research in Thuringia, Germany).
A novel taxane with improved tolerability and therapeutic activity in a panel of human tumor xenografts. (1999)

Clinically available taxanes represent one of the most promising class of antitumor agents, despite several problems with their solubility and toxicity. In an attempt to improve the pharmacological profile of taxanes, a new series of analogues was synthesized from 14beta-hydroxy-10-deacetylbaccatin III and tested in a panel of human tumor cell lines. On the basis of the pattern of cytotoxicity and lack of cross-resistance in tumor cell lines expressing the typical multidrug-resistant phenotype, a compound (IDN5109) was selected for preclinical development. A comparative efficacy study of IDN5109 and paclitaxel was performed using a large panel of human tumor xenografts, characterized by intrinsic (seven tumors) or acquired (four tumors) resistance to cisplatin or doxorubicin, including four ovarian, one breast, one cervical, three lung, one colon, and one prostatic carcinoma. Drugs were delivered i.v. according to the same schedule (four times every 4th day). IDN5109 achieved a very high level of activity (percentage tumor weight inhibition >70%; log10 cell kill >1) in all but one of the tested tumors. Compared to paclitaxel, IDN5109 exhibited a significantly superior activity in six tumors (including the four tumors that were resistant to paclitaxel) and a comparable activity against the other five paclitaxel-responsive tumors. Additional advantages of IDN5109 over paclitaxel were also suggested by its toxicity profile. IDN5109 was not only less toxic (maximal tolerated doses were 90 and 54 mg/kg for IDN5109 and paclitaxel, respectively), but it also appeared to be endowed with a reduced neurotoxic potential and an improved profile of tolerability compared to the parent drug. Furthermore, the best antitumor efficacy was often already reached with doses lower than the maximal tolerated dose, suggesting an improved therapeutic index for the new drug. In conclusion, the results support the preclinical interest of IDN5109 in terms of the toxicity profile and of the efficacy with particular reference to the ability to overcome multiple mechanisms of drug resistance.
Antiangiogenic therapies for glioblastoma (2014)

Glioblastoma is the most prevalent malignant primary brain tumor in adults and to date effective durable treatments are lacking. Preclinical studies underscore the importance of neovascularization for tumor survival, making angiogenesis an important treatment target. Early clinical experience in recurrent glioblastoma suggested that antiangiogenic agents may provide clinical benefit by prolonging progression-free survival, improving quality of life and decreasing peritumoral edema. Two recent Phase III randomized trials of antiangiogenic therapy at initial diagnosis suggested improvement in progression-free survival, but failed to show an overall survival benefit. Ongoing preclinical research focuses on mechanisms of resistance and potential predictive biomarkers. Identification of targets to resistance pathways and of predictive biomarkers will hopefully improve efficacy of antiangiogenic therapies.
Microfabrication of a digital microfluidic platform integrated with an on-chip electrochemical cell (2013)

We report on an IC compatible microfabrication process proposed for a novel monolithic lab-on-a-chip (LOC) with an electrochemical cell embedded in an electrowetting on dielectric (EWOD) digital microfluidic device. The optimized process focused on the surface modification of Teflon, selective exposure for the electrochemical module and recovery of surface properties by one-step annealing at low temperature. The optimum modification time and annealing temperature were 20 s and 210 °C, respectively. The experimental results from atomic force microscope and contact angle (CA) measurement revealed the effects of surface roughness and apparent CA on the wettability for different etch times. The multifunctionality of droplet creation, merger and transportation in the EWOD microfluidic module and sensitive electrochemical detection for the redox probe were realized simultaneously. The proposed microfabrication process has many advantages of remarkable simplicity, prominent repeatability, low cost and compatibility with standard IC processes. It shows great promise for the microsystem of the microfluidic unit and detecting cell, and gives a brilliant conception for the future fabrication of monolithic LOC integrated with functional detection.
MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to DNA double-strand breaks (2008)

The product of the Nijmegen breakage syndrome gene (NBS1) plays crucial roles in DNA damage response through its association with many proteins, including MRE11 and RAD50. However, it remains to be determined exactly how NBS1 accumulates at or near DNA double-strand breaks. Here we report that MDC1 directly binds to NBS1 and targets NBS1 to the sites of DNA damage. The MDC1-NBS1 interaction occurs through a specific region (residues 200-420) of MDC1, which contains multiple consensus casein kinase 2 (CK2) phosphorylation sites. In addition, this interaction requires both the forkhead-associated (FHA) and tandem BRCA1 C-terminal (BRCT) domains of NBS1. Disruption of the MDC1-NBS1 interaction results in failure of NBS1 accumulation at DNA double-strand breaks and impairment of intra-S checkpoint activation. These studies provide important mechanistic insights as to how MDC1 regulates NBS1 and the intra-S-phase checkpoint in response to DNA damage.
Physical properties of the HCT EUV source (2003)

The paper describes recent progress on the development of an EUV source based on a hollow cathode triggered gas discharge (HCT). The principle of operation has been described in previous publications. When operated with Xe, a repetition frequency up to 4 kHz, conversion efficiency of 0.55% inband radiation in 2&pi; and a pinch size below 3mm in length was demonstrated. Today's requirements on a commercial EUV source for volume production of wafers still exceed the current performance by large factors both in terms of output power and life time. This paper will discuss the roadmap to high power and will also show elements of the way to extended life time. Particular focus will be put onto the physical limits of Xe as radiator and the advantages of using Sn instead. It will be demonstrated that the spectral efficiency of Sn is a factor of 3 higher than Xe.
Intriguing properties of neural networks (2013)

Deep neural networks are highly expressive models that have recently achieved state of the art performance on speech and visual recognition tasks. While their expressiveness is the reason they succeed, it also causes them to learn uninterpretable solutions that could have counter-intuitive properties. In this paper we report two such properties. First, we find that there is no distinction between individual high level units and random linear combinations of high level units, according to various methods of unit analysis. It suggests that it is the space, rather than the individual units, that contains of the semantic information in the high layers of neural networks. Second, we find that deep neural networks learn input-output mappings that are fairly discontinuous to a significant extend. We can cause the network to misclassify an image by applying a certain imperceptible perturbation, which is found by maximizing the network's prediction error. In addition, the specific nature of these perturbations is not a random artifact of learning: the same perturbation can cause a different network, that was trained on a different subset of the dataset, to misclassify the same input.
A Unified Stochastic Model for Detecting and Tracking Faces (2005)

We propose merging face detection and face tracking into a single probabilistic framework. The motivation stems from a broader project in algorithmic modeling, centered on the design and analysis of the online computational process in visual recognition. Detection is represented as a tree-structured graphical network in which likelihoods are assigned to each history or "trace" of processing, thereby introducing a new probabilistic component into coarse-to-fine search strategies. When embedded within a temporal Markov framework, the resulting tracking system yields encouraging results.
Evidence for a reversible oxygen radical-mediated component of reperfusion injury: reduction by recombinant human superoxide dismutase administered at the time of reflow. (1987)

It has been suggested that the beneficial effects of reperfusing ischemic myocardium might be in part reversed by the occurrence of "reperfusion injury." One possible mechanism could be the generation of oxygen free radicals. Superoxide dismutase enzymatically scavenges superoxide radicals by dismutation to hydrogen peroxide. This study tested the hypothesis that administration of recombinant human superoxide dismutase (h-SOD) at the time of reflow after a period of prolonged global ischemia would result in improved recovery of myocardial metabolism and function by preventing or reducing a potentially harmful component of reperfusion. We also sought to determine whether catalase, an enzymatic scavenger of hydrogen peroxide, was a necessary addition for optimal benefit. Langendorff perfused rabbit hearts were subjected to 30 min of normothermic (37 degrees C) total global ischemia. At the moment of reperfusion, 12 control hearts received a 10 ml bolus of normal perfusate followed by 15 min of reperfusion with normal perfusate (group I), 12 hearts received 60,000 IU of h-SOD as a bolus followed by a continuous infusion of 100 IU/ml for 15 min (group II), and 12 hearts received 60,000 IU of h-SOD and 60,000 IU of catalase as a bolus followed by 100 IU/ml of both enzymes for 15 min (group III). Myocardial ATP and phosphocreatine (PCr) content and intracellular pH during ischemia and reperfusion were continuously monitored with 31P nuclear magnetic resonance (NMR) spectroscopy. During 30 min of normothermic global ischemia intracellular pH dropped from 7.11-7.18 to 5.58-5.80 in all three groups of hearts. Likewise myocardial PCr content fell rapidly to 7% to 8% and ATP fell more slowly to 29% to 36% of preischemic control content. After 45 min of reperfusion PCr recovered to 65 +/- 5% of control in untreated (group I) hearts compared with 89 +/- 8% in h-SOD-treated (group II) hearts (p less than .01 vs group I) and with 83 +/- 6% of control in h-SOD/catalase-treated (group III) hearts (p less than .05 vs group I). Recovery of isovolumic left ventricular developed pressure was 68 +/- 5% of control in h-SOD-treated (group II) hearts and 66 +/- 6% of control in h-SOD/catalase-treated (group III) hearts after 45 min of reflow, compared with 48 +/- 6% of control in untreated (group I) hearts (p less than .005 for groups II and III vs group I). The NMR data confirmed equal depletion of ATP and PCr content in all three groups of hearts.(ABSTRACT TRUNCATED AT 400 WORDS)
Mutational Analysis of the Saccharomyces cerevisiae ABD1 Gene: Cap Methyltransferase Activity Is Essential for Cell Growth (1996)

RNA (guanine-7-)-methyltransferase is the enzyme responsible for methylating the 5' cap structure of eukaryotic mRNA. The Saccharomyces cerevisiae enzyme is a 436-amino-acid protein encoded by the essential ABD1 gene. In this study, deletion and point mutations in ABD1 were tested for the ability to support growth of an abd1 null strain. Elimination of 109 amino acids from the N terminus had no effect on cell viability, whereas a more extensive N-terminal deletion of 155 residues was lethal, as was a C-terminal deletion of 55 amino acids. Alanine substitution mutations were introduced at eight conserved residues within a 206-amino-acid region of similarity between ABD1 and the methyltransferase domain of the vaccinia virus capping enzyme. ABD1 alleles H253A (encoding a substitution of alanine for histidine at position 253), T282A, E287A, E361A, and Y362A were viable, whereas G174A, D178A, and Y254A were either lethal or severely defective for growth. Alanine-substituted and amino-truncated ABD1 proteins were expressed in bacteria, purified, and tested for cap methyltransferase activity in vitro. Mutations that were viable in yeast cells had either no effect or only a moderate effect on the specific methyltransferase activity of the mutated ABD1 protein, whereas mutations that were deleterious in vivo yielded proteins that were catalytically defective in vitro. These findings substantiate for the first time the long-held presumption that cap methylation is an essential function in eukaryotic cells.
A low-cost control IC for single-transistor ZVS cold-cathode fluorescent lamp inverters and DC/DC converters (2002)

The paper reviews the various inverter topologies for cold-cathode fluorescent lamps, discusses the analysis and control of the class E inverter, and introduces a new control IC developed for such inverters and also for ZVS DC/DC power converters. The IC features a zero-voltage detector, switch overdissipation protection, soft start, pulse-by-pulse current limit, overvoltage protection, and on/off switching with a low-current stand-by mode. The primary use of the IC is in inverters for cold-cathode fluorescent lamps for display backlight applications, but the IC is also suitable for controlling ZVS quasi-resonant and multi-resonant DC/DC power converters.
Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults (2014)

National Institute for Health Research, Wellcome Trust, and Medical Research Council.
Spin Injection and Detection in Semiconductors—Electrical Issues and Device Aspects (2007)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> Spin selectivity has already been demonstrated for both injection and (recently) detection contacts on semiconductors, but a clear demonstration of a magnetoresistance signal is still lacking. After outlining the various categories of device proposals and the associated choice of semiconductor material, we summarize the various injection contact technologies that have been reported and assess their potential for practical device applications in terms of electrical efficiency, bias dependence (both intrinsic and extrinsic), and performance in unipolar devices. We then focus on the design of an all-electrical injection–detection device in GaAs and demonstrate that a correct design of the semiconductor channel and contact regions is the key for preserving the spin sensitivity that is provided by the contacts. </para>
Differences in Expression of Key DNA Damage Repair Genes after Epigenetic-Induced BRCAness Dictate Synthetic Lethality with PARP1 Inhibition (2015)

Abstract The triple-negative breast cancer (TNBC) subtype represents a cancer that is highly aggressive with poor patient outcome. Current preclinical success has been gained through synthetic lethality, targeting genome instability with PARP inhibition in breast cancer cells that harbor silencing of the homologous recombination (HR) pathway. Histone deacetylase inhibitors (HDACi) are a class of drugs that mediate epigenetic changes in expression of HR pathway genes. Here, we compare the activity of the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA), the class I/IIa HDAC inhibitor valproic acid (VPA), and the HDAC1/2–specific inhibitor romidepsin (ROMI) for their capability to regulate DNA damage repair gene expression and in sensitizing TNBC to PARPi. We found that two of the HDACis tested, SAHA and ROMI, but not VPA, indeed inhibit HR repair and that RAD51, BARD1, and FANCD2 represent key proteins whose inhibition is required for HDACi-mediated therapy with PARP inhibition in TNBC. We also observed that restoration of BRCA1 function stabilizes the genome compared with mutant BRCA1 that results in enhanced polyploid population after combination treatment with HDACi and PARPi. Furthermore, we found that overexpression of the key HR protein RAD51 represents a mechanism for this resistance, promoting aberrant repair and the enhanced polyploidy observed. These findings highlight the key components of HR in guiding synthetic lethality with PARP inhibition and support the rationale for utilizing the novel combination of HDACi and PARPi against TNBC in the clinical setting. Mol Cancer Ther; 14(10); 2321–31. ©2015 AACR.
Human Lymphoblastoid Cell Line Producing Specific Antibody against Rh‐Antigen D (1980)

A lymphoblastoid cell line producing specific anti-Rh antibody against D determinant was established by Epstein-Barr virus (EBV) infection. The lymphocytes were from an immunized male donor with high titre of anti-D antibody. The cells were preselected by rosetting them with Rh-positive erythrocytes before EBV infection. The cell line produced specific antibody of IgG class, namely IgG1 subclass, but it also produced nonspecific IgM and IgG. By rerosetting the cell line, the specific antibody-producing population could be enriched and the antibody titre increased in the culture supernatant to the level of immune sera.
Coactivation of GABA A and GABA B Receptor Results in Neuroprotection During In Vitro Ischemia (2004)

Antiepileptic drugs targeting GABAergic transmission can exert neuroprotective effects against ischemia by increasing endogenous GABA levels and via the activation of both GABA(A) and GABA(B) receptors.
EFFECT OF A MALARIA SUPPRESSION PROGRAM ON THE INCIDENCE OF AFRICAN BURKITT'S LYMPHOMA (1989)

From 1977 to 1982, the authors attempted a malaria suppression trial in North Mara District, Tanzania, to see whether the incidence of Burkitt's lymphoma (BL) could be lowered by reducing the level of malarial infection in a child population below 10 years of age. Immediately after initiation of the suppression trial, the prevalence of malaria fell drastically in the Mara children; however, soon after, the rate of malarial infection rose again in the trial area in spite of continued chloroquine distribution, and by 1981 the prevalence of malarial infection again reached the high levels that had prevailed in the North Mara lowlands before 1977. However, during the period of chloroquine distribution in North Mara, the level of malarial infection there was constantly lower than that observed in a comparison area in South Mara, although the two areas had been similar with respect to malaria endemicity prior to the intervention. During the years of chloroquine distribution in North Mara, the incidence rate of BL there fell considerably, from about 4 per 100,000 population to about 1 per 100,000 population, and it rose again to pretrial levels in 1984, that is, about two years after the chloroquine distribution had been terminated. This apparent association between malaria suppression and decline in BL incidence at first seemed to indicate that malaria is a causal factor in BL production. A close scrutiny of the survey data revealed, however, that the decline in BL incidence might have started several years before the chloroquine distribution began; thus it appears that the malaria suppression could not have been the sole cause of the BL decline.
Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors (1998)

Central antinociceptive effects of cannabinoids have been well documented. However, relatively little is known about the peripheral effects of the cannabinoids on inflammation. In the present study, we evaluated the effects of peripherally administered cannabinoids on three indices of inflammation: carrageenan-induced thermal hyperalgesia, carrageenan-induced edema, and capsaicin-induced plasma extravasation. In addition, we determined the effect of cannabinoids on capsaicin-evoked neuropeptide release from isolated rat hindpaw skin. Our results indicate that cannabinoids produce antihyperalgesia via interaction with a peripheral CB1 receptor. Peripheral, but not systemic, administration of 0.01 ng anandamide inhibited the induction of hyperalgesia. Peripheral administration of anandamide also attenuated hyperalgesia after its development via interaction with the CB1 cannabinoid receptor subtype as indicated by its reversal with the CB1 receptor antagonist SR 141716A. Additionally, peripheral, but not systemic, administration of 0.01 ng anandamide inhibited edema. Peripherally administered cannabinoids also interacted with CB1 receptors to inhibit capsaicin-evoked plasma extravasation into the hindpaw. One potential mechanism for the anti-inflammatory actions of the cannabinoids is the inhibition of neurosecretion from the peripheral terminals of nociceptive primary afferent fibers. This hypothesis is supported by the finding that anandamide inhibited capsaicin-evoked release of calcitonin gene-related peptide from isolated hindpaw skin. Collectively, these results indicate that cannabinoids reduce inflammation via interaction with a peripheral CB1 receptor. A potential mechanism for this effect is the inhibition of neurosecretion from capsaicin-sensitive primary afferent fibers.
Geometrically enhanced extraordinary magnetoresistance in semiconductor-metal hybrids (2010)

Extraordinary magnetoresistance (EMR) arises in hybrid systems consisting of semiconducting material with an embedded metallic inclusion. We have investigated such systems with the use of finite-element modeling, with our results showing good agreement to existing experimental data. We show that this effect can be dramatically enhanced by over four orders of magnitude as a result of altering the geometry of the conducting region. The significance of this result lies in its potential application to EMR magnetic field sensors utilizing more familiar semiconducting materials with nonoptimum material parameters, such as silicon. Our model has been extended further with a geometry based on the microstructure of the silver chalcogenides, consisting of a randomly sized and positioned metallic network with interspersed droplets. This model has shown a large and quasilinear magnetoresistance analogous to experimental findings.