gebhart/patrepeval huggingface dataset:
Roll‐To‐Roll Ultrathin Flexible Ceramic for Cost Effective Coating (2015)

This paper presents ENrG's 2015 introduction of its goal to produce an in-line, coatable format of its Thin E-Strate® product. The 20 microns thick product, targeted between 100-300 meters long, with initial widths up to 5 centimeters, is being developed for customers capable of coating in roll-to-roll (R2R) form. Unlike plastic films in which temperature and humidity affect roll-to-roll handling and alignment, Thin E-Strate® is stable, inert and is translucent for two-sided coating registration. This flexible ceramic can handle higher temperature processing, does not absorb moisture and is corrosion resistant. Thin E_Strate®, a flexible zirconia based ceramic membrane, was originally introduced in 2010 at 40 microns thick. Even though so thin, the membrane is gas-tight, fully dense, strong, thermal shock tolerant and chemically inert. Inherent properties of the membrane are compatible with many applications including wearable electronics, mechanical sensors, medical electronics, microbatteries, solar photovoltaic, power electronics, solid-state lighting, transparent infrared windows, fuel cells, and superconductors. These uses tap into additional membrane properties via application-specific coatings. Many of these market opportunities require the thin ceramic to be supplied in a R2R form for more economical processing.
Pain Threshold in Patients with Rheumatoid Arthritis and Effect of Manual Oscillations (1999)

Using a pressure algometer pain threshold (PT) measurements were carried out in the paraspinal area as well as at the knee and ankle joints in 30 adults with active rheumatoid arthritis (RA) and in 30 healthy adults. The group of RA patients was then randomly divided in two. In 15 RA patients a manual oscillation technique was applied at T12 and L4 for 12 minutes. The 15 other patients were resting. Immediately after the experimental procedure the PT was measured again at the same points in all patients. The RA patients showed a significantly (p < 0.05) lower PT than the healthy adults at all investigated points, which suggests that in RA certain changes arise in the peripheral and central nociceptive processing system, as mentioned in the literature. In the second measurement session for the RA patients the PT was significantly higher (p<0.05) after manual oscillations than after rest, at the paraspinal area of T6, L1 and L3. Further research into the long-term effect of repeated manual oscillation sessions is warranted.
Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death (2006)

For assessing risk in individual persons, the use of the 10 contemporary biomarkers that we studied adds only moderately to standard risk factors.
Biosynthesis of terpenoids: YchB protein of Escherichia coli phosphorylates the 2-hydroxy group of 4-diphosphocytidyl-2C-methyl- d -erythritol (2000)

A comparative analysis of all published complete genomes indicated that the putative orthologs of the unannotated ychB gene of Escherichia coli follow the distribution of the dxs, dxr, and ygbP genes, which have been shown to specify enzymes of the deoxyxylulose phosphate pathway of terpenoid biosynthesis, thus suggesting that the hypothetical YchB protein also is involved in that pathway. To test this hypothesis, the E. coli ychB gene was expressed in a homologous host. The recombinant protein was purified to homogeneity and was shown to phosphorylate 4-diphosphocytidyl-2C-methyl-D-erythritol in an ATP-dependent reaction. The reaction product was identified as 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate by NMR experiments with various (13)C-labeled substrate samples. A (14)C-labeled specimen of this compound was converted efficiently into carotenoids by isolated chromoplasts of Capsicum annuum. The sequence of E. coli YchB protein is similar to that of the protein predicted by the tomato cDNA pTOM41 (30% identity), which had been implicated in the conversion of chloroplasts to chromoplasts.
Staurosporine-Derived Inhibitors Broaden the Scope of Analog-Sensitive Kinase Technology (2013)

Analog-sensitive (AS) kinase technology is a powerful approach for studying phospho-signaling pathways in diverse organisms and physiological processes. The key feature of this technique is that a kinase-of-interest can be mutated to sensitize it to inhibitor analogs that do not target wild-type (WT) kinases. In theory, this enables specific inhibition of any kinase in cells and in mouse models of human disease. Typically, these inhibitors are identified from a small library of molecules based on the pyrazolopyrimidine (PP) scaffold. However, we recently identified a subset of native human kinases, including the Ephrin A kinase family, that are sensitive to commonly used PP inhibitors. In an effort to develop a bioorthogonal AS-kinase inhibitor and to extend this technique to PP-sensitive kinases, we sought an alternative inhibitor scaffold. Here we report the structure-based design of synthetically tractable, potent, and extremely selective AS-kinase inhibitors based on the natural product staurosporine. We demonstrate that these molecules, termed staralogs, potently target AS kinases in cells, and we employ X-ray crystallography to elucidate their mechanism of efficacy. Finally, we demonstrate that staralogs target AS mutants of PP-sensitive kinases at concentrations where there is little to no inhibition of native human kinases. Thus, staralogs represent a new class of AS-kinase inhibitors and a core component of the chemical genetic tool kit for probing kinase-signaling pathways.
[Combination with SN-38 on human colon cancer LoVo cells]. (2009)

These findings suggest the anti-proliferation effect of bevacizumab and SN-38 was schedule-dependent, and the synergistic effect of Bevacizumab and SN-38 was related to drug modulation of the HIF-1alpha and MAP kinase pathway.
Filtroporation: A simple, reliable technique for transfection and macromolecular loading of cells in suspension (1999)

Cultured Chinese hamster ovary (CHO) cells suspended in their growth medium were forced by gas pressure through the uniformly sized micropores of filter membranes. This procedure caused transient damage to the plasma membrane, which increased the permeability of the cells to exogenous molecules. This “filtroporation” was indicated by uptake of fluorescent dextran molecules up to 500,000 MW in cells deemed viable by trypan blue dye exclusion. The macromolecular uptake was increased if the driving pressure was increased at constant micropore size, or if the micropore size was decreased at constant driving pressure. Larger membrane perturbations permitted uptake of a luciferase reporter plasmid, which resulted in transfection of the CHO cells with the surviving cells expressing luciferase activity after 2 days in culture. This simple and general new method of porating cells in suspension may be optimized to incorporate the desired macromolecules while retaining the maximum viability. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 65: 341–346, 1999.
Listeria monocytogenes as a Vector for Anti-Cancer Therapies (2010)

The intracellular pathogen Listeria monocytogenes represents a promising therapeutic vector for the delivery of DNA, RNA or protein to cancer cells or to prime immune responses against tumour-specific antigens. A number of biological properties make L. monocytogenes a promising platform for development as a vector for either gene therapy or as an anti-cancer vaccine vector. L. monocytogenes is particularly efficient in mediating internalization into host cells. Once inside cells, the bacterium produces specific virulence factors which lyse the vaculolar membrane and allow escape into the cytoplasm. Once in the cytosol, L. monocytogenes is capable of actin-based motility and cell-to-cell spread without an extracellular phase. The cytoplasmic location of L. monocytogenes is significant as this potentiates entry of antigens into the MHC Class I antigen processing pathway leading to priming of specific CD8(+) T cell responses. The cytoplasmic location is also beneficial for the delivery of DNA (bactofection) by L. monocytogenes whilst cell-to-cell spread may facilitate access of the vector to cells throughout the tumour. Several preclinical studies have demonstrated the ability of L. monocytogenes for intracellular gene or protein delivery in vitro and in vivo, and this vector has also displayed safety and efficacy in clinical trial. Here, we review the features of the L. monocytogenes host-pathogen interaction that make this bacterium such an attractive candidate with which to induce appropriate therapeutic responses. We focus primarily upon work that has led to attenuation of the pathogen, demonstrated DNA, RNA or protein delivery to tumour cells as well as research that shows the efficacy of L. monocytogenes as a vector for tumour-specific vaccine delivery.
Amino acid sequence of the .beta. chain of human fibrinogen (1979)

The beta chain of human fibrinogen contains 461 amino acid residues, 15 of which are methionines. The calculated molecular weight, independent of a single carbohydrate cluster, is 52 230. In this regard, we have isolated and characterized all 16 cyanogen bromide fragments. In one case (CNI), we have concentrated on a disputed portion of a previously reported fragment. The arrangement of the cyanogen bromide peptides was deduced by the use of overlap fragments obtained from the tryptic digestion of modified and unmodified beta-chains and from digestions with staphylococcal protease, as well as by considerations involving the plasmic digestion products of fibrinogen. In one case two adjacent fragments were aligned by homology with the corresponding segments of the gamma chain. The homology of the beta chain with the gamma chain is especially strong over the course of the carboxy-terminal two-thirds of the sequence. Neither of these chains appears to be homologous with the alpha chain in these regions. With a few minor exceptions, the sequence reported in this article is in agreement with data reported by other groups in Stockholm and Munich.
CasAB: Building Precise Bitmap Indices via Cascaded Bloom Filters (2009)

Bitmap indices are widely used in massive and read-mostly datasets such as data warehouses and scientific databases. Recently, Bloom filters were used to encode bitmap indices into approximate bitmaps(AB). The salient advantage of this technique is that bitmaps can be directly accessed without decompression, and the query time is proportional in the size of the region being queried. This technique, however, introduces false positives due to the nature of Bloom filters, therefore, only approximate query results can be achieved. To eliminate false positives, we proposed a novel bitmap index encoding scheme, namely cascaded approximate bitmaps(CasAB) based on multi-level Bloom filter cascading, which can achieve precise query results at the cost of slightly more space and time overhead. An efficient CasAB construction algorithm and a query algorithm are given. Space and time complexities of CasAB are analyzed theoretically, and the minimum space size can be pre-computed based on the cardinality of the attribute. Experiments show that the query precision of CasAB is always 100% and space and time overhead is similar to that of AB.
Castration-induced increases in insulin-like growth factor-binding protein 2 promotes proliferation of androgen-independent human prostate LNCaP tumors. (2003)

Activation of alternative growth factor pathways after androgen withdrawal is one mechanism mediating androgen-independent (AI) progression in advanced prostate cancer. Insulin-like growth factor (IGF) I activation is modulated by a family of IGF binding proteins (IGFBPs). Although IGFBP-2 is one of the most commonly overexpressed genes in hormone refractory prostate cancer, the functional significance of changes in IGF-I signaling during AI progression remains poorly defined. In this article, we characterize changes in IGFBP-2 in the LNCaP tumor model after androgen withdrawal and evaluate its functional significance in AI progression using gain-of-function and loss-of-function analyses. IGFBP-2 mRNA and protein levels increase 2-3-fold after androgen withdrawal in LNCaP cells in vitro in LNCaP tumors during AI progression in vivo. Increased IGFBP-2 levels after castration were also identified using a human prostate tissue microarray of untreated and posthormone therapy-treated prostatectomy specimens. LNCaP cell transfectants that stably overexpressed IGFBP-2 progressed more rapidly after castration than control tumors. Antisense oligonucleotides (ASOs) targeting the translation initiation site of IGFBP-2 reduced IGFBP-2 mRNA and protein expression by >70% in a dose-dependent and sequence-specific manner. ASO-induced decreases in IGFBP-2-reduced LNCaP cell growth rates and increased apoptosis 3-fold. LNCaP tumor growth and serum prostate-specific antigen levels in mice treated with castration plus adjuvant IGFBP-2 ASOs were significantly reduced compared with mismatch control oligonucleotides. Increased IGFBP-2 levels after androgen ablation may represent an adaptive response that helps potentiate IGF-I-mediated survival and mitogenesis and promote androgen-independent tumor growth. Inhibiting IGFBP-2 expression using ASO technology may offer a treatment strategy to delay AI progression.
Paired-pulse depression of unitary quantal amplitude at single hippocampal synapses (2004)

At central synapses, quantal size is generally regarded as fluctuating around a fixed mean with little change during short-term synaptic plasticity. We evoked quantal release by brief electric stimulation at single synapses visualized with FM 1-43 dye in hippocampal cultures. The majority of quantal events evoked at single synapses were monovesicular, based on examination of amplitude distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor-mediated responses. Consistent with previous findings, the quantal size did not change during paired-pulse facilitation (PPF), supporting the notion that the evoked events were monoquantal. However, during paired-pulse depression (PPD), there was a significant decrease in unitary quantal size, which was not due to postsynaptic receptor desensitization. This asymmetry of quantal modulation during PPF and PPD was demonstrated at the same single synapse at different extracellular calcium concentrations. Our results indicate that PPF can be fully accounted for by an increase of release probability, whereas PPD may be caused by decreases in both release probability and quantal size. One possible explanation is that the release of a quantum of neurotransmitter from synaptic vesicles is not invariant but subject to rapid calcium-dependent modulation during short-term synaptic plasticity.
Imitation from Observation: Learning to Imitate Behaviors from Raw Video via Context Translation (2017)

Imitation learning is an effective approach for autonomous systems to acquire control policies when an explicit reward function is unavailable, using supervision provided as demonstrations from an expert, typically a human operator. However, standard imitation learning methods assume that the agent receives examples of observation-action tuples that could be provided, for instance, to a supervised learning algorithm. This stands in contrast to how humans and animals imitate: we observe another person performing some behavior and then figure out which actions will realize that behavior, compensating for changes in viewpoint, surroundings, object positions and types, and other factors. We term this kind of imitation learning "imitation-from-observation," and propose an imitation learning method based on video prediction with context translation and deep reinforcement learning. This lifts the assumption in imitation learning that the demonstration should consist of observations in the same environment configuration, and enables a variety of interesting applications, including learning robotic skills that involve tool use simply by observing videos of human tool use. Our experimental results show the effectiveness of our approach in learning a wide range of real-world robotic tasks modeled after common household chores from videos of a human demonstrator, including sweeping, ladling almonds, pushing objects as well as a number of tasks in simulation.
Synergistic Activation of Human Immunodeficiency Virus Type 1 Promoter Activity by NF-κB and Inhibitors of Deacetylases: Potential Perspectives for the Development of Therapeutic Strategies (2002)

The transcription factor NF-kappaB plays a central role in the human immunodeficiency virus type 1 (HIV-1) activation pathway. HIV-1 transcription is also regulated by protein acetylation, since treatment with deacetylase inhibitors such as trichostatin A (TSA) or sodium butyrate (NaBut) markedly induces HIV-1 transcriptional activity of the long terminal repeat (LTR) promoter. Here, we demonstrate that TSA (NaBut) synergized with both ectopically expressed p50/p65 and tumor necrosis factor alpha/SF2 (TNF)-induced NF-kappaB to activate the LTR. This was confirmed for LTRs from subtypes A through G of the HIV-1 major group, with a positive correlation between the number of kappaB sites present in the LTRs and the amplitude of the TNF-TSA synergism. Mechanistically, TSA (NaBut) delayed the cytoplasmic recovery of the inhibitory protein IkappaBalpha. This coincided with a prolonged intranuclear presence and DNA binding activity of NF-kappaB. The physiological relevance of the TNF-TSA (NaBut) synergism was shown on HIV-1 replication in both acutely and latently HIV-infected cell lines. Therefore, our results open new therapeutic strategies aimed at decreasing or eliminating the pool of latently HIV-infected reservoirs by forcing viral expression.
Differential expression and/or activation of P38MAPK, erk1/2, and jnk during the initiation and progression of prostate cancer (2003)

Erk1/2, jnk, and p38MAPKs are differentially expressed and/or activated during prostate cancer progression. Activation of both erk1/2 and p38MAPK occurs concomitant with prostatic epithelial cell proliferation and the initiation of prostate cancer while inactivation is contemporaneous with the emergence of the poorly differentiated metastatic and androgen-independent phenotype.
CRISPR-mediated Genome Editing Restores Dystrophin Expression and Function in mdx Mice (2015)

Duchenne muscular dystrophy (DMD) is a degenerative muscle disease caused by genetic mutations that lead to the disruption of dystrophin in muscle fibers. There is no curative treatment for this devastating disease. Clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) has emerged as a powerful tool for genetic manipulation and potential therapy. Here we demonstrate that CRIPSR-mediated genome editing efficiently excised a 23-kb genomic region on the X-chromosome covering the mutant exon 23 in a mouse model of DMD, and restored dystrophin expression and the dystrophin-glycoprotein complex at the sarcolemma of skeletal muscles in live mdx mice. Electroporation-mediated transfection of the Cas9/gRNA constructs in the skeletal muscles of mdx mice normalized the calcium sparks in response to osmotic shock. Adenovirus-mediated transduction of Cas9/gRNA greatly reduced the Evans blue dye uptake of skeletal muscles at rest and after downhill treadmill running. This study provides proof evidence for permanent gene correction in DMD.
3'-Hydroxyesorubicin. Synthesis and antitumor activity. (1990)

A novel route to 4'-deoxy anthracycline analogues has been developed starting from previously unavailable, optically active 4,6-dideoxy-hex-1-enitol 9. Coupling of daunomycinone (11) or 14-O-tert-butyldimethylsilyladriamycinone (12) with glycosyl chloride 10 in Koenigs-Knorr condition gave mainly alpha anomers, which were successfully deblocked to final 3'-deamino-4'-deoxy-3'-hydroxydaunorubicin (7) and 3'-deamino-3'-hydroxyesorubicin (8). Analogues were evaluated in vitro against P388 and L1210 leukemia and M5076 cells and in vivo against P388 leukemia. Compared with doxorubicin (1), 3'-hydroxyesorubicin (8) showed in vitro similar cytotoxic potential and in vivo higher antitumor activity.
Mineral nutrition of Pythium marinum, a marine facultative parasite (1973)

Pythium marinum Sparrow, isolated from lesions on Porphyra miniata, required Na + , Ca 2+ , and Mg 2+ in quantities far exceeding those reported to be required by terrestrial species of Pythium. Unlike most of its terrestrial counterparts, P. marinum required alkaline pH values for good growth, with a pH of 7.8 providing maximum growth under the conditions examined. The requirement for large amounts of Na + ions appeared to have a specific nutritional basis rather than a purely osmotic function. Growth at various temperatures indicated that the fungus is a facultative psychrophile with the optimum growth temperature between 15 and 20 °C. The nutritional data show that P. marinum is able to grow in a wide range of salt concentrations and is well adapted to the marine environment.
Expression of HLA-G Is Associated With Prognosis in Esophageal Squamous Cell Carcinoma (2007)

The detection of HLA-G expression might serve as a clinical marker in the diagnosis or prediction of clinical outcomes for certain types of carcinoma. The aim of this study was to determine whether the detection of HLA-G has any important clinical applications for patients with esophageal squamous cell carcinoma (ESCC) by using immunohistochemical methods. We observed that the HLA-G protein was expressed in 90.9% (110/121) of the primary sites of ESCC but not in the normal esophageal tissues. The expression of HLA-G in the tumors was significantly correlated with histologic grade, depth of invasion, nodal status, host immune response, and clinical stage of disease. Patients with positive HLA-G expression had a significantly worse prognosis. In multivariate analysis, HLA-G was an independent prognostic factor. Our results indicate that expression of HLA-G is a characteristic feature of ESCC and suggest that immunostaining by anti-HLA-G antibodies may be a potentially useful prognostic indicator.
What Makes a Good Answer? The Role of Context in Question Answering. (2003)

Abstract: Question answering systems have proven to be helpful to users because they can provide succinct answers that do not require users to wade through a large number of documents. However, despite recent advances in the underlying question answering technology, the problem of designing effective interfaces has been largely unexplored. We conducted a user study to investigate this area and discovered that, overall, users prefer paragraph-sized chunks of text over just an exact phrase as the answer to their questions. Furthermore, users generally prefer answers embedded in context, regardless of the perceived reliability of the source documents. When researching a topic, increasing the amount of text returned to users significantly decreases the number of queries that they pose to the system, suggesting that users utilize supporting text to answer related questions. We believe that these results can serve to guide future developments in question answering interfaces.