gebhart/patrepeval huggingface dataset:
Identification of new drug sensitivity genes using genetic suppressor elements: protein arginine N-methyltransferase mediates cell sensitivity to DNA-damaging agents. (2003)

Genetic suppressor elements (GSEs) are cDNA fragments encoding either truncated proteins, acting as dominant-negative mutants, or inhibitory antisense RNA segments counteracting with the gene from which they are derived. To identify genes controlling the cell response to cytotoxic agents, a normalized retroviral library of randomly fragmented cDNAs from Chinese hamster cell line DC-3F was screened for GSEs conferring resistance to the topoisomerase II inhibitor 9-OH-ellipticine. From 218 cDNA fragments isolated, 11 functional GSEs, corresponding to at least 8 independent genes, were selected. The gene corresponding to the most abundant GSE encodes two proteins, p77 and p82, highly homologous to proteins detected in various species and carrying the sequence motifs characteristic of the protein arginine N-methyltransferase family. Furthermore, a methylase activity was observed on myelin basic protein in immunoprecipitates of hemagglutinin-tagged p77 and p82. Therefore, p77 and p82 are the first identified members of a new protein arginine N-methyltransferase family. A decreased expression of these enzymes is associated with either resistance or hypersensitivity to a broad range of DNA-damaging agents. Our data indicate that down-regulation of these enzymes in the GSE-expressing cells would alter one or several steps downstream of the drug-target interaction in the drug-response pathway.
Alterations of the Oropharyngeal Microbial Flora After Adenotonsillectomy in Children (2007)

Adenotonsillectomy reduced oropharyngeal carriage of potential respiratory pathogens. Changes in the carriage rate of GABHS, however, had no beneficial effect on recurrence of throat infections.
Performance of smart lightwave receivers with linear equalization (1992)

Signal processing techniques can be used to reduce linear and nonlinear distortion in high-speed lightwave systems caused by fiber dispersion and nonideal responses of optoelectronic and electronic components. The improvement in the performance of 2.5 and 10 Gb/s intensity modulation, direct detection systems is assessed for receivers which utilize an analog taped delay line equalizer to compensate for signal distortion. Synchronous and fractionally spaced equalizers are evaluated. Smart receivers that jointly optimize the decision time, decision threshold, and equalizer tap weights under a minimum bit error ration criterion are considered. This yields the optimum system performance and allows consideration of both reduced distortion and enhanced noise arising from the signal processing. The effectiveness of the equalization is determined as a function of several important system parameters. Three-tap and five-tap synchronous equalizers yield virtually the same improvement in receiver sensitivity. Depending on the system, a five-tap fractionally spaced equalizer with half-bit-period tap spacing may or may not be significantly more effective than a three-tap synchronous equalizer.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Sorafenib targets BRAF and VEGFR in metastatic thyroid carcinoma (2007)

6019 Background. There is no effective therapy for patients with metastatic thyroid cancer not cured by surgery or treatment with I 131 . Sorafenib is a promising multi-tyrosine kinase inhibitor for patients with metastatic PTC (mPTC). Although the primary targets of sorafenib are thought to include BRAF and VEGFR, this has been the subject of debate. Whether sorafenib primarily acts on the tumor cells (TC) or endothelial cells (EC) and how BRAF mutation status (45% of PTC harbor V600E) relates to response is also unknown. Methods. Responses of patients with metastatic, iodine-refractory PTC, enrolled into our phase II study of sorafenib were monitored by PET at 4 wks and CTs every 2 mos. Sorafenib activity was studied using immunohistochemistry (IHC) for pERK, pAKT, and pVEGFR-2, while Ki-67 showed proliferating cells in tumor tissue pre- and on treatment. BRAF mutation status was determined by DNA sequencing. Results. Of 15 patients, five patients achieved a PR, three are stable (SD), two progressed, and three patients with SD withdrew due to toxicity. Target lesions decreased on average 31%. Eight of 10 PET scans showed decreased activity at 4 weeks. IHC on tissue from 2 patients (at 1 and 2 wks, both BRAF wt ) showed 50% decrease in pERK (downstream of VEGFR2 and BRAF) and 30% decrease in pAKT (downstream of VEGFR2). p-ERK and p-AKT were altered in both the TC and EC. Ki-67 decreased from 10% to &lt;1%. No change in VEGFR-2 was seen; but, pVEGFR-2 completely disappeared in one sample while the other showed a small decrease. Quantitative analysis using a multispectral imaging system confirmed the changes observed by IHC. In tissue from a patient at 17 months on sorafenib, the decrease in pERK and pAKT appeared to be the same or reversed, suggesting compensatory changes in these pathways in resistant but stable disease. Conclusions. Our study shows the early clinical and biologic activity of sorafenib in patients with mPTC and the targets of early suppression. Importantly, it also reveals compensatory changes in target molecules in cells resistant to therapy. These cells are the likely source of tumor resistance that has been seen to develop to other similar targeted agents. Sorafenib is the first viable treatment option for patients with mPTC, and these results provide key insights into the mechanisms of action and resistance of this drug. No significant financial relationships to disclose.
Using the ATL HDI 1000 to collect demodulated RF data for monitoring HIFU lesion formation (2003)

The ability to accurately track and monitor the progress of lesion formation during HIFU (High Intensity Focused Ultrasound) therapy is important for the success of HIFU-based treatment protocols. To aid in the development of algorithms for accurately targeting and monitoring formation of HIFU induced lesions, we have developed a software system to perform RF data acquisition during HIFU therapy using a commercially available clinical ultrasound scanner (ATL HDI 1000, Philips Medical Systems, Bothell, WA). The HDI 1000 scanner functions on a software dominant architecture, permitting straightforward external control of its operation and relatively easy access to quadrature demodulated RF data. A PC running a custom developed program sends control signals to the HIFU module via GPIB and to the HDI 1000 via Telnet, alternately interleaving HIFU exposures and RF frame acquisitions. The system was tested during experiments in which HIFU lesions were created in excised animal tissue. No crosstalk between the HIFU beam and the ultrasound imager was detected, thus demonstrating synchronization. Newly developed acquisition modes allow greater user control in setting the image geometry and scanline density, and enables high frame rate acquisition. This system facilitates rapid development of signal-processing based HIFU therapy monitoring algorithms and their implementation in image-guided thermal therapy systems. In addition, the HDI 1000 system can be easily customized for use with other emerging imaging modalities that require access to the RF data such as elastographic methods and new Doppler-based imaging and tissue characterization techniques.
Mitochondrial thioredoxin reductase in bovine adrenal cortex (1999)

Mitochondrial thioredoxin reductase was purified from bovine adrenal cortex. The enzyme is a first protein component in the mitochondrial thioredoxin-dependent peroxide reductase system. The purified reductase exhibited an apparent molecular mass of 56 kDa on SDS/PAGE, whereas the native protein was about 100 kDa, suggesting a homodimeric structure. It catalysed NADPH-dependent reduction of 5, 5'dithiobis(2-nitrobenzoic acid) and thioredoxins from various origins but not glutathione, oxidized dithiothreitol, DL-alpha-lipoic acid, or insulin. Amino acid and nucleotide sequence analyses revealed that it had a presequence composed of 21 amino acids which had features characteristic of a mitochondrial targeting signal. The amino acid sequence of the mature protein was similar to that of bovine cytosolic thioredoxin reductase (57%) and of human glutathione reductase (34%) and less similar to that of Escherichia coli (19%) or yeast (17%) enzymes. Human and bovine cytosolic thioredoxin reductase were recently identified to contain selenocysteine (Sec) as one of their amino acid constituents. We also identified Sec in the C-terminal region of mitochondrial (mt)-thioredoxin reductase by means of MS and amino acid sequence analyses of the C-terminal fragment. The four-amino acid motif, Gly-Cys-Sec-Gly, which is conserved among all Sec-containing thioredoxin reductases, probably functions as the third redox centre of the enzyme, as the mitochondrial reductase was inhibited by 1-chloro-2,4-dinitrobenzene, which was reported to modify Sec and Cys covalently. It is known that mammalian thioredoxin reductase is different from bacterial or yeast enzyme in, for example, their subunit molecular masses and domain structures. These two different types of enzymes with similar activity are suggested to have evolved convergently. Our data clearly show that mitochondria, which might have originated from symbiotic prokaryotes, contain thioredoxin reductase similar to the cytosolic enzyme and different from the bacterial one.
Characterization of proteinase A glycoforms from recombinant Saccharomyces cerevisiae.“ (1993)

Proteinase A produced by Saccharomyces cerevisiae carrying the gene PEP4 (which encodes the prepro-proteinase A on multicopy plasmids) was isolated and characterized by means of SDS/PAGE, laser desorption m.s. (l.d.m.s.) and high-performance capillary electrophoresis. Although proteinase A is normally located in the yeast vacuole, overexpression resulted in it being secreted. SDS/PAGE revealed that the product isolated from the culture medium comprised an approx, 7:3 mixture of two different forms of proteinase A, the apparent molecular masses of which were 42 and 40 kDa respectively. The exact mass of each form, measured by l.d.m.s., was 40,755 and 38,132 Da respectively. Further analysis employing N-glycosidase F digestion and CNBr cleavage revealed that the larger molecule was native proteinase A bearing carbohydrate moieties at Asn68 and Asn269, whereas the smaller molecule was a proteinase A variant glycoform lacking the carbohydrate moiety at Asn269. Capillary electrophoresis of both the normal and underglycosylated proteinase A glycoforms revealed charge heterogeneities attributable to differences in the phosphorylation level of the carbohydrate moiety at Asn68.
Firefly Luciferase as a Marker for Herpesvirus (pseudorabies virus) Replication in Vitro and in Vivo (1991)

Insertion of reporter genes into complex viral genomes and monitoring virus replication by detecting the corresponding protein products is increasingly used in pathogenesis studies. We present here the isolation and characterization of a recombinant neurotropic alpha-herpesvirus, pseudorabies virus (PrV), which stably carries the gene encoding firefly luciferase. To express the enzyme the complete open reading frame for luciferase was fused to the promoter and first seven codons of the non-essential glycoprotein gX gene of PrV. A recombinant PrV carrying the luciferase gene inserted into the gX gene and exhibiting strong luciferase activity after infection of cultured cells was further characterized. Kinetic analyses showed that luciferase activity was detectable as early as 90 min after infection. Luciferase expression could be monitored in cell extracts in a luminometer. For facilitating plaque isolation of luciferase recombinant viruses it was also visualized in situ on sensitive film. Kinetic experiments in mice proved the suitability of luciferase as an excellent marker for following herpesvirus spread in the animal. By way of luciferase detection we show that PrV invasion of the central nervous system after intranasal infection of mice occurred independently of replication in non-neural tissues such as lung or thymus. Furthermore, comparison of isogenic luciferase recombinant PrV strains carrying intact or deleted glycoprotein gI genes showed differences in the organotropism between these two viruses.
Exploiting a probabilistic hierarchical model for generation (2000)

Previous stochastic approaches to generation do not include a tree-based representation of syntax. While this may be adequate or even advantageous for some applications, other applications profit from using as much syntactic knowledge as is available, leaving to a stochastic model only those issues that are not determined by the grammar. We present initial results showing that a tree-based model derived from a tree-annotated corpus improves on a tree model derived from an unannotated corpus, and that a tree-based stochastic model with a hand-crafted grammar outperforms both.
Gene therapy for muscular dystrophy: current progress and future prospects (2009)

Muscular dystrophies refer to a group of inherited disorders characterized by progressive muscle weakness, wasting and degeneration. So far, there is no effective treatment but new gene-based therapies are currently being developed with particular noted advances in using conventional gene replacement strategies, RNA-based approaches, or cell-based gene therapy with a main focus on Duchenne muscular dystrophy (DMD). DMD is the most common and severe form of muscular dystrophy and current treatments are far from adequate. However, genetic and cell-based therapies, in particular exon skipping induced by antisense strategies, and corrective gene therapy via functionally engineered dystrophin genes hold great promise, with several clinical trials ongoing. Proof-of-concept of exon skipping has been obtained in animal models, and most recently in clinical trials; this approach represents a promising therapy for a subset of patients. In addition, gene-delivery-based strategies exist both for antisense-induced reading frame restoration, and for highly efficient delivery of functional dystrophin mini- and micro-genes to muscle fibres in vivo and muscle stem cells ex-vivo. In particular, AAV-based vectors show efficient systemic gene delivery to skeletal muscle directly in vivo, and lentivirus-based vectors show promise of combining ex vivo gene modification strategies with cell-mediated therapies.
Is Tau Aggregation Toxic or Protective? (2008)

Abnormal protein deposits are a common feature of many human diseases including Alzheimer's disease. In Alzheimer's disease, the appearance of tangles, composed of the microtubule associated protein tau, correlates with both cell death and symptom severity. However, are tau filaments simply markers of disease progression, or are they directly responsible for cell death? Due to conflicting findings from cell and animal models, it remains controversial whether tau polymers or smaller pre-fibrillar aggregates or tau monomers are the toxic species. Indeed, if monomeric or oligomeric species are mediators of disease, formation of larger tau filaments may prove beneficial to affected cells. This review will examine the findings regarding the toxicity of various tau species.
Metabolites of Siamenoside I and Their Distributions in Rats (2016)

Siamenoside I is the sweetest mogroside that has several kinds of bioactivities, and it is also a constituent of Siraitiae Fructus, a fruit and herb in China. Hitherto the metabolism of siamenoside I in human or animals remains unclear. To reveal its metabolic pathways, a high-performance liquid chromatography-electrospray ionization-ion trap-time of flight-multistage mass spectrometry (HPLC-ESI-IT-TOF-MS(n)) method was used to profile and identify its metabolites in rats. Altogether, 86 new metabolites were identified or tentatively identified, and 23 of them were also new metabolites of mogrosides. In rats, siamenoside I was found to undergo deglycosylation, hydroxylation, dehydrogenation, deoxygenation, isomerization, and glycosylation reactions. Among them, deoxygenation, pentahydroxylation, and didehydrogenation were novel metabolic reactions of mogrosides. The distributions of siamenoside I and its 86 metabolites in rat organs were firstly reported, and they were mainly distributed to intestine, stomach, kidney, and brain. The most widely distributed metabolite was mogroside IIIE. In addition, eight metabolites were bioactive according to literature. These findings would help to understand the metabolism and effective forms of siamenoside I and other mogrosides in vivo.
Route Visualization Using Detail Lenses (2009)

We present a method designed to address some limitations of typical route map displays of driving directions. The main goal of our system is to generate a printable version of a route map that shows the overview and detail views of the route within a single, consistent visual frame. Our proposed visualization provides a more intuitive spatial context than a simple list of turns. We present a novel multifocus technique to achieve this goal, where the foci are defined by points of interest (POI) along the route. A detail lens that encapsulates the POI at a finer geospatial scale is created for each focus. The lenses are laid out on the map to avoid occlusion with the route and each other, and to optimally utilize the free space around the route. We define a set of layout metrics to evaluate the quality of a lens layout for a given route map visualization. We compare standard lens layout methods to our proposed method and demonstrate the effectiveness of our method in generating aesthetically pleasing layouts. Finally, we perform a user study to evaluate the effectiveness of our layout choices.
Tetrad Analysis in Higher Plants. A Budding Technology (2000)

Tetrad analysis, the ability to manipulate and individually study the four products of a single meiotic event, has been critical to understanding the mechanisms of heredity. The Arabidopsis quartet (qrt) mutation, which causes the four products of male meiosis to remain attached, enables plant biologists to apply this powerful tool to investigations of gamete development, cell division, chromosome dynamics, and recombination. Here we highlight several examples of how qrt has been used to perform tetrad analysis and suggest additional applications including a genetic screen for gametophytic mutants and methods for investigating gene interactions by synthetic lethal analysis.
Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types (2003)

Multicellular tumor spheroids (MCTS) are used as organotypic models of normal and solid tumor tissue. Traditional techniques for generating MCTS, such as growth on nonadherent surfaces, in suspension, or on scaffolds, have a number of drawbacks, including the need for manual selection to achieve a homogeneous population and the use of nonphysiological matrix compounds. In this study we describe a mild method for the generation of MCTS, in which individual spheroids form in hanging drops suspended from a microtiter plate. The method has been successfully applied to a broad range of cell lines and shows nearly 100% efficiency (i.e., one spheroid per drop). Using the hepatoma cell line, HepG2, the hanging drop method generated well-rounded MCTS with a narrow size distribution (coefficient of variation [CV] 10% to 15%, compared with 40% to 60% for growth on nonadherent surfaces). Structural analysis of HepG2 and a mammary gland adenocarcinoma cell line, MCF-7, composed spheroids, revealed highly organized, three-dimensional, tissue-like structures with an extensive extracellular matrix. The hanging drop method represents an attractive alternative for MCTS production, because it is mild, can be applied to a wide variety of cell lines, and can produce spheroids of a homogeneous size without the need for sieving or manual selection. The method has applications for basic studies of physiology and metabolism, tumor biology, toxicology, cellular organization, and the development of bioartificial tissue.
An osmotically tolerant inner medullary collecting duct cell line from an SV40 transgenic mouse (1993)

The terminal inner medullary collecting duct (IMCD) plays an important role in determining the final urinary composition. Currently, there is no continuous cell line derived from this nephron segment. We have developed a cell line derived from the terminal IMCD of mice transgenic for the early region of simian virus SV40 (large T antigen). This cell line, mIMCD-3, retains many differentiated characteristics of this nephron segment including high transepithelial resistance (1,368 +/- 172 omega.cm2), inhibition of apical-to-basal sodium flux by amiloride (41 +/- 7%) and by atrial natriuretic peptide (ANP) (40 +/- 9%), the presence of the amiloride-sensitive sodium channel as determined by Western blot analysis, and accumulation of the major organic osmolytes in response to hypertonic stress. Significantly, mIMCD-3 cells adapted readily and were able to grow in hypertonic medium supplemented with NaCl and urea up to 910 mosmol/kgH2O. These extreme osmotic conditions exist in the renal medulla in vivo but are known to be lethal to most other cells. This cell line should be highly useful for the study of the cellular adaptation to osmotic stress and the cell biology and transport physiology of this nephron segment.
Reviews (1990)

Journal Article Reviews Get access Corruption in British Politics, 1895–1930. By Geoffrey Searle. Oxford: Oxford University Press, 1989. 460 pp. ISBN 0-19-822-915-1. £19.95. EWEN GREEN EWEN GREEN University of Reading Search for other works by this author on: Oxford Academic Google Scholar Twentieth Century British History, Volume 1, Issue 2, 1990, Pages 219–220, https://doi.org/10.1093/tcbh/1.2.219 Published: 01 January 1990
Searching in metric spaces by spatial approximation (2003)

We propose a novel data structure to search in metric spaces. A metric space is formed by a collection of objects and a distance function defined among them, which satisfies the triangular inequality. The goal is, given a set of objects and a query, retrieve those objects close enough to the query. The number of distances computed to achieve this goal is the complexity measure. Our data structure, called sa-tree ("spatial approximation tree"), is based on approaching spatially the searched objects. We analyze our method and show that the number of distance evaluations to search among n objects is o(n). We show experimentally that the sa-tree is the best existing technique when the metric space is high-dimensional or the query has low selectivity. These are the most difficult cases in real applications.
Identification and Isolation of Melanoma-Associated Antigens with Monoclonal Antibodies (1982)

The monoclonal antibodies distributed at the first Workshop on Monoclonal Antibodies to Melanoma have been tested by immunoprecipitation, and one group of antigens (90 kd) has been found to be identical by sequential immunoprecipitation. These results are in good agreement with those from other laboratories. In addition, antigens from a new group of hybridomas, generated since the first Workshop, were studied. Some of these antigens are unique and others are duplicates of the original set. Finally, a melanoma-associated antigen (260 kd) was purified by immunoaffinity chromatography.