gebhart/patrepeval huggingface dataset:
Characteristics and outcome of patients with acute myeloid leukemia refractory to 1 cycle of high-dose cytarabine-based induction chemotherapy (2010)

Pretreatment characteristics and outcome of patients treated with induction regimens containing high-dose ara-C (HiDAC) at M. D. Anderson Cancer Center refractory to 1 cycle of induction were compared with similar patients achieving a complete response (CR). Among 1597 patients treated with HiDAC-based induction from 1995 to 2009, 285 were refractory to 1 cycle. Median age was 59 years (range, 18-85 years). Induction regimens included HiDAC with anthracyclines (n = 181; 64%) or HiDAC with nonanthracycline chemotherapy (n = 104; 36%). Refractory patients were older (median age, 59 vs 56 years; P < .001), more likely with unfavorable cytogenetics (P < .001) and antecedent hematologic disorder (P < .001), and had a higher presentation white blood cell count (P = .04), but not a higher incidence of FLT3 mutations (P = .85), than those achieving CR. Forty-three patients (22%) responded to salvage (35 CR and 8 CR without platelet recovery). With a median follow-up of 72 months (range, 27-118 months) in responders, 11 are alive. Nineteen patients (7%) were alive and in CR for at least 6 months, including 9 who underwent allogeneic stem cell transplantation. On multivariate analysis, severe thrombocytopenia, leukocytosis, increasing marrow blast percentage, unfavorable cytogenetics, and salvage not including allogeneic stem cell transplantation were associated with a worse survival. Alternative strategies are needed for these patients.
A Novel Palladium-Mediated Coupling Approach to 2,3-Disubstituted Benzo[b]thiophenes and Its Application to the Synthesis of Tubulin Binding Agents (2001)

[structure: see text]. Flexible, convergent access to 2,3-disubstituted benzo[b]thiophenes has been developed. The most concise approach involves sequential coupling of o-bromoiodobenzenes with benzylmercaptan and zinc acetylides to give benzyl o-ethynylphenyl sulfides which react with iodine to give 3-iodobenzo[b]thiophenes in a 5-endo-dig iodocyclization. These iodides can be further elaborated using palladium-mediated coupling and/or metalation techniques. This method has been applied to the synthesis of some novel tubulin binding agents.
Le typage génomique : de la cytogénétique moléculaire aux puces à ADN (2001)

Les premieres observations de la destabilisation du genome dans les cellules tumorales datent du debut du xxe siecle. Cependant, si les etudes de cytogenetique ont permis d'etablir une nouvelle classification des hemopathies, la complexite des remaniements observes dans les tumeurs solides est longtemps restee un obstacle aux tentatives de caracterisation d'un type tumoral particulier sur la base d'aberrations structurales specifiques. L'application, a partir de 1993, de la methode d'hybridation genomique comparative (CGH) a permis l'emergence d'une image plus claire. En effet, dans tous les types tumoraux analyses, la CGH montre que la cancerisation s'accompagne d'anomalies quantitatives qui s'expriment sous forme de gains ou de pertes de materiel genetique. Ces gains et ces pertes peuvent affecter des regions dont les tailles varient entre un bras chromosomique entier et quelques megabases (Mb). Il est apparu que, tous types tumoraux confondus, tous les chromosomes sont le siege d'au minimum une region de gain ou de perte. Par ailleurs, on notera que les profils de gains et de pertes n'etaient pas identiques d'un type tumoral a un autre, confortant l'hypothese selon laquelle il serait possible de construire une grille d'interpretation phenotypique des cancers sur la base de leurs patrons d'anomalies genomiques. Toutefois, la mise en œuvre d'un tel objectif etait limitee par le manque de resolution de la CGH. En effet, la CGH utilise comme cibles d'hybridation des chromosomes en metaphase, ce qui implique que la precision des resultats est de l'ordre de la bande chromosomique. Ces limitations sont en passe d'etre levees par le remplacement recent de la CGH sur chromosomes en metaphase par la CGH sur reseaux d'ADN clones (CGH-array). Les chromosomes cedent la place aux clones d'ADN (clones genomiques - BAC, YAC ou cosmides - ou ADNc). Cette evolution technologique permet donc de faire passer la resolution d'un niveau cytogenetique (quelques Mb) a un niveau moleculaire (2 a 100 kb selon la cible). De plus, avec l'avancement du sequencage du genome humain, il sera bientot possible de relier immediatement des donnees concernant une cible clonee (BAC ou autre) a des donnees de sequence. Enfin, si la CGH sur chromosomes se prete mal a une automatisation des methodes, il n'en est pas de meme pour la CGH sur reseau d'ADN.
Mycoplasma pneumoniae Attachment to Glutaraldehyde-Treated Human WiDr Cell Cultures (1986)

Attachment of Mycoplasma pneumoniae to host cells initiates disease, and the attachment components may represent important protective immunogens for preventing disease. We have studied the mechanisms of attachment using in vitro cell culture systems and selected pathogenic and nonpathogenic strains of M. pneumoniae. Attachment of the pathogenic strains M129 and PI-1428 was several fold greater than attachment of the nonpathogenic strain, and attachment of strains M129 and PI-1428 was reduced by 21 to 63% when human WiDr cell monolayers were exposed to neuraminidase, supporting the concept that M. pneumoniae attaches to mammalian cells by a neuraminidase-sensitive glycoconjugate. While attachment of the two pathogenic strains was markedly reduced by treating the WiDr cells with glutaraldehyde, glutaraldehyde treatment produced minimal effects on the attachment of the nonpathogenic strain B176. Glutaraldehyde treatment also altered the temperature dependence of attachment by the pathogenic strains. Because glutaraldehyde-treated WiDr cell monolayers showed little difference in attachment between pathogenic and nonpathogenic strains, glutaraldehyde-treated cells are not appropriate cell substrates for studying M. pneumoniae attachment mechanisms or identifying immunogens for vaccine development.
The immunobiology of Guillain‐Barré syndromes (2005)

This presentation highlights aspects of the immunobiology of the Guillain-Barré syndromes (GBS), the world's leading cause of acute autoimmune neuromuscular paralysis. Understanding the key pathophysiological pathways of GBS and developing rational, specific immunotherapies are essential steps towards improving the clinical outcome of this devastating disorder. Much of the research into GBS over the last decade has focused on the forms mediated by anti-ganglioside antibodies, and we have made substantial progress in our understanding in several related areas. Particular highlights include (a) the emerging correlations between anti-ganglioside antibodies and specific clinical phenotypes, notably between anti-GM1/anti-GD1a antibodies and the acute motor axonal variant and anti-GQ1b/anti-GT1a antibodies and the Miller Fisher syndrome; (b) the identification of molecular mimicry between GBS-associated Campylobacter jejuni oligosaccharides and GM1, GD1a, and GT1a gangliosides as a mechanism for anti-ganglioside antibody induction; (c) the development of rodent models of GBS with sensory ataxic or motor phenotypes induced by immunisation with GD1b or GM1 gangliosides, respectively. Our work has particularly studied the motor nerve terminal as a model site of injury, and through combined active and passive immunisation paradigms, we have developed murine neuropathy phenotypes mediated by anti-ganglioside antibodies. This has been achieved through use of glycosyltransferase and complement regulator knock-out mice, both for cloning anti-ganglioside antibodies and inducing disease. Through such studies, we have proven a neuropathogenic role for murine anti-ganglioside antibodies and human GBS-associated antisera and identified several determinants that influence disease expression including (a) the level of immunological tolerance to microbial glycans that mimic self-gangliosides; (b) the ganglioside density in target tissue; (c) the level of complement activation and the neuroprotective effects of endogenous complement regulators; and (d) the role of calcium influx through complement pores in mediating axonal injury. Such studies provide us with clear information on an antibody-mediated pathogenesis model for GBS and should lead to rational therapeutic testing of agents that are potentially suitable for use in humans.
A Statistical Model for Multilingual Entity Detection and Tracking (2004)

Entity detection and tracking is a relatively new addition to the repertoire of natural language tasks.In this paper, we present a statistical language-independent framework for identifying and tracking named, nominal and pronominal references to entities within unrestricted text documents, and chaining them into clusters corresponding to each logical entity present in the text.Both the mention detection model and the novel entity tracking model can use arbitrary feature types, being able to integrate a wide array of lexical, syntactic and semantic features.In addition, the mention detection model crucially uses feature streams derived from different named entity classifiers.The proposed framework is evaluated with several experiments run in Arabic, Chinese and English texts; a system based on the approach described here and submitted to the latest Automatic Content Extraction (ACE) evaluation achieved top-tier results in all three evaluation languages.
Isolation of an inhibitor selective for collagen-stimulated platelet aggregation from the soft tick Ornithodoros moubata. (1993)

Soluble extracts from the soft tick Ornithodoros moubata were found to inhibit collagen-, ADP-, and thrombin-stimulated platelet aggregation. One inhibitory component was purified to homogeneity by a combination of gel filtration, ion-exchange, and reverse phase high pressure liquid chromatography. The purified activity, named moubatin, is a protein of molecular weight 17,000 and it inhibits the aggregation of washed human platelets stimulated by collagen with an IC50 of approximately 50 nM in the standard assay. At a concentration of moubatin that maximally inhibited collagen-stimulated platelet aggregation, no inhibition of aggregation initiated by other effectors, including arachidonic acid, thrombin, ristocetin, and the calcium ionophore A23187, was observed. Moubatin also inhibits collagen-dependent aggregation in plasma. At a higher concentration of moubatin (> 1 microM) it was also possible to demonstrate an inhibitory effect on the final extent of aggregation induced by a low concentration of ADP. Although moubatin selectively inhibits platelet activation by collagen, it has only a minimal effect on the adhesion of platelets to collagen. The amino acid sequences of peptides derived from proteolytic cleavage of moubatin suggest that moubatin is a unique protein, consistent with its novel functional activity.
Contemplating systematic software reuse in a project-centric company (2008)

Systematic software reuse is still the most promising strategy for increasing productivity and improving quality in the software industry. Although it is simple in concept, successful software reuse implementation is difficult in practice. A reason put forward for this is the dependence of software reuse on the context in which it is implemented. This paper describes an interpretive case study aimed at investigating the potential for the implementation of systematic software reuse in a project-centric company. The study confirmed the need for systematic software reuse and identified the reuse issues that could present challenges. The study also revealed a number of problems relating to the project-centric structure for which systematic reuse provides potential solutions.
Stat3: linking inflammation to epithelial cancer - more than a "gut" feeling? (2010)

Inflammation is an important environmental factor that promotes tumourigenesis and the progression of established cancerous lesions, and recent studies have started to dissect the mechanisms linking the two pathologies. These inflammatory and infectious conditions trigger immune and stromal cell release of soluble mediators which facilitate survival and proliferation of tumour cells in a paracrine manner. In addition, (epi-)genetic mutations affecting oncogenes, tumour-suppressor genes, chromosomal rearrangements and amplifications trigger the release of inflammatory mediators within the tumour microenvironment to promote neoplastic growth in an autocrine manner. These two pathways converge in tumour cells and result in activation of the latent signal transducer and activator of transcription 3 (Stat3) which mediates a transcriptional response favouring survival, proliferation and angiogenesis. The abundance of cytokines that activate Stat3 within the tumour microenvironment, which comprises of members of the interleukin (IL) IL6, IL10 and IL17/23 families, underpins a signaling network that simultaneously promotes the growth of neoplastic epithelium, fuels inflammation and suppresses the host's anti-tumour immune response. Accordingly, aberrant and persistent Stat3 activation is a frequent observation in human cancers of epithelial origin and is often associated with poor outcome.Here we summarize insights gained from mice harbouring mutations in components of the Stat3 signaling cascade and in particular of gp130, the shared receptor for the IL6 family of cytokines. We focus on the various feed-back and feed-forward loops in which Stat3 provides the signaling node in cells of the tumour and its microenvironment thereby functionally linking excessive inflammation to neoplastic growth. Although these observations are particularly pertinent to gastrointestinal tumours, we suggest that the tumour's addiction to persistent Stat3 activation is likely to also impact on other epithelial cell-derived cancers. These insights provide clues to the judicious interference of the gp130/Stat3 signaling cascade in therapeutically targeting cancer.
Characterization of a mutation within the NDP gene in a family with a manifesting female carrier (1993)

Journal Article Characterization of a mutation within the NDP gene in a family with a manifesting female carrier Get access Z.-Y. Chen, Z.-Y. Chen Search for other works by this author on: Oxford Academic PubMed Google Scholar E.M. Battinelli, E.M. Battinelli Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Woodruff, G. Woodruff 1Department of Ophthalmology,University of OxfordOxford OX1 3QU, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar I. Young, I. Young 2Clinical Genetics, City HospitalHucknall, Nottingham Search for other works by this author on: Oxford Academic PubMed Google Scholar X.O. Breakfield, X.O. Breakfield Search for other works by this author on: Oxford Academic PubMed Google Scholar I.W. Craig I.W. Craig * 3Genetics Laboratory, Department of Biochemistry, University at OxfordOxford OX1 3QU, UK *To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Molecular Genetics, Volume 2, Issue 10, October 1993, Pages 1727–1729, https://doi.org/10.1093/hmg/2.10.1727 Published: 01 October 1993 Article history Received: 19 July 1993 Revision received: 02 August 1993 Accepted: 02 August 1993 Published: 01 October 1993
A new driving method for a-Si AMOLED displays based on voltage feedback (2005)

We present a new driving technique for active-matrix organic light-emitting diode displays using amorphous silicon backplanes. The technique uses voltage feedback to compensate for threshold voltage shift of TFTs. Measurement results show less than 3.5% change in OLED current over 2700 hours of bias stress. © 2005 SID.
Multiplex target protein imaging in tissue sections by mass spectrometry – TAMSIM (2007)

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-MS) is becoming a popular tool for imaging histological sections. Currently, this technology is used to image naturally occurring molecules. Here we report a novel development for multiplex imaging of candidate proteins. Rather than detecting whatever molecules happen to be present and above the detection threshold in the desorption pixel, we attach photocleavable mass tags to antibodies to target proteins. 'Staining' of histological sections is carried out similarly to common immunohistochemical procedures with chemiluminescent or fluorescent detection using all antibodies of a multiplex simultaneously. Mass tags with discrete masses are released from their respective antibodies by a laser pulse at 355 nm without added matrix. After scanning, mass spectrometry images are created for the mass of each tag. In contrast to fluorescent tags, mass tags do not exhibit mutual quenching. Sections of healthy human pancreatic tissue were imaged to visualize synaptophysin in neuroendocrine cells, and sections from human lymph node and liver invaded by metastatic melanoma to localize the cancer markers PS100 and HMB45 simultaneously. All these proteins are below the detection threshold of direct MALDI-MS imaging. This method is termed TAMSIM for TArgeted multiplex Mass Spectrometry IMaging.
Molecular Genetic Identification of a Pathway for Heme Binding to Cytochrome b 6 (1997)

Heme binding to cytochrome b6 is resistant, in part, to denaturing conditions that typically destroy the noncovalent interactions between the b hemes and their apoproteins, suggesting that one of two b hemes of holocytochrome b6 is tightly bound to the polypeptide. We exploited this property to define a pathway for the conversion of apo- to holocytochrome b6, and to identify mutants that are blocked at one step of this pathway. Chlamydomonas reinhardtii strains carrying substitutions in either one of the four histidines that coordinate the bh or bl hemes to the apoprotein were created. These mutations resulted in the appearance of distinct immunoreactive species of cytochrome b6, which allowed us to specifically identify cytochrome b6 with altered bh or bl ligation. In gabaculine-treated (i.e. heme-depleted) wild type and site-directed mutant strains, we established that (i) the single immunoreactive band, observed in strains carrying the bl site-directed mutations, corresponds to apocytochrome b6 and (ii) the additional band present in strains carrying bh site-directed mutations corresponds to a bl-heme-dependent intermediate in the formation of holocytochrome b6. Five nuclear mutants (ccb strains) that are defective in holocytochrome b6 formation display a phenotype that is indistinguishable from that of strains carrying site-directed bh ligand mutants. The defect is specific for cytochrome b6 assembly, because the ccb strains can synthesize other b cytochromes and all c-type cytochromes. The ccb strains, which define four nuclear loci (CCB1, CCB2, CCB3, and CCB4), provide the first evidence that a b-type cytochrome requires trans-acting factors for its heme association.
Site-directed mutagenesis of a catabolite repression operator sequence in Bacillus subtilis. (1990)

Catabolite repression of the Bacillus subtilis alpha-amylase gene (amyE) involves an operator sequence located just downstream of the promoter (amyR), overlapping the transcription start site. Oligonucleotide site-directed mutagenesis of this sequence identified bases required for catabolite repression. Two mutations increased both the 2-fold symmetry of the operator and the repression ratio. Although many mutations reduced the repression ratio 3- to 11-fold, some also caused a 2-fold or greater increase in amylase production. Others caused hyperproduction without affecting catabolite repression. Homologous sequences in other catabolite-repressed B. subtilis promoters suggest a common regulatory site may be involved in catabolite repression.
Visualization of optical deflection and switching operations by a domain-engineered-based LiNbO_3 electro-optic device (2003)

An electro-optic device applied as an optical beam deflector and switch at different wavelengths has been built and tested. The electro-optic device is based on domain-engineered lithium niobate (LiNbO3). In this paper, for the first time, its operation has been visualized by an imaging camera. The device has been characterized both at the visible wavelength (632.8 nm) and at a typical telecom wavelength (1532 nm). Furthermore, the device has been tested as an amplitude modulator in the mid-infrared region as well, at a wavelength of ~4.3 microm, where no Pockels cells are available. A detailed description of this device is given, and the experimental results are discussed.
Early arrival waveform tomography on near-surface refraction data (2006)

Abstract We develop a waveform-tomography method for estimating the velocity distribution that minimizes the waveform misfit between the predicted and observed early arrivals in space-time seismograms. By fitting the waveforms of early arrivals, early arrival waveform tomography (EWT) naturally takes into account more general wave-propagation effects compared to the high-frequency method of traveltime tomography, meaning that EWT can estimate a wider range of slowness wavenumbers. Another benefit of EWT is more reliable convergence compared to full-waveform tomography, because an early-arrival misfit function contains fewer local minima. Synthetic test results verify that the waveform tomogram is much more accurate than the traveltime tomogram and that this algorithm has good convergence properties. For marine data from the Gulf of Mexico, the statics problem caused by shallow, gassy muds was attacked by using EWT to obtain a more accurate velocity model. Using the waveform tomogram to correct for statics, the stacked section was significantly improved compared to using the normal move-out (NMO) velocity, and moderately improved compared to using the traveltime tomogram. Inverting high-resolution land data from Mapleton, Utah, showed an EWT velocity tomogram that was more consistent with the ground truth (trench log) than the traveltime tomogram. Our results suggest that EWT can provide supplemental, shorter-wavelength information compared to the traveltime tomogram for both shallow and moderately deep seismic data.
1-(Aminoalkyl)-2-phenylindoles as novel pure estrogen antagonists (1990)

A number of 1-(omega-aminoalkyl)-5-hydroxy-2-(4-hydroxyphenyl)indoles were synthesized and studied for their binding affinities for the calf uterine estrogen receptor and estrogen antagonistic activities. Highest binding affinities were found with derivatives bearing a methyl group in position 3 and a hexamethylene chain between the indole and amino nitrogen atoms. Values for relative binding affinity (RBA) are between 20 and 30 for derivatives 5b, 5c, 5f, and 5h (17 beta-estradiol = 100). In the mouse uterine weight test, no significant agonistic (estrogenic) activity was observed up to a daily dose of 125 micrograms/animal, except for derivatives 5c, 5j, and 5l. 2-Phenylindoles with amino (5b), pyrrolidino (5f), piperidino (5h), and morpholino (5k) groups as the amino function completely suppressed estrone-stimulated uterine growth as a dose of 125 micrograms/animal (100% antagonism). Therefore, these derivatives can be considered as first examples of nonsteroidal pure antiestrogens.