gebhart/patrepeval huggingface dataset:
Association between Recurrent Concussion and Late-Life Cognitive Impairment in Retired Professional Football Players (2005)

Our findings suggest that the onset of dementia-related syndromes may be initiated by repetitive cerebral concussions in professional football players.
Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia (2002)

We investigated whether increasing the dose of imatinib mesylate might overcome drug resistance in patients with Philadelphia chromosome-positive (Ph(+)) chronic myelogenous leukemia (CML) whose disease manifests relapse or refractoriness to therapy. Fifty-four patients with Ph(+) CML in chronic phase and with hematologic or cytogenetic resistance or relapse on imatinib mesylate therapy at 400 mg orally daily were treated with a higher dose of 400 mg orally twice daily (800 mg daily, 47 patients; or 600 mg daily increased from 300 mg daily, 7 patients). Among 20 patients treated for hematologic resistance or relapse, 13 (65%) achieved a complete (n = 9) or partial (n = 4) hematologic response, but only 1 had a cytogenetic partial response (Ph reduction from 100% to 10%) and 1 had a minor response (Ph reduction from 100% to 50%). Among 34 patients treated for cytogenetic resistance or relapse, 19 (56%) achieved a complete (n = 6) or partial (n = 7) cytogenetic response. We conclude that higher doses of imatinib mesylate may overcome disease-poor response to conventional doses and that this approach deserves further evaluation as frontline therapy for newly diagnosed CML.
Elaboration of bromoarylnitriles (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElaboration of bromoarylnitrilesWilliam E. Parham and Lawrence D. JonesCite this: J. Org. Chem. 1976, 41, 7, 1187–1191Publication Date (Print):April 1, 1976Publication History Published online1 May 2002Published inissue 1 April 1976https://pubs.acs.org/doi/10.1021/jo00869a023https://doi.org/10.1021/jo00869a023research-articleACS PublicationsRequest reuse permissionsArticle Views874Altmetric-Citations64LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Blockade of sensory neuron action potentials by a static magnetic field in the 10 mT range (1995)

To characterize the inhibitory effect of a static magnetic field, action potentials (AP) were elicited by intracellular application of 1 ms depolarizing current pulses of constant amplitude to the somata of adult mouse dorsal root ganglion neurons in monolayer dissociated cell culture. During the control period, < 5% of stimuli failed to elicit AP. During exposure to an approximately 11 mT static magnetic field at the cell position produced by an array of four permanent center-charged neodymium magnets of alternating polarity (MAG-4A), 66% of stimuli failed to elicit AP. The number of failures was maximal after about 200-250 s in the field and returned gradually to baseline over 400-600 s. A direct or indirect effect on the conformation of AP generating sodium channels could account for these results because 1) failure was preceded often by reduction of maximal rate of rise, an indirect measure of sodium current; 2) recovery was significantly prolonged in more than one-half of neurons that were not stimulated during exposure to the MAG-4A field; and 3) resting membrane potential, input resistance, and chronaxie were unaffected by the field. The effect was diminished or prevented by moving the MAG-4A array along the X or Z axis away from the neuron under study and by increasing the distance between magnets in the XY plane. Reduction of AP firing during exposure to the approximately 0.1 mT field produced by a MAG-4A array of micromagnets was about the same as that produced by a MAG-4A array of the large magnets above. The approximately 28 mT field produced at cell position by two magnets of alternating polarity and the approximately 88 mT field produced by a single magnet had no significant effect on AP firing. These findings suggest that field strength alone cannot account for AP blockade.
The use of gene therapy vs. corticotomy surgery in accelerating orthodontic tooth movement (2011)

Selective gene therapy with RANKL has been experimentally tested as an alternative method to corticotomy surgery, showing higher effectiveness than surgical methods used for acceleratory purposes in orthodontics.
Acrylamide Fragment Inhibitors that Induce Unprecedented Conformational Distortions in Enterovirus 71 3C and SARS-CoV-2 Main Protease (2020)

ABSTRACT RNA viruses are critically dependent upon virally encoded proteases that cleave the viral polyproteins into functional mature proteins. Many of these proteases are structurally conserved with an essential catalytic cysteine and this offers the opportunity to irreversibly inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that selectively target the active site cysteine of the 3C protease (3C pro ) of Enterovirus 71, the causative agent of hand, foot and mouth disease in humans, altering the substrate binding region. Further, we effectively re-purpose these hits towards the main protease (M pro ) of SARS-CoV-2 which shares the 3C-like fold as well as similar catalytic-triad. We demonstrate that the hit fragments covalently link to the catalytic cysteine of M pro to inhibit its activity. In addition, we provide the first demonstration that targeting the active site cysteine of M pro can also have profound allosteric effects, distorting secondary structures required for formation of the active dimeric unit of M pro . These new data provide novel mechanistic insights into the design of EV71 3C pro and SARS-CoV-2 M pro inhibitors and identify acrylamide-tagged pharmacophores for elaboration into more selective agents of therapeutic potential.
Sensitivity–bandwidth product for electro-optic modulators (2001)

For lumped-element electro-optic modulators, the sensitivity ( partial differentialphi/ partial differentialV) of the phase, phi , in response to an applied voltage V is related to the optical group delay, T(g) , and the bandwidth, Domega . This relationship imposes a fundamental trade-off between the sensitivity and the bandwidth of electro-optic modulators: ( partial differentialphi/ partial differentialV)Domega= (dn/dV)(omega /n) , where n is the optical index. A similar relationship for traveling-wave modulators sets an upper limit on ( partial differentialphi/ partial differentialV) that is proportional to T(g) .
Enhanced antiviral effect in cell culture of type 1 interferon and ribozymes targeting HCV RNA (2001)

We have recently shown that the replication of an HCV-poliovirus (PV) chimera that is dependent upon the hepatitis C virus (HCV) 5' untranslated region (UTR) can be inhibited by treatment with ribozymes targeting HCV RNA. To determine the antiviral effects of anti-HCV ribozyme treatment in combination with type 1 interferon (IFN), we analysed the replication of this HCV-PV chimera in HeLa cells treated with anti-HCV ribozyme and/or IFN-alpha2a, IFN-alpha2b, or consensus IFN. The anti-HCV ribozyme, or any of the IFNs alone have significant inhibitory effects on HCV-PV replication compared to control treatment (> or = 85%, P < 0.01). The maximal inhibition due to IFN treatment (94%, P < 0.01) was achieved with > or = 50 U/ml for either IFN-alpha2a or IFN-alpha2b compared to control treatment. A similar level of inhibition in viral replication could be achieved with a 5-fold lower dose of IFN if ribozyme targeting the HCV 5' UTR was given in combination. For consensus IFN, the dose could be reduced by > 12.5-fold if ribozyme targeting the HCV 5' UTR was given in combination. Conversely, the dose of ribozyme could be reduced 3-fold if given in combination with any of the IFN preparations. Moreover, treatment with low doses (1-25 U/mL) of IFN-alpha2a, IFN-alpha2b, or consensus IFN in combination with anti-HCV ribozyme resulted in > 98% inhibition of HCV-PV replication compared to control treatment (P < 0.01). These results demonstrate that IFN and ribozyme each have a beneficial antiviral effect that is augmented when given in combination.
Acetylated and Methylated β-Cyclodextrins as Viable Soluble Supports for the Synthesis of Short 2′-Oligodeoxyribo-nucleotides in Solution (2012)

Novel soluble supports for oligonucleotide synthesis 11a-c have been prepared by immobilizing a 5′-O-protected 3′-O-(hex-5-ynoyl)thymidine (6 or 7) to peracetylated or permethylated 6-deoxy-6-azido-β-cyclodextrins 10a or 10b by Cu(I)-promoted 1,3-dipolar cycloaddition. The applicability of the supports to oligonucleotide synthesis by the phosphoramidite strategy has been demonstrated by assembling a 3′-TTT-5′ trimer from commercially available 5′-O-(4,4′-dimethoxytrityl)thymidine 3′-phosphoramidite. To simplify the coupling cycle, the 5′-O-(4,4′-dimethoxytrityl) protecting group has been replaced with an acetal that upon acidolytic removal yields volatile products. For this purpose, 5′-O-(1-methoxy-1-methylethyl)-protected 3′-(2-cyanoethyl-N,N-diisopropyl-phosphoramidite)s of thymidine (5a), N⁴-benzoyl-2′-deoxycytidine (5b) and N⁶-benzoyl-2′-deoxyadenosine (5c) have been synthesized and utilized in synthesis of a pentameric oligonucleotide 3′-TTCAT-5′ on the permethylated cyclodextrin support 11c.
B-concentration dependence on anisotropy field of CoFeB thin film for gigahertz frequency use (2005)

B was added to the high moment CoFe thin films (Co/sub 35/Fe/sub 65/, Co/sub 25/Fe/sub 75/, and Co/sub 15/Fe/sub 85/) using synchronous triple-RF magnetron sputtering to obtain the films with large anisotropy fields greater than 500 Oe. These films required inductor core materials operating at the frequencies of several gigahertz. Magnetic properties and the crystalline structure of the CoFeB films were investigated. It was found that the B addition increased the anisotropy field to 400-700 Oe and that the increase in anisotropy field was associated with changes in the crystalline structure, crystallite sizes, and crystallite orientation. The results indicated that CoFeB films have potential for use in magnetic cores and inductors operating at gigahertz frequencies.
Infectious RNA transcripts derived from cloned cDNA of papaya mosaic virus: effect of mutations to the capsid and polymerase proteins (1993)

Genomic length cDNAs of papaya mosaic virus (PMV) RNA were generated utilizing reverse transcriptase (RNase H-) for first strand synthesis, Sequenase for second strand synthesis and primers specific for the 5' and 3' termini of the viral genome. These cDNAs were cloned into plasmid pUC18 and infectious RNA transcripts were synthesized in vitro from a bacteriophage T7 RNA polymerase promoter incorporated into the 5' specific primer. The infectivity of transcripts was 16% that of native PMV RNA. Increasing the poly(A) tail length from A24 to A71 produced a 43% increase in infectivity. Transcripts synthesized with or without an m7GpppG cap structure were biologically active although uncapped transcripts were much less infectious. The addition of up to 2434 non-viral nucleotides at the 3' end of transcripts decreased but did not abolish infectivity. Insertions of two amino acid residues within the polymerase coding region inactivated viral transcripts. A single amino acid deletion within the capsid protein (CP) produced local lesions of a reduced size as compared to native PMV RNA. Viral particles could not be observed in crude extracts from lesions produced by this deletion mutant suggesting that it exists as a naked RNA species within the host. Mutations to the CP suggest that it is required not only for viral assembly but also for some other unidentified function(s) during the replication cycle.
Resistance extraction using a routing algorithm (1993)

Article Free Access Share on Resistance extraction using a routing algorithm Authors: Lorenz Ladage View Profile , Rainer Leupers View Profile Authors Info & Claims DAC '93: Proceedings of the 30th international Design Automation ConferenceJuly 1993 Pages 38–42https://doi.org/10.1145/157485.164559Published:01 July 1993Publication History 7citation265DownloadsMetricsTotal Citations7Total Downloads265Last 12 Months25Last 6 weeks2 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Fast Semantic Extraction Using a Novel Neural Network Architecture (2007)

Semantic understanding of text plays an important role in many fashionable tasks such as information (e.g. opinion) extraction, in web-crawling systems, question and answering based systems (e.g. for call centers), as well as in machine translation, summarization and search. End user applications typically have to deal with an enormous quantity of data, e.g. web based systems process large numbers of documents, and interactive human-machine applications require almost instant response. While complete semantic understanding is still a far-distant goal of natural language processing, several intermediate processing tasks are useful for the tasks described above. These range from syntactic analysis (such as part-of-speech labeling and parsing) to semantic analysis (word-sense disambiguation, semantic-role labeling, named entity extraction, co-reference resolution and entailment). Unfortunately, the state-of-the-art solutions of many of these tasks are simply too slow for the applications previously described. For example, state-of-the-art syntactic parsers typically have cubic complexity in the sentence length [2], and several semantic extraction algorithms use the parse-tree as an initial feature. In this work, we focus on the semantic role labeling problem: being able to give a semantic role to a syntactic consituent of a sentence. (However, our results could extend to other domains as
Dynamic behavior of microscale particles controlled by standing bulk acoustic waves (2014)

We analyze the dynamic behavior of a spherical microparticle submerged in a fluid medium, driven to the node of a standing bulk acoustic wave created by two opposing transducers. We derive the dynamics of the fluid-particle system taking into account the acoustic radiation force and the time-dependent and time-independent drag force acting on the particle. Using this dynamic model, we characterize the transient and steady-state behavior of the fluid-particle system as a function of the particle and fluid properties and the transducer operating parameters. The results show that the settling time and percent overshoot of the particle trajectory are dependent on the ratio of the acoustic radiation force and time-independent damping force. In addition, we show that the particle oscillates around the node of the standing wave with an amplitude that depends on the ratio of the time-dependent drag forces and the particle inertia.
Acute myelofibrosis: report of a case and review of current literature. (1989)

Acute myelofibrosis is a rare hematologic disorder characterized by pancytopenia, normal erythrocyte morphology, extensive marrow fibrosis, and a rapidly fatal clinical course. The etiology of this disease is unknown, but the malignant cell may be of megakaryocytic lineage. Although allogeneic bone marrow transplantation may be effective in achieving complete hematologic remission, optimal management of this rare and often rapidly fatal disease remains to be defined.
A 300 MHz digital double-sideband to single-sideband converter in 1 μm CMOS (1995)

A 43-tap FIR Hilbert transform digital filter chip is described which implements both a double-sideband (DSB) to single-sideband (SSB) conversion with a decimation-by-2 and the converse operation of a SSB to DSB conversion with an interpolation-by-2. Over 70 dB of image rejection is achieved by the Hilbert transform filter. The 3.57/spl times/7.07 mm/sup 2/, 45 000 transistor chip was fabricated in a 1 /spl mu/m N-well CMOS process and operates at sample rates in excess of 300 MHz.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Research note. Effects of early summer drought on the crown density of Norway spruce (1997)

Norway spruce (Picea abies (L.) Karst.) is sensitive to drought stress. The species loses needles during and shortly after droughts, followed by a rapid recovery (Gruber, 1990). Past periods of regional decline in Norway spruce have been linked to drought, especially where the species does not grow naturally or where non-local provenances have been introduced (Innes, 1993). A study of changes in forest condition in Britain 1989 to 1992 reports that change in crown density in Norway spruce covaries with soil moisture deficits, annual potential evapotranspiration and depositions of sulphur (Mather et al., 1995). The results suggest that trees which tolerate the independent stresses of pollution and drought will exhibit signs of decline under circumstances of combined water and pollution stress (Macrez and Hubac, 1988; Pierre and Queiroz, 1988). Early summer drought occurred in southeastern Norway in 1992 and again in 1993. This paper explores the relationship between drought and crown density for Norway spruce, as observed in the national monitoring scheme
Internal and external autocrine VEGF/KDR loops regulate survival of subsets of acute leukemia through distinct signaling pathways (2004)

Besides being expressed on endothelial cells, vascular endothelial growth factor receptors (VEGFRs) are also functional on subsets of leukemias, resulting in autocrine loops that sustain leukemia migration and proliferation. While recent evidence suggests that VEGF supports hematopoietic stem cell survival via an internal loop, the molecular mechanisms whereby autocrine stimulation of VEGFR-2 (KDR) promotes leukemia growth are not well understood. Here we show on acute myeloid primary leukemias and cell lines that VEGF/KDR autocrine loops operate both internally and externally. First, we demonstrate that KDR is constitutively phosphorylated and located at the nucleus of VEGF-producing leukemias. Treatment with anti-VEGF antibody, which acts externally, blocked KDR nuclear translocation and inhibited nuclear factor kappa B (NF-kappaB; p65 and c-rel) activation. In contrast, a KDR-specific intracellular inhibitor failed to block KDR nuclear translocation, but inhibited the constitutive activation of mitogen activated protein kinase (MAPK)/Erk and the phosphatidylinositol 3-kinase/AKT pathways. Notably, treatment with the anti-VEGF antibody alone had little effect on cell survival, while the internal inhibitor induced leukemia apoptosis, and the 2 drugs produced synergistic effects, together and with chemotherapy, reducing cell survival to a larger extent than either agent alone. Our results demonstrate that internal and external VEGF/KDR autocrine loops regulate leukemia survival via different mechanisms, and suggest that blocking both may have therapeutic potential.
Respiratory syncytial virus (RSV): a scourge from infancy to old age (2019)

Respiratory syncytial virus (RSV) is the most common single cause of respiratory hospitalisation of infants and is the second largest cause of lower respiratory infection mortality worldwide. In adults, RSV is an under-recognised cause of deterioration in health, particularly in frail elderly persons. Infection rates typically rise in late autumn and early winter causing bronchiolitis in infants, common colds in adults and insidious respiratory illness in the elderly. Virus detection methods optimised for use in children have low detection rate in adults, highlighting the need for better diagnostic tests. There are many vaccines under development, mostly based on the surface glycoprotein F which exists in two conformations (prefusion and postfusion). Much of the neutralising antibody appears to be to the prefusion form. Vaccines being developed include live attenuated, subunit, particle based and live vectored agents. Different vaccine strategies may be appropriate for different target populations: at-risk infants, school-age children, adult caregivers and the elderly. Antiviral drugs are in clinical trial and may find a place in disease management. RSV disease is one of the major remaining common tractable challenges in infectious diseases and the era of vaccines and antivirals for RSV is on the near horizon.
Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy (2003)

It is generally believed that increase in adult contractile cardiac mass can be accomplished only by hypertrophy of existing myocytes. Documentation of myocardial regeneration in acute stress has challenged this dogma and led to the proposition that myocyte renewal is fundamental to cardiac homeostasis. Here we report that in human aortic stenosis, increased cardiac mass results from a combination of myocyte hypertrophy and hyperplasia. Intense new myocyte formation results from the differentiation of stem-like cells committed to the myocyte lineage. These cells express stem cell markers and telomerase. Their number increased >13-fold in aortic stenosis. The finding of cell clusters with stem cells making the transition to cardiogenic and myocyte precursors, as well as very primitive myocytes that turn into terminally differentiated myocytes, provides a link between cardiac stem cells and myocyte differentiation. Growth and differentiation of these primitive cells was markedly enhanced in hypertrophy, consistent with activation of a restricted number of stem cells that, through symmetrical cell division, generate asynchronously differentiating progeny. These clusters strongly support the existence of cardiac stem cells that amplify and commit to the myocyte lineage in response to increased workload. Their presence is consistent with the notion that myocyte hyperplasia significantly contributes to cardiac hypertrophy and accounts for the subpopulation of cycling myocytes.
RVX-208, an Inducer of ApoA-I in Humans, Is a BET Bromodomain Antagonist (2013)

Increased synthesis of Apolipoprotein A-I (ApoA-I) and HDL is believed to provide a new approach to treating atherosclerosis through the stimulation of reverse cholesterol transport. RVX-208 increases the production of ApoA-I in hepatocytes in vitro, and in vivo in monkeys and humans, which results in increased HDL-C, but the molecular target was not previously reported. Using binding assays and X-ray crystallography, we now show that RVX-208 selectively binds to bromodomains of the BET (Bromodomain and Extra Terminal) family, competing for a site bound by the endogenous ligand, acetylated lysine, and that this accounts for its pharmacological activity. siRNA experiments further suggest that induction of ApoA-I mRNA is mediated by BET family member BRD4. These data indicate that RVX-208 increases ApoA-I production through an epigenetic mechanism and suggests that BET inhibition may be a promising new approach to the treatment of atherosclerosis.