pinecone/core-2020-05-10-deduplication huggingface dataset:
Differential inhibition of human atherosclerotic plaque-induced platelet activation by dimeric GPVI-Fc and anti-GPVI antibodies: functional and imaging studies

BACKGROUND 
Glycoprotein VI (GPVI) is the essential platelet collagen receptor in atherothrombosis, but its inhibition causes only a mild bleeding tendency. Thus, targeting this receptor has selective antithrombotic potential. 

OBJECTIVES 
We compared compounds interfering with platelet PVI-atherosclerotic plaque interaction to improve current antiatherothrombotic therapy. 

METHODS 
Human atherosclerotic plaque-induced platelet aggregation was measured in anticoagulated blood under static and arterial flow conditions (550/s, 1,100/s, and 1,500/s). Inhibition by dimeric GPVI-Fc masking GPVI binding sites on collagen was compared with that of 3 anti-GPVI antibodies: BLO8-1, a human domain antibody; 5C4, a fragment antigen-binding (Fab fragment) of monoclonal rat immunoglobulin G; and m-Fab-F, a human recombinant sFab against GPVI dimers. 

RESULTS 
GPVI-Fc reduced plaque-triggered platelet aggregation in static blood by 51%, BLO8-1 by 88%, and 5C4 by 93%. Under arterial flow conditions BLO8-1 and 5C4 almost completely inhibited platelet aggregation, while preserving platelet adhesion on plaque. Inhibition by GPVI-Fc, even at high concentrations, was less marked but increased with shear rate. Advanced optical imaging revealed rapid persistent GPVI-Fc binding to collagen under low and high shear flow, upstream and downstream of plaque fragments. Particularly at low shear, platelets adhered in plaque flow niches to GPVI-Fc free segments of collagen fibers and recruited other platelets onto aggregates. 

CONCLUSIONS 
Anti-GPVI antibodies inhibit atherosclerotic plaque-induced platelet aggregation under static and flow conditions more effectively than GPVI-Fc. However, potent platelet inhibition by GPVI-Fc at higher shear (1,500/s) suggests localized antithrombotic efficacy at denuded or fissured stenotic high-risk lesions without systemic bleeding. The compound-specific differences have relevance for clinical trials targeting GPVI-collagen interaction on top of established antiplatelet therapies in patients with spontaneous plaque rupture or intervention-associated plaque injury.The study was supported by grants from advanceCOR GmbH (JJ), the August-Lenz foundation, the Deutsche Forschungsgemeinschaft SFB1123/Z01 (MB), and the British Heart Foundation (SMJ and RWF; grants RG/09/003/27122 and PG/10/011/28199). Two-photon laser scanning microscopy experiments have been supported by the Deutsche Forschungsgemeinschaft (INST 409/97-1) and the LMU.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.jacc.2015.03.57
Clinical development of new drug–radiotherapy combinations

In countries with the best cancer outcomes, approximately 60% of patients receive radiotherapy as part of their treatment, which is one of the most cost-effective cancer treatments. Notably, around 40% of cancer cures include the use of radiotherapy, either as a single modality or combined with other treatments. Radiotherapy can provide enormous benefit to patients with cancer. In the past decade, significant technical advances, such as image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic radiotherapy, and proton therapy enable higher doses of radiotherapy to be delivered to the tumour with significantly lower doses to normal surrounding tissues. However, apart from the combination of traditional cytotoxic chemotherapy with radiotherapy, little progress has been made in identifying and defining optimal targeted therapy and radiotherapy combinations to improve the efficacy of cancer treatment. The National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group (CTRad) formed a Joint Working Group with representatives from academia, industry, patient groups and regulatory bodies to address this lack of progress and to publish recommendations for future clinical research. Herein, we highlight the Working Group’s consensus recommendations to increase the number of novel drugs being successfully registered in combination with radiotherapy to improve clinical outcomes for patients with cancer.National Institute for Health ResearchThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/nrclinonc.2016.7
Measurement of the cross-section for W boson production in association with b-jets in pp collisions at root s = 7 TeV with the ATLAS detector

This paper reports a measurement of the W +b-jets (W +b+ X and W +bb¯¯+X) production cross-section in proton-proton collisions at a centre-of-mass energy of 7 TeV at the LHC. These results are based on data corresponding to an integrated luminosity of 4.6 fb−1, collected with the ATLAS detector. Cross-sections are presented as a function of jet multiplicity and of the transverse momentum of the leading b-jet for both the muon and electron decay modes of the W boson. The W +b-jets cross-section, corrected for all known detector effects, is quoted in a limited kinematic range. Combining the muon and electron channels, the fiducial cross-section for W +b-jets is measured to be 7.1 ± 0.5 (stat) ± 1.4 (syst) pb, consistent with the next-to-leading order QCD prediction, corrected for non-perturbative and double-parton interactions (DPI) contributions, of 4.70 ± 0.09 (stat) +0.60−0.49 (scale) ±0.06 (PDF) ±0.16 (non-pert) +0.52−0.38 (DPI) pbG. Aad … P. Jackson … L. Lee … A. Petridis … N. Soni … M.J. White … et al. [ATLAS Collaboration
The VIMOS Public Extragalactic Redshift Survey (VIPERS). The coevolution of galaxy morphology and colour to z ~ 1

RT acknowledges financial support from the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007- 2013)/ERC grant agreement n. 202686.Context. The study of the separation of galaxy types into different classes that share the same characteristics, and of the evolution of the specific parameters used in the classification are fundamental for understanding galaxy evolution.Aims. We explore the evolution of the statistical distribution of galaxy morphological properties and colours combining high-quality imaging data from the CFHT Legacy Survey with the large number of redshifts and extended photometry from the VIPERS survey.Methods. Galaxy structural parameters were combined with absolute magnitudes, colours and redshifts in order to trace evolution in a multi-parameter space. Using a new method we analysed the combination of colours and structural parameters of early- and late-type galaxies in luminosity-redshift space.Results. We find that both the rest-frame colour distributions in the (U−B) vs. (B−V) plane and the Sérsic index distributions are well fitted by a sum of two Gaussians, with a remarkable consistency of red-spheroidal and blue-disky galaxy populations, over the explored redshift (0.5 < z < 1) and luminosity (−1.5 < B−B∗ < 1.0) ranges. The combination of the rest-frame colour and Sérsic index as a function of redshift and luminosity allows us to present the structure of both galaxy types and their evolution. We find that early-type galaxies display only a slow change in their concentrations after z = 1. Their high concentrations were already established at z ~ 1 and depend much more strongly on their luminosity than redshift. In contrast, late-type galaxies clearly become more concentrated with cosmic time with only little evolution in colour, which remains dependent mainly on their luminosity.Conclusions. The combination of rest-frame colours and Sérsic index as a function of redshift and luminosity leads to a precise statistical description of the structure of galaxies and their evolution. Additionally, the proposed method provides a robust way to split galaxies into early and late types.Publisher PDFPeer reviewe
Exploring dependence between categorical variables: Benefits and limitations of using variable selection within Bayesian clustering in relation to log-linear modelling with interaction terms

AbstractThis manuscript is concerned with relating two approaches that can be used to explore complex dependence structures between categorical variables, namely Bayesian partitioning of the covariate space incorporating a variable selection procedure that highlights the covariates that drive the clustering, and log-linear modelling with interaction terms. We derive theoretical results on this relation and discuss if they can be employed to assist log-linear model determination, demonstrating advantages and limitations with simulated and real data sets. The main advantage concerns sparse contingency tables. Inferences from clustering can potentially reduce the number of covariates considered and, subsequently, the number of competing log-linear models, making the exploration of the model space feasible. Variable selection within clustering can inform on marginal independence in general, thus allowing for a more efficient exploration of the log-linear model space. However, we show that the clustering structure is not informative on the existence of interactions in a consistent manner. This work is of interest to those who utilize log-linear models, as well as practitioners such as epidemiologists that use clustering models to reduce the dimensionality in the data and to reveal interesting patterns on how covariates combine
Tank Monitoring: A pAMN Case Study

AbstractThe introduction of probabilistic behaviour into the B-Method is a recent development. In addition to allowing probabilistic behaviour to be modelled, the relationship between expected values of the machine state can be expressed and verified. This paper explores the application of probabilistic B to a simple case study: tracking the volume of liquid held in a tank by measuring the flow of liquid into it. The flow can change as time progresses, and sensors are used to measure the flow with some degree of accuracy and reliability, modelled as non-deterministic and probabilistic behaviour respectively. At the specification level, the analysis is concerned with the expectation clause in the probabilistic B machine and its consistency with machine operations. At the refinement level, refinement and equivalence laws on probabilistic GSL are used to establish that a particular design of sensors delivers the required level of reliability
Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial

SummaryBackgroundProgesterone administration has been shown to reduce the risk of preterm birth and neonatal morbidity in women at high risk, but there is uncertainty about longer term effects on the child.MethodsWe did a double-blind, randomised, placebo-controlled trial of vaginal progesterone, 200 mg daily taken from 22–24 to 34 weeks of gestation, on pregnancy and infant outcomes in women at risk of preterm birth (because of previous spontaneous birth at ≤34 weeks and 0 days of gestation, or a cervical length ≤25 mm, or because of a positive fetal fibronectin test combined with other clinical risk factors for preterm birth [any one of a history in a previous pregnancy of preterm birth, second trimester loss, preterm premature fetal membrane rupture, or a history of a cervical procedure to treat abnormal smears]). The objective of the study was to determine whether vaginal progesterone prophylaxis given to reduce the risk of preterm birth affects neonatal and childhood outcomes. We defined three primary outcomes: fetal death or birth before 34 weeks and 0 days gestation (obstetric), a composite of death, brain injury, or bronchopulmonary dysplasia (neonatal), and a standardised cognitive score at 2 years of age (childhood), imputing values for deaths. Randomisation was done through a web portal, with participants, investigators, and others involved in giving the intervention, assessing outcomes, or analysing data masked to treatment allocation until the end of the study. Analysis was by intention to treat. This trial is registered at ISRCTN.com, number ISRCTN14568373.FindingsBetween Feb 2, 2009, and April 12, 2013, we randomly assigned 1228 women to the placebo group (n=610) and the progesterone group (n=618). In the placebo group, data from 597, 587, and 439 women or babies were available for analysis of obstetric, neonatal, and childhood outcomes, respectively; in the progesterone group the corresponding numbers were 600, 589, and 430. After correction for multiple outcomes, progesterone had no significant effect on the primary obstetric outcome (odds ratio adjusted for multiple comparisons [OR] 0·86, 95% CI 0·61–1·22) or neonatal outcome (OR 0·62, 0·38–1·03), nor on the childhood outcome (cognitive score, progesterone group vs placebo group, 97·3 [SD 17·9] vs 97·7 [17·5]; difference in means −0·48, 95% CI −2·77 to 1·81). Maternal or child serious adverse events were reported in 70 (11%) of 610 patients in the placebo group and 59 (10%) of 616 patients in the progesterone group (p=0·27).InterpretationVaginal progesterone was not associated with reduced risk of preterm birth or composite neonatal adverse outcomes, and had no long-term benefit or harm on outcomes in children at 2 years of age.FundingEfficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. The EME Programme is funded by the MRC and NIHR, with contributions from the Chief Scientist Office in Scotland and National Institute for Social Care and Research in Wales
‘Like sugar and honey’: The embedded ethics of a larval control project in The Gambia

AbstractThis paper describes a malaria research project in The Gambia to provoke thinking on the social value of transnational research. The Larval Control Project (LCP) investigated the efficacy of a microbial insecticide to reduce vector density and, ultimately, clinical malaria in Gambian children. The LCP’s protocol delineated a clinical surveillance scheme that involved Village Health Workers (VHWs) supported by project nurses. Combining insights from ethnographic fieldwork conducted at the Medical Research Council (MRC) Laboratories in Farafenni from 2005 to 2009, open-ended interviews with project nurses, and eight focus group discussions held with participant mothers in October 2007, we consider the social impact of the LCP’s investigative method against the backdrop of several years of research activity. We found that while participants associated the LCP with the clinical care it provided, they also regarded the collaboration between the nurses and VHWs added additional benefits. Organised around the operational functions of the trial, small-scale collaborations provided the platform from which to build local capacity. While ethical guidelines emphasise the considerations that must be added to experimental endeavour in southern countries (e.g. elaborating processes of informed consent, developing strategies of community engagement or providing therapeutic access to participants after the trial concludes), these findings suggest that shifting attention from supplementing ethical protocols to the everyday work of research – embedding ethics through scientific activity – may provide a sounder basis to reinforce the relationship between scientific rigour and social value
Changes in IgE sensitization and total IgE levels over 20 years of follow-up

BackgroundCross-sectional studies have reported a lower prevalence of sensitization in older adults, but few longitudinal studies have examined whether this is an aging or a year-of-birth cohort effect.ObjectiveWe sought to assess changes in sensitization and total IgE levels in a cohort of European adults as they aged over a 20-year period.MethodsLevels of serum specific IgE to common aeroallergens (house dust mite, cat, and grass) and total IgE levels were measured in 3206 adults from 25 centers in the European Community Respiratory Health Survey on 3 occasions over 20 years. Changes in sensitization and total IgE levels were analyzed by using regression analysis corrected for potential differences in laboratory equipment and by using inverse sampling probability weights to account for nonresponse.ResultsOver the 20-year follow-up, the prevalence of sensitization to at least 1 of the 3 allergens decreased from 29.4% to 24.8% (−4.6%; 95% CI, −7.0% to −2.1%). The prevalence of sensitization to house dust mite (−4.3%; 95% CI, −6.0% to −2.6%) and cat (−2.1%; 95% CI, −3.6% to −0.7%) decreased more than sensitization to grass (−0.6%; 95% CI, −2.5% to 1.3%). Age-specific prevalence of sensitization to house dust mite and cat did not differ between year-of-birth cohorts, but sensitization to grass was most prevalent in the most recent ones. Overall, total IgE levels decreased significantly (geometric mean ratio, 0.63; 95% CI, 0.58-0.68) at all ages in all year-of-birth cohorts.ConclusionAging was associated with lower levels of sensitization, especially to house dust mite and cat, after the age of 20 years
Modelling Cities as a Collection of TeraSystems – Computational Challenges in Multi-Agent Approach

AbstractAgent-based modeling techniques are ideal for modeling massive complex systems such as insect colonies or biological cellular systems and even cities. However these models themselves are extremely complex to code, test, simulate and analyze. This paper discusses the challenges in using agent-based models to model complete cities as a complex system. In this paper we argue that Cities are actually a collection of various complex models which are themselves massive multiple systems, each of millions of agents, working together to form one system consisting of an order of a billion agents of different types – such as people, communities and technologies interacting together. Because of the agent numbers and complexity challenges, the present day hardware architectures are unable to cope with the simulations and processing of these models. To accommodate these issues, this paper proposes a Tera (to denote the order of millions)-modeling framework, which utilizes current technologies of Cloud computing and Big data processing, for modeling a city, by allowing infinite resources and complex interactions. This paper also lays the case for bringing together research communities for interdisciplinary research to build a complete reliable model of a city
Biotech rice: Current developments and future detection challenges in food and feed chain

AbstractBackgroundTo improve agricultural practices and the food/feed security, plant breeding techniques were developed, including transgenesis commonly using Agrobacterium tumefaciens or biolistic technologies. To guarantee the traceability of GMO in food/feed chain and the consumer's freedom of choice, regulatory frameworks were established in many countries around the world, such as in Europe. Their implementations, including detection systems usually based on qPCR, are becoming complex and expensive regarding the number of analysis to perform. Moreover, the dispersion of publicly available information about developed GMO prevents to accurately estimate the efficiency of the standard detection system applied to unauthorized GMO.Scope and approachTo illustrate this problem, the case of rice, one of the leading staple crops, was investigated. An overview of worldwide developed biotech rice generated by transgenesis was thus conducted, based on 1067 peer-reviewed publications, and analysed regarding inter alia their expressed genes of interest and the corresponding traits, their transformation processes and the elements composing their transgenic cassettes. From this work, the power and weakness of the standard detection system, notably used by the European enforcement laboratories, are evaluated. To strengthen this system, especially with unauthorized GMO, additional strategies are suggested. Moreover, given the growing interest for biotech rice produced by new plant breeding techniques, related challenges for their detection are discussed.Key findings and conclusionsAccording to all collected information, suitable detection strategies, combining qPCR to additional technologies (e.g., DNA walking and NGS), are proposed to cover most of inventoried biotech rice. The present approach, including the data centralization to subsequently suggest appropriated detection strategies, can be extended to biotech events from different species
Intravitreal chemotherapy for vitreous seeding in retinoblastoma: Recent advances and perspectives

AbstractFor decades intravitreal chemotherapy (IViC) remained virtually banished from the therapeutic armamentarium against retinoblastoma, except as a heroic attempt of salvage before enucleation in only eyes with refractory vitreous seeding. Very recently, we have initiated a reappraisal of this route of administration by (1) profiling eligibility criteria, (2) describing a safety-enhanced injection procedure, (3) adjusting the tumoricidal dose of melphalan, and (4) reporting an unprecedented efficacy in terms of tumor control of vitreous seeding. Since then, intravitreal chemotherapy is being progressively implemented worldwide with great success, but still awaits formal validation by the ongoing prospective phase II clinical trial. As far as preliminary results are concerned, IViC appears to achieve complete vitreous response in 100% of the 35 newly recruited patients irrespective of the previous treatment regimen, including external beam radiotherapy and/or intra-arterial melphalan. In other words, vitreous seeding, still considered as the major cause of primary and secondary enucleation, can now be controlled by IViC. However, sterilization of vitreous seeding does not necessarily translate into eye survival, unless the retinal source of the seeds receives concomitant therapy. In conclusion, IViC, an unsophisticated and cost-effective treatment, is about to revolutionize the eye survival prognosis of vitreous disease in advanced retinoblastoma
Transverse momentum, rapidity, and centrality dependence of inclusive charged-particle production in sNN=5.02 TeV p+Pb collisions measured by the ATLAS experiment

AbstractMeasurements of the per-event charged-particle yield as a function of the charged-particle transverse momentum and rapidity are performed using p+Pb collision data collected by the ATLAS experiment at the LHC at a centre-of-mass energy of sNN=5.02TeV. Charged particles are reconstructed over pseudorapidity |η|<2.3 and transverse momentum between 0.1 GeV and 22 GeV in a dataset corresponding to an integrated luminosity of 1 μb−1. The results are presented in the form of charged-particle nuclear modification factors, where the p+Pb charged-particle multiplicities are compared between central and peripheral p+Pb collisions as well as to charged-particle cross sections measured in pp collisions. The p+Pb collision centrality is characterized by the total transverse energy measured in −4.9<η<−3.1, which is in the direction of the outgoing lead beam. Three different estimations of the number of nucleons participating in the p+Pb collision are carried out using the Glauber model and two Glauber–Gribov colour-fluctuation extensions to the Glauber model. The values of the nuclear modification factors are found to vary significantly as a function of rapidity and transverse momentum. A broad peak is observed for all centralities and rapidities in the nuclear modification factors for charged-particle transverse momentum values around 3 GeV. The magnitude of the peak increases for more central collisions as well as rapidity ranges closer to the direction of the outgoing lead nucleus