Caractérisation et modélisation de polymères PVA

Les hydrogels type PVA (alcool polyvinylique) sont utilisés pour de nombreuses applications telles que le génie tissulaire, la pharmacie et la validation de diverses méthodes d'élastographie. Le potentiel des polymères de PVA ayant déjà été démontré par le passé, cette étude vise à caractériser et modéliser leur comportement en fonction de la méthode d'élaboration employée

Biomechanical behaviour of human bile duct wall and impact of cadaveric preservation processes.

International audienceBiliary diseases are the third most common cause of surgical digestive disease. There is a close relationship between the mechanical performance of the bile duct and its physiological function. Data of biomechanical properties of human main bile duct are scarce in literature. Furthermore, mechanical properties of soft tissues are affected by these preservation procedures. The aim of the present work was, on the one hand, to observe the microstructure of the human bile duct by means of histological analysis, on the other hand, to characterize the mechanical behavior and describe the impact of different preservation processes. A mechanical study in a controlled environment consisting of cyclic tests was made. The results of the mechanical tests are discussed and explained using the micro-structural observations. The results show an influence of the loading direction, which is representative of an anisotropic behavior. A strong hysteresis due to the viscoelastic properties of soft tissues was also observed. Embalming and freezing preservation methods had an impact on the biomechanical properties of human main bile duct, with fiber network deterioration. That may further provide a useful quantitative baseline for anatomical and surgical training using embalming and freezing

Detecting Recent Crop Phenology Dynamics in Corn and Soybean Cropping Systems of Kentucky

Accurate phenological information is essential for monitoring crop development, predicting crop yield, and enhancing resilience to cope with climate change. This study employed a curve-change-based dynamic threshold approach on NDVI (Normalized Differential Vegetation Index) time series to detect the planting and harvesting dates for corn and soybean in Kentucky, a typical climatic transition zone, from 2000 to 2018. We compared satellite-based estimates with ground observations and performed trend analyses of crop phenological stages over the study period to analyze their relationships with climate change and crop yields. Our results showed that corn and soybean planting dates were delayed by 0.01 and 0.07 days/year, respectively. Corn harvesting dates were also delayed at a rate of 0.67 days/year, while advanced soybean harvesting occurred at a rate of 0.05 days/year. The growing season length has increased considerably at a rate of 0.66 days/year for corn and was shortened by 0.12 days/year for soybean. Sensitivity analysis showed that planting dates were more sensitive to the early season temperature, while harvesting dates were significantly correlated with temperature over the entire growing season. In terms of the changing climatic factors, only the increased summer precipitation was statistically related to the delayed corn harvesting dates in Kentucky. Further analysis showed that the increased corn yield was significantly correlated with the delayed harvesting dates (1.37 Bu/acre per day) and extended growing season length (1.67 Bu/acre per day). Our results suggested that seasonal climate change (e.g., summer precipitation) was the main factor influencing crop phenological trends, particularly corn harvesting in Kentucky over the study period. We also highlighted the critical role of changing crop phenology in constraining crop production, which needs further efforts for optimizing crop management practices

Review: optical fiber sensors for civil engineering applications

Optical fiber sensor (OFS) technologies have developed rapidly over the last few decades, and various types of OFS have found practical applications in the field of civil engineering. In this paper, which is resulting from the work of the RILEM technical committee “Optical fiber sensors for civil engineering applications”, different kinds of sensing techniques, including change of light intensity, interferometry, fiber Bragg grating, adsorption measurement and distributed sensing, are briefly reviewed to introduce the basic sensing principles. Then, the applications of OFS in highway structures, building structures, geotechnical structures, pipelines as well as cables monitoring are described, with focus on sensor design, installation technique and sensor performance. It is believed that the State-of-the-Art review is helpful to engineers considering the use of OFS in their projects, and can facilitate the wider application of OFS technologies in construction industry

Simulation Study of Photon-to-Digital Converter (PDC) Timing Specifications for LoLX Experiment

The Light only Liquid Xenon (LoLX) experiment is a prototype detector aimed to study liquid xenon (LXe) light properties and various photodetection technologies. LoLX is also aimed to quantify LXe's time resolution as a potential scintillator for 10~ps time-of-flight (TOF) PET. Another key goal of LoLX is to perform a time-based separation of Cerenkov and scintillation photons for new background rejection methods in LXe experiments. To achieve this separation, LoLX is set to be equipped with photon-to-digital converters (PDCs), a photosensor type that provides a timestamp for each observed photon. To guide the PDC design, we explore requirements for time-based Cerenkov separation. We use a PDC simulator, whose input is the light information from the Geant4-based LoLX simulation model, and evaluate the separation quality against time-to-digital converter (TDC) parameters. Simulation results with TDC parameters offer possible configurations supporting a good separation. Compared with the current filter-based approach, simulations show Cerenkov separation level increases from 54% to 71% when using PDC and time-based separation. With the current photon time profile of LoLX simulation, the results also show 71% separation is achievable with just 4 TDCs per PDC. These simulation results will lead to a specification guide for the PDC as well as expected results to compare against future PDC-based experimental measurements. In the longer term, the overall LoLX results will assist large LXe-based experiments and motivate the assembly of a LXe-based TOF-PET demonstrator system.Comment: 5 pages, 7 figure

Brexit’s Effect on Citizens, Human Rights & Immigration

This report records the roundtable on “Brexit’s Effect on Citizens, Human Rights and Immigration” organised by Dr Adrienne Yong on 11 June 2019 at City, University of London funded by the Higher Education Innovation Fund (HEIF) 2018/19. Speakers included: • Hannah Wilkins (House of Commons Library) • Blanca Grey (Home Office)1 • Paul Erdunast (Immigration Law Practitioner’s Association - ILPA) • Christopher Desira (Seraphus Solicitors) • Nicole Masri (Rights of Women) • Ollie Persey (Public Law Project) • Katarzyna Zagrodniczek (East European Resource Centre) • Mihai Calin Bica (Roma Support Group) • Dr Adrienne Yong (City, University of London) • Dr Michaela Benson (Goldsmiths, University of London) • Madeleine Sumption (Migration Observatory) • Sheona York (Kent Law Clinic) A host of unique legal questions were raised in the aftermath of the UK’s referendum result where the electorate voted in favour of leaving the EU on the 23 June 2016. Opinion has been split as to whether the UK and EU have indeed struck a fair deal for citizens, with arguments that citizens have been used as bargaining chips throughout the process to achieve a deal. As negotiations progressed towards the original mandated date of withdrawal, 29 March 2019, various schemes emerged to handle post-Brexit immigration of EU citizens in the UK and reciprocal arrangements for British citizens in the EU. This is now reflected in the EU Settlement Scheme, the Immigration and Social Security Co-ordination Bill, and the reciprocity agreed with EU Member States as to British citizens in the EU. These issues and more were discussed at the roundtable

Impedance Responses Reveal β2-Adrenergic Receptor Signaling Pluridimensionality and Allow Classification of Ligands with Distinct Signaling Profiles

The discovery that drugs targeting a single G protein-coupled receptor (GPCR) can differentially modulate distinct subsets of the receptor signaling repertoire has created a challenge for drug discovery at these important therapeutic targets. Here, we demonstrate that a single label-free assay based on cellular impedance provides a real-time integration of multiple signaling events engaged upon GPCR activation. Stimulation of the β2-adrenergic receptor (β2AR) in living cells with the prototypical agonist isoproterenol generated a complex, multi-featured impedance response over time. Selective pharmacological inhibition of specific arms of the β2AR signaling network revealed the differential contribution of Gs-, Gi- and Gβγ-dependent signaling events, including activation of the canonical cAMP and ERK1/2 pathways, to specific components of the impedance response. Further dissection revealed the essential role of intracellular Ca2+ in the impedance response and led to the discovery of a novel β2AR-promoted Ca2+ mobilization event. Recognizing that impedance responses provide an integrative assessment of ligand activity, we screened a collection of β-adrenergic ligands to determine if differences in the signaling repertoire engaged by compounds would lead to distinct impedance signatures. An unsupervised clustering analysis of the impedance responses revealed the existence of 5 distinct compound classes, revealing a richer signaling texture than previously recognized for this receptor. Taken together, these data indicate that the pluridimensionality of GPCR signaling can be captured using integrative approaches to provide a comprehensive readout of drug activity

The terrestrial biosphere model farm

Model Intercomparison Projects (MIPs) are fundamental to our understanding of how the land surface responds to changes in climate. However, MIPs are challenging to conduct, requiring the organization of multiple, decentralized modeling teams throughout the world running common protocols. We explored centralizing these models on a single supercomputing system. We ran nine offline terrestrial biosphere models through the Terrestrial Biosphere Model Farm: CABLE, CENTURY, HyLand, ISAM, JULES, LPJ-GUESS, ORCHIDEE, SiB-3, and SiB-CASA. All models were wrapped in a software framework driven with common forcing data, spin-up, and run protocols specified by the Multi-scale Synthesis and Terrestrial Model Intercomparison Project (MsTMIP) for years 1901–2100. We ran more than a dozen model experiments. We identify three major benefits and three major challenges. The benefits include: (a) processing multiple models through a MIP is relatively straightforward, (b) MIP protocols are run consistently across models, which may reduce some model output variability, and (c) unique multimodel experiments can provide novel output for analysis. The challenges are: (a) technological demand is large, particularly for data and output storage and transfer; (b) model versions lag those from the core model development teams; and (c) there is still a need for intellectual input from the core model development teams for insight into model results. A merger with the open-source, cloud-based Predictive Ecosystem Analyzer (PEcAn) ecoinformatics system may be a path forward to overcoming these challenges

Phase 2 study of aficamten in patients with obstructive hypertrophic cardiomyopathy

Background: Left ventricular outflow tract (LVOT) obstruction is a major determinant of heart failure symptoms in obstructive hypertrophic cardiomyopathy (oHCM). Aficamten, a next-in-class cardiac myosin inhibitor, may lower gradients and improve symptoms in these patients. Objectives: This study aims to evaluate the safety and efficacy of aficamten in patients with oHCM. Methods: Patients with oHCM and LVOT gradients ≥30 mm Hg at rest or ≥50 mm Hg with Valsalva were randomized 2:1 to receive aficamten (n = 28) or placebo (n = 13) in 2 dose-finding cohorts. Doses were titrated based on gradients and ejection fraction (EF). Safety and changes in gradient, EF, New York Heart Association functional class, and cardiac biomarkers were assessed over a 10-week treatment period and after a 2-week washout. Results: From baseline to 10 weeks, aficamten reduced gradients at rest (mean difference: −40 ± 27 mm Hg, and −43 ± 37 mm Hg in Cohorts 1 and 2, P = 0.0003 and P = 0.0004 vs placebo, respectively) and with Valsalva (−36 ± 27 mm Hg and −53 ± 44 mm Hg, P = 0.001 and <0.0001 vs placebo, respectively). There were modest reductions in EF (−6% ± 7.5% and −12% ± 5.9%, P = 0.007 and P < 0.0001 vs placebo, respectively). Symptomatic improvement in ≥1 New York Heart Association functional class was observed in 31% on placebo, and 43% and 64% on aficamten in Cohorts 1 and 2, respectively (nonsignificant). With aficamten, N-terminal pro–B-type natriuretic peptide was reduced (62% relative to placebo, P = 0.0002). There were no treatment interruptions and adverse events were similar between treatment arms. Conclusions: Aficamten resulted in substantial reductions in LVOT gradients with most patients experiencing improvement in biomarkers and symptoms. These results highlight the potential of sarcomere-targeted therapy for treatment of oHCM

Efficacy and safety of aficamten in symptomatic non-obstructive hypertrophic cardiomyopathy: results from the REDWOOD-HCM trial, cohort 4

Background This open-label phase 2 trial evaluated the safety and efficacy of aficamten in patients with nonobstructive hypertrophic cardiomyopathy (nHCM). Methods Patients with symptomatic nHCM (left ventricular outflow tract obstruction gradient ≤ 30 mmHg, left ventricular ejection fraction [LVEF] ≥ 60%, N-terminal pro-B-type natriuretic peptide [NT-proBNP] > 300 pg/mL) received aficamten 5–15 mg once daily (doses adjusted according to echocardiographic LVEF) for 10 weeks. Results We enrolled 41 patients (mean ± SD age 56 ± 16 years; 59% female). At Week 10, 22 (55%) patients experienced an improvement of ≥ 1 New York Heart Association class; 11 (29%) became asymptomatic. Clinically relevant improvements in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores occurred in 22 (55%) patients. Symptom relief was paralleled by reductions in NT-proBNP levels (56%; P < 0.001) and high-sensitivity cardiac troponin I (22%; P < 0.005). Modest reductions in LVEF (mean ± SD) of −5.4% ± 10 to 64.6% ± 9.1 were observed. Three (8%) patients had asymptomatic reduction in LVEF < 50% (range: 41%–48%), all returning to normal after 2 weeks of washout. One patient with prior history of aborted sudden cardiac death experienced a fatal arrhythmia during the study. Conclusions Aficamten administration for symptomatic nHCM was generally safe and was associated with improvements in heart failure symptoms and cardiac biomarkers