An external sensing system in Plasmodium falciparum-infected erythrocytes

Additional file 4. ItG-pRBC were treated with 10 ng/ml TNF for 60, 30, 15 and 5 min and the cellular proteins were extracted and separated by SDS-PAGE, followed by Western blot probed with anti-HSP90 and AB4 antibodies. The 90kDa protein recognized by the two antibodies showed similar expression patterns

Synthesis and Antiplasmodial Activity of Betulinic Acid and Ursolic Acid Analogues

More than 40% of the World population is at risk of contracting malaria, which affects primarily poor populations in tropical and subtropical areas. Antimalarial pharmacotherapy has utilised plant-derived products such as quinine and artemisinin as well as their derivatives. However, worldwide use of these antimalarials has caused the spread of resistant parasites, resulting in increased malaria morbidity and mortality. Considering that the literature has demonstrated the antimalarial potential of triterpenes, specially betulinic acid (1) and ursolic acid (2), this study investigated the antimalarial activity against P. falciparum chloroquine-sensitive 3D7 strain of some new derivatives of 1 and 2 with modifications at C-3 and C-28. The antiplasmodial study employed flow cytometry and spectrofluorimetric analyses using YOYO-1, dihydroethidium and Fluo4/AM for staining. Among the six analogues obtained, compounds 1c and 2c showed excellent activity (IC50 = 220 and 175 nM, respectively) while 1a and b demonstrated good activity ( IC50 = 4 and 5 mu M, respectively). After cytotoxicity evaluation against HEK293T cells, 1a was not toxic, while 1c and 2c showed IC50 of 4 mu M and a selectivity index (SI) value of 18 and 23, respectively. Moreover, compound 2c, which presents the best antiplasmodial activity, is involved in the calcium-regulated pathway(s).Instituto Nacional de Ciencia e Tecnologia para Inovacao Farmaceutica (INCTif, Brazil)Instituto Nacional de Ciencia e Tecnologia para Inovacao Farmaceutica (INCT-if, Brazil)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), BrazilConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq-Brazil)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), BrazilCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES-Brazil)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), BrazilFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil)Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Brazil)Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Brazil)FAPESPFAPES

Boosting background suppression in the NEXT experiment through Richardson-Lucy deconvolution

Next-generation neutrinoless double beta decay experiments aim for half-life sensitivities of similar to 10(27) yr, requiring suppressing backgrounds to < 1 count/tonne/yr. For this, any extra background rejection handle, beyond excellent energy resolution and the use of extremely radiopure materials, is of utmost importance. The NEXT experiment exploits differences in the spatial ionization patterns of double beta decay and single-electron events to discriminate signal from background. While the former display two Bragg peak dense ionization regions at the opposite ends of the track, the latter typically have only one such feature. Thus, comparing the energies at the track extremes provides an additional rejection tool. The unique combination of the topology-based background discrimination and excellent energy resolution (1% FWHM at the Q-value of the decay) is the distinguishing feature of NEXT. Previous studies demonstrated a topological background rejection factor of 5 when reconstructing electron-positron pairs in the Tl-208 1.6 MeV double escape peak (with Compton events as background), recorded in the NEXT-White demonstrator at the Laboratorio Subterraneo de Canfranc, with 72% signal efficiency. This was recently improved through the use of a deep convolutional neural network to yield a background rejection factor of similar to 10 with 65% signal efficiency. Here, we present a new reconstruction method, based on the Richardson-Lucy deconvolution algorithm, which allows reversing the blurring induced by electron diffusion and electroluminescence light production in the NEXT TPC. The new method yields highly refined 3D images of reconstructed events, and, as a result, significantly improves the topological background discrimination. When applied to real-data 1.6 MeV e(-)e(+) pairs, it leads to a background rejection factor of 27 at 57% signal efficiency.The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the European Union's Framework Programme for Research and Innovation Horizon 2020 (2014-2020) under the Grant Agreements No. 674896, 690575 and 740055; the Ministerio de Economia y Competitividad and the Ministerio de Ciencia, Innovacion y Universidades of Spain under grants FIS2014-53371-C04, RTI2018-095979, the Severo Ochoa Program grants SEV-2014-0398 and CEX2018-000867-S, and the Maria de Maeztu Program MDM-2016-0692; the Generalitat Valenciana under grants PROMETEO/2016/120 and SEJI/2017/011; the Portuguese FCT under project PTDC/FIS-NUC/2525/2014 and under projects UID/04559/2020 to fund the activities of LIBPhys-UC; the U.S. Department of Energy under contracts No. DE-AC02-06CH11357 (Argonne National Laboratory), DE-AC02-07CH11359 (Fermi National Accelerator Laboratory), DE-FG02-13ER42020 (Texas A&M) and DE-SC0019223/DE-SC0019054 (University of Texas at Arlington); the University of Texas at Arlington (U.S.A.); and the Pazy Foundation (Israel) under grants 877040 and 877041. DGD acknowledges Ramon y Cajal program (Spain) under contract number RYC-2015-18820. JM-A acknowledges support from Fundacion Bancaria "la Caixa" (ID 100010434), grant code LCF/BQ/PI19/11690012. AS acknowledges support from the Kreitman School of Advanced Graduate Studies at Ben-Gurion University. Documen

Izaña Atmospheric Research Center. Activity Report 2015-2016

This report is a summary of the many activities at the Izaña Atmospheric Research Center to the broader community. The combination of operational activities, research and development in state-of-the-art measurement techniques, calibration and validation and international cooperation encompass the vision of WMO to provide world leadership in expertise and international cooperation in weather, climate, hydrology and related environmental issues

Summary Report of PQRI Workshop on Nanomaterial in Drug Products: Current Experience and Management of Potential Risks

At the Product Quality Research Institute (PQRI) Workshop held last January 14-15, 2014, participants from academia, industry, and governmental agencies involved in the development and regulation of nanomedicines discussed the current state of characterization, formulation development, manufacturing, and nonclinical safety evaluation of nanomaterial-containing drug products for human use. The workshop discussions identified areas where additional understanding of material attributes, absorption, biodistribution, cellular and tissue uptake, and disposition of nanosized particles would continue to inform their safe use in drug products. Analytical techniques and methods used for in vitro characterization and stability testing of formulations containing nanomaterials were discussed, along with their advantages and limitations. Areas where additional regulatory guidance and material characterization standards would help in the development and approval of nanomedicines were explored. Representatives from the US Food and Drug Administration (USFDA), Health Canada, and European Medicines Agency (EMA) presented information about the diversity of nanomaterials in approved and newly developed drug products. USFDA, Health Canada, and EMA regulators discussed the applicability of current regulatory policies in presentations and open discussion. Information contained in several of the recent EMA reflection papers was discussed in detail, along with their scope and intent to enhance scientific understanding about disposition, efficacy, and safety of nanomaterials introduced in vivo and regulatory requirements for testing and market authorization. Opportunities for interaction with regulatory agencies during the lifecycle of nanomedicines were also addressed at the meeting. This is a summary of the workshop presentations and discussions, including considerations for future regulatory guidance on drug products containing nanomaterials

Izaña Atmospheric Research Center. Activity Report 2019-2020

Editors: Emilio Cuevas, Celia Milford and Oksana Tarasova.[EN]The Izaña Atmospheric Research Center (IARC), which is part of the State Meteorological Agency of Spain (AEMET), is a site of excellence in atmospheric science. It manages four observatories in Tenerife including the high altitude Izaña Atmospheric Observatory. The Izaña Atmospheric Observatory was inaugurated in 1916 and since that date has carried out uninterrupted meteorological and climatological observations, contributing towards a unique 100-year record in 2016. This reports are a summary of the many activities at the Izaña Atmospheric Research Center to the broader community. The combination of operational activities, research and development in state-of-the-art measurement techniques, calibration and validation and international cooperation encompass the vision of WMO to provide world leadership in expertise and international cooperation in weather, climate, hydrology and related environmental issues.[ES]El Centro de Investigación Atmosférica de Izaña (CIAI), que forma parte de la Agencia Estatal de Meteorología de España (AEMET), representa un centro de excelencia en ciencias atmosféricas. Gestiona cuatro observatorios en Tenerife, incluido el Observatorio de Izaña de gran altitud, inaugurado en 1916 y que desde entonces ha realizado observaciones meteorológicas y climatológicas ininterrumpidas y se ha convertido en una estación centenaria de la OMM. Estos informes resumen las múltiples actividades llevadas a cabo por el Centro de Investigación Atmosférica de Izaña. El liderazgo del Centro en materia de investigación y desarrollo con respecto a las técnicas de medición, calibración y validación de última generación, así como la cooperación internacional, le han otorgado una reputación sobresaliente en lo que se refiere al tiempo, el clima, la hidrología y otros temas ambientales afines

Dental Health and Mortality in People With End-Stage Kidney Disease Treated With Hemodialysis: A Multinational Cohort Study

Background Dental disease is more extensive in adults with chronic kidney disease, but whether dental health and behaviors are associated with survival in the setting of hemodialysis is unknown. Study Design Prospective multinational cohort. Setting & Participants 4,205 adults treated with long-term hemodialysis, 2010 to 2012 (Oral Diseases in Hemodialysis [ORAL-D] Study). Predictors Dental health as assessed by a standardized dental examination using World Health Organization guidelines and personal oral care, including edentulousness; decayed, missing, and filled teeth index; teeth brushing and flossing; and dental health consultation. Outcomes All-cause and cardiovascular mortality at 12 months after dental assessment. Measurements Multivariable-adjusted Cox proportional hazards regression models fitted with shared frailty to account for clustering of mortality risk within countries. Results During a mean follow-up of 22.1 months, 942 deaths occurred, including 477 cardiovascular deaths. Edentulousness (adjusted HR, 1.29; 95% CI, 1.10-1.51) and decayed, missing, or filled teeth score ≥ 14 (adjusted HR, 1.70; 95% CI, 1.33-2.17) were associated with early all-cause mortality, while dental flossing, using mouthwash, brushing teeth daily, spending at least 2 minutes on oral hygiene daily, changing a toothbrush at least every 3 months, and visiting a dentist within the past 6 months (adjusted HRs of 0.52 [95% CI, 0.32-0.85], 0.79 [95% CI, 0.64-0.97], 0.76 [95% CI, 0.58-0.99], 0.84 [95% CI, 0.71-0.99], 0.79 [95% CI, 0.65-0.95], and 0.79 [95% CI, 0.65-0.96], respectively) were associated with better survival. Results for cardiovascular mortality were similar. Limitations Convenience sample of clinics. Conclusions In adults treated with hemodialysis, poorer dental health was associated with early death, whereas preventive dental health practices were associated with longer survival