Molecular evidence for a single origin of ultrafiltration-based excretory organs

Under embargo until: 2021-06-23Excretion is an essential physiological process, carried out by all living organisms, regardless of their size or complexity.1, 2, 3 Both protostomes (e.g., flies and flatworms) and deuterostomes (e.g., humans and sea urchins) possess specialized excretory organs serving that purpose. Those organs exhibit an astonishing diversity, ranging from units composed of just few distinct cells (e.g., protonephridia) to complex structures, built by millions of cells of multiple types with divergent morphology and function (e.g., vertebrate kidneys).4,5 Although some molecular similarities between the development of kidneys of vertebrates and the regeneration of the protonephridia of flatworms have been reported,6,7 the molecular underpinnings of the development of excretory organs have never been systematically studied in a comparative context.4 Here, we show that a set of transcription factors (eya, six1/2, pou3, sall, lhx1/5, and osr) and structural proteins (nephrin, kirre, and zo1) is expressed in the excretory organs of a phoronid, brachiopod, annelid, onychophoran, priapulid, and hemichordate that represent major protostome lineages and non-vertebrate deuterostomes. We demonstrate that the molecular similarity observed in the vertebrate kidney and flatworm protonephridia6,7 is also seen in the developing excretory organs of those animals. Our results show that all types of ultrafiltration-based excretory organs are patterned by a conserved set of developmental genes, an observation that supports their homology. We propose that the last common ancestor of protostomes and deuterostomes already possessed an ultrafiltration-based organ that later gave rise to the vast diversity of extant excretory organs, including both proto- and metanephridia.acceptedVersio

ISO 50001: 2018 and Its Application in a Comprehensive Management System with an Energy-Performance Focus

[EN] Business progress and human development are linked to the efficient management of energy resources. The research in this paper contributes to the generalized application of good practices that reduce the vulnerability of companies. The research focuses on energy efficiency through comprehensive management systems (CMS), and "thought based on risks and opportunities", considering the discussion about the revision of ISO 50001:2018, the basic approach of the model and the route to implement CMS for quality, safety and health in the workplace, environmental management, energy efficiency, and other risk components. This implementation route, with the acronym CMS QHSE3+, places special emphasis on the functions of strategic planning, operational and risk management, and controls, as well as on deliverables and references to examples, templates, standards, and documents, to facilitate its application general in small and medium enterprises and in the management of energy efficiency.We express our gratitude for the support received, to CAJACOPI ATLÁNTICO, QUARA Group, ASTEQ Technology, Simón Bolivar University, the Universitat Politècnica de València, SANTO TORIBIO Business Group, and to all the personalities and companies who offered us their contributions and their valuable points of view.Poveda-Orjuela, PP.; García-Díaz, JC.; Pulido-Rojano, A.; Cañón-Zabala, G. (2019). ISO 50001: 2018 and Its Application in a Comprehensive Management System with an Energy-Performance Focus. 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Development of a framework of key performance indicators to identify reductions in energy consumption in a medical devices production facility. International Journal of Ambient Energy, 39(2), 202-210. doi:10.1080/01430750.2017.1278718Castrillón Mendoza, R., Rey Hernández, J., Velasco Gómez, E., San José Alonso, J., & Rey Martínez, F. (2018). Analysis of the Methodology to Obtain Several Key Indicators Performance (KIP), by Energy Retrofitting of the Actual Building to the District Heating Fuelled by Biomass, Focusing on nZEB Goal: Case of Study. Energies, 12(1), 93. doi:10.3390/en12010093Chiu, T.-Y., Lo, S.-L., & Tsai, Y.-Y. (2012). Establishing an Integration-Energy-Practice Model for Improving Energy Performance Indicators in ISO 50001 Energy Management Systems. Energies, 5(12), 5324-5339. doi:10.3390/en5125324Laskurain, I., Ibarloza, A., Larrea, A., & Allur, E. (2017). Contribution to Energy Management of the Main Standards for Environmental Management Systems: The Case of ISO 14001 and EMAS. Energies, 10(11), 1758. doi:10.3390/en10111758Al-Sakkaf, S., Kassas, M., Khalid, M., & Abido, M. A. (2019). An Energy Management System for Residential Autonomous DC Microgrid Using Optimized Fuzzy Logic Controller Considering Economic Dispatch. Energies, 12(8), 1457. doi:10.3390/en12081457Zobel, T., & Malmgren, C. (2016). Evaluating the Management System Approach for Industrial Energy Efficiency Improvements. Energies, 9(10), 774. doi:10.3390/en9100774Laskurain, I., Heras-Saizarbitoria, I., & Casadesús, M. (2015). Fostering renewable energy sources by standards for environmental and energy management. Renewable and Sustainable Energy Reviews, 50, 1148-1156. doi:10.1016/j.rser.2015.05.050Stoeglehner, G., Niemetz, N., & Kettl, K.-H. (2011). Spatial dimensions of sustainable energy systems: new visions for integrated spatial and energy planning. Energy, Sustainability and Society, 1(1). doi:10.1186/2192-0567-1-2Calvillo, C. F., Sánchez-Miralles, A., & Villar, J. (2016). Energy management and planning in smart cities. Renewable and Sustainable Energy Reviews, 55, 273-287. doi:10.1016/j.rser.2015.10.133Blaauwbroek, N., Nguyen, P. H., Konsman, M. J., Shi, H., Kamphuis, R. I. G., & Kling, W. L. (2015). Decentralized Resource Allocation and Load Scheduling for Multicommodity Smart Energy Systems. IEEE Transactions on Sustainable Energy, 6(4), 1506-1514. doi:10.1109/tste.2015.2441107Mao, M., Jin, P., Hatziargyriou, N. D., & Chang, L. (2014). Multiagent-Based Hybrid Energy Management System for Microgrids. IEEE Transactions on Sustainable Energy, 1-1. doi:10.1109/tste.2014.2313882Carli, R., & Dotoli, M. (2019). Decentralized control for residential energy management of a smart users microgrid with renewable energy exchange. IEEE/CAA Journal of Automatica Sinica, 6(3), 641-656. doi:10.1109/jas.2019.1911462The ISO 27k Forumhttps://www.iso27001 security.com/html/iso27000.htmlIntroduction to the Basic Concepts of General Systems Theory. Cinta de Moebiohttp://www.redalyc.org/articulo.oa?id=10100306Von Bertalanffy, L. (1950). The Theory of Open Systems in Physics and Biology. Science, 111(2872), 23-29. doi:10.1126/science.111.2872.23Hernandis Ortuño, B., & Briede Westermeyer, J. C. (2009). AN EDUCATIONAL APPLICATION FOR A PRODUCT DESIGN AND ENGINEERING SYSTEMS USING INTEGRATED CONCEPTUAL MODELS. Ingeniare. Revista chilena de ingeniería, 17(3). doi:10.4067/s0718-33052009000300017Howard, T. J., Culley, S. J., & Dekoninck, E. (2008). Describing the creative design process by the integration of engineering design and cognitive psychology literature. Design Studies, 29(2), 160-180. doi:10.1016/j.destud.2008.01.001Conceptual Model and Route to Implement a Comprehensive Management System QHSE3+, in New Trends in Operations Research and Administrative Sciences. An Approach from Latin American Studieshttps://bonga.unisimon.edu.co/handle/20.500.12442/2601Golini, R., Kalchschmidt, M., & Landoni, P. (2015). Adoption of project management practices: The impact on international development projects of non-governmental organizations. International Journal of Project Management, 33(3), 650-663. doi:10.1016/j.ijproman.2014.09.006Marcelino-Sádaba, S., González-Jaen, L. F., & Pérez-Ezcurdia, A. (2015). Using project management as a way to sustainability. From a comprehensive review to a framework definition. Journal of Cleaner Production, 99, 1-16. doi:10.1016/j.jclepro.2015.03.020Archer, N. ., & Ghasemzadeh, F. (1999). An integrated framework for project portfolio selection. 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SEAM4US: An intelligent energy management system for underground stations. Applied Energy, 166, 150-164. doi:10.1016/j.apenergy.2016.01.029Matrawy, K. K., Mahrous, A.-F., & Youssef, M. S. (2015). Energy management and parametric optimization of an integrated PV solar house. Energy Conversion and Management, 96, 377-383. doi:10.1016/j.enconman.2015.02.088Kyriakarakos, G., Dounis, A. I., Arvanitis, K. G., & Papadakis, G. (2012). A fuzzy logic energy management system for polygeneration microgrids. Renewable Energy, 41, 315-327. doi:10.1016/j.renene.2011.11.019Johansson, M. T., & Thollander, P. (2018). A review of barriers to and driving forces for improved energy efficiency in Swedish industry– Recommendations for successful in-house energy management. Renewable and Sustainable Energy Reviews, 82, 618-628. doi:10.1016/j.rser.2017.09.052Jovanović, B., & Filipović, J. (2016). ISO 50001 standard-based energy management maturity model – proposal and validation in industry. Journal of Cleaner Production, 112, 2744-2755. doi:10.1016/j.jclepro.2015.10.023Majernik, M., Bosak, M., Stofova, L., & Szaryszova, P. (2015). INNOVATIVE MODEL OF INTEGRATED ENERGY MANAGEMENT IN COMPANIES. Quality Innovation Prosperity, 19(1). doi:10.12776/qip.v19i1.384Implementation of ISO 50001 in Industry in The Netherlands. ECEE Industry Summer Studywww.eceee.orgDe Groot, H. L. F., Verhoef, E. T., & Nijkamp, P. (2001). Energy saving by firms: decision-making, barriers and policies. Energy Economics, 23(6), 717-740. doi:10.1016/s0140-9883(01)00083-4Development of the EMAS Sectoral Reference Documents on Best Environmental Management Practice. Learning from Frontrunners Promoting Best Practice. Publications Office of the European Unionhttps://publications.jrc.ec.europa.eu/repository/bitstream/JRC84966/lfna26291enn.pd

Quality-of-life analysis of pembrolizumab vs brentuximab vedotin for relapsed/refractory classical Hodgkin lymphoma

KEYNOTE-204 (NCT02684292) demonstrated a progression-free survival advantage for pembrolizumab over brentuximab vedotin (BV) in patients who had relapsed or refractory classical Hodgkin lymphoma (R/R cHL) following, or who were ineligible for, autologous stem cell transplantation (ASCT). Health-related quality of life (HRQoL), measured by patient-reported outcomes (PROs) from KEYNOTE-204, are reported from patients who received ≥1 dose of study treatment and completed ≥1 PRO assessment. The EORTC QoL Questionnaire Core 30 (QLQ-C30) and EuroQoL EQ-5D were administered at baseline, every 6 weeks until week 24, and every 12 weeks thereafter. Prespecified end points included least squares mean (LSM) changes from baseline to week 24 and time to true deterioration (TTD; ≥10-point decline from baseline). Comparisons were evaluated using 2-sided P values uncontrolled for multiplicity. High compliance at baseline (.90%) and through week 24 (.80%) was demonstrated across treatment groups (PRO analysis set: Pembrolizumab, n = 146; BV, n = 150). The EORTC QLQ-C30 global health status (GHS)/ quality of life (QoL) score improved from baseline to week 24 on pembrolizumab and worsened on BV and demonstrated significant LSM differences at 24 weeks (GHS/QoL: 8.60 [95% confidence interval, 3.89-13.31]; P = .0004). Significant improvements were observed in each QLQ-C30 domain except emotional and cognitive functioning. Compared with BV, pembrolizumab prolonged TTD for GHS/QoL (hazard ratio, 0.40 [95% CI, 0.22-0.74]; P = .003) and each QLQ-C30 domain except cognitive functioning. In conclusion, pembrolizumab demonstrated overall improvements in PROs of HRQoL measures over BV in the KEYNOTE-204 study. These data and previously reported efficacy results support pembrolizumab as the preferred treatment option for patients with R/R cHL who are ineligible for or experience relapse after ASCT

(Photo)physical properties of new molecular glasses end-capped with thiophene rings composed of diimide and imine units

New symmetrical arylene bisimide derivatives formed by using electron-donating-electron-accepting systems were synthesized. They consist of a phthalic diimide or naphthalenediimide core and imine linkages and are end-capped with thiophene, bithiophene, and (ethylenedioxy)thiophene units. Moreover, polymers were obtained from a new diamine, N,N′-bis(5- aminonaphthalenyl)naphthalene-1,4,5,8-dicarboximide and 2,5- thiophenedicarboxaldehyde or 2,2′-bithiophene-5,5′-dicarboxaldehyde. The prepared azomethine diimides exhibited glass-forming properties. The obtained compounds emitted blue light with the emission maximum at 470 nm. The value of the absorption coefficient was determined as a function of the photon energy using spectroscopic ellipsometry. All compounds are electrochemically active and undergo reversible electrochemical reduction and irreversible oxidation processes as was found in cyclic voltammetry and differential pulse voltammetry (DPV) studies. They exhibited a low electrochemically (DPV) calculated energy band gap (Eg) from 1.14 to 1.70 eV. The highest occupied molecular orbital and lowest unoccupied molecular orbital levels and Eg were additionally calculated theoretically by density functional theory at the B3LYP/6-31G(d,p) level. The photovoltaic properties of two model compounds as the active layer in organic solar cells in the configuration indium tin oxide/poly(3,4-(ethylenedioxy)thiophene):poly(styrenesulfonate)/active layer/Al under an illumination of 1.3 mW/cm2 were studied. The device comprising poly(3-hexylthiophene) with the compound end-capped with bithiophene rings showed the highest value of Voc (above 1 V). The conversion efficiency of the fabricated solar cell was in the range of 0.69-0.90%

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Gliclazide may have an antiapoptotic effect related to its antioxidant properties in human normal and cancer cells

Experimental and clinical studies suggest that gliclazide may protect pancreatic β-cells from apoptosis induced by an oxidative stress. However, the precise mechanism(s) of this action are not fully understood and requires further clarification. Therefore, using human normal and cancer cells we examined whether the anti-apoptotic effects of this sulfonylurea is due to its free radical scavenger properties. Hydrogen peroxide (H2O2) as a model trigger of oxidative stress was used to induce cell death. Our experiments were performed on human normal cell line (human umbilical vein endothelial cell line, HUVEC-c) and human cancer cell lines (human mammary gland cell line, Hs578T; human pancreatic duct epithelioid carcinoma cell line, PANC-1). To assess the effect of gliclazide the cells were pre-treated with the drug. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay was employed to measure the impact of gliclazide on cell viability. Generation of reactive oxygen species, mitochondrial membrane potential (∆Ψm), and intracellular Ca2+ concentration [Ca2+] were monitored. Furthermore, the morphological changes associated with apoptosis were determined using double staining with Hoechst 33258-propidium iodide (PI). Gliclazide protects the tested cells from H2O2-induced cell death most likely throughout the inhibition of ROS production. Moreover, the drug restored loss of ΔΨm and diminished intracellular [Ca2+] evoked by H2O2. Double staining with Hoechst 33258-PI revealed that pre-treatment with gliclazide diminished the number of apoptotic cells. Our findings indicate that gliclazide may protect both normal and cancer human cells against apoptosis induced by H2O2. It appears that the anti-apoptotic effect of the drug is most likely associated with reduction of oxidative stress

Week 48 resistance analyses of the once-daily, single-tablet regimen darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in adults living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) >= 400 copies/mL at failure/later time points. Post hoc analyses were deep sequencing in AMBER, and HIV-1 proviral DNA from baseline samples (VL = 3 thymidine analog-associated mutations (24% not fully susceptible to tenofovir) detected at screening. All achieved VL <50 copies/mL at week 48 or prior discontinuation. D/C/F/TAF has a high genetic barrier to resistance; no darunavir, primary PI, or tenofovir RAMs were observed through 48 weeks in AMBER and EMERALD. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. In EMERALD, baseline archived RAMs to darunavir, emtricitabine, and tenofovir in participants with prior VF did not preclude virologic response

Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Altres ajuts: This study was sponsored by Janssen.Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52-96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF