Permutation flowshop scheduling problem with total core idle time minimization

-Part of special issue 10th IFAC Conference on Manufacturing Modelling, Management and Control MIM 2022: Nantes, France, 22-24 June 2022 -Copyright © 2022 The Authors. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/)In this paper, we present a deterministic permutation flowshop scheduling problem with a new objective function, the total core idle time. The interest of this objective is related to reduce the energy consumption of the system, taking into account that the energy needed during the processing times is constant, and that machines are switched off during the front and back idle times. Therefore, the energy consumption is dependent on the time where machines are in stand-by mode, i.e during the idle time of machines between jobs, named as core idle times. Constructive heuristics and metaheuristics are adapted from the permutation flowshop scheduling literature for classical objectives as makespan and total completion time. Additionally, a new variant of one of the metaheuristic is proposed, the VBIH-P. An experimental evaluation has been carried out to analyse the performance of all the methods. The results show an excellent performance of the VBIH-P compared to the adapted methods

A relação entre trabalho, cooperação e solidariedade na formação da Cooperativa Colonizadora Multiativa Fernheim Ltda no Chaco Paraguaio

Work, cooperation and solidarity are values that together that enable people to earn a living as an alternative to the exacerbated competition fostered by the capitalist model. The article analyzes the case of the Fernheim Cooperative, located in the Paraguayan Chaco, which is desert-like area with a small population. This analysis demonstrates how an experiment strongly based on these three values: work, cooperation and solidarity, can last over time and change the reality of a region. Keywords: work, cooperation, solidarity, Mennonites, Paraguayan Chaco.Trabalho, cooperação e solidariedade são valores que, articulados, tornam possível a superação e a subsistência das pessoas como alternativa à exacerbada competitividade preconizada pelo modelo capitalista. O presente artigo refere-se a uma análise do caso da Cooperativa Fernheim, localizada no Chaco paraguaio, que é desértico e concentra o mínimo de população. Esta análise possibilita demonstrar como uma experiência baseada fortemente nestes três valores: trabalho, cooperação e solidariedade, pode durar ao longo do tempo e mudar a realidade de uma região. Palavras-chave: trabalho, cooperação, solidariedade, menonitas, Chaco paraguaio

Preclinical evaluation of strasseriolides A–D, potent antiplasmodial macrolides isolated from Strasseria geniculata CF-247,251.

Background: Malaria is a global health problem for which novel therapeutic compounds are needed. To this end, a recently published novel family of antiplasmodial macrolides, strasseriolides A–D, was herein subjected to in vivo efficacy studies and preclinical evaluation in order to identify the most promising candidate(s) for further development. Methods: Preclinical evaluation of strasseriolides A–D was performed by MTT-based cytotoxicity assay in THLE-2 (CRL-2706) liver cells, cardiotoxicity screening using the FluxOR™ potassium assay in hERG expressed HEK cells, LC–MS-based analysis of drug-drug interaction involving CYP3A4, CYP2D6 and CYP2C9 isoforms inhibition and metabolic stability assays in human liver microsomes. Mice in vivo toxicity studies were also accomplished by i.v. administration of the compounds (vehicle: 0.5% HPMC, 0.5% Tween 80, 0.5% Benzyl alcohol) in mice at 25 mg/kg dosage. Plasma were prepared from mice blood samples obtained at different time points (over a 24-h period), and analysed by LC-MS to quantify compounds. The most promising compounds, strasseriolides C and D, were subjected to a preliminary in vivo efficacy study in which transgenic GFP-luciferase expressing Plasmodium berghei strain ANKA-infected Swiss Webster female mice (n = 4–5) were treated 48 h post-infection with an i.p. dosage of strasseriolide C at 50 mg/kg and strasseriolide D at 22 mg/kg for four days after which luciferase activity was quantified on day 5 in an IVIS Lumina II imager. Results: Strasseriolides A–D showed no cytotoxicity, no carditoxicity and no drug-drug interaction problems in vitro with varying intrinsic clearance (CLint). Only strasseriolide B was highly toxic to mice in vivo (even at 1 mg/kg i.v. dosage) and, therefore, discontinued in further in vivo studies. Strasseriolide D showed statistically significant activity in vivo giving rise to lower parasitaemia levels (70% lower) compared to the controls treated with vehicle. Conclusions: Animal efficacy and preclinical evaluation of the recently discovered potent antiplasmodial macrolides, strasseriolides A–D, led to the identification of strasseriolide D as the most promising compound for further development. Future studies dealing on structure optimization, formulation and establishment of optimal in vivo dosage explorations of this novel compound class could enhance their clinical potency and allow for progress to later stages of the developmental pipeline.This work was funded by the European Commission FP7 Marie Curie Initial Training Network “ParaMet” [grant agreement 290080], the Instituto de Salud Carlos III Subdirección General de Redes y Centros de Investigación Cooperativa-Red de Investigación Cooperativa en Enfermedades Tropicales (RICET: RD16/0027/0014, RD16/0027/0015, and RD12/0018/0005), the Plan Nacional (PID2019-109623RB-100 and SAF 2016-79957-R) and by the Junta de Andalucía (BIO-199). The polarimeter, HPLC, IR, NMR equipment, and plate reader used in this work were purchased via grants for scientific and technological infrastructures from the Ministerio de Ciencia e Innovación [Grants Nos. PCT- 010000-2010-4 (NMR), INP-2011-0016-PCT-010000 ACT6 (polarimeter, HPLC, and IR), and PCT-01000-ACT7, 2011-13 (plate reader)].Peer reviewe

Preclinical evaluation of strasseriolides A–D, potent antiplasmodial macrolides isolated from Strasseria geniculata CF-247,251.

Background: Malaria is a global health problem for which novel therapeutic compounds are needed. To this end, a recently published novel family of antiplasmodial macrolides, strasseriolides A–D, was herein subjected to in vivo efficacy studies and preclinical evaluation in order to identify the most promising candidate(s) for further development. Methods: Preclinical evaluation of strasseriolides A–D was performed by MTT-based cytotoxicity assay in THLE-2 (CRL-2706) liver cells, cardiotoxicity screening using the FluxOR™ potassium assay in hERG expressed HEK cells, LC–MS-based analysis of drug-drug interaction involving CYP3A4, CYP2D6 and CYP2C9 isoforms inhibition and metabolic stability assays in human liver microsomes. Mice in vivo toxicity studies were also accomplished by i.v. administration of the compounds (vehicle: 0.5% HPMC, 0.5% Tween 80, 0.5% Benzyl alcohol) in mice at 25 mg/kg dosage. Plasma were prepared from mice blood samples obtained at different time points (over a 24-h period), and analysed by LC-MS to quantify compounds. The most promising compounds, strasseriolides C and D, were subjected to a preliminary in vivo efficacy study in which transgenic GFP-luciferase expressing Plasmodium berghei strain ANKA-infected Swiss Webster female mice (n = 4–5) were treated 48 h post-infection with an i.p. dosage of strasseriolide C at 50 mg/kg and strasseriolide D at 22 mg/kg for four days after which luciferase activity was quantified on day 5 in an IVIS Lumina II imager. Results: Strasseriolides A–D showed no cytotoxicity, no carditoxicity and no drug-drug interaction problems in vitro with varying intrinsic clearance (CLint). Only strasseriolide B was highly toxic to mice in vivo (even at 1 mg/kg i.v. dosage) and, therefore, discontinued in further in vivo studies. Strasseriolide D showed statistically significant activity in vivo giving rise to lower parasitaemia levels (70% lower) compared to the controls treated with vehicle. Conclusions: Animal efficacy and preclinical evaluation of the recently discovered potent antiplasmodial macrolides, strasseriolides A–D, led to the identification of strasseriolide D as the most promising compound for further development. Future studies dealing on structure optimization, formulation and establishment of optimal in vivo dosage explorations of this novel compound class could enhance their clinical potency and allow for progress to later stages of the developmental pipeline.This work was funded by the European Commission FP7 Marie Curie Initial Training Network “ParaMet” [grant agreement 290080], the Instituto de Salud Carlos III Subdirección General de Redes y Centros de Investigación Cooperativa-Red de Investigación Cooperativa en Enfermedades Tropicales (RICET: RD16/0027/0014, RD16/0027/0015, and RD12/0018/0005), the Plan Nacional (PID2019-109623RB-100 and SAF 2016-79957-R) and by the Junta de Andalucía (BIO-199). The polarimeter, HPLC, IR, NMR equipment, and plate reader used in this work were purchased via grants for scientific and technological infrastructures from the Ministerio de Ciencia e Innovación [Grants Nos. PCT- 010000-2010-4 (NMR), INP-2011-0016-PCT-010000 ACT6 (polarimeter, HPLC, and IR), and PCT-01000-ACT7, 2011-13 (plate reader)]

Discovery of New Compounds Active against Plasmodium falciparum by High Throughput Screening of Microbial Natural Products

Due to the low structural diversity within the set of antimalarial drugs currently available in the clinic and the increasing number of cases of resistance, there is an urgent need to find new compounds with novel modes of action to treat the disease. Microbial natural products are characterized by their large diversity provided in terms of the chemical complexity of the compounds and the novelty of structures. Microbial natural products extracts have been underexplored in the search for new antiparasitic drugs and even more so in the discovery of new antimalarials. Our objective was to find new druggable natural products with antimalarial properties from the MEDINA natural products collection, one of the largest natural product libraries harboring more than 130,000 microbial extracts. In this work, we describe the optimization process and the results of a phenotypic high throughput screen (HTS) based on measurements of Plasmodium lactate dehydrogenase. A subset of more than 20,000 extracts from the MEDINA microbial products collection has been explored, leading to the discovery of 3 new compounds with antimalarial activity. In addition, we report on the novel antiplasmodial activity of 4 previously described natural productsThis work was supported by the Junta de Andalucía [BIO-199, P09-CVI- 5367], the VI Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008-2011, Instituto de Salud Carlos III-Subdirección General de Redes y Centros de Investigación Cooperativa-Red de Investigación Cooperativa en Enfermedades Tropicales (RICET FIS Network: RD12/0018/0017),the Plan Nacional (SAF2013-48999-R), the FEDER funds from the EU and the PARAMET network (FP7-PEOPLE-2011-ITN. GA290080) to DG-P. Research of FV and OG was supported by the Instituto de Salud Carlos III-Subdirección General de Redes y Centros de Investigación Cooperativa-Red de Investigación Cooperativa en Enfermedades Tropicales (RICET FIS Network: RD12/0018/0005) and the FEDER funds from the EU and the PARAMET network (FP7-PEOPLE-2011-ITN. GA290080). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Acompañamiento psicosocial en dos comunidades de Manabí tras el terremoto del 16 de abril: una perspectiva desde la salud colectiva y los derechos humanos (Tema Central)

This paper intends to present two experiences of psychosocial accompaniment that were carried out in the province of Manabí, Ecuador in the next months following the earthquake of April 16, 2016. The first one takes place in the neighborhood Ebony in Jama and the second in the neighborhood Los Cañonazos in Portoviejo. In both cases, the accompaniment is aimed to the strengthening of the community organization, which reveals the perverse effects associated with disasters, such as land concentration or environmental discrimination. The phases: contact establishment, activities, methodology and conclusions are described, from a perspective of collective health and human rights. Keywords: earthquake Ecuador, Manabí, psychosocial accompaniment, collective health, human rights.El artículo presenta dos experiencias de acompañamiento psicosocial que se realizaron en la provincia de Manabí en Ecuador en los meses posteriores al terremoto del 16 de abril de 2016. La primera transcurrió en el barrio Ébano en Jama, y la segunda en el barrio Los Cañonazos en Portoviejo. En ambos casos, el acompañamiento se orientó al fortalecimiento del tejido comunitario que pone de manifiesto los efectos perversos asociados a los desastres, tales como la concentración de tierras o la discriminación ambiental. Para esto, se describen las fases de puesta de contacto, las actividades realizadas, la metodología utilizada y las conclusiones sobre el acompañamiento realizado, bajo una perspectiva de la salud colectiva y derechos humanos

Synthesis and in vitro phototoxicity of multifunctional Zn(II)meso-tetrakis(4-carboxyphenyl)porphyrin-coated gold nanoparticles assembled via axial coordination with imidazole ligands

Hypothesis Metalloporphyrins are extensively investigated for their ability to form reactive oxygen species and as potent photosensitisers for use in photodynamic therapy. However, their hydrophobicity generally causes solubility issues concerning in vivo delivery due to lack of distribution and low clearance from the body. Immobilising porphyrins on carriers, such as gold nanoparticles (GNP), can overcome some of these drawbacks. The mode of assembling the porphyrins to the carrier influences the properties of the resulting drug delivery systems. Experiments We describe the synthesis and characterisation of new porphyrin decorated water soluble GNP and we explore Zn-imidazole axial coordination as the mode of linking the porphyrin to the metallic core of the nanoparticles. Quantification of singlet oxygen production, toxicity in dark, cellular uptake by SK-BR-3 cells and phototoxicity have been assessed. Findings Axial coordination limits the number of porphyrins on the gold surface, reduces the formation of aggregates, and diminishes metal exchange in the porphyrin, all of which contribute to enhance the efficiency of singlet oxygen generation from the immobilised porphyrin. In vitro experiments on SK-BR-3 cells reveal a fast uptake followed by more than 80% cell death after irradiation with low doses of light

Accesibilidad al consumo de marihuana en escolarizados colombianos 2016

Introduction: Marijuana use is a public health problem and becomes relevant in the school population. Objective: To describe the accessibility of marijuana use by sociodemographic characteristics, family relationships and consumption in Colombian schoolchildren in 2016. Material and methods: Descriptive, cross-sectional, secondary study of the National Study of Psychoactive Substance Consumption in Colombia School Population - 2016, with a sample of 80,018 students, through univariate and bivariate analysis. Results: A sample of 80,018 schoolchildren was analyzed, the average age of marijuana use is 15.55 years; 51.9% were women. The majority of schoolchildren study in mixed schools (96.11%); 37.3% consider that it would be easy for them to obtain marijuana; Those who stated that they were current users of marijuana, those who stated that all their friends were users, and those who lived with a consumer were the ones who perceived it to be very easy to access marijuana (88.0%, 80.1%, and 71.6%, respectively). Conclusions: There is a high proportion of adolescents who perceive a very easy access to marijuana, consumers or those who are related to consumers were the ones who perceived a greater proportion of easy access to marijuana. Interventions that can counteract this phenomenon are suggested.Introducción: El consumo de marihuana es una problemática de salud pública y cobra relevancia en la población escolar. Objetivo: Describir la accesibilidad de consumo de marihuana por características sociodemográficas, relaciones familiares y de consumo en escolarizados colombianos 2016. Material y métodos: Estudio descriptivo, transversal, secundario del Estudio Nacional de Consumo de Sustancias Psicoactivas en Población Escolar Colombia - 2016, con una muestra de 80.018 estudiantes, mediante análisis univariado y bivariado. Resultados: Se analizó una muestra de 80.018 escolares, el promedio de edad de consumo de marihuana es de 15,55 años; el 51.9% eran mujeres. La mayoría de escolares estudian en colegios mixtos (96.11%); un 37.3% considera que le sería fácil conseguir marihuana; aquellos que manifestaron ser consumidores actuales de marihuana, los que manifiestan que todos sus amigos son consumidores y aquellos que conviven con un consumidor mostraron ser los que percibían muy fácil acceder a la marihuana (88,0%, 80.1% y 71,6% respectivamente). Conclusiones: Existe una alta proporción de adolescentes que perciben un acceso muy fácil a la marihuana, los consumidores o aquellos que se relacionan con consumidores fueron quienes percibían en mayor proporción un fácil acceso a la marihuana. Se sugieren intervenciones que puedan contrarrestar este fenómeno

Evolución de la Infección por Virus de la Inmunodeficiencia Humana en un Hospital del Callao

Objetivos: Describir la evolución histórica e identificar los factores asociados a la infección por el Virus de la Inmunodeficiencia Humana en un hospital de la Región Callao. Materiales y métodos: Análisis de una fuente secundaria. El tamaño de la muestra fue censal según el registro del Programa de Control de Enfermedades de Transmisión Sexual y SIDA (PROCETSS) del Hospital San José, Región Callao durante el periodo 2004 - 2018. Resultados: Participaron 1944 pacientes de ambos sexos, con una edad media de 38,99 años (DE=11,27; Rango: 15 a 85). Respecto al género se observó predomino del sexo masculino con el 79,0% (n=1536). El 90,4% (n=1758) eran peruanos y el 9,1% (n=177) venezolanos. Además de ello se ha reportado con más frecuencia, conductas de riesgo en los adultos con el 93,0 % (n=1807) y 5,7%(n=111) hombres que tenían sexo con hombres (HSH). Como coinfección principal al VIH se encontró la tuberculosis (TBC) con el 4,6% (n=90) y como enfermedad oportunista la Sífilis con el 0,7% (n=14). Conclusión: La frecuencia de infección por el VIH tuvo un incremento en los últimos tres años, destaca la presencia de extranjeros, principalmente de nacionalidad venezolana. La tuberculosis fue la coinfección principal y la sífilis la enfermedad oportunista más frecuente a la infección por VIH

mtDNA Haplogroup A Enhances the Effect of Obesity on the Risk of Knee OA in a Mexican Population

[Abstract] To evaluate the influence of mitochondrial DNA haplogroups on the risk of knee OA in terms of their interaction with obesity, in a population from Mexico. Samples were obtained from (n = 353) knee OA patients (KL grade ≥ I) and (n = 364) healthy controls (KL grade = 0) from Mexico city and Torreon (Mexico). Both Caucasian and Amerindian mtDNA haplogroups were assigned by single base extension assay. A set of clinical and demographic variables, including obesity status, were considered to perform appropriate statistical approaches, including chi-square contingency tables, regression models and interaction analyses. To ensure the robustness of the predictive model, a statistical cross-validation strategy of B = 1000 iterations was used. All the analyses were performed using boot, GmAMisc and epiR package from R software v4.0.2 and SPSS software v24. The frequency distribution of the mtDNA haplogroups between OA patients and healthy controls for obese and non-obese groups showed the haplogroup A as significantly over-represented in knee OA patients within the obese group (OR 2.23; 95% CI 1.22-4.05; p-value = 0.008). The subsequent logistic regression analysis, including as covariate the interaction between obesity and mtDNA haplogroup A, supported the significant association of this interaction (OR 2.57; 95% CI 1.24-5.32; p-value = 0.011). The statistical cross-validation strategy confirmed the robustness of the regression model. The data presented here indicate a link between obesity in knee OA patients and mtDNA haplogroup A.This work is supported by Grants from Fondo de Investigación Sanitaria (PI17/00210, PI16/02124, PI20/00614, RETIC-RIER-RD16/0012/0002 and PRB3-ISCIII-PT17/0019/0014) integrated in the National Plan for Scientific Program, Development and Technological Innovation 2013–2016 and funded by the ISCIII-General Subdirection of Assessment and Promotion of Research-European Regional Development Fund (FEDER) “A way of making Europe” and Grant IN607A2017/11 from Xunta de Galicia. The authors further acknowledge AE CICA-INIBIC (ED431E 2018/03) for financial support. IRP is supported by Contrato Miguel Servet-II Fondo de Investigación Sanitaria (CPII17/00026) and AD-S is supported by Grant IN606A-2018/023 from Xunta de Galicia, Spain. The Biomedical Research Networking Center (CIBER) is an initiative from Instituto de Salud Carlos III (ISCIII)Xunta de Galicia; IN607A2017/11Xunta de Galicia; ED431E 2018/03Xunta de Galicia; IN606A-2018/02