Evaluating social choice techniques into intelligent environments by agent based social simulation

The primary hypothesis stated by this paper is that the use of social choice theory in Ambient Intelligence systems can improve significantly users satisfaction when accessing shared resources. A research methodology based on agent based social simulations is employed to support this hypothesis and to evaluate these benefits. The result is a six-fold contribution summarized as follows. Firstly, several considerable differences between this application case and the most prominent social choice application, political elections, have been found and described. Secondly, given these differences, a number of metrics to evaluate different voting systems in this scope have been proposed and formalized. Thirdly, given the presented application and the metrics proposed, the performance of a number of well known electoral systems is compared. Fourthly, as a result of the performance study, a novel voting algorithm capable of obtaining the best balance between the metrics reviewed is introduced. Fifthly, to improve the social welfare in the experiments, the voting methods are combined with cluster analysis techniques. Finally, the article is complemented by a free and open-source tool, VoteSim, which ensures not only the reproducibility of the experimental results presented, but also allows the interested reader to adapt the case study presented to different environments

Normal Proliferation and Tumorigenesis but Impaired Pancreatic Function in Mice Lacking the Cell Cycle Regulator Sei1

Sei1 is a positive regulator of proliferation that promotes the assembly of Cdk4-cyclin D complexes and enhances the transcriptional activity of E2f1. The potential oncogenic role of Sei1 is further suggested by its overexpression in various types of human cancers. To study the role of Sei1, we have generated a mouse line deficient for this gene. Sei1-null fibroblasts did not show abnormalities regarding proliferation or susceptibility to neoplastic transformation, nor did we observe defects on Cdk4 complexes or E2f activity. Sei1-null mice were viable, did not present overt pathologies, had a normal lifespan, and had a normal susceptibility to spontaneous and chemically-induced cancer. Pancreatic insulin-producing cells are known to be particularly sensitive to Cdk4-cyclin D and E2f activities, and we have observed that Sei1 is highly expressed in pancreatic islets compared to other tissues. Interestingly, Sei1-null mice present lower number of islets, decreased β-cell area, impaired insulin secretion, and glucose intolerance. These defects were associated to nuclear accumulation of the cell-cycle inhibitors p21Cip1 and p27Kip1 in islet cells. We conclude that Sei1 plays an important role in pancreatic β-cells, which supports a functional link between Sei1 and the core cell cycle regulators specifically in the context of the pancreas

Activation of p21 limits acute lung injury and induces early senescence after acid aspiration and mechanical ventilation

The p53/p21 pathway is activated in response to cell stress. However, its role in acute lung injury has not been elucidated. Acute lung injury is associated with disruption of the alveolo-capillary barrier leading to acute respiratory distress syndrome (ARDS). Mechanical ventilation may be necessary to support gas exchange in patients with ARDS, however, high positive airway pressures can cause regional overdistension of alveolar units and aggravate lung injury. Here, we report that acute lung injury and alveolar overstretching activate the p53/p21 pathway to maintain homeostasis and avoid massive cell apoptosis. A systematic pooling of transcriptomic data from animal models of lung injury demonstrates the enrichment of specific p53- and p21-dependent gene signatures and a validated senescence profile. In a clinically relevant, murine model of acid aspiration and mechanical ventilation, we observed changes in the nuclear envelope and the underlying chromatin, DNA damage and activation of the Tp53/p21 pathway. Absence of Cdkn1a decreased the senescent response, but worsened lung injury due to increased cell apoptosis. Conversely, treatment with lopinavir/ritonavir led to Cdkn1a overexpression and ameliorated cell apoptosis and lung injury. The activation of these mechanisms was associated with early markers of senescence, including expression of senescence-related genes and increases in senescence-associated heterochromatin foci in alveolar cells. Autopsy samples from lungs of patients with ARDS revealed increased senescence-associated heterochromatin foci. Collectively, these results suggest that acute lung injury activates p53/p21 as an anti-apoptotic mechanism to ameliorate damage, but with the side effect of induction of senescence

Psychological impact on care professionals due to the SARS-Cov-2 virus in Spain

Objective:To analyze the psychological impact of the SARS-Cov-2 pandemic on nursesin Spain in three different dimensions: exposure to stressors, perceived emotions, andstress coping. Background: On March 11, 2019, the World Health Organization recognized a globalpandemic caused by a SARS-Cov-2 virus, COVID-19, which rapidly spread across theplanet, involving a community health emergency of international scope.Introduction:The pandemic situation in health centers has led to significant changesin the work environment, compromising care professionals’ physical and psychologicalhealth and resulting in strong physical and mental exhaustion.Methods: An observational, descriptive, cross-sectional study was carried out, betweenFebruary and April 2021, in a large sample of 1360 participants. The researchers con-ducted the dissemination of a validated questionnaire to working nurses in Spain.Results:The sex variable in relation to the study dimensions (stressors, perceived emo-tions, and coping strategies) showed a mean for stressors of 62.2±10.5 in women and59.8±12.5 in men (p=0.010), showing statistically significant differences. Age was aprotective factor for all dimensions (p<0.001). Time of experience showed statisticallysignificant differences for stressors and coping strategies in professionals with more than15 years of experience. Discussion: Female nurses who are younger, have less work experience, have not builta family of their own, and live in smaller or indoor flats may be more vulnerable to theeffects of the COVID-19 pandemic on their mental health. Other national and inter-national studies, in this line, have shown an important psychological impact on theseprofessionals.Conclusion:It is necessary to design and adopt effective strategies and measures for theprotection of nurses’ mental health, as well as for the prevention and early diagnosis ofpossible mental health problems

Sirt1 protects from K-Ras-driven lung carcinogenesis.

The NAD+-dependent deacetylase SIRT1 can be oncogenic or tumor suppressive depending on the tissue. Little is known about the role of SIRT1 in non-small cell lung carcinoma (NSCLC), one of the deadliest cancers, that is frequently associated with mutated K-RAS Therefore, we investigated the effect of SIRT1 on K-RAS-driven lung carcinogenesis. We report that SIRT1 protein levels are downregulated by oncogenic K-RAS in a MEK and PI3K-dependent manner in mouse embryo fibroblasts (MEFs), and in human lung adenocarcinoma cell lines. Furthermore, Sirt1 overexpression in mice delays the appearance of K-RasG12V-driven lung adenocarcinomas, reducing the number and size of carcinomas at the time of death and extending survival. Consistently, lower levels of SIRT1 are associated with worse prognosis in human NSCLCs. Mechanistically, analysis of mouse Sirt1-Tg pneumocytes, isolated shortly after K-RasG12V activation, reveals that Sirt1 overexpression alters pathways involved in tumor development: proliferation, apoptosis, or extracellular matrix organization. Our work demonstrates a tumor suppressive role of SIRT1 in the development of K-RAS-driven lung adenocarcinomas in mice and humans, suggesting that the SIRT1-K-RAS axis could be a therapeutic target for NSCLCs.We thank Jesus Herranz for his biostatistical advice; and Alba de Martino, Patricia Gonzalez, Maria Gomez, and Zaira Vega, from the Histopathology Unit at the CNIO, for their work in mouse histopathology. Work in the laboratory of P.J.F.-M. was funded by the IMDEA Food, the Spanish Association against Cancer (aecc) and the Ramon Areces (CIVP18A3891) Foundation. Work in the laboratory of M.S. was funded by the CNIO and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (SAF project), the European Research Council (ERC Advanced Grant), the European Union (RISK-IR project), and the Botin Foundation and Banco Santander (Santander Universities Global Division). Work in the laboratory of DH was funded by Rutgers Cancer Institute of New Jersey, the Alex's Lemonade Stand Foundation Shark Tank Award and by the National Institutes of Health Grant K99/R00 CA197869. Work in the laboratory of M.S.C. was supported by a grant (SAF2012-40026) from the Spanish Ministry of Science and Innovation. L.F.C-M. was supported by a PhD Fellowship from the Portuguese Foundation for Science and Technology (FCT-MCTES, SFRH/BD/124022/2016).S

Fatty acids homeostasis during fasting predicts protection from chemotherapy toxicity.

Fasting exerts beneficial effects in mice and humans, including protection from chemotherapy toxicity. To explore the involved mechanisms, we collect blood from humans and mice before and after 36 or 24 hours of fasting, respectively, and measure lipid composition of erythrocyte membranes, circulating micro RNAs (miRNAs), and RNA expression at peripheral blood mononuclear cells (PBMCs). Fasting coordinately affects the proportion of polyunsaturated versus saturated and monounsaturated fatty acids at the erythrocyte membrane; and reduces the expression of insulin signaling-related genes in PBMCs. When fasted for 24 hours before and 24 hours after administration of oxaliplatin or doxorubicin, mice show a strong protection from toxicity in several tissues. Erythrocyte membrane lipids and PBMC gene expression define two separate groups of individuals that accurately predict a differential protection from chemotherapy toxicity, with important clinical implications. Our results reveal a mechanism of fasting associated with lipid homeostasis, and provide biomarkers of fasting to predict fasting-mediated protection from chemotherapy toxicity.General: We thank Prof. Jose Maria. Ordovas for his kind suggestions; nutritionists Helena Marcos-Pasero, Elena Aguilar-Aguilar and Isabel Espinosa-Salinas for their help with volunteers management; Rosa Serrano for her help with animal experiments; Susana Molina for her advice with PBMC isolation; Luisa Mariscal, Domingo Fernandez, Lola Martinez, Diego Megias, Patricia Gonzalez, Fernando Pelaez, Anabel Sanz, Carolina Pola, Celia de la Calle, Ana Ortega, Ana Sagrera, Jose Miguel Frade, Elena Lopez-Guadamillas, Maribel Munoz, Susana Llanos, Andres Fernandez, Aranzazu Sierra, Andres Lopez, Noemi Haro and Ildefonso Rodriguez for their excellent technical and scientific support. Work at the laboratory of P.J.F.M. is funded by the Ramon Areces Foundation, (CIVP18A3891), Asociacion Espanola contra el Cancer-AECC (SIRTBIO-LABAE18008FERN), a Ramon y Cajal Award from the Spanish Ministry of Science, Innovation and Universities (MICINN) (RYC-2017-22335), RETOS projects Program of MICINN (SAF2017-85766-R) and the Portuguese Foundation for Science and Technology (FCT-MCTES, SFRH/BD/124022/2016). Work at the laboratory of ARM was funded by the MICINN (PID2019-110183RB-C21), Regional Government of Community of Madrid (P2018/BAA-4343-ALIBIRD2020-CM) and the Ramon Areces Foundation. Work at the laboratory of A.D.R. Funded by the Comunidad de Madrid-Talento Grant 2018-T1/BMD-11966 and the MICINN PID-2019-106893RA-100. Work at the laboratory of L.D. is funded by projects from the Health Research Fund (ISCIII FIS PI14/01374 and FISPI17/00508) and from a Manuel de Oya research fellowship from the Beer and Health Foundation. Work at the laboratory of A.E. is funded by a Ramon y Cajal Award from MICINN (RYC-2013-13546) and RETOS projects Program of the MICINN, co-funded by the European Regional Development Fund (ERDF) (SAF2015-67538-R). Work in the laboratory of M.S. was funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Council (ERC-2014-AdG/669622), and the "laCaixa" Foundation.S