Simulación del sistema de ventilación en la empresa GRUMINTOR S.A.

El presente trabajo de investigación se realizó con la finalidad de simular el sistema de ventilación de la mina Grumintor 3 de la empresa GRUMINTOR S.A ubicada en el Cantón Camilo Ponce Enríquez de la Provincia del Azuay, por consiguiente, se hizo necesario el levantamiento de información in situ de la topografía, dimensiones seccionales y condiciones termohigrométricas de las labores subterráneas, posteriormente se simuló el sistema de ventilación principal y secundario de la mina con uso de los software Ventsim y Vuma aplicados para ventilación de minas subterráneas basados en modelamientos 3D, finalmente en base a la normativa vigente de seguridad y salud del trabajador en el ámbito minero se verificó que las condiciones mencionadas anteriormente estén en los parámetros permisibles para realizar actividades mineras subterráneas. Como resultado se obtuvo que las condiciones térmicas son adecuadas, sin embargo, existe un ambiente muy húmedo, finalmente en cuanto a la velocidad de las corrientes aire son medianamente adecuadas y por ende la falta de caudal de aire para cumplir con los requerimientos, por tal razón se recomendó la implementación de un ventilador en la boca mina de ingreso peatonal para suplir el caudal faltante necesario para cumplir con el requerimiento y la construcción de una chimenea cerca del frente de exploración para una mejor circulación del corrientes de aire contaminado para mejorar la atmósfera minera y velocidad del flujo de aire.The present study aimed to simulate the ventilation system of the Grumintor 3 mine of the company GRUMINTOR S.A., located in the Camilo Ponce Enríquez canton of Azuay province, therefore, it was necessary to collect in situ information of the topography, sectional dimensions and thermohygrometric conditions of the underground workings, Afterwards, the main and secondary ventilation system of the mine was simulated with the use of Ventsim and Vuma software applied for underground mine ventilation based on 3D modeling. Finally, based on the current regulations on worker safety and health in the mining area, it was verified that the conditions mentioned above are within the permissible parameters for underground mining activities. As a result, it was found that the thermal conditions are adequate; however, there is a very humid environment. Finally, regarding the speed of air currents are moderately adequate and therefore, the lack of air flow to meet the requirements; for this reason, it was recommended the implementation of a fan in the mine mouth of pedestrian entrance to supply the missing flow necessary to meet the requirement and the construction of a chimney near the exploration front for better circulation of contaminated air currents to improve the mining atmosphere and air flow velocity

Are you ready for change? Farsight for construction: Exploratory scenarios for Queensland’s construction industry to 2036

The future of work and employment is a global hot topic with interconnected and powerful forces shaping jobs, industries and entire economies. Farsight, prepared in partnership with Construction Skills Queensland, examines the future of construction work in the state. Specifically, the report discusses critical trends and alternative scenarios for the future of Queensland’s construction workforce. Eighty leading experts across the state contributed to this future through a range of thinking and participation in interviews and workshops – where they considered what the industry could look like in 2036, and how job profiles and skills requirements might change to align with that future. A comprehensive scan of trends impacting the industry was undertaken, 25 of which are discussed in this report. This industry input and trends scan culminated in the development of four scenarios (Figure 1) that capture key areas of uncertainty and impact for jobs and skills in the industry. Each scenario is possible and takes the reader down an evidence-based journey about a plausible future. Because the future is not exact, there are multiple paths leading to multiple scenarios. Our scenarios describe a range of futures – some we would like to happen or others we would like to avoid. The aim in scenario planning is to be objective and inform decision-makers to identify, select and implement optimal strategies to achieve a better future – for all involved. Farsight was designed to help the industry understand what could happen in the future, and to identify what future(s) the industry wants and what steps could be taken to move toward desired futures. The scenarios were defined using a strategic foresight process that involves the identification of two spectrums that capture a range of plausible outcomes. The end points are extreme possibilities, with each relatively independent of the other. The outcomes of Farsight rests upon a set of trends compiled and synthesised by the research team. Crossing the axes defines the scenario space and the four scenarios which detail the tools we will need to keep stay nimble, relevant and effective in a global marke

Computational Drug Target Screening through Protein Interaction Profiles

The development of computational methods to discover novel drug-target interactions on a large scale is of great interest. We propose a new method for virtual screening based on protein interaction profile similarity to discover new targets for molecules, including existing drugs. We calculated Target Interaction Profile Fingerprints (TIPFs) based on ChEMBL database to evaluate drug similarity and generated new putative compound-target candidates from the non-intersecting targets in each pair of compounds. A set of drugs was further studied in monoamine oxidase B (MAO-B) and cyclooxygenase-1 (COX-1) enzyme through molecular docking and experimental assays. The drug ethoxzolamide and the natural compound piperlongumine, present in Piper longum L, showed hMAO-B activity with IC50 values of 25 and 65μM respectively. Five candidates, including lapatinib, SB-202190, RO-316233, GW786460X and indirubin-3′-monoxime were tested against human COX-1. Compounds SB-202190 and RO-316233 showed a IC50 in hCOX-1 of 24 and 25μM respectively (similar range as potent inhibitors such as diclofenac and indomethacin in the same experimental conditions). Lapatinib and indirubin3′-monoxime showed moderate hCOX-1 activity (19.5% and 28% of enzyme inhibition at 25μM respectively). Our modeling constitutes a multi-target predictor for large scale virtual screening with potential in lead discovery, repositioning and drug safetyThis study was supported by grant R01 LM006910 (GH) “Discovering and Applying Knowledge in Clinical Databases” from the U.S. National Library of Medicine, “Angeles Alvariño, Plan Galego de Investigación, Innovación e Crecemento 2011–2015 (I2C)” and European Social Fund (ESF)S

Maintaining lung health with longstanding HIV

Purpose of review: Human immunodeficiency virus (HIV) is now managed as a chronic disease. Non-infectious pulmonary conditions have replaced infection as the biggest threat to lung health, particularly as HIV cohorts age, but there is no consensus on how best to maintain long-term lung health. We review the epidemiology and pathogenesis of chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension (PAH), and lung cancer in HIV-seropositive individuals. Recent findings: Diagnoses of COPD are now up to 50% more prevalent in HIV-seropositive individuals than HIV-uninfected controls, and prospective pulmonary function studies find significant impairment in 7% to more than 50% of HIV-seropositive individuals. The prevalence of HIV–PAH is 0.2–0.5%, and lung cancer is two to three times more prevalent in HIV-seropositive individuals. Although host factors such as age and smoking have a role, HIV is an independent contributor to the pathogenesis of COPD, PAH, and lung cancer. Chronic inflammation, immune senescence, oxidative stress, and direct effects of viral proteins are all potential pathogenetic mechanisms. Despite their prevalence, non-infectious lung diseases remain underrecognized and evidence for effective screening strategies in HIV-seropositive individuals is limited. Summary: COPD, PAH, and lung cancer are a growing threat to lung health in the highly active antiretroviral therapy era necessitating early recognitio

Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma.

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action

Digitalized transcranial electrical stimulation: A consensus statement

Objective: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES. Methods: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. Results: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity. Conclusions: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases. Significance: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials

Distinct Effects of IL-18 on the Engraftment and Function of Human Effector CD8+ T Cells and Regulatory T Cells

IL-18 has pleotropic effects on the activation of T cells during antigen presentation. We investigated the effects of human IL-18 on the engraftment and function of human T cell subsets in xenograft mouse models. IL-18 enhanced the engraftment of human CD8+ effector T cells and promoted the development of xenogeneic graft versus host disease (GVHD). In marked contrast, IL-18 had reciprocal effects on the engraftment of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in the xenografted mice. Adoptive transfer experiments indicated that IL-18 prevented the suppressive effects of Tregs on the development of xenogeneic GVHD. The IL-18 results were robust as they were observed in two different mouse strains. In addition, the effects of IL-18 were systemic as IL-18 promoted engraftment and persistence of human effector T cells and decreased Tregs in peripheral blood, peritoneal cavity, spleen and liver. In vitro experiments indicated that the expression of the IL-18Rα was induced on both CD4 and CD8 effector T cells and Tregs, and that the duration of expression was less sustained on Tregs. These preclinical data suggest that human IL-18 may have use as an adjuvant for immune reconstitution after cytotoxic therapies, and to augment adoptive immunotherapy, donor leukocyte infusions, and vaccine strategies

In Situ-Targeting of Dendritic Cells with Donor-Derived Apoptotic Cells Restrains Indirect Allorecognition and Ameliorates Allograft Vasculopathy

Chronic allograft vasculopathy (CAV) is an atheromatous-like lesion that affects vessels of transplanted organs. It is a component of chronic rejection that conventional immuno-suppression fails to prevent, and is a major cause of graft loss. Indirect allo-recognition through T cells and allo-Abs are critical during CAV pathogenesis. We tested whether the indirect allo-response and its impact on CAV is down-regulated by in situ-delivery of donor Ags to recipient's dendritic cells (DCs) in lymphoid organs in a pro-tolerogenic fashion, through administration of donor splenocytes undergoing early apoptosis. Following systemic injection, donor apoptotic cells were internalized by splenic CD11chi CD8α+ and CD8− DCs, but not by CD11cint plasmacytoid DCs. Those DCs that phagocytosed apoptotic cells in vivo remained quiescent, resisted ex vivo-maturation, and presented allo-Ag for up to 3 days. Administration of donor apoptotic splenocytes, unlike cells alive, (i) promoted deletion, FoxP3 expression and IL-10 secretion, and decreased IFN-γ-release in indirect pathway CD4 T cells; and (ii) reduced cross-priming of anti-donor CD8 T cells in vivo. Targeting recipient's DCs with donor apoptotic cells reduced significantly CAV in a fully-mismatched aortic allograft model. The effect was donor specific, dependent on the physical characteristics of the apoptotic cells, and was associated to down-regulation of the indirect type-1 T cell allo-response and secretion of allo-Abs, when compared to recipients treated with donor cells alive or necrotic. Down-regulation of indirect allo-recognition through in situ-delivery of donor-Ag to recipient's quiescent DCs constitutes a promising strategy to prevent/ameliorate indirect allorecognition and CAV

Apoptotic cell-based therapies against transplant rejection: role of recipient’s dendritic cells

One of the ultimate goals in transplantation is to develop novel therapeutic methods for induction of donor-specific tolerance to reduce the side effects caused by the generalized immunosuppression associated to the currently used pharmacologic regimens. Interaction or phagocytosis of cells in early apoptosis exerts potent anti-inflammatory and immunosuppressive effects on antigen (Ag)-presenting cells (APC) like dendritic cells (DC) and macrophages. This observation led to the idea that apoptotic cell-based therapies could be employed to deliver donor-Ag in combination with regulatory signals to recipient’s APC as therapeutic approach to restrain the anti-donor response. This review describes the multiple mechanisms by which apoptotic cells down-modulate the immuno-stimulatory and pro-inflammatory functions of DC and macrophages, and the role of the interaction between apoptotic cells and APC in self-tolerance and in apoptotic cell-based therapies to prevent/treat allograft rejection and graft-versus-host disease in murine experimental systems and in humans. It also explores the role that in vivo-generated apoptotic cells could have in the beneficial effects of extracorporeal photopheresis, donor-specific transfusion, and tolerogenic DC-based therapies in transplantation