Evaluation of Collaborative Robot Sustainable Integration in Manufacturing Assembly by Using Process Time Savings

Collaborative robots are enablers of flexibility in the current dynamic and uncertain manufacturing environment. Decision making on its implementation requires technical feasibility, involving productivity and workforce implications that should be faced in an integrated perspective in processes where many components of different materials are assembled in products of increasing diversity and complexity. This study introduces two new parametric models for collaborative robotics, formulated in order to evaluate the differential cost of assembly (economic dimension) and the differential income from taxes that supports short-term workforce displacement (social dimension) in cobot implementation. Updated techno-economical parameters are selected for assessing feasibility ranges of application in different production scenarios. Next, the influence curves of productivity gain for a feasible implementation of cobot establish thresholds for decision making under both criteria. The results show the need for productivity gains that are significantly lower in high-wage scenarios than in low-wage scenarios; however, in a joint approach, breakeven productivity gain is always higher for the social dimension threshold than for the economic requirement of cost-effective manufacturing, with a higher gap in low-wage cases. The detailed analysis of a real case study of cobot implementation for assembly demonstrates the practical application of models and potential for future research.     

Photodynamic therapy of melanoma with new,structurally similar,NIR-absorbing ruthenium (II) complexes promotes tumor growth control via distinct hallmarks of immunogenic cell death

Cancer therapies that generate T cell-based anti-cancer immune responses are critical for clinical success and are favored over traditional therapies. One way to elicit T cell immune responses and generate long-lasting anti-cancer immunity is through induction of immunogenic cell death (ICD), a form of regulated cell death that promotes antigenicity and adjuvanticity within dying cells. Therefore, research in the last decade has focused on developing cancer therapies which stimulate ICD. Herein, we report novel photodynamic therapy (PDT) compounds with immunomodulatory and ICD inducing properties. PDT is a clinically approved, minimally invasive anti-cancer treatment option and has been extensively investigated for its tumor-destroying properties, lower side effects, and immune activation capabilities. In this study, we explore two structurally related ruthenium compounds, ML19B01 and ML19B02, that can be activated with near infrared light to elicit superior cytotoxic properties. In addition to its direct cell killing abilities, we investigated the effect of our PSs on immunological pathways upon activation. PDT treatment with ML19B01 and ML19B02 induced differential expression of reactive oxygen species, proinflammatory response-mediating genes, and heat shock proteins. Dying melanoma cells induced by ML19B01-PDT and ML19B02-PDT contained ICD hallmarks such as calreticulin, ATP, and HMGB1, initiated activation of antigen presenting cells, and were efficiently phagocytosed by bone marrow-derived dendritic cells. Most importantly, despite the distinct profiles of ICD hallmark inducing capacities, vaccination with both PDT-induced dying cancer cells established anti-tumor immunity that protected mice against subsequent challenge with melanoma cells.     

The Effect of Nutrition on Aging—A Systematic Review Focusing on Aging-Related Biomarkers

Despite the increasing life expectancy, an individual’s later years tends to be accompanied by a decrease in the quality of life. Though biological changes that occur through the natural process of aging cannot be controlled, the risk factors associated with lifestyle can. Thus, the main goal of this systematic review was to evaluate how nutrition can modulate aging. For this purpose, thirty-six studies were selected on (i) the efficiency of nutrition’s effect on aging, (ii) the evaluation of biomarkers that promote healthy aging, and (iii) how to increase longevity through nutrition, and their quality was assessed. The results showed that choosing low carbohydrate diets or diets rich in vegetables, fruits, nuts, cereals, fish, and unsaturated fats, containing antioxidants, potassium, and omega-3 decreased cardiovascular diseases and obesity risk, protected the brain from aging, reduced the risk of telomere shortening, and promoted an overall healthier life. With this study, the conclusion is that since the biological processes of aging cannot be controlled, changing one’s nutritional patterns is crucial to prevent the emergence and development of diseases, boost longevity, and, mostly, to enhance one’s quality of life and promote healthy aging.     

Terapia Hormonal e Hipertensão em Mulheres na Pós-Menopausa: Resultados do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil)

BackgroundHypertension is a major risk factor for cardiovascular morbidity and mortality in post-menopausal women. Although menopausal hormone therapy (MHT) is a very effective treatment for vasomotor symptoms during this period, the influence of this therapy on blood pressure is not yet clear.ObjectiveTo evaluate the relationship between the use of MHT and hypertension in participants of the ELSA-Brasil.MethodsA cross-sectional study using the baseline ELSA-Brasil data in a cohort of 2,138 women who had experienced natural menopause. This study analyzed hypertension, defined as arterial pressure ≥140/90 mmHg or previous antihypertensive use, and use of MHT, with participants being classified into never, past, and current users. Associations were assessed using an adjusted logistic regression model, with statistical significance set at p<0.05.ResultsOverall, 1,492 women (69.8%) had never used MHT, 457 (21.4%) had used it in the past, and 189 (8.8%) were current users. The use of MHT was more common in women who had a body mass index (BMI) <25 kg/m²and triglyceride levels <150 mg/dl, and who were physically less inactive, non-smokers, and non-diabetics. Current MHT users were less likely to have hypertension (OR=0.59; 95% CI: 0.41-0.85) compared to those who had never used MHT. In most cases, MHT was started at or before 59 years of age, within 10 years of becoming menopausal, and its use lasted for up to five years.ConclusionCurrent MHT use was not related to hypertension, particularly in healthy women and in those under 60 years of age.     

Asparaginase display of polypeptides in the periplasm of Escherichia coli: potential rapid pepscan technique for antigen epitope mapping

Asparaginase of Escherichia coli, a tetramer of identical subunits, was tested as a vector to display linear peptides on the surface of each enzyme subunit. A recombinant gene encoding a chimeric protein composed of asparaginase, a tetanus toxin peptide (TTP) spacer (831-854 fragment), and the foreign cholesteryl ester transfer protein C-terminal fragment (CETPC) was expressed and targeted to the periplasm of E. coli. The purified chimeric enzyme exhibited approximately 83% activity of the native enzyme, allowing the rapid screening of recombinant clones. In contrast, an asparaginase-CETPC fusion protein without the TTP spacer produced only about 23% activity of the native enzyme. Rats immunized with bacterial cells containing the chimeric enzymes induced CETP-specific immunoresponse. In contrast, rats inoculated with the cells expressing asparaginase only did not generate specific anti-CETP antibodies. Our study showed that asparaginase of E. coli was an effective carrier for displaying foreign peptides or epitopes. Moreover, the use of the TTP spacer appeared to play a critical role in maintaining the catalytic activity of the chimeric enzymes by redirecting the foreign CETPC peptide to the surface of the enzyme. The chimeric enzyme constructs fusing asparaginase with foreign peptides via a TTP spacer could be utilized as a rapid pepscan technique for antigen epitope mapping. The fusion protein of asparaginase-TTP-CETPC could also be useful for the development of a vaccine against atherosclerosis.     

Plasminogen activator inhibitor-1 controls bone marrow-derived cells therapeutic effect through MMP9 signaling: role in physiological and pathological wound healing

We assessed the role of plasminogen activator inhibitor-1 (PAI-1) and matrix metalloproteinase 9 (MMP9) in wound healing process and in the bone marrow mononuclear cells (BMMNC)-related effects on physiological and pathological wound healing. A full thickness excision wound was created by removal of the skin on the midback of irradiated and nonirradiated animals. Angiogenesis and re-epithelialization were markedly increased in PAI-1-/- mice compared to wild-type (WT) animals. We revealed high MMP activity in tissue of PAI-1-/- animals. Of interest, the wound healing process was reduced in PAI-1-/-:MMP9-/- animals compared to PAI-1-/- mice, suggesting a key role of MMP9 in beneficial effect of PAI-1 deficiency on wound closure. To unravel the role of PAI-1 in BMMNC relative effects, mice were treated with or without local injection of BMMNC isolated from WT, PAI-1-/-, and PAI-1-/-: MMP9-/- animals for 14 days (10(6) cells, n = 6 per group). In WT nonirradiated mice, transplantation of BMMNC isolated from PAI-1-/- animals enhanced wound formation when compared with WT BMMNC. BMMNC differentiation into cells with endothelial phenotype was enhanced by PAI-1 deficiency. These effects were abrogated in PAI-1-/-:MMP9-/- and MMP9-/- BMMNC. In addition, using chimeric mice, we demonstrated that PAI-1 deficiency environment increased the BMMNC-GFP recruitment to the wound site, whereas this effect was abrogated when using PAI-1-/-:MMP9-/- BMMNC. PAI-1 deficiency, at least through MMP9 upregulation, enhanced wound healing and BMMNC therapeutic potential in irradiated and nonirradiated animals.