A Theoretical Model with Which to Safely Optimize the Configuration of Hydraulic Suspension of Modular Trailers in Special Road Transport

The dimensions and weight of machines, structures, and components that need to be transported safely by road are growing constantly. One of the safest and most widely used transport systems on the road today due to their versatility and configuration are modular trailers. These trailers have hydraulic pendulum axles that are that are attached in pairs to the rigid platform above. In turn, these modular trailers are subject to limitations on the load that each axle carries, the tipping angle, and the oil pressure of the suspension system in order to guarantee safe transport by road. Optimizing the configuration of these modular trailers accurately and safely is a complex task. Factors to be considered include the load’s characteristics, the trailer’s mechanical properties, and road route conditions including the road’s slope and camber, precipitation and direction, and force of the wind. This paper presents a theoretical model that can be used for the optimal configuration of hydraulic cylinder suspension of special transport by road using modular trailers. It considers the previously mentioned factors and guarantees the safe stability of road transport. The proposed model was validated experimentally by placing a nacelle wind turbine at different points within a modular trailer. The weight of the wind turbine was 42,500 kg and its dimensions were 5133 × 2650 × 2975 mm. Once the proposed model was validated, an optimization algorithm was employed to find the optimal center of gravity for load, number of trailers, number of axles, oil pressures, and hydraulic configuration. The optimization algorithm was based on the iterative and automatic testing of the proposed model for different positions on the trailer and different hydraulic configurations. The optimization algorithm was tested with a cylindrical tank that weighed 108,500 kg and had dimensions of 19,500 × 3200 × 2500 mm. The results showed that the proposed model and optimization algorithm could safely optimize the configuration of the hydraulic suspension of modular trailers in special road transport, increase the accuracy and reliability of the calculation of the load configuration, save time, simplify the calculation process, and be easily implemented

Autologous stem cell transplantation may be curative for patients with follicular lymphoma with early therapy failure without the need for immunotherapy

Objective/Background: Patients with follicular lymphoma (FL) with early therapy failure (ETF) within 2 years of frontline therapy have poor overall survival (OS). We recently reported the results of autologous stem cell transplantation (ASCT) in patients from the Grupo Español de Linfomas y Trasplantes de Médula Ósea (GELTAMO) registry treated with rituximab prior to ASCT and with ETF after first-line immunochemotherapy, leading to 81% 5-year OS since ASCT. We explored whether ASCT is also an effective option in the pre-rituximab era—that is, in patients treated in induction and rescued only with chemotherapy. Methods: ETF was defined as relapse/progression within 2 years of starting first-line therapy. We identified two groups: the ETF cohort (n = 87) and the non-ETF cohort (n = 47 patients receiving ASCT but not experiencing ETF following first-line therapy). Results: There was a significant difference in 5-year progression-free survival between the ETF and non-ETF cohorts (43% vs. 57%, respectively; p = .048). Nevertheless, in patients with ETF with an interval from first relapse after primary treatment to ASCT of <1 year, no differences were observed in 5-year progression-free survival (48% vs. 66%, respectively; p = .44) or in 5-year OS (69% vs. 77%, p = .4). Patients in the ETF cohort transplanted in complete remission showed a plateau in the OS curves, at 56%, beyond 13.7 years of follow-up. Conclusion: ASCT may be a curative option for ETF in patients who respond to rescue chemotherapy, without the need for immunotherapy or other therapies, and should be considered as an early consolidation, especially in patients with difficult access to rituximab

Effects of adrenergic-stimulated lipolysis and cytokine production on in vitro mouse adipose tissue-islet interactions.

Inflammatory cytokines and non-esterified fatty acids (NEFAs) are obesity-linked factors that disturb insulin secretion. The aim of this study was to investigate whether pancreatic adipose tissue (pWAT) is able to generate a NEFA/cytokine overload within the pancreatic environment and as consequence to impact on insulin secretion. Pancreatic fat is a minor fat depot, therefore we used high-fat diet (HFD) feeding to induce pancreatic steatosis in mice. Relative Adipoq and Lep mRNA levels were higher in pWAT of HFD compared to chow diet mice. Regardless of HFD, Adipoq and Lep mRNA levels of pWAT were at least 10-times lower than those of epididymal fat (eWAT). Lipolysis stimulating receptors Adrb3 and Npr1 were expressed in pWAT and eWAT, and HFD reduced their expression in eWAT only. In accordance, HFD impaired lipolysis in eWAT but not in pWAT. Despite expression of Npr mRNA, lipolysis was stimulated solely by the adrenergic agonists, isoproterenol and adrenaline. Short term co-incubation of islets with CD/HFD pWAT did not alter insulin secretion. In the presence of CD/HFD eWAT, glucose stimulated insulin secretion only upon isoproterenol-induced lipolysis, i.e. in the presence of elevated NEFA. Isoproterenol augmented Il1b and Il6 mRNA levels both in pWAT and eWAT. These results suggest that an increased sympathetic activity enhances NEFA and cytokine load of the adipose microenvironment, including that of pancreatic fat, and by doing so it may alter beta-cell function

Chronic Use Of Pravastatin Reduces Insulin Exocytosis And Increases Beta-cell Death In Hypercholesterolemic Mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)We have previously demonstrated that hypercholesterolemic LDL receptor knockout (LDLr-/-) mice secrete less insulin than wild-type mice. Removing cholesterol from isolated islets using methyl-beta-cyclodextrin reversed this defect. In this study, we hypothesized that in vivo treatment of LDLr-/- mice with the HMGCoA reductase inhibitor pravastatin would improve glucose-stimulated insulin secretion. Female LDLr-/- mice were treated with pravastatin (400 mg/L) for 1-3 months. Isolated pancreatic islets were assayed for insulin secretion rates, intracellular calcium oscillations, cholesterol levels, NAD(P)H and SNARE protein levels, apoptosis indicators and lipidomic profile. Two months pravastatin treatment reduced cholesterol levels in plasma, liver and islets by 35%, 25% and 50%, respectively. Contrary to our hypothesis, pravastatin treatment increased fasting and fed plasma levels of glucose and decreased markedly (40%) fed plasma levels of insulin. In addition, ex vivo glucose stimulated insulin secretion was significantly reduced after two and three months (36-48%, p<0.05) of pravastatin treatment. Although reducing insulin secretion and insulinemia, two months pravastatin treatment did not affect glucose tolerance because it improved global insulin sensitivity. Pravastatin induced islet dysfunction was associated with marked reductions of exocytosis-related SNARE proteins (SNAP25, Syntaxin 1A, VAMP2) and increased apoptosis markers (Bax/Bcl2 protein ratio, cleaved caspase-3 and lower NAD(P)H production rates) observed in pancreatic islets from treated mice. In addition, several oxidized phospholipids, tri- and diacylglycerols and the proapoptotic lipid molecule ceramide were identified as markers of pravastatin-treated islets. Cell death and oxidative stress (H2O2 production) were confirmed in insulin secreting INS-1E cells treated with pravastatin. These results indicate that chronic treatment with pravastatin impairs the insulin exocytosis machinery and increases beta-cell death. These findings suggest that prolonged use of statins may have a diabetogenic effect. (C) 2016 Elsevier Ireland Ltd. All rights reserved.3444252Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil [2011/50400-0, 2011/51349-8]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), BrazilCNPqFAPESPCAPESFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Characterization of a composite material reinforced with vulcanized rubber

The paper is intended to propose a method to characterize the adhesion of a thermoplastic matrix composite material that is reinforced with continuous fibers and over-injected vulcanized rubber. The behaviour of the material based on the thermoplastic matrix and the adhesive is studied. In addition, the combination of factors that provides the greatest possible adhesion of the rubber to the composite is analyzed. Test methods are also analysed and suggested to characterize the adhesion force of the vulcanized rubber to the thermoplastic composite

Chronic Use Of Pravastatin Reduces Insulin Exocytosis And Increases β-cell Death In Hypercholesterolemic Mice.

We have previously demonstrated that hypercholesterolemic LDL receptor knockout (LDLr(-/-)) mice secrete less insulin than wild-type mice. Removing cholesterol from isolated islets using methyl-beta-cyclodextrin reversed this defect. In this study, we hypothesized that in vivo treatment of LDLr(-/-) mice with the HMGCoA reductase inhibitor pravastatin would improve glucose-stimulated insulin secretion. Female LDLr(-/-) mice were treated with pravastatin (400mg/L) for 1-3 months. Isolated pancreatic islets were assayed for insulin secretion rates, intracellular calcium oscillations, cholesterol levels, NAD(P)H and SNARE protein levels, apoptosis indicators and lipidomic profile. Two months pravastatin treatment reduced cholesterol levels in plasma, liver and islets by 35%, 25% and 50%, respectively. Contrary to our hypothesis, pravastatin treatment increased fasting and fed plasma levels of glucose and decreased markedly (40%) fed plasma levels of insulin. In addition, ex vivo glucose stimulated insulin secretion was significantly reduced after two and three months (36-48%, p<0.05) of pravastatin treatment. Although reducing insulin secretion and insulinemia, two months pravastatin treatment did not affect glucose tolerance because it improved global insulin sensitivity. Pravastatin induced islet dysfunction was associated with marked reductions of exocytosis-related SNARE proteins (SNAP25, Syntaxin 1A, VAMP2) and increased apoptosis markers (Bax/Bcl2 protein ratio, cleaved caspase-3 and lower NAD(P)H production rates) observed in pancreatic islets from treated mice. In addition, several oxidized phospholipids, tri- and diacylglycerols and the proapoptotic lipid molecule ceramide were identified as markers of pravastatin-treated islets. Cell death and oxidative stress (H2O2 production) were confirmed in insulin secreting INS-1E cells treated with pravastatin. These results indicate that chronic treatment with pravastatin impairs the insulin exocytosis machinery and increases β-cell death. These findings suggest that prolonged use of statins may have a diabetogenic effect.344-34

Foaming of EVA/starch blends: Characterization of the structure, physical properties, and biodegradability

Foams produced from blends of an ethylene-vinyl acetate copolymer (EVA) with high VA (vinyl acetate) content (28%) and corn starch have been successfully fabricated using an improved compression molding technique. A detailed characterization of the structure and physical properties has been carried out. The results showed that the corn starch acts as filler for EVA, showing a good compatibility with the polyolefin. Different types of cellular structure (closed, partially interconnected, and fully interconnected) and cell sizes were obtained depending on the relative density and the amount of starch included in the composition. Besides, the addition of starch allows tailoring the physical properties of the composite foams. An increase in the starch content leads to an increase of the density, compressive strength, hardness, and thermal conductivity and a decrease of the elasticity. Finally, biodegradability tests showed how increases the biodegradation with the amount of starch in the foam, which reaches 60% at 100 days for the foam with 70% of starch. POLYM. ENG. SCI., 2012. (C) 2011 Society of Plastics EngineersFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Pancreatic fat cells of humans with type 2 diabetes display reduced adipogenic and lipolytic activity.

Obesity, especially visceral fat accumulation, increases the risk of type 2 diabetes (T2D). The purpose of this study was to investigate the impact of T2D on the pancreatic fat depot. Pancreatic fat pads from 17 partial pancreatectomized patients (PPP) were collected, pancreatic preadipocytes isolated and in vitro differentiated. Patients were grouped using HbA1c into normal glucose tolerant (NGT), prediabetic (PD) and T2D. Transcriptome profiles of preadipocytes and adipocytes were assessed by RNAseq. Insulin sensitivity was estimated by quantifying AKT phosphorylation on western blots. Lipogenic capacity was assessed with oil red O staining, lipolytic activity via fatty acid release. Secreted factors were measured using ELISA. Comparative transcriptome analysis of preadipocytes and adipocytes indicates defective upregulation of genes governing adipogenesis (NR1H3), lipogenesis (FASN, SCD, ELOVL6, FADS1) and lipolysis (LIPE) during differentiation of cells from T2D-PPP. In addition, the ratio of leptin/adiponectin mRNA was higher in T2D than in NGT-PPP. Preadipocytes and adipocytes of NGT-PPP were more insulin sensitive than T2D-PPP cells in regard to AKT phosphorylation. Triglyceride accumulation was similar in NGT and T2D adipocytes. Despite a high expression of the receptors NPR1 and NPR2 in NGT and T2D adipocytes, lipolysis was stimulated by ANP 1.74-fold in NGT cells only. This stimulation was further increased by the PDE5 inhibitor dipyridamole (3.09-fold). Dipyridamole and forskolin increased lipolysis receptor-independently 1.88-fold and 1.48-fold, respectively, solely in NGT cells. In conclusion, the metabolic status persistently affects differentiation and lipolysis of pancreatic adipocytes. These alterations could aggravate the development of T2D