Análise e simulação do processo de dobragem de um tubo elíptico utilizando um aço avançado de elevada resistência

Dissertação de mestrado integrado em Engenharia Mecânica

Carbon materials as new generation of new electron shuttles for the anaerobic degradation of environmental xenobiotics

Tese de Doutoramento em Engenharia Química e Biológica

Reduction in left ventricular hypertrophy in hypertensive patients treated with enalapril, losartan or the combination of enalapril and losartan

OBJECTIVE: To compare the regression of left ventricular hypertrophy in patients with moderate hypertension treated with enalapril, losartan or a combination of the two drugs at lower doses. METHODS: Patients of both sexes with moderate hypertension confirmed by ambulatory monitoring of arte-rial blood pressure and with left ventricular hypertrophy on echocardiogram were assigned to three groups: enalapril (35 mg/day, n=15), losartan (175 mg/day, n=15) and enalapril+losartan (15 mg+100 mg/day, n=16). The patients received the drugs for 10 months. RESULTS: The three therapeutic regimens were equally effective in reducing blood pressure and left ventricular mass index (LVMI, g/m²): 141±3.9 to 123±3.6 in the enalapril group (p<0.05), from 147±3.8 to 133±2.8 in the losartan group (p<0.05), and from 146±3.0 to 116±4.0 in the enalapril+losartan group (p<0.05). However, the percent reduction of LVMI was significantly greater (p<0.01) in the enalapril+losartan group (20.5±5.0%) than in enalapril (12.4±3.2%) and the losartan (9.1±2.1%) groups. Normalization of LVMI was obtained in 10 out of the 16 patients who received enalapril+ losartan, in 6 out of the 15 patients who received only enalapril and in 4 out of the 15 patients treated with losartan. CONCLUSION: The combination of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist (AT1 receptor antagonist) in patients produced an additional effect on the reduction of left ventricular hypertrophy. This finding may depend on a more complete inhibition of the cardiac renin-angiotensin.

Meta-Analysis of Ultrafiltration versus Diuretics Treatment Option for Overload Volume Reduction in Patients with Acute Decompensated Heart Failure

Introduction: Although diuretics are mainly used for the treatment of acute decompensated heart failure (ADHF), inadequate responses and complications have led to the use of extracorporeal ultrafiltration (UF) as an alternative strategy for reducing volume overloads in patients with ADHF. Objective: The aim of our study is to perform meta-analysis of the results obtained from studies on extracorporeal venous ultrafiltration and compare them with those of standard diuretic treatment for overload volume reduction in acute decompensated heart failure. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched using a pre‑specified criterion. Pooled estimates of outcomes after 48 h (weight change, serum creatinine level, and all-cause mortality) were computed using random effect models. Pooled weighted mean differences were calculated for weight loss and change in creatinine level, whereas a pooled risk ratio was used for the analysis of binary all-cause mortality outcome. Results: A total of nine studies, involving 613 patients, met the eligibility criteria. The mean weight loss in patients who underwent UF therapy was 1.78 kg [95% Confidence Interval (CI): −2.65 to −0.91 kg; p < 0.001) more than those who received standard diuretic therapy. The post-intervention creatinine level, however, was not significantly different (mean change = −0.25 mg/dL; 95% CI: −0.56 to 0.06 mg/dL; p = 0.112). The risk of all-cause mortality persisted in patients treated with UF compared with patients treated with standard diuretics (Pooled RR = 1.00; 95% CI: 0.64–1.56; p = 0.993). Conclusion: Compared with standard diuretic therapy, UF treatment for overload volume reduction in individuals suffering from ADHF, resulted in significant reduction of body weight within 48 h. However, no significant decrease of serum creatinine level or reduction of all-cause mortality was observed.

Effects of motive-oriented therapeutic relationship in a ten-session general psychiatric treatment of borderline personality disorder: a randomized controlled trial.

Background: Motive-oriented therapeutic relationship (MOTR) was postulated to be a particularly helpful therapeutic ingredient in the early treatment phase of patients with personality disorders, in particular with borderline personality disorder (BPD). The present randomized controlled study using an add-on design is the first study to test this assumption in a 10-session general psychiatric treatment with patients presenting with BPD on symptom reduction and therapeutic alliance. Methods: A total of 85 patients were randomized. They were either allocated to a manual-based short variant of the general psychiatric management (GPM) treatment (in 10 sessions) or to the same treatment where MOTR was deliberately added to the treatment. Treatment attrition and integrity analyses yielded satisfactory results. Results: The results of the intent-to-treat analyses suggested a global efficacy of MOTR, in the sense of an additional reduction of general problems, i.e. symptoms, interpersonal and social problems (F1, 73 = 7.25, p < 0.05). However, they also showed that MOTR did not yield an additional reduction of specific borderline symptoms. It was also shown that a stronger therapeutic alliance, as assessed by the therapist, developed in MOTR treatments compared to GPM (Z55 = 0.99, p < 0.04). Conclusions: These results suggest that adding MOTR to psychiatric and psychotherapeutic treatments of BPD is promising. Moreover, the findings shed additional light on the perspective of shortening treatments for patients presenting with BPD. © 2014 S. Karger AG, Basel.

An extension of the Marsden-Ratiu reduction for Poisson manifolds

We propose a generalization of the reduction of Poisson manifolds by distributions introduced by Marsden and Ratiu. Our proposal overcomes some of the restrictions of the original procedure, and makes the reduced Poisson structure effectively dependent on the distribution. Different applications are discussed, as well as the algebraic interpretation of the procedure and its formulation in terms of Dirac structures.

Advances in pharmacological studies of silymarin

Silymarin is the flavonoids extracted from the seeds of Silybum marianum (L) Gearth as a mixture of three structural isomers: silybin, silydianin and silychristin, the former being the most active component. Silymarin protects liver cell membrane against hepatotoxic agents and improves liver function in experimental animals and humans. It is generally accepted that silymarin exerts a membrane-stabilizing action preventing or inhibiting membrane peroxidation. The experiments with soybean lipoxygenase showed that the three components of silymarin brought about a concentration-dependent non-competitive inhibition of the lipoxygenase. The experiments also showed an analogous interaction with animal lipoxygenase, thus showing that an inhibition of the peroxidation of the fatty acid in vivo was self-evident. Silybin almost completely suppressed the formation of PG at the highest concentration (0.3 mM) and proved to be an inhibitor of PG synthesis in vitro. In our experiments, silybin at lower dose (65 mg/Kg) decreased liver lipoperoxide content and microsomal lipoperoxidation to 84.5% and 68.55% of those of the scalded control rats respectively, and prevented the decrease of liver microsomal cytochrome p-450 content and p-nitroanisole-0-demethylase activity 24 h post-scalding. Effects of silymarin on cardiovascular systen have been studied in this university since 1980. O. O silymarin 800 mg/Kg/d or silybin 600 mg/Kg/d reduced plasma total cholesterol, LDL-C and VLDL-C. They however, enhanced HDL-C in hyperlipenic rats. Further studies showed that silymarin enhanced HDL-C in hyperlipemic rats. Further studies showed that silymarin enhanced HDL-C but didn't affect HDL-C, a property of this component which is beneficial to treatment of atherosclerosis. The results showed silymarin 80 mg or silybin 60 mg decreased in vitro platelet aggregation (porcentagem) in rats. The maximal platelet aggregation induced by ADP declined significantly, and time to reach maximal platelet aggregation and five-minute disaggregation didn't change. In our experiments, iv silybin 22,4 mg/kg lowered the amplitude and duration of diastolic blood pressure (DBP) more than those of systolic (SBP), but the descending aortic blood flow, cardiac contractility and ECG did not change significantly in anesthetized open-chest cats. The results indicated a reduction of peripheral resistance and dilatatory action on the resistant blood vessels. These effects are beneficial to coronary heart disease. We also observed the effects of silybin on morphological change, the release of glutamic oxaloacetate aminotrasferase (GOT) and lactate dehydrogenase (LDH) as well as the radioactivity of 3H-TdR incorporated into DNA in normal cardiac cells and cells infected by coxsackie B5, virus os newborn rats. The results showed that silynin did not affect the morphology of normal cell, and that the pathological change of cells infected by virus was delayed and reduced as compared to control. We have investigated the effect of silybin on synthesis and release of LTs in the cultured porcine cerebral basilar arteries (PCBA). Silybin 100 and 500 µmol/L declined the amounts of LTs released from the PCBA incubsated in the presence of A 23187, AA and indomenthacin. The result suggests that silybin can inhibit the activity of 5-lipoxygenase of cerebral blood vessel and may protect the brain from ischemia.

Dissecting carotenoid from structural components of carotenoid-based coloration: a field experiment with great tits (Parus major).

Carotenoid-based yellowish to red plumage colors are widespread visual signals used in sexual and social communication. To understand their ultimate signaling functions, it is important to identify the proximate mechanism promoting variation in coloration. Carotenoid-based colors combine structural and pigmentary components, but the importance of the contribution of structural components to variation in pigment-based colors (i.e., carotenoid-based colors) has been undervalued. In a field experiment with great tits (Parus major), we combined a brood size manipulation with a simultaneous carotenoid supplementation in order to disentangle the effects of carotenoid availability and early growth condition on different components of the yellow breast feathers. By defining independent measures of feather carotenoid content (absolute carotenoid chroma) and background structure (background reflectance), we demonstrate that environmental factors experienced during the nestling period, namely, early growth conditions and carotenoid availability, contribute independently to variation in yellow plumage coloration. While early growth conditions affected the background reflectance of the plumage, the availability of carotenoids affected the absolute carotenoid chroma, the peak of maximum ultraviolet reflectance, and the overall shape, that is, chromatic information of the reflectance curves. These findings demonstrate that environment-induced variation in background structure contributes significantly to intraspecific variation in yellow carotenoid-based plumage coloration.

The application of chemometrics on Infrared and Raman spectra as a tool for the forensic analysis of paints

The aim of this work is to evaluate the capabilities and limitations of chemometric methods and other mathematical treatments applied on spectroscopic data and more specifically on paint samples. The uniqueness of the spectroscopic data comes from the fact that they are multivariate - a few thousands variables - and highly correlated. Statistical methods are used to study and discriminate samples. A collection of 34 red paint samples was measured by Infrared and Raman spectroscopy. Data pretreatment and variable selection demonstrated that the use of Standard Normal Variate (SNV), together with removal of the noisy variables by a selection of the wavelengths from 650 to 1830 cm−1 and 2730-3600 cm−1, provided the optimal results for infrared analysis. Principal component analysis (PCA) and hierarchical clusters analysis (HCA) were then used as exploratory techniques to provide evidence of structure in the data, cluster, or detect outliers. With the FTIR spectra, the Principal Components (PCs) correspond to binder types and the presence/absence of calcium carbonate. 83% of the total variance is explained by the four first PCs. As for the Raman spectra, we observe six different clusters corresponding to the different pigment compositions when plotting the first two PCs, which account for 37% and 20% respectively of the total variance. In conclusion, the use of chemometrics for the forensic analysis of paints provides a valuable tool for objective decision-making, a reduction of the possible classification errors, and a better efficiency, having robust results with time saving data treatments.

A randomized controlled clinical trial evaluating the performance and safety of platelets treated with MIRASOL pathogen reduction technology.

BACKGROUND: Pathogen reduction of platelets (PRT-PLTs) using riboflavin and ultraviolet light treatment has undergone Phase 1 and 2 studies examining efficacy and safety. This randomized controlled clinical trial (RCT) assessed the efficacy and safety of PRT-PLTs using the 1-hour corrected count increment (CCI(1hour) ) as the primary outcome. STUDY DESIGN AND METHODS: A noninferiority RCT was performed where patients with chemotherapy-induced thrombocytopenia (six centers) were randomly allocated to receive PRT-PLTs (Mirasol PRT, CaridianBCT Biotechnologies) or reference platelet (PLT) products. The treatment period was 28 days followed by a 28-day follow-up (safety) period. The primary outcome was the CCI(1hour) determined using up to the first eight on-protocol PLT transfusions given during the treatment period. RESULTS: A total of 118 patients were randomly assigned (60 to PRT-PLTs; 58 to reference). Four patients per group did not require PLT transfusions leaving 110 patients in the analysis (56 PRT-PLTs; 54 reference). A total of 541 on-protocol PLT transfusions were given (303 PRT-PLTs; 238 reference). The least square mean CCI was 11,725 (standard error [SE], 1.140) for PRT-PLTs and 16,939 (SE, 1.149) for the reference group (difference, -5214; 95% confidence interval, -7542 to -2887; p<0.0001 for a test of the null hypothesis of no difference between the two groups). CONCLUSION: The study failed to show noninferiority of PRT-PLTs based on predefined CCI criteria. PLT and red blood cell utilization in the two groups was not significantly different suggesting that the slightly lower CCIs (PRT-PLTs) did not increase blood product utilization. Safety data showed similar findings in the two groups. Further studies are required to determine if the lower CCI observed with PRT-PLTs translates into an increased risk of bleeding.

Dynamical modeling and analysis of large cellular regulatory networks.

The dynamical analysis of large biological regulatory networks requires the development of scalable methods for mathematical modeling. Following the approach initially introduced by Thomas, we formalize the interactions between the components of a network in terms of discrete variables, functions, and parameters. Model simulations result in directed graphs, called state transition graphs. We are particularly interested in reachability properties and asymptotic behaviors, which correspond to terminal strongly connected components (or "attractors") in the state transition graph. A well-known problem is the exponential increase of the size of state transition graphs with the number of network components, in particular when using the biologically realistic asynchronous updating assumption. To address this problem, we have developed several complementary methods enabling the analysis of the behavior of large and complex logical models: (i) the definition of transition priority classes to simplify the dynamics; (ii) a model reduction method preserving essential dynamical properties, (iii) a novel algorithm to compact state transition graphs and directly generate compressed representations, emphasizing relevant transient and asymptotic dynamical properties. The power of an approach combining these different methods is demonstrated by applying them to a recent multilevel logical model for the network controlling CD4+ T helper cell response to antigen presentation and to a dozen cytokines. This model accounts for the differentiation of canonical Th1 and Th2 lymphocytes, as well as of inflammatory Th17 and regulatory T cells, along with many hybrid subtypes. All these methods have been implemented into the software GINsim, which enables the definition, the analysis, and the simulation of logical regulatory graphs.

Reduction in the expression of glucose transporter protein GLUT 2 in preneoplastic and neoplastic hepatic lesions and reexpression of GLUT 1 in late stages of hepatocarcinogenesis.

Expression of two important glucose transporter proteins, GLUT 2 (which is the typical glucose transporter in hepatocytes of adult liver) and the erythroid/brain type glucose transporter GLUT 1 (representing the typical glucose transporter in fetal liver parenchyma), was studied immunocytochemically during hepatocarcinogenesis in rats at different time points between 7 and 65 wk after cessation of 7-wk administration of 12 mg/kg of body weight of N-nitrosomorpholine p.o. (stop model). Foci of altered hepatocytes excessively storing glycogen (GSF) and mixed cell foci (MCF) composed of both glycogenotic and glycogen-poor cells were present at all time points studied. Seven wk after withdrawal of the carcinogen, GSF were the predominant type of focus of altered hepatocytes. Morphometrical evaluation of the focal lesions revealed that the number and volume fraction of GSF increased steadily until Wk 65. MCF were rare at 7 wk, increased slightly in number and size until Wk 37, but showed a pronounced elevation in their number and volume fraction from Wk 37 to Wk 65. In both GSF and MCF, GLUT 2 was generally decreased or partially absent at all time points. Consequently, foci of decreased GLUT 2 expression showed a steady increase in number and volume fraction from Wk 7 to Wk 65. GLUT 1 was lacking in GSF but occurred in some MCF from Wk 50 onward. The liver type glucose transporter GLUT 2 was decreased in all adenomas and hepatocellular carcinomas (HCC). In three of seven adenomas and 10 of 12 carcinomas, expression of GLUT 1 was increased compared with normal liver parenchyma. In two cases of adenoid HCC, cells of ductular formations coexpressed GLUT 2 and GLUT 1. In contrast, normal bile ducts, bile duct proliferations, and cystic cholangiomas expressed only GLUT 1. Seven of 12 HCC contained many microvessels intensely stained for GLUT 1, a phenomenon never observed in normal liver. Whenever adenoid tumor formations occurred, GLUT 1-positive microvessels were located in the immediate vicinity of these formations. Only in one HCC were such microvessels found in the absence of adenoid formations. Our studies indicate that a reduction of GLUT 2 expression occurs already in early preneoplastic hepatic foci and is maintained throughout hepatocarcinogenesis, including benign and malignant neoplasms. Reexpression of GLUT 1, however, appears in a few MCF and in the majority of adenomas and carcinomas.

Reduction in the proportion of fevers associated with Plasmodium falciparum parasitaemia in Africa: a systematic review.

BACKGROUND: Malaria is almost invariably ranked as the leading cause of morbidity and mortality in Africa. There is growing evidence of a decline in malaria transmission, morbidity and mortality over the last decades, especially so in East Africa. However, there is still doubt whether this decline is reflected in a reduction of the proportion of malaria among fevers. The objective of this systematic review was to estimate the change in the Proportion of Fevers associated with Plasmodium falciparum parasitaemia (PFPf) over the past 20 years in sub-Saharan Africa. METHODS: Search strategy. In December 2009, publications from the National Library of Medicine database were searched using the combination of 16 MeSH terms.Selection criteria. Inclusion criteria: studies 1) conducted in sub-Saharan Africa, 2) patients presenting with a syndrome of 'presumptive malaria', 3) numerators (number of parasitologically confirmed cases) and denominators (total number of presumptive malaria cases) available, 4) good quality microscopy.Data collection and analysis. The following variables were extracted: parasite presence/absence, total number of patients, age group, year, season, country and setting, clinical inclusion criteria. To assess the dynamic of PFPf over time, the median PFPf was compared between studies published in the years ≤2000 and > 2000. RESULTS: 39 studies conducted between 1986 and 2007 in 16 different African countries were included in the final analysis. When comparing data up to year 2000 (24 studies) with those afterwards (15 studies), there was a clear reduction in the median PFPf from 44% (IQR 31-58%; range 7-81%) to 22% (IQR 13-33%; range 2-77%). This dramatic decline is likely to reflect a true change since stratified analyses including explanatory variables were performed and median PFPfs were always lower after 2000 compared to before. CONCLUSIONS: There was a considerable reduction of the proportion of malaria among fevers over time in Africa. This decline provides evidence for the policy change from presumptive anti-malarial treatment of all children with fever to laboratory diagnosis and treatment upon result. This should insure appropriate care of non-malaria fevers and rationale use of anti-malarials.

Fluorescence imaging reveals the nuclear behavior of peroxisome proliferator-activated receptor/retinoid X receptor heterodimers in the absence and presence of ligand.

In a global approach combining fluorescence recovery after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS), and fluorescence resonance energy transfer (FRET), we address the behavior in living cells of the peroxisome proliferator-activated receptors (PPARs), a family of nuclear receptors involved in lipid and glucose metabolism, inflammation control, and wound healing. We first demonstrate that unlike several other nuclear receptors, PPARs do not form speckles upon ligand activation. The subnuclear structures that may be observed under some experimental conditions result from overexpression of the protein and our immunolabeling experiments suggest that these structures are subjected to degradation by the proteasome. Interestingly and in contrast to a general assumption, PPARs readily heterodimerize with retinoid X receptor (RXR) in the absence of ligand in living cells. PPAR diffusion coefficients indicate that all the receptors are engaged in complexes of very high molecular masses and/or interact with relatively immobile nuclear components. PPARs are not immobilized by ligand binding. However, they exhibit a ligand-induced reduction of mobility, probably due to enhanced interactions with cofactors and/or chromatin. Our study draws attention to the limitations and pitfalls of fluorescent chimera imaging and demonstrates the usefulness of the combination of FCS, FRAP, and FRET to assess the behavior of nuclear receptors and their mode of action in living cells.

Application of compositional data analysis to geochemical data of marine sediments

In an earlier investigation (Burger et al., 2000) five sediment cores near the RodriguesTriple Junction in the Indian Ocean were studied applying classical statistical methods(fuzzy c-means clustering, linear mixing model, principal component analysis) for theextraction of endmembers and evaluating the spatial and temporal variation ofgeochemical signals. Three main factors of sedimentation were expected by the marinegeologists: a volcano-genetic, a hydro-hydrothermal and an ultra-basic factor. Thedisplay of fuzzy membership values and/or factor scores versus depth providedconsistent results for two factors only; the ultra-basic component could not beidentified. The reason for this may be that only traditional statistical methods wereapplied, i.e. the untransformed components were used and the cosine-theta coefficient assimilarity measure.During the last decade considerable progress in compositional data analysis was madeand many case studies were published using new tools for exploratory analysis of thesedata. Therefore it makes sense to check if the application of suitable data transformations,reduction of the D-part simplex to two or three factors and visualinterpretation of the factor scores would lead to a revision of earlier results and toanswers to open questions . In this paper we follow the lines of a paper of R. Tolosana-Delgado et al. (2005) starting with a problem-oriented interpretation of the biplotscattergram, extracting compositional factors, ilr-transformation of the components andvisualization of the factor scores in a spatial context: The compositional factors will beplotted versus depth (time) of the core samples in order to facilitate the identification ofthe expected sources of the sedimentary process.Kew words: compositional data analysis, biplot, deep sea sediments