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Overdenture retaining bar stress distribution: A finite-element analysis
No full textObjective. Evaluate the stress distribution on the peri-implant bone tissue and prosthetic components of bar-clip retaining systems for overdentures presenting different implant inclinations, vertical misfit and framework material. Materials and methods. Three-dimensional models of a jaw and an overdenture retained by two implants and a bar-clip attachment were modeled using specific software (SolidWorks 2010). The studied variables were: latero-lateral inclination of one implant (-10 degrees, -5 degrees, 0 degrees, +5 degrees, +10 degrees); vertical misfit on the other implant (50, 100, 200 mu m); and framework material (Au type IV, Ag-Pd, Ti cp, Co-Cr). Solid models were imported into mechanical simulation software (ANSYS Workbench 11). All nodes on the bone's external surface were constrained and a displacement was applied to simulate the settling of the framework on the ill-fitted component. Von Mises stress for the prosthetic components and maximum principal stress to the bone tissue were evaluated. Results. The +10 degrees inclination presented the worst biomechanical behavior, promoting the highest stress values on the bar framework and peri-implant bone tissue. The -5 degrees group presented the lowest stress values on the prosthetic components and the lowest stress value on peri-implant bone tissue was observed in -10 degrees. Increased vertical misfit caused an increase on the stress values in all evaluated structures. Stiffer framework materials caused a considerable stress increase in the framework itself, prosthetic screw of the fitted component and peri-implant bone tissue. Conclusions. Inclination of one implant associated with vertical misfit caused a relevant effect on the stress distribution in bar-clip retained overdentures. Different framework materials promoted increased levels of stress in all the evaluated structures734274279FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2011-16463-
Trees as huge flowers and flowers as oversized floral guides: the role of floral color change and retention of old flowers in Tibouchina Pulchra
No full textFloral color changes and retention of old flowers are frequently combined phenomena restricted to the floral guide or single flowers in few-flowered inflorescences. They are thought to increase the attractiveness over long distances and to direct nearby pollinators toward the rewarding flowers. In Tibouchina pulchra, a massively flowering tree, the whole flower changes its color during anthesis. On the first day, the flowers are white and on the next 3 days, they change to pink. This creates a new large-scale color pattern in which the white pre-changed flowers contrast against the pink post-changed ones over the entire tree. We describe the spectral characteristics of floral colors of T. pulchra and test bumblebees' response to this color pattern when viewed at different angles (simulating long and short distances). The results indicated the role of different color components in bumblebee attraction and the possible scenario in which this flower color pattern has evolved. We tested bumblebees' preference for simulated trees with 75% pink and 25% white flowers resembling the color patterns of T. pulchra, and trees with green leaves and pink flowers (control) in long-distance approach. We also compared an artificial setting with three pink flowers and one white flower (T pulchra model) against four pink flowers with white floral guides (control) in short-distance approach. Bumblebees spontaneously preferred the simulated T. pulchra patterns in both approaches despite similar reward. Moreover, in short distances, pollinator visits to peripheral, non-rewarding flowers occurred only half as frequently in the simulated T pulchra when compared to the control. Thefore, this exceptional floral color change and the retention of old flowers in T. pulchra favors the attraction of pollinators over long distances in a deception process while it honestly directs them toward the rewarding flowers at short distances possibly exploring their innate color preferences6CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP303084/2011-12010/51494-5; 2012/50425-
NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice
No full textAdult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD+) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD+ precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmdmdx/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD+ may reprogram dysfunctional SCs and improve life span in mammals352629214361443H.Z., D.R., K.J.M., J.A., and the EPFL have filed a provisional patent application on the use of NAD boosting to enhance SC function. We thank T. Langer for sharing the Phb plasmids; S. Wang and M. Knobloch for technical help in McSC and NSC experiments; H. Li, L. Mouchiroud, P. Moral Quiros, and all members of the Auwerx and Schoonjans groups for helpful discussions; and the EPFL histology and flow cytometry core facilities for technical assistance. H.Z. is the recipient of a doctoral scholarship from the China Scholarship Council and a fellowship from CARIGEST SA. D.D. was supported by a fellowship from Associazione Italiana per la Ricerca sul Cancro. K.J.M. is supported by the University of Ottawa and the Heart and Stroke Foundation of Canada. J.A. is the Nestlé Chair in Energy Metabolism, and his research is supported by EPFL, the NIH (grant R01AG043930), Krebsforschung Schweiz/SwissCancerLeague (grant KFS-3082-02-2013), Systems X (grant SySX.ch 2013/153), and the Swiss National Science Foundation (grant 31003A-140780
Antibodies for Rickettsia spp. in patients with negative serology for dengue virus, leptospirosis, and meningococcal disease in municipalities of São Paulo State, Brazil
No full textBrazilian spotted fever is an infectious disease with a high mortality rate if not treated early. Differential diagnosis is difficult, as the first clinical signs are non-specific and can be confused with other diseases. The aim of the study was to investigate evidence of infection with Rickettsia rickettsii and Rickettsia parkeri in negative sera samples, collected in 2014, from patients with suspected leptospirosis, dengue fever, and meningococcal disease in Atibaia and Bragança Paulista municipalities of the State of São Paulo. The samples stored at the Institute Adolfo Lutz in Campinas were tested using an indirect immunofluorescence assay (IFA) with IgG and IgM against R. rickettsii and R. parkeri. Real-time polymerase chain reaction (PCR) testing was performed for the sera samples of patients who died (n = 3), those with initial suspicion of meningococcal disease (n = 6), and those with positive IFA results. Of 258 samples from Bragança Paulista, 4 (1.6%) were positive, with IgG titers of 1:64 and 1:128 against R. rickettsii and R. parkeri, respectively. Of 155 samples from Atibaia, 2 (1.3%) were positive, with IgG titers of 1:64 and 1:128 against R. rickettsii and R. parkeri, respectively. No sample showed positive PCR results. This serological investigation suggests there is evidence of exposure to Rickettsia spp. in residents of areas that have environmental conditions favorable to the spread of bacteria, in which Brazilian spotted fever incidence was not previously confirmed49
A checklist of woody leguminosae in the South American corridor of dry vegetation
No full textA checklist for woody Leguminosae in the South American Corridor of Dry Vegetation was based on published data (286 floristic lists) and collections from nine herbaria. A total of 781 species (117 genera and 16 tribes) were found. The Chaco showed highest species richness, despite having the lowest taxonomic distinctness index (Delta*). Data from herbaria formed a large contribution to the evaluation of the diversity of the vegetation studied. Each vegetation type has a considerable number of endemic species, demonstrating the importance of conserving all types of seasonally dry vegetation present in South America2071138FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2010/01281-
Clinical use of the co‐formulation of insulin degludec and insulin aspart
No full textTo provide a review of the available data and practical use of insulin degludec with insulin aspart (IDegAsp). Premixed insulins provide basal and prandial glucose control; however, they have an intermediate‐acting prandial insulin component and do not provide as effective basal coverage as true long‐acting insulins, owing to the physicochemical incompatibility of their individual components, coupled with the inflexibility of adjustment. The molecular structure of the co‐formulation of IDegAsp, a novel insulin preparation, allows these two molecules to coexist without affecting their individual pharmacodynamic profiles. Clinical evidence in phase 2/3 trials of IDegAsp efficacy and safety in type 1 and type 2 diabetes mellitus (T1DM and T2DM) have been assessed and summarised. In people with T2DM, once‐ and twice‐daily dosing provides similar overall glycaemic control (HbA1c) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal‐time or premix insulin regimens. In insulin‐naïve patients with T2DM, IDegAsp can be started once or twice‐daily, based on individual need. People switching from more than once‐daily basal or premix insulin therapy can be converted unit‐to‐unit to once‐daily IDegAsp, although this strategy should be assessed by the physician on an individual basis. IDegAsp offers physicians and people with T2DM a simpler insulin regimen than other available basal‐bolus or premix‐based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins.70865766
Strengthening of reinforced concrete beams using ultra high performance fiber reinforced concrete
No full textOrientadores: José Luiz Antunes de Oliveira e Sousa, Thomaz Eduardo Teixeira ButtignolDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Civil, Arquitetura e UrbanismoResumo: O concreto de ultra alto desempenho reforçado com fibras (CUADRF) é um material relativamente recente com excepcionais propriedades mecânicas e de durabilidade com uma vasta gama de aplicações na engenharia estrutural. Neste trabalho discute-se como a aplicação do CUADRF em vigas de concreto armado pode ser uma solução para o aumento da capacidade de carga e da ductilidade em geral. São discutidas as principais propriedades do concreto de ultra alto desempenho reforçado com fibras em seus estados fresco e endurecido de modo a explicitar sua viabilidade como material de reforço em vigas. Dentre os benefícios do uso do CUADRF como material de reforço estão o aumento da resistência mecânica, da rigidez dos elementos, maior capacidade resistente à fadiga e à corrosão das armaduras, maior capacidade de absorção de energia e redistribuição de esforços, e maior ductilidade. É aplicado um método de empacotamento de partículas para determinação do traço do CUAD a partir da granulometria dos componentes adotados e realizado um estudo experimental para avaliação das propriedades do material obtido por meio de ensaios de resistência à compressão e módulo de elasticidade. É estudada de modo analítico e experimental a aplicação do CUADRF como camada de reforço na região comprimida de vigas de concreto armado superarmadas. Neste caso, é observado que a substituição do cobrimento pelo CUADRF promove ganhos da ordem 45% na capacidade de carga última e de 32% na rigidez à flexão. É possível observar um potencial ganho na ductilidade das vigas devido à redistribuição de esforços internos, mostrando-se um método adequado de reforço estrutural. Foi observado um modo de ruptura pelo descolamento da camada de reforço, indicando a necessidade de atenção quanto ao papel das tensões de cisalhamento neste tipo de reforço. Tal falha pode ser evitada utilizando-se outros métodos para aprimorar a transferência de tensões na interfaceAbstract: Ultra-High Performance Fiber Reinforced Concrete (UHPFRC) is a relatively recent material with exceptional mechanical and durability properties with a wide range of applications in structural engineering. In this work, it is discussed how the application of UHPFRC as a strengthening layer can be a solution for the increase of load bearing capacity and the ductility of reinforced concrete structures. The main properties of UHPFRC in its fresh and hardened state are discussed in order to make explicit its viability as strengthening and rehabilitation material in beams. Among the benefits of using UHPFRC as a strengthening material are: increased mechanical strength, increased stiffness of the elements, improved corrosion protection of the steel reinforcement, greater energy absorption and ductility and greater stress redistribution capacity. It was used a particle packing method to design the mix of the UHPC from the particle size distribution of the concrete components and an experimental study was carried out to evaluate the properties of the material by means of compressive strength and modulus of elasticity tests. The application of the UHPFRC as strengthening layer in the compressed region of over-reinforced concrete beams is studied in analytical and experimental ways. In this case it is observed that the replacement of concrete cover by UHPFRC promotes gains in the order of 45% in the load bearing capacity and 32% in flexural stiffness. It is possible to observe a potential to increase the beam¿s ductility due to the redistribution of internal stresses, proving to be an adequate strengthening technique. In the tests, it was observed a failure due to the debonding of the strengthening layer, indicating a need to pay special attention to the role of shear stresses in strengthened beams. Such failure can be avoided by using different means of bonding between the strengthening layer and the substrateMestradoEstruturas e GeotécnicaMestre em Engenharia Civil88882-435158/2019-01CAPE
Drugs in early clinical development for Systemic Lupus Erythematosus
No full textWhile immunosuppressive therapy has positively impacted the prognosis of systemic lupus erythematosus (SLE), many patients still do not respond to traditional therapy. Thus, active SLE disease remains a significant problem. Furthermore, conventional immunosuppressive treatments for SLE are associated a high risk of side effects. These issues call for improvement in our current therapeutic armamentarium. In this review, the authors highlight the recent developments in therapies for SLE, and present an overview of drugs which are in early clinical development for SLE. There are many new therapeutic approaches being developed, including those focused on B-cell targets, T-cell downregulation, co-stimulatory blockade, anti-cytokine agents, and kinase inhibition, and Toll-like receptor inhibition. They also discuss peptide therapy as a potential method to re-establish immune tolerance, and some of the challenges ahead in developing and testing novel agents for SLE. Many novel agents are currently in development for SLE, but this encouraging news is tempered by several disappointments in clinical trials and provides a timely moment to reflect on the future of therapeutic development in SLE. It seems likely that biological heterogeneity between patients is a major contributor to difficulty in drug design in SLE.255573583CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP300447/2009-4, 471343/2011-0, 302205/2012-8, 473328/2013-5, 304255/2015-72008/02917-0, 2009/06049-6, 2009/15286-
p.Q192R SNP of PON1 seems not to be associated with carotid atherosclerosis risk factors in an asymptomatic and normolipidemic brazilian population sample
No full textEvidências sugerem que a paroxonase 1 (PON1) confere importantes propriedades antioxidantes e antiinflamatórias quando associada à lipoproteína de alta densidade (HDL). Investigar as relações entre o SNP p.Q192R da PON1, parâmetros bioquímicos e aterosclerose carotídea em uma amostra populacional brasileira assintomática e normolipidêmica. Foram estudados 584 voluntários (mulheres, n = 326; homens, n = 258; idade entre 19-75 anos). Foi extraído DNA genômico total e o SNP foi detectado na plataforma de genotipagem TaqMan® SNP OpenArray®(Applied Biosystems, Foster City, CA). Foram dosadas lipoproteínas e apolipoproteínas plasmáticas, e a atividade da PON1 foi medida utilizando-se paraoxon como substrato. Foi utilizada ultrassonografia bidimensional de alta resolução para determinar a espessura íntimo‑medial das artérias carótidas (EIMc) e a presença de placas ateroscleróticas carotídeas em um subgrupo de indivíduos (n = 317). A presença de p.192Q esteve associada a um aumento significativo da atividade da PON1 (RR = 12,30 (11,38); RQ = 46,96 (22,35); QQ = 85,35 (24.83) μmol/min; p < 0,0001), HDL-C (RR = 45 (37); RQ = 62 (39); QQ= 69 (29) mg/dL; p < 0,001) e apo A-1 (RR = 140,76 ± 36,39; RQ = 147,62 ± 36,92; QQ = 147,49 ± 36,65 mg/dL; p = 0,019). A análise de regressãostepwise mostrou que heterozigotos e portadores de p.192Q influenciaram 58% da atividade da PON1 em relação ao paraoxon. A análise de regressão linear univariada demonstrou que não houve associação entre o SNP p.Q192R e a EIMc média; como resultado, na análise de regressão múltipla nenhuma variável foi selecionada com 5% de significância. Os parâmetros estudados não se associaram à presença de placas carotídeas na análise de regressão logística. Em indivíduos de baixo risco, a presença da variante p.192Q daPON1 mostrou-se associada a um perfil lipídico plasmático benéfico e à ausência de aterosclerose de carótida10514552CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP159980/2012-7471380/2008-13Evidences suggest that paraoxonase 1 (PON1) confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL). To investigate the relationships between p.Q192R SNP ofPON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample. We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age). Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA). Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317). The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38); RQ = 46.96 (22.35); QQ = 85.35 (24.83) μmol/min; p < 0.0001), HDL-C (RR= 45 (37); RQ = 62 (39); QQ = 69 (29) mg/dL; p < 0.001) and apo A-I (RR = 140.76 ± 36.39; RQ = 147.62 ± 36.92; QQ = 147.49 ± 36.65 mg/dL; p = 0.019). Stepwise regression analysis revealed that heterozygous and p.192Q carriers influenced by 58% PON1 activity towards paraoxon. The univariate linear regression analysis demonstrated that p.Q192R SNP was not associated with mean cIMT; as a result, in the multiple regression analysis, no variables were selected with 5% significance. In logistic regression analysis, the studied parameters were not associated with the presence of carotid plaques. In low-risk individuals, the presence of the p.192Q variant ofPON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosi
Moments of genome evolution by double cut-and-join
No full textWe study statistical estimators of the number of genomic events separating two genomes under a Double Cut-and Join (DCJ) rearrangement model, by a method of moment estimation. We first propose an exact, closed, analytically invertible formula for the expected number of breakpoints after a given number of DCJs. This improves over the heuristic, recursive and computationally slower previously proposed one. Then we explore the analogies of genome evolution by DCJ with evolution of binary sequences under substitutions, permutations under transpositions, and random graphs. Each of these are presented in the literature with intuitive justifications, and are used to import results from better known fields. We formalize the relations by proving a correspondence between moments in sequence and genome evolution, provided substitutions appear four by four in the corresponding model. Eventually we prove a bounded error on two estimators of the number of cycles in the breakpoint graph after a given number of rearrangements, by an analogy with cycles in permutations and components in random graphs16FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2013/25084-