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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
731

Variação genética do éxon 8 de HLA-G em pacientes críticos

Graebin, Pietra January 2012 (has links)
Pacientes críticos são indivíduos internados em Unidades de Terapia Intensiva (UTI) e se caracterizam por apresentar um quadro patológico crítico e complexo, decorrente de fragilidades fisiológicas graves, podendo evoluir para sepse, sepse severa, choque séptico ou óbito. Muitos recursos financeiros são investidos no controle da sepse em hospitais públicos e privados, e a sepse é a maior causa de morte entre as UTIs brasileiras. O desfecho de um paciente crítico é influenciado por vários fatores, entre eles, os genéticos. A molécula HLA-G apresenta variabilidade proteica limitada e expressão tecidual restrita. A interação entre moléculas de HLA-G e os receptores KIR e LILR desencadeia diversas atividades imunomodulatórias. Na região 3’ UTR localizam-se os polimorfismos +2960INDEL, +3142C>G e +3187A>G que podem regular a expressão de HLA-G. Até o momento, apenas um estudo investigou a expressão de sHLA-G5 em pacientes críticos com choque séptico, e se observou que o aumento dos níveis de sHLA-G5 foram preditivos de sobrevivência entre os pacientes que evoluíram para choque séptico. O objetivo do presente trabalho foi determinar as frequências alélicas do polimorfismo +2960INDEL e dos seguintes SNPs: +3003C>T, +3010C>G, +3027A>C,+3142 C>G e +3187A>G, bem como avaliar a influência dessas variantes na evolução para sepse, choque séptico e óbito entre pacientes críticos. Foram analisadas 698 amostras provenientes de pacientes críticos do Hospital São Lucas – PUCRS. O éxon 8 da região 3’ UTR foi amplificado por PCR e encaminhado para sequenciamento direto (ABI 3730 XL DNA Sequencer). A inferência haplotípica foi determinada pelo software PHASE versão 2.1. A frequência haplotípica, desequilíbrio de ligação (DL), Equilíbrio De Hardy-Weinberg (EHW) e teste de heterozigosidade foram estimados pelo software ARLEQUIN versão 3.5. Os dados foram submetidos ao pacote estatístico SPSS versão 18.0. Observaram-se as seguintes frequências alélicas e genotípicas, respectivamente: +2960INDEL, DEL= 0,578 e IN= 0,421, DELDEL= 0,310, DELIN= 0,536 e ININ= 0,152; +3003C>T, C= 0,109 e T= 0,890, CC= 0,012, CT= 0,194 e TT= 0,793; +3010C>G, CC= 0,521 e G= 0,478, CC= 0,250, CG= 0,540 e GG= 0,208; +3027A>C, A= 0,034 e C= 0,965, AA= 0,001, AC= 0,006 e CC= 0,932; +3035C>T, C= 0,861 e T= 0,141, CC= 0,733, CT= 0,255 e TT= 0,010; +3142C>G, C= 0,463 e G= 0,536, CC= 0,180, CG= 0,565 e GG= 0,253 e +3187A>G, A= 0,699 e G= 0,304, AA= 0,448, AG= 0,503 e GG= 0,048. Os polimorfismos +2960INDEL, +3010C>G, +3142C>G e +3187A>G não corresponderam ao EHW e apresentaram heterozigosidade observada maior do que a esperada. Os dois haplótipos mais frequentes foram DTGCCCG (27,90%) e ITCCCGA (26,65%), confirmando a heterogeneidade da população brasileira. A região 3’ UTR está sob seleção balanceadora, em que a seleção dos heterozigotos pode ser vantajosa, permitindo o balanço entre altas e baixas expressões de HLA-G, conforme o contexto biológico. Todos os sítios polimórficos apresentaram forte DL entre si. Entre os pacientes críticos que evoluíram para sepse, observou-se uma associação entre os portadores do alelo +2960IN e choque séptico (Chi-Square, p= 0,036). Entre os pacientes críticos, observou-se uma associação entre os portadores do haplótipo +2960IN_+3142G_+3187A e choque séptico (Chi-Square, p=0,038). E os pacientes críticos com sepse e portadores do haplótipo +2960IN_+3142G_+3187A (Chi-Square, p=0,023) também foram mais suscetíveis a evoluírem para choque séptico. Observou-se, pela primeira vez, uma associação entre o haplótipo +2960IN_+3142G_+3187A e os desfechos de pacientes críticos. Mais estudos são necessários para confirmação desses resultados e outros parâmetros poderiam ser considerados, como níveis de IL-10 e glicocorticóides endógenos, além do perfil de citocinas liberado por pacientes críticos. Devido às propriedades imunomodulatórias descritas para a molécula de HLA-G, futuramente os seus polimorfismos e sua expressão poderiam ser empregadas em abordagens clínicas nos mais variados contextos imunológicos. A amostra estudada está de acordo com as freqüências alélicas, genotípicas e haplotípicas observadas na população brasileira e novos polimorfismos poderiam ser investigados no éxon 8 da região 3’ UTR do HLA-G. / Critically ill patients are individuals hospitalized in Intensive Care Units (ICU) and are characterized by presenting pathologic complex conditions due to serious physiological weaknesses that may evolve to sepsis, septic shock or even death. Massive resources have been invested in sepsis control both in public and private sectors, although sepsis is still the major cause of death in Brazilians ICUs. Several factors influence the outcome of a critically ill patient, including genetic factors. HLA-G molecule is characterized by limited protein variability and restricted tissue expression. HLA-G binding to KIR and LILR receptors triggers various immunoregulatory activities. The HLA-G gene 3’ UTR presents a 14 bp insertion/deletion at +2960, a SNP at +3142C>G and a SNP at +3187A>G that may regulate HLA-G expression. So far, only one study has investigated HLA-G expression in critically ill patients with septic shock, observing that increased sHLA-G5 levels were predictive of survival among septic shock patients. The aim of this study was to assess the frequencies of 14 pb insertion/deletion polymorphism at +2960INDEL, and the followings SNPs: +3003C>T, +3010C>G, +3027A>C, +3035C>T, +3142C>G and +3187A>G in exon 8 at the 3’ UTR of the HLA-G gene and correlate these variants with different clinical outcomes in critically ill patients. 698 samples were obtained from ICU patients from São Lucas-PUCRS Hospital and the exon 8 at the 3’ UTR of the HLA-G gene was sequenced. The haplotype inference was determinated by PHASE version 2.1 software. Haplotype frequency, linkage disequilibrium (LD), Hardy-Weinberg Equilibrium (HWE) and heterozigosity test were estimated by ARLEQUIN version 3.5 software. The data were submitted to the package SPSS version 18.0 software. The followings allelic and genotypic frequencies were observed, respectively: +2960INDEL, DEL= 0.578 and IN= 0.421, DELDEL= 0.310, DELIN= 0.536 and ININ= 0.152; +3003C>T, C= 0.109 and T= 0.890, CC= 0.012, CT= 0.194 and TT= 0.793; +3010C>G, CC= 0.521 and G= 0.478, CC= 0.250, CG= 0.540 and GG= 0.208; +3027A>C, A= 0.034 and C= 0.965, AA= 0.001, AC= 0.006 and CC= 0.932; +3035C>T, C= 0.861 and T= 0.141, CC= 0.733, CT= 0.255 and TT= 0.010; +3142C>G, C= 0.463 and G= 0.536, CC= 0.180, CG= 0.565 and GG= 0.253 and +3187A>G, A= 0.699 and G= 0.304, AA= 0.448, AG= 0.503 and GG= 0.048. The +2960INDEL, +3010C>G, +3142C>G and +3187A>G polymorphisms were not on HWE and had higher observed heterozygosity than expected. The two most frequent haplotypes were DTGCCCG (27.90%) and ITCCCGA (26.65%). The Brazilian population is a heterogeneous population, and these data agree with this statement. The 3’ UTR is under balancing selection and heterozygote selection is advantageous, allowing the balance between high and low expression of HLA-G, according to the biological context. All polymorphic sites showed strong LD between them. Among critically ill patients who developed sepsis, there was an association between the allele +2960IN and septic shock (Chi-Square, p = 0.036). Among all critically ill patients, there was an association between carriers of the haplotype +2960IN_+3142 G_+3187A and septic shock (Chi-Square, p = 0.038). Critically ill patients with sepsis who carrier the haplotype +2960IN_+3142 G_+3187A were also more susceptible to progression to septic shock (Chi-Square, p = 0.023). For the first time, an association between +2960IN_+3142G_+3187A haplotype and outcomes of critically ill patients was observed. More studies are needed to confirm these results and other parameters could be considered, as IL-10 and endogenous glucocorticoids levels and cytokine profile released by critically ill patients. Because of the immunomodulatory properties described for the HLA-G molecule, in future its polymorphisms and its expression could be used in clinical approaches in various immune contexts. These results are according to allelic, genotypic and haplotypic frequencies observed in Brazilian population, and new polymorphisms could be investigated in exon 8 at the 3 'UTR of HLA-G gene.
732

Genomic context analytics of genes for universal stress proteins from petroleum-degrading Alcanivorax

Kashim, Zainab Abimbola 08 1900 (has links)
Alcanivorax species are gram negative bacteria that usually require aliphatic hydrocarbon as the sole carbon source for growth. The ability to use petroleum in polluted environments as energy source makes Alcanivorax species biotechnologically relevant in bioremediation. Universal stress proteins confer ability to respond to unfavourable environments, thus the present study was done to analyse the genomic context of genes for universal stress proteins in Alcanivorax genomes. A combination of bioinformatics and visual analytics approaches were used to analyze genome-enabled data including sequences and gene expression datasets. On the basis of transcription unit and adjacent genes, two types of Alcanivorax USP genes observed were (i) adjacent to cyclic nucleotide-binding and oxygen sensing functions; and (ii) adjacent to sulfate transporter function. Both types of genes encode two universal stress protein domains (pfam00582) also referred to as tandem-type universal stress proteins. The sequence and structural characteristics of each of the four USP domains in Alcanivorax needs to be further investigated. This dissertation research evaluated data from Alcanivorax borkumensis cells (grown on either pyruvate or hexadecane as carbon source) that were stressed with 1-octanol and data collected at 15 min, 30 min, 60 min and 90 min after 1-octanol addition. The two genes for Alcanivorax borkumensis SK2 universal stress proteins, ABO_1340 and ABO_1511, had the same direction of expression for adjacent genes. A limitation of this research was that findings based on bioinformatics and visual analytics methods may need confirmation by molecular methods. The differences observed may also reflect the quality of the annotations provided for genes. The sequence and structural characteristics of each of the four USP domains in Alcanivorax needs to be further investigated. Further research is needed on the relationship between number, length and order of genes in operons that include genes for universal stress proteins. Additionally, in vitro studies to confirm the functional prediction made from the genomic context of the universal stress protein in Alcanivorax genome. The knowledge discovered from this genome context analytics research could contribute to improving the performance of Alcanivorax species in bioremediation of environments polluted with petroleum / College of Agriculture and Environmental Sciences / M. Sc. (Environmental Science)
733

Hypoxic gene regulation and high-throughput genetic mapping

Baird, Nathan Alder, 1979- 03 1900 (has links)
xi, 52 p. ; ill. (some col.) A print copy of this title is available through the UO Libraries under the call number: SCIENCE QH445.2 .B35 2008 / Activation of Heat shock proteins (Hsps) is critical to adaptation to low oxygen levels (hypoxia) and enduring the oxidative stress of reoxygenation. Hsps are known to be regulated by Heat shock factor (Hsf), but my results demonstrate an unexpected regulatory link between the oxygen sensing and heat shock pathways. Hsf transcription is upregulated during hypoxia due to direct binding by Hypoxia-inducible Factor-1 (HIF-1) to HIF-1 response elements in an Hsf intron. This increase in Hsf transcripts is necessary for full Hsp induction during hypoxia and reoxygenation. The HIF-1-dependent increase in Hsps has a functional impact, as reduced production of Hsps decreases viability of adult flies exposed to hypoxia and reoxygenation. Thus, HIF-1 control of Hsf transcriptional levels is a regulatory mechanism for sensitizing heat shock pathway activity in order to maximize production of protective Hsps. This cross-regulation represents a mechanism by which the low oxygen response pathway has assimilated complex new functions by regulating the heat shock pathway's key transcriptional activator. Beyond studying the regulation of specific genes. I have also developed a method to identify small, yet important, changes within entire genomes. Genetic variation is the foundation of phenotypic traits, as well as many disease states. Variation can be caused by inversions, insertions, deletions, duplications, or single nucleotide polymorphisms (SNPs) within a genome. However, identifying a genetic change that is the cause of a specific phenotype or disease has been a difficult and laborious task for researchers. I developed a technique to quickly and accurately map genetic changes due to natural phenotypic variation or produced by genetic screens. I utilized massively parallel, high-throughput sequencing and restriction site associated DNA (RAD) markers, which are short tags of DNA adjacent to the restriction sites. These RAD markers generate a genome-wide signature of fragments for any restriction enzyme. Taken together with the fact that the vast majority of organisms have SNPs that disrupt restriction site sequences, the differences in the restriction fragment profiles between individuals can be compared. In addition, by using bulk segregant analysis, RAD tags can be used as high-density genetic markers to identify a genetic region that corresponds to a trait of interest. This dissertation includes both previously published and unpublished co-authored materials. / Adviser: Eric Johnson
734

A nonlinear investigation of corrugation instabilities in magnetic accretion shocks

Ernst, Scott 03 1900 (has links)
xi, 172 p. : ill. (some col.) / Accretion shock waves are present in many important astrophysical systems and have been a focus of research for decades. These investigations provide a large body of understanding as to the nature, characteristics, and evolutionary behaviors of accretion shock waves over a wide range of conditions. However, largely absent are investigations into the properties of accretion shock waves in the presence of strong magnetic fields. In such cases these strong magnetic fields can significantly alter the stability behaviors and evolution of the accretion shock wave through the production and propagation of magnetic waves as well as magnetically constrained advection. With strong magnetic fields likely found in a number of accretion shock systems, such as compact binary and protostellar systems, a better understanding of the behaviors of magnetic accretion shock waves is needed. A new magnetohydrodynamics simulation tool, IMOGEN, was developed to carry out an investigation of instabilities in strong, slow magnetic accretion shocks by modelling their long-term, nonlinear evolution. IMOGEN implements a relaxed, second-order, total variation diminishing, monotonic upwind scheme for conservation laws and incorporates a staggered-grid constrained transport scheme for magnetic advection. Through the simulated evolution of magnetic accretion shocks over a wide range of initial conditions, it has been shown, for sufficiently high magnetic field strengths, that magnetic accretion shocks are generally susceptible to corrugation instabilities, which arise in the presence of perturbations of the initial shock front. As these corrugation instabilities grow, they manifest as magnetic wave propagation in the upstream region of the accretion column, which propagate away from the accretion shock front, and as density columns, or fingers, that grow into the higher density downstream flow, defined and constrained by current loops created during the early evolution of the instability. / Committee in charge: Dr. James Schombert, Chair; Dr. James Imamura, Advisor; Dr. Alan Rempel, Member; Dr. John Toner, Member; Dr. Kent Stevens, Outside Member
735

Analysis of heat shock protein genes expression in spruce bark beetle \kur{Ips typographus} and their importance for survival upon exposure to heat

ŠVEHLOVÁ, Kateřina January 2011 (has links)
The aim of this work was to examine the expression of certain Hsp genes upon heat exposure in spruce bark beetle Ips typographus. We determined the level in unstressed and heat-exposed animals, and attempted to assess the importance of Hsp proteins for animals' survival upon heat treatment. We used RNA interference to knock down the expression of these genes, and analyzed the influence on animals exposed to elevated temperatures.
736

Interlucina 12, procalcitonina e protína C - reativa em crianças com sepse e choque séptico

Martin, Joelma Gonçalves [UNESP] 26 May 2009 (has links) (PDF)
Made available in DSpace on 2014-06-11T19:32:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-05-26Bitstream added on 2014-06-13T18:43:12Z : No. of bitstreams: 1 martin_jg_dr_botfm.pdf: 229557 bytes, checksum: 8ac04c0bae3f323bc75baa932f60ad46 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Problemas com diagnóstico de sepse são indicativos da necessidade de enfocar mediadores bioquímicos capazes, não somente de distinguir as diferentes causas de inflamação, mas também de indicar a gravidade dos pacientes. Avaliar o comportamento da Interleucina-12 (IL-12), proteína C-reativa (PCR), e procalcitonina (PCT) e sua utilidade em diferenciar crianças com sepse e quadros correlatos. Crianças sépticas foram incluídas prospectivamente e divididas em dois subgrupos: sepse (GS; n=46) e choque séptico (GCS; n=41). IL-12, PCR e PCT foram medidas à admissão (T0) e 12 horas mais tarde (T12h). Valores de PCT foram classificados como: sepse improvável, sepse possível, infecção bacteriana complicada por inflamção sistêmica e choque séptico. A gravidade da doença foi medida pelo escore PRISM. Em T0, houve uma maior frequência de crianças com choque séptico com níveis mais elevados de PCT, quando comparados com o grupo sepse [GCS: 30 (69,7%) > GS: 14 (29,8%); p < 0,05], o mesmo ocorrendo em T12h. PRISM foi maior para os pacientes do GCS do que do GS. Em T12h, os níveis de IL-12 foram maiores no GCS [T12: 1,32 (0-61.0) > T0: 0,24 (0-226,43; p= 0,018]. Os níveis de PCR não foram diferentes entre os grupos ou tempos de coleta. PCT parece ser útil no diagnóstico precoce de sepse e choque séptico, sendo relacionada com a gravidade da doença. PCR e IL-12 não diferenciaram sepse e choque séptico. / Problems with sepsis diagnosis are indications of the need to focus on biochemical mediators capable not only of distinguishing the different causes of inflammation, but also of indicating the severity of patients. Objectives: To examine the behavior of interleukin-12 (IL-12), C-reactive protein (CRP), and procalcitonin (PCT) and the utility of them to differentiate children with septic conditions. Methods: Septic children, prospectively enrolled, were divided into sepsis (SG; n = 47) and septic shock (SSG; n = 43) groups. IL-12, PCT and CRP were measured at admission (T0) and 12 hours later (T12). Values of PCT were ranked as: unlikely sepsis; possible sepsis; systemic inflammation; septic shock. Disease severity was assessed by PRISM score. Results: At T0, there was a higher frequency of SSG with higher PCT compared with SG [SSG: 30 (69.7%) > SG: 14 (29.8%); p < 0.05], similarly at T12h. PRISM was higher for SSG patients with higher PCT than SG patients. At T12, IL-12 levels were higher in SSG [T12: 1,32 (0 – 61,0) > T0: 0,24 (0 – 226,43); p = 0,018]. CRP levels were not different for groups and moments. Conclusions: PCT appears to be helpful in early diagnosis of pediatric septic conditions, being related to disease severity. CRP and IL-12 did not differentiate septic conditions.
737

Dynamics of Blast Wave and Cellular H2-Air Flame Interaction in a Hele-Shaw Cell

La Flèche, Maxime 24 September 2018 (has links)
The present thesis investigates the interaction of a shock wave with a cellular flame and the ensuing mechanisms on the dynamics of the subsequent flame deformation. The inter- action is known to disrupt the flame surface through the Richtmyer-Meshkov instability, hence potentially enhancing the local combustion rates. This study aims to clarify the evolution of a flame when perturbed head-on by a shock wave. Two novel series of experiments were conducted in a vertically-oriented Hele-Shaw cell, which could successfully isolate a quasi-bidimensional cellular flame structure at ambient conditions. In the first configuration, the passage of the shock wave arising in the burned products of a deflagration wave was investigated, while both waves propagated in the same outward direction. In the other configuration, the shock wave centrally emerged in the unburned gases and collided with a cellular flame front traveling in the opposite direction. The event was captured using a Z-type Schlieren imaging system to visualize the growth of the flame cells. Shock characterization was determined in the Hele-Shaw apparatus to estimate the strength of the blast wave generated by energy deposition using a high-voltage igniter or by decoupled detonation from a detonation tube. A combustion study was also performed to determine the laminar flame speed in a mixture of hydrogen-air according to different equivalence ratios in the apparatus. The experiments revealed that inherent cellular flame instabilities are well developed in the observation scale of the Hele-Shaw geometry. The shock-flame complex was therefore analyzed experimentally for selected mixtures. As the shock wave traversed the interface separating the burned and unburned gases, the flame became more corrugated. Following the interaction, the flame cusps were stretched and/or flattened. At later times, the wrinkled interface was reversed and developed finer scales. A time scale analysis was performed to identify the contribution of the competing effects of Richtmyer-Meshkov and Rayleigh-Taylor instabilities on the flame interface deformation. For the case of a shock wave traversing the flame interface from the unburned to the burned side, the early perturbations were mainly governed by the Richtmyer-Meshkov instability. Finally, Rayleigh-Taylor instability resulted from the decaying pressure profile of the blast wave and tended to stabilize the perturbed interface to eventually reverse the cellular structure. Experimental and inert numerical results on the flame cell’s amplitude growth were found to be in good agreement.
738

Shock Metamorphism in Ordinary Chondrites: Constraining Pressure and Temperature History

January 2016 (has links)
abstract: Shock metamorphism in meteorites constrains the impact histories of asteroids and planets. Shock-induced high-pressure (HP) minerals can provide more precise estimates of shock conditions than shock-induced deformation effects. In this research, I use shock features, particularly HP minerals, in ordinary-chondrite samples to constrain not only shock pressures but also the pressure-temperature-time (P-T-t) paths they experienced. Highly shocked L5/6 chondrites Acfer 040, Mbale, NWA 091 and Chico and LL6 chondrite NWA 757 were used to investigate a variety of shock pressures and post-shock annealing histories. NWA 757 is the only highly shocked LL chondrite that includes abundant HP minerals. The assemblage of ringwoodite and majoritic garnet indicates an equilibration shock pressure of ~20 GPa, similar to many strongly shocked L chondrites. Acfer 040 is one of the only two chondrite samples with bridgmanite (silicate perovskite), suggesting equilibration pressure >25 GPa. The bridgmanite, which is unstable at low-pressure, was mostly vitrified during post-shock cooling. Mbale demonstrates an example of elevated post-shock temperature resulting in back-transformation of ringwoodite to olivine. In contrast, majoritic garnet in Mbale survives as unambiguous evidence of strong shock. In these two samples, HP minerals are exclusively associated with shock melt, indicating that elevated shock temperatures are required for rapid mineral transformations during the transient shock pulse. However, elevated post-shock temperatures can destroy HP minerals: in temperature sequence from bridgmanite to ringwoodite then garnet. NWA 091 and Chico are impact melt breccias with pervasive melting, blackening of silicates, recrystallization of host rock but no HP minerals. These features indicate near whole-rock-melting conditions. However, the elevated post-shock temperatures of these samples has annealed out HP signatures. The observed shock features result from a complex P-T-t path and may not directly reflect the peak shock pressure. Although HP minerals provide robust evidence of high pressure, their occurrence also requires high shock temperatures and rapid cooling during the shock pulse. The most highly shocked samples lack HP signatures but have abundant high-temperature features formed after pressure release. / Dissertation/Thesis / Doctoral Dissertation Geological Sciences 2016
739

Characterization of the Dynamic Strength of Aluminium at Extreme Strain Rates and Pressures

January 2017 (has links)
abstract: The study of response of various materials to intense dynamic loading events, such as shock loading due to high-velocity impacts, is extremely important in a wide variety of military and industrial applications. Shock loading triggers extreme states, leading to high pressures and strain rates, and neglecting strength is a typical approximation under such conditions. However, recent results have shown that strength effects are larger than expected, so they must be taken into account. Recently, hydrodynamic instabilities, the most common being the Rayleigh-Taylor (RTI) and Richtmyer-Meshkov (RMI) instabilities, have been used to infer the dynamic strength of materials at high pressure conditions. In our experiments and simulations, a novel RMI approach is used, in which periodic surface perturbations are made on high purity aluminium target, which was laser ablated to create a rippled shock front. Due to the slow linear growth rate of RMI, the evolution of the perturbations on the back surface of the sample as a result of the rippled shock can be measured via Transient Imaging Displacement Interferometry (TIDI). The velocity history at the free surface was recorded by spatially resolved laser velocimetry. These measurements were compared with the results from the simulations, which were implemented using rate independent and rate dependent material models, to characterize the dynamic strength of the material. Simulations using the elastic-perfectly plastic model, which is rate independent, failed to provide a value of dynamic yield strength that would match experimental measurements of perturbation amplitudes. The Preston-Tonks-Wallace (PTW) model, which is rate dependent model, worked well for aluminium. This model was, in turn, used as a reference for calibrating the rate dependent Steinberg-Lund model and the results from simulations using the calibration models were also compared to experimental measurements. / Dissertation/Thesis / Masters Thesis Mechanical Engineering 2017
740

Associação das HSP 60 e 70 com fatores de risco cardiovascular em mulheres na pós-menopausa tratadas de câncer de mama. / High Risk for Cardiovascular Disease in Postmenopausal Breast Cancer Survivors.

Buttros, Daniel de Araújo Brito 19 April 2018 (has links)
Submitted by Daniel De Araujo Brito Buttros (danielbuttros@hotmail.com) on 2018-06-14T10:28:06Z No. of bitstreams: 1 DOUTORADO DANIEL BUTTROS.pdf: 8920662 bytes, checksum: 8d3d25caa8f04b9c86ef89d60f2cab83 (MD5) / Approved for entry into archive by Sulamita Selma C Colnago null (sulamita@btu.unesp.br) on 2018-06-14T17:51:10Z (GMT) No. of bitstreams: 1 buttros_dab_dr_bot.pdf: 8920662 bytes, checksum: 8d3d25caa8f04b9c86ef89d60f2cab83 (MD5) / Made available in DSpace on 2018-06-14T17:51:10Z (GMT). No. of bitstreams: 1 buttros_dab_dr_bot.pdf: 8920662 bytes, checksum: 8d3d25caa8f04b9c86ef89d60f2cab83 (MD5) Previous issue date: 2018-04-19 / Objetivo: Avaliar os fatores de risco cardiovascular em mulheres na pós-menopausa tratadas de câncer de mama comparadas a mulheres na pós-menopausa sem câncer de mama e a associação das heat shock proteins (HSP) 60 e 70 com o câncer de mama em mulheres na pós-menopausa. Métodos: Realizou-se estudo clínico de corte transversal com 96 mulheres tratadas de câncer de mama comparadas a 192 mulheres na pós-menopausa (controle), com idades entre 45 e 75 anos. Foram incluídas no grupo principal mulheres com amenorréia > 12 meses e idade ≥ 45 anos, com diagnóstico histológico de câncer de mama, sem doença metastática e sem doença cardiovascular (DCV) estabelecida. O grupo controle foi constituído por mulheres com amenorréia > 12 meses, idade ≥ 45 anos, sem câncer de mama e DCV. Os grupos foram pareados por idade, tempo de menopausa e índice de massa corpórea (IMC) na proporção 1 caso para 2 controles, conforme cálculo amostral, com o mínimo de 92 pacientes tratadas de câncer de mama. Dados clínicos e antropométricos (IMC e circunferência da cintura) foram coletados por meio de entrevista e exame físico. Para análise bioquímica foram solicitados colesterol total, HLD, LDL, triglicerídeos, glicose e insulina. Foram consideradas com síndrome metabólica (SM), as mulheres que apresentaram três ou mais critérios diagnósticos: circunferência da cintura (CC) > 88 cm; TG ³ 150 mg/dL; HDL colesterol < 50 mg/dL; pressão arterial ³ 130/85 mmHg; glicose ³ 100 mg/dL. Para determinação das concentrações plasmáticas de HSP 60 e 70 foram empregados imunoensaios pela técnica de ELISA. A doença aterosclerótica foi determinada pela espessura do complexo médio-intimal (CMI > 1mm) das artérias carótidas e/ou pela presença de placa ateromatosa, avaliadas pela ultrassonografia carotídea (scanner 14 duplex). Para análise estatística foram empregados: Teste t-student, Distribuição Gama (variáveis assimétricas), Teste do Qui-Quadrado e Regressão Logística (odds ratio-OR). Resultados: A média de idade das pacientes tratadas de câncer de mama foi de 59,8 ± 9,0 anos com tempo médio de seguimento de 4,2 ± 2,0 anos. Na comparação entre os grupos, mulheres tratadas de câncer de mama apresentaram valores médios elevados da pressão sistólica e diastólica (p<0.001) e valores médios de triglicerídeos e glicose, acima dos valores desejáveis (p<0.05). As pacientes do grupo principal apresentaram valores mais altos de HSP 60 e mais baixos de HSP 70 quando comparados ao controle (p<0.05). Foi observada maior ocorrência de diabetes, SM e placa ateromatosa entre as mulheres tratadas de câncer mama quando comparadas ao controle (19,8% vs 6,8%; 54,2% vs 30,7%; 19.8% vs 9.4%, respectivamente) (p<0.05). Na análise de risco ajustado para idade, tempo de menopausa e IMC, as mulheres tratadas de câncer de mama apresentaram risco significativamente aumentado para SM (OR=4.21; IC 95% 2.28-7.76), presença de placa ateromatosa (OR=2.61; IC 95% 1.19-5.72), diabetes (OR=4.42; IC 95% 1.86-10.49), hipertrigliceridemia (OR=2.32; IC 95% 1.33-4.0) e circunferência de cintura aumentada (OR=11.22; IC 95% 4.0 – 31.65), quando comparadas as mulheres sem câncer de mama. Conclusão: Mulheres tratadas de câncer de mama apresentaram maior risco para síndrome metabólica, diabetes, doença aterosclerótica, hipertrigliceridemia e obesidade abdominal, importantes fatores de risco para doença cardiovascular, quando comparadas as mulheres na pós-menopausa sem câncer de mama. Assim como, mulheres tratadas de câncer de mama apresentaram valores elevados de HSP 60 e diminuídos de HSP 70 quando comparadas às mulheres sem câncer. / To evaluate cardiovascular risk factors in postmenopausal breast cancer survivors as compared to postmenopausal women without breast cancer and the association of heat shock proteins (HSP) 60 and 70 with breast cancer in postmenopausal women. Methods: In this cross-sectional study, 96 postmenopausal breast cancer survivors were compared with 192 postmenopausal women (controls), aged 45 to 75 years. The principal group included women with amenorrhea > 12 months and age ≥45 years, with histological diagnosis of breast cancer, without metastatic disease and without established cardiovascular disease (CVD). The control group consisted of women with amenorrhea > 12 months, age ≥45 years, without breast cancer and CVD. The groups were matched by age, time since menopause, and body mass index (BMI) in the proportion 1 case for 2 controls, according to the sample calculation, with a minimum of 92 breast cancer survivors. Clinical and anthropometric data (BMI and waist circumference) were collected by interview and physical examination. For biochemical analysis, total cholesterol, HLD, LDL, triglycerides, glucose and insulin levels were measured. Women who presented three or more of the following criteria were diagnosed as having metabolic syndrome (MetS): waist circumference (WC)> 88 cm; TG≥ 150 mg/dL; HDL cholesterol <50 mg/dL; blood pressure ≥ 130/85 mmHg; glucose ≥ 100 mg/dL. For measuring plasma concentrations of HSP 60 and 70, immunoassays by ELISA technique were used. Atherosclerotic disease was determined by the intima-media thickness (IMT> 1mm) of the carotid arteries and / or by the presence of atheromatous plaque, assessed by carotid ultrasound (scanner duplex). For statistical nalysis, Student's t-test, Gamma Distribution (asymmetric variables), Chi-Square Test, and Logistic Regression (odds ratio-OR) were used. Results: The mean (± SD) age of breast cancer survivors was 59.8 ± 9.0 years, with a mean (± SD) follow-up of 4.2 ± 2.0 years. The breast cancer survivors presented high mean values of systolic and distal pressure (p <0.001), and mean values of triglycerides and glucose, above the desirable values (p <0.05). Patients with breast cancer had higher levels of HSP 60 and lower HSP 70 when compared to control (p <0.05). There was a higher occurrence of diabetes, MetS, and atheromatous plaque among the breast cancer survivors when compared to the control group (19.8% vs 6.8%, 54.2% vs. 30.7%, 19.8% vs. 9.4% respectively) (p <0.05). In the risk analysis adjusted for age, time since menopause and BMI, women treated for breast cancer had a significantly increased risk for MetS (OR = 4.21, 95% CI 2.28-7.76), presence of atheromatous plaque (OR = 2.61, CI 95% CI 1.19-5.72), diabetes (OR=4.42; IC 95% 1.86-10.49), hypertriglyceridemia (OR = 2.32, 95% CI 1.33-4.0) and large waist circumference (OR = 11.22, 95% CI 4.0 - 31.65 ) when compared to women without breast cancer. Conclusion: Postmenopausal breast cancer survivors had a higher risk for metabolic syndrome, diabetes, atherosclerotic disease, hypertriglyceridemia and abdominal obesity, important risk factors for cardiovascular disease when compared to postmenopausal women without breast cancer. Similarly, women treated for breast cancer presented high levels of HSP 60 and decreased HSP 70 when compared to women without cancer.

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