The purpose of this analysis is to evaluate the usefulness of Fourier Transform Infrared (FTIR) spectroscopy in the detection of Herpes Simplex Virus 1 (hsv1) infection at an early stage. The raw absorption values were standardized to eliminate inter-sampling error. Wilcoxon-Mann-Whitney (WMW) statistic's Z score was calculated to select significant spectral regions. Partial least squares modeling was performed because of multicollinearity. Kolmogorov-Smirnov statistic showed models for healthy tissues from different time groups were not from same distribution. The additional 24 hour dataset was evaluated using the following methods. Variables were selected by WMW Z score. Difference of Composites statistic, DC, was created as a disease indicator and evaluated using area under the ROC curve, specificities, and confidence intervals using bootstrap algorithm. The specificity of DC was high, however the confidence intervals were large. Future studies are required with larger sample sizes to test this statistic's usefulness.

Background: Aortic stenosis (AS) is the most common heart valve disease in Europe and North America. Age-related calcification of the valve is the commonest cause of acquired AS, especially in patients older than 70 years.Conventional surgical aortic valve replacement (SAVR) and the novel, minimally invasive transcatheter aortic valve implantation (TAVI), effectively preserve left ventricular (LV) function, relieve symptoms and improve survival in patients with severe symptomatic AS. However, patients with impaired LV function may carry significant operative risk, and long recovery time. In addition, such patients might have other comorbidities, and hence adding another challenge. Thus evaluation of ventricular function before and after AVR, as well as critical evaluation of TAVI patients should contribute to better clinical outcome. Methods: We studied LV function by conventional echocardiography before and after SAVR in the following groups; (I) 86 patients (aged 71±10 years) with severe AS and LV dysfunction; (II) 112 consecutive elderly AS patients (aged 77±2 years) and compared them with 72 younger patients (aged 60±1 years); (III)66 patients (age 70±2 years, 53 male) who underwent AVR for severe AS with concurrent LV dysfunction; (IV) 89 consecutive patients with symptomatic severeAS who underwent successful TAVI, 45 of whom received trans-apical TAVI (TA)(age 80.8±4.9 year, 26 male) and 44 trans-femoral TAVI (TF) (age 82.9±5.8 year,22 male).The conventional echocardiographic measurements were made according to the guidelines. Severe AS was identified by aortic valve mean pressure gradient >40mmHg or valve area <1.0 cm2. LV systolic dysfunction was identified as ejection fraction (EF) <50%. LV long-axis function was presented by mitral annular plane systolic excursion ( MAPSE ) at lateral wall and septal wall, which were measured from apical four-chamber view. Also from the same view, LV septal and lateral wall deformation using STE as well as global longitudinal systolic strain. The LV systolic twist as the net difference between apical rotation and basal rotation was measured from the parasternal apical and basal short-axis views in the TAVI patients. Results: Study I: In the low flow and high gradient group, operative (30-day) mortality was 10%, and peri-operative mortality was associated with lower mean LVEF, higher mitral E:A ratio, peak systolic pulmonary artery pressure (PSPAP), and higher serum creatinine (all p<0.001), NYHA class III–IV, concomitant coronary artery bypass graft (CABG), urgent surgery, and longer bypass-time (all p< 0.05). Mortality at 4 years was 17%. Univariate predictors of 4-year mortality were: lower EF (p<0.001), presence of restrictive LV filling (p<0.001), raised PSPAP (p<0.001) and CABG (p=0.037). However, only EF<40 % (p=0.03), the presence of restrictive LV filling (p=0.033) and raised PSPAP (p<0.01)independently predicted mortality in this group.Study II: Elderly patients had higher NYHA class, more frequent atrial fibrillation (AF), coronary artery disease (CAD), emergency operation and use of bioprosthetic valves. They also had shorter E-wave deceleration time (DT) and larger left atria (LA) (p<0.05 for all). 30-day mortality was 12% vs 4 % (Log Rank x2=3.02, p=0.08) and long term mortality was 18% vs 7% (Log Rank x2=4.38,p=0.04) in the two groups, respectively. Age was not related to mortality after adjustment for other variables. Among all variables, anemia (OR 4.20, CI:1.02–6.86, p=0.04), cardiopulmonary bypass (CPB) time (OR 1.02, CI 1.01–1.04,p<0.01), significant patient prosthesis mismatch (PPM) (OR 5.43, CI 1.04–18.40,p<0.05) were associated with 30-day mortality in elderly patients. Their long-term mortality was related to CBP time (OR 1.02, CI 1.00–1.05, p=0.04),PPM (OR 4.64, CI 1.33–16.11, p=0.02) and raised LA pressure: DT (OR 0.94, CI0.84–0.99, p=0.03) and pulmonary artery systolic pressure (PASP) (OR 1.12, CI1.03–1.19, p<0.001).STUDY III: Following SAVR peak aortic pressure gradient (AOPG) decreased and indexed valve area increased (64±3 to 19±1 mmHg and 0.30±0.01 to 0.89±0.03 cm2/m2, p<0.001 for both). LVEF increased (from 45±1 to 54±2%;p<0.001), LV end diastolic and end-systolic dimensions fell (LVEDD index: from 33±1 to 30±1 mm/m2; and LVESD index: from 27±1 to 20±1 mm/m2; (p<0.01 forboth). LV diastolic dysfunction improved as evidenced by the fall in E/A ratio (from 2.6±0.2 to 1.9±0.4) and prolongation of total filling time; (from 29.2±0.6 to31.4±0.5 s/min, p=0.01 for both). Among all echocardiographic variables, LV dimensions (LVEDD index, OR 0.70, CI 0.52–0.97, p<0.05; LVESD index, OR 0.57, CI 0.40–0.85, p=0.005) were the two independent predictors of post-operative LV functional recovery on multivariate analysis. A cut-off value ofpre-operative LVESD index<=27.5 mm/m2 was 85% sensitive and 72% specific inpredicting intermediate-term recovery of LV function after AVR (AUC, 0.72, p=0.002). STUDY IV: Before TAVI, there was no difference between the two patient groups in gender, age, body surface area (BSA) and baseline LV function. However, left ventricular mass index (LVMi), left atrial volume index (LAVi) and tricuspid regurgitation pressure drop (TRPdrop) were increased in the TA group (p<0.05).One week after TAVI, aortic pressure gradient (AOPG) markedly dropped in thetwo groups (both p<0.001), LVEDD index and LVESD index fell but EF andmyocardial strain remained unchanged. Overall cavity twist reduced (p<0.048).Significant LVESD index reduction was only seen in TF group (p=0.02) with a slight increase in LVEF (p=0.04). Lateral MAPSE increased only in the TF group(p=0.02). LV longitudinal systolic strain remained unchanged in TA patients while apical lateral strain increased in TF group. LV apical rotation fell in the two groups but basal rotation increased only in the TA patients (p=0.02). LAVi reduced in bothgroups and to a greater extent in TF TAVI (p=0.006), as did TRPdrop (p<0.001). Conclusion: SAVR and TAVI are two effective treatments for severe AS patients.The severity of pre-operative systolic and diastolic LV dysfunction is the major predictor of mortality following SAVR for low-flow and high gradient AS.Peri-operative AVR survival is encouraging in the elderly. Long term mortality in the elderly is related to PPM, LV diastolic dysfunction and secondary pulmonary hypertension. LV functional recovery was evident in most patients with LV dysfunction after SAVR. A lower prevalence of LV functional recovery in patients with large pre-operative LVESD index might signify the loss of contractile reserveand thus predict post-operative functional recovery. TAVI results in significant early improvement of segmental and overall ventricular function, particularly in patients receiving the trans-femoral approach. The delayed recovery of the trans-apical TAVI group, we studied, might reflect worse pre-procedural diastolic cavity function.

Understanding variability of heath status is highly likely to be an important component of personalized medicine to predict health status of individuals and to promote personal health. Evidences of Genome Wide Association Study and gene expression study indicating that genetic factors affect the risk susceptibility of individuals have suggested adding genetic factors as a component of health status measurements. In order to validate or to predict health risk status with collected personal data such as clinical measurements or genomic data, it is important to have a well-established profile of diseases. The primary effort of this work was to find genomic evidence relevant to coronary artery disease. Two major methods of genomic analysis, gene expression profiling and GWAS on gene expression, were performed to dissect transcriptional and genotypic fingerprints of coronary artery disease. Blood-informative transcriptional Axes that can be described by 10 covariating transcripts per each Axis were utilized as a crucial measure of gene expression analysis. This study of the relationship between gene expression variation and various measurements of coronary artery disease delivered compelling results showing strong association between two transcriptional Axes and incident of myocardial infarction. 244 transcripts closely correlated with death by cardiovascular disease related events were also showing clear association with those two transcriptional Axes. These results suggest potential transcripts for use in risk prediction for the advent of myocardial infarction and cardiac death.

Submitted by Aelson Maciera (aelsoncm@terra.com.br) on 2017-08-16T20:00:07Z No. of bitstreams: 1 DissDMBS.pdf: 821487 bytes, checksum: 497fc9b102478d03042a1c3d10a45c19 (MD5) / Approved for entry into archive by Ronildo Prado (bco.producao.intelectual@gmail.com) on 2018-01-29T18:10:09Z (GMT) No. of bitstreams: 1 DissDMBS.pdf: 821487 bytes, checksum: 497fc9b102478d03042a1c3d10a45c19 (MD5) / Approved for entry into archive by Ronildo Prado (bco.producao.intelectual@gmail.com) on 2018-01-29T18:10:17Z (GMT) No. of bitstreams: 1 DissDMBS.pdf: 821487 bytes, checksum: 497fc9b102478d03042a1c3d10a45c19 (MD5) / Made available in DSpace on 2018-01-29T18:14:39Z (GMT). No. of bitstreams: 1 DissDMBS.pdf: 821487 bytes, checksum: 497fc9b102478d03042a1c3d10a45c19 (MD5) Previous issue date: 2017-06-13 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Regression models for binary response variables are very common in several areas of knowledge. The most used model in these situations is the logistic regression model, which assumes that the logit of the probability of a certain event is a linear function of the predictors variables. When this assumption is not reasonable, it is common to make some changes in the model, such as: transformation of predictor variables and/or add quadratic or cubic terms to the model. The problem with this approach is that it hinders parameter interpretation, and in some areas it is fundamental to interpret the parameters. Thus, a common approach is to categorize the quantitative covariates. This work aims to propose two new classes of categorization methods for continuous variables in binary regression models. The first class of methods is univariate and seeks to maximize the association between the response variable and the categorized covariate using measures of association for qualitative variables. The second class of methods is multivariate and incorporates the predictor variables correlation structure through the joint categorization of all covariates. To evaluate the performance, we applied the proposed methods and four existing categorization methods in 3 credit scoring databases and in two simulated cenarios. The results in the real databases suggest that the proposed univariate class of categorization methods performs better than the existing methods when we compare the predictive power of the logistic regression model. The results in the simulated databases suggest that both proposed classes perform better than the existing methods. Regarding computational performance, the multivariate method is inferior and the univariate method is superior to the existing methods. / Modelos de regressão para variáveis resposta binárias são muito comuns em diversas áreas do conhecimento. O modelo mais utilizado nessas situações é o modelo de regressão logística, que assume que o logito da probabilidade de ocorrência de um dos valores da variável resposta é uma função linear das variáveis preditoras. Quando essa suposição não é razoável, algumas possíveis alternativas são: realizar transformação das variáveis preditoras e/ou inserir termos quadráticos ou cúbicos no modelo. O problema dessa abordagem é que ela dificulta bastante a interpretação dos parâmetros do modelo e, em algumas áreas, é fundamental que eles sejam interpretáveis. Assim, uma abordagem muitas vezes utilizada é a categorização das variáveis preditoras quantitativas do modelo. Sendo assim, este trabalho tem como objetivo propor duas novas classes de métodos de categorização de variáveis contínuas em modelos de regressão para variáveis resposta binárias. A primeira classe de métodos é univariada e busca maximizar a associação entre a variável resposta e a covariável categorizada utilizando medidas de associação para variáveis qualitativas. Já a classe de métodos multivariada tenta incorporar a estrutura de dependência entre as covariáveis do modelo através da categorização conjunta de todas as variáveis preditoras. Para avaliar o desempenho, aplicamos as classes de métodos propostas e quatro métodos de categorização existentes em 3 bases de dados relacionadas à área de risco de crédito e a dois cenários de dados simulados. Os resultados nas bases reais sugerem que a classe univariada proposta têm um desempenho superior aos métodos existentes quando comparamos o poder preditivo do modelo de regressão logística. Já os resultados nas bases de dados simuladas sugerem que ambas as classes propostas possuem um desempenho superior aos métodos existentes. Em relação ao desempenho computacional, o método multivariado mostrou-se inferior e o univariado é superior aos métodos existentes.

abstract: Synthetic gene networks have evolved from simple proof-of-concept circuits to complex therapy-oriented networks over the past fifteen years. This advancement has greatly facilitated expansion of the emerging field of synthetic biology. Multistability is a mechanism that cells use to achieve a discrete number of mutually exclusive states in response to environmental inputs. However, complex contextual connections of gene regulatory networks in natural settings often impede the experimental establishment of the function and dynamics of each specific gene network. In this work, diverse synthetic gene networks are rationally designed and constructed using well-characterized biological components to approach the cell fate determination and state transition dynamics in multistable systems. Results show that unimodality and bimodality and trimodality can be achieved through manipulation of the signal and promoter crosstalk in quorum-sensing systems, which enables bacterial cells to communicate with each other. Moreover, a synthetic quadrastable circuit is also built and experimentally demonstrated to have four stable steady states. Experiments, guided by mathematical modeling predictions, reveal that sequential inductions generate distinct cell fates by changing the landscape in sequence and hence navigating cells to different final states. Circuit function depends on the specific protein expression levels in the circuit. We then establish a protein expression predictor taking into account adjacent transcriptional regions’ features through construction of ~120 synthetic gene circuits (operons) in Escherichia coli. The predictor’s utility is further demonstrated in evaluating genes’ relative expression levels in construction of logic gates and tuning gene expressions and nonlinear dynamics of bistable gene networks. These combined results illustrate applications of synthetic gene networks to understand the cell fate determination and state transition dynamics in multistable systems. A protein-expression predictor is also developed to evaluate and tune circuit dynamics. / Dissertation/Thesis / Doctoral Dissertation Biomedical Engineering 2017

Este trabalho apresenta todo um projeto de um sistema de supervisão e controle de um trocador de calor, desde os ensaios experimentais para a elaboração de um modelo matemático até a implementação do sistema de controle e supervisão em microcomputador. O sistema implementado consiste de um software didático e um sistema de aquisição de dados que irão realizar a supervisão e controle de um trocador de calor tipo casco e tubos. Neste software didático é possível implementar o controle PID e suas variações PI-D e I-PD além de permitir a implementação do sistema de controle adaptativo estrutura gain scheduling o qual muda os parâmetros de um controle PID de acordo com a mudança da dinâmica do trocador de calor. Como o trocador de calor apresenta um tempo morto em sua dinâmica, então optou-se por adicionar ao software didático um controle com algoritmo preditivo estrutura Preditor de Smith desta forma é possível realizar ensaios com e sem o algoritmo preditivo para uma comparação de resultados. Este sistema de supervisão e controle do trocador de calor poderá ser usado como ferramenta didática para alunos de diversos cursos, onde é possível realizar ensaios de diferentes estruturas de controle para posterior comparação e estudo de seus resultados. Resultados práticos de todas as estruturas de controle que o software implementa são apresentados e comparados neste trabalho. / This work presents thorough a supervision and control system project of a heat exchanger, from the experimental tests for the mathematical model rising to the control system implementation and supervision in a microcomputer. The implemented system consists of didactic software and a data acquisition system that will perform the supervision and control of a heat exchanger shell and tube type. In this didactic software it is possible to implement the PID control and its variations PI-D and I-PD besides allowing the implementation of the adaptive control system gain scheduling structure, which changes the PID control parameters according to the changes of the heat exchanger dynamics. As the heat exchanger presents dead time on its dynamics, it was opted to add to the didactic software a control with Smith Predictor structure predictive algorithm, thus it is possible to perform tests with and without the predictive algorithm for result comparison. This supervision and control system of the heat exchanger will be able to be used as a didactic tool for students from several courses, where it is possible to perform tests with different control structures to further comparison and study of its results. Pratical results of all the control structures that the software implements are presented and compared in this work.

Made available in DSpace on 2014-08-20T14:37:50Z (GMT). No. of bitstreams: 1 tese_isabel cristina_pereira.pdf: 914766 bytes, checksum: c37475e752545b7fee514cfc04ce4f2e (MD5) Previous issue date: 2012-06-27 / The longevity of dogs has increased the number of neoplasm cases, and the breast neoplasm is one of the most frequent diagnosed in this species. The female dogs are important as a study population as they present similarities between the breast neoplasms developed in humans and canines, thus allowing the use of the compared pathology in an attempt to have a better understanding of the disease. Changes in calcium and magnesium levels may be related to the presence and occurrence of breast neoplasms, but there is no defined standardization of these changes. The study aimed to analyze epidemiological data in canine patients with breast neoplasms, determine levels of serum calcium and magnesium in dogs with breast neoplasms before and after excision, and associate variation of calcium and magnesium blood levels with the neoplasms malignity. The study had a sample of 53 females 53 female dogs with tumors in the mammary gland, from which we obtained data of descriptive characteristics of the sample, regarding the review of the animal, exposure to risk factors and tumor development, associated with the morphological characteristics and anatomical location. Excision of tumor masses was performed for histopathological analysis evaluating the surgical margin and classifying the patients according to the biological behavior and malignancy degree: high malignancy (HM), intermediate malignancy (IM), low malignancy (LM) and benign (B). In further study, there was a loss of 17 dogs in the study for the analysis of mineral levels the period of 180 days and analyzed 36 dogs with mammary neoplasms and 28 healthy dogs without breast tumors were studied as controls. Dogs were evaluated on day zero (before surgery) in regard to assessments of tumor mass, and on that date, surgery was carried out in order to send the tumoral part for anatomopathologic evaluation taking into account the classification in biological behavior. Serum calcium and magnesium dosage (absorbance spectrophotometry) was performed prior to the excision of tumors (on day zero) and at 60 and 180 days after surgery, and at the same time interval the serum levels of minerals in the control group were evaluated. Of the 53 dogs studied, 24 showed high malignant tumors, 12 intermediate malignant tumors, 13 low malignancy tumors and four benign tumors. The elderly patients were the most frequent ones in the malignancy group. There was no relationship between biological behavior when compared to: age range, size, breed, time of onset and development, previous ovariohysterectomy and the use of contraceptives. As for location, of the 171 breasts affected, the development of neoplasms of greater malignancy occurred in medial abdominal and inguinal mammary glands. It was demonstrated the relationship between margin involvement and development of pulmonary metastasis. The neoplasic mobility and consistency were identified as prognostic factors for dogs with mammary neoplasms, while the other variables studied were not related to prognosis, while the other studied variables were not related with the prognosis. Data concerning the 36 females suffering from canine mammary neoplasms, which were observed, 13 had tumors of high malignancy (HM), nine of intermediate malignancy (IM), 10 of low malignancy (LM) and four benign (B). The average of calcium levels in the control group was 10.07 mg / dl and magnesium of 2.04 mg / dl. Mean levels of calcium serum of patients in group LM and IM were respectively 8.63 mg / dl and 8.77 mg / dl, both differing statistically (p <0.001) from the control group. The patients in the HM group had a mean calcium of 12.00 mg / dl and differed significantly (p <0.001) from the mean levels obtained in the control group. Regarding the serum levels of magnesium, it was demonstrated statistical difference between the control group (2.04 mg / dl) and the LM groups (p <0.001), IM groups (p = 0.002) and HM groups (p <0.001), with averages of 57 mg / dl, 1.67 mg / dl and 2.56 mg / dl, respectively. Both in the serum levels of calcium and magnesium no statistical differences between control group and group L were shown. It was observed that in animals with mammary neoplasms, the blood values of the studied minerals differed between the first and last collection in the LM groups (p = 0.0125) and HM groups (p = 0,0,0087) in the levels of calcium and in the same LM groups (p = 0.0124) and MA (p = 0.0015) in the levels of magnesium. The results showed that neoplasm mobility and consistency were correlated with malignancy and worse prognosis of the patient, and a strong relationship between margin involvement and lung metastases. Also, dogs with tumors of low malignancy and intermediate malignancy have hypocalcemia and hypomagnesemia, as well as in the cases of malignant neoplasms there is high hypercalcemia and hypermagnesemia, both going back to the physiological levels after six months of surgical excision / A longevidade dos cães tem aumentado a casuística de neoplasmas, sendo que o neoplasma mamário é um dos mais frequentes diagnosticados nesta espécie. As fêmeas caninas são importantes como população de estudo das neoplasias uma vez que existem similaridades entre os neoplasmas mamários desenvolvidos em humanos e caninos, possibilitando desta forma o uso da patologia comparada, buscando maior entendimento da doença. Alterações nos níveis de cálcio e magnésio podem estar relacionadas a presença e ocorrência de neoplasmas mamários, porém não existe uma padronização definida dessas alterações. O trabalho teve como objetivos analisar dados epidemiológicos em pacientes caninos com neoplasmas mamários e determinar níveis de cálcio e magnésio séricos e após exérese; e associar variação de níveis sanguíneos de cálcio e magnésio com a malignidade dos neoplasmas. O estudo teve uma amostra de 53 fêmeas caninas com tumoração em glândula mamária, das quais foram obtidos dados de características descritivas da amostra referentes a resenha do animal, exposição a fatores de risco e do desenvolvimento tumoral, associado as características morfológicas e localização anatômica. Foi realizada exérese das massas tumorais para análise histopatológica avaliando margem cirúrgica e classificando os pacientes segundo comportamento biológico e diferentes graus de malignidade: alta malignidade (AM), malignidade intermediária (MI), baixa malignidade (BM) e benignos (B). Na continuação do estudo, houve uma perda de 17 cães para o estudo de análise de níveis de minerais no período de 180 dias, sendo estudadas 36 fêmeas com neoplasmas mamários e 28 cães saudáveis sem tumores mamários, como controles. Os cães foram avaliados no dia zero (prévio à cirurgia) em relação à massa tumoral e nessa data foi realizada exérese para encaminhamento de peça tumoral para avaliação anatomopatológica e classificados segundo comportamento biológico. A dosagem sérica de cálcio e magnésio (espectrofotometria de absorbância), foi realizada prévia à exérese dos tumores (no dia zero) e aos 60 e 180 dias após o procedimento cirúrgico, no mesmo intervalo de tempo foram avaliadas as dosagens séricas dos minerais no grupo controle. Das 53 cadelas estudadas, 24 apresentavam tumores de alta malignidade, 12 de malignidade intermediária, 13 de baixa malignidade e quatro eram benignos. Os pacientes idosos foram frequentes no grupo de maior malignidade. Não houve relação entre comportamento biológico quando comparado com: faixa de idade, porte, raça, tempo de aparecimento e desenvolvimento ovariohisterectomia prévia e uso de contraceptivos. Quanto a localização, das 171 mamas acometidadas, o desenvolvimento de neoplasma de maior malignidade ocorreu em mamas inguinais e abdominais mediais. Foi demonstrado relação entre comprometimento de margem e desenvolvimento de metástase pulmonar. A mobilidade e consistência neoplásica foram identificados como fatores prognósticos para cães com neoplasma mamário, enquanto as outras variáveis estudadas não foram relacionadas com o prognóstico. Dados referentes às 36 fêmeas caninas portadoras de neoplasmas mamários, que foram acompanhadas, 13 apresentaram tumores de alta malignidade (AM), nove de malignidade intermediária (MI), 10 de baixa malignidade (BM) e quatro benignos (B). A média dos níveis de Cálcio do grupo controle foi de 10,07mg/dl e do magnésio de 2,04mg/dl. Os níveis médios de cálcio sérico dos pacientes do grupo BM e MI foi respectivamente 8,63mg/dl e 8,77mg/dl, ambos diferindo estatisticamente (p< 0,001) do grupo controle. Os pacientes do grupo de AM apresentaram média de cálcio de 12,00mg/dl e diferiram significantemente (p< 0,001) dos níveis médios obtidos no grupo controle. Em relação aos níveis séricos de magnésio foi demonstrado diferença estatística entre o grupo controle (2,04mg/dl) e os grupos BM (p< 0,001), MI (p=0,002) e AM (p< 0,001), com médias de 1,57 mg/dl, 1,67mg/dl e 2,56mg/dl respectivamente. Tanto nos níveis séricos de cálcio quanto de magnésio não foram demonstradas diferenças estatísticas entre o grupo controle e o grupo B. Foi observado que, nos animais com neoplasmas mamários, os valores sanguíneos dos minerais estudados diferiram entre a primeira e última coleta nos grupos BM (p=0,0125) e AM (p=0,0,0087) quanto aos níveis de cálcio e nos mesmos grupos BM (p=0,0124) e AM (p=0,0015) quanto aos níveis de magnésio. Os resultados permitiram concluir que mobilidade e consistência do neoplasma, foram relacionadas com malignidade e pior prognóstico do paciente além de uma forte relação entre comprometimento de margem e metástase pulmonar. Ainda, cães portadores de neoplasias de baixa malignidade e malignidade intermediária apresentam hipocalcemia e hipomagnesemia, assim como nos casos de neoplasmas de alta malignidade ocorre hipercalcemia e hipermagnesemia, ambos retornando aos níveis fisiológicos após seis meses da exérese cirúrgica.

Submitted by Maria Beatriz Vieira (mbeatriz.vieira@gmail.com) on 2016-10-10T15:20:52Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) dissertacao_cyrano_busato.pdf: 492572 bytes, checksum: 5744ab314d2b9cd92f0f936a4b74b6fe (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2016-10-11T21:14:42Z (GMT) No. of bitstreams: 2 dissertacao_cyrano_busato.pdf: 492572 bytes, checksum: 5744ab314d2b9cd92f0f936a4b74b6fe (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2016-10-11T21:16:29Z (GMT) No. of bitstreams: 2 dissertacao_cyrano_busato.pdf: 492572 bytes, checksum: 5744ab314d2b9cd92f0f936a4b74b6fe (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-10-11T21:16:36Z (GMT). No. of bitstreams: 2 dissertacao_cyrano_busato.pdf: 492572 bytes, checksum: 5744ab314d2b9cd92f0f936a4b74b6fe (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2013-06-10 / Sem bolsa / Em um programa de melhoramento de híbridos de arroz, os dados provenientes de ensaios de VCU são geralmente analisados pela Análise de Variância (ANOVA), que não permite analisar dados desbalanceados, entretanto a metodologia BLUP (Best linear undebiased predictor) pode possibilitar a análise de dados desbalanceados e indicar além das constituições genéticas de melhor desempenho, também as de desempenho mais estável. O presente trabalho objetiva avaliar a aplicabilidade da metodologia BLUP, através do Software SELEGEN REML/BLUP em um programa de híbridos de arroz. O trabalho foi conduzido na safra 2009/2010, 2010/2011 e 2011/2012 em quatro regiões distintas produtoras de arroz do Rio grande do Sul, sendo, a região SUL, Litoral NORTE, Fronteira OESTE e no município de Capão do Leão. Foram analisados os dados dos ensaios de VCU de todos os locais e dos três anos através de ANOVA e do SELEGEN e analisou-se as diferenças nas seleções de híbridos de arroz quanto ao caráter rendimento de grãos. O delineamento experimental foi de blocos ao acaso, com três repetições, por local a cada ano e região. Os resultados mostram que o SELEGEN possibilita a seleção de híbridos de alto potencial produtivo e estabilidade de produção, além de oferecer fácil interpretação e forma de trabalhar com dados desbalanceados. A utilização de ferramentas estatísticas que possibilitem a análise de grande número de dados é de extrema importância em um programa de melhoramento de híbridos, pois auxilia o melhorista a buscar grupos genéticos de melhor capacidade de combinação de forma objetiva, focando nas constituições de elevado e estável potencial produtivo. Além disso, com o passar dos anos e ciclos de seleção, os dados gerados podem contribuir para a predição de desempenho, proporcionando redução de custos e tempo no desenvolvimento de híbridos superiores em arroz irrigado. / In a breeding program of hybrid rice data from VCU trials are usually analyzed by analysis of variance (ANOVA), which do not allow unbalanced data however the methodology BLUP (Best Linear undebiased predictor) can analyze unbalanced data and indicate beyond genetic constitutions best and more stable performance. This study aims to evaluate the applicability of the BLUP methodology through Software SELEGEN REML/BLUP in a program of hybrid rice. The study was conducted in 2009/2010, 2010/2011 and 2011/2012 seasons at four distinct producing regions of rice in Rio Grande do Sul state, in the SOUTH region, NORTH coast, WEST Border and Capão do Leão District. Data from VCU trials were analyzed including all locations and the three years through ANOVA and through SELEGEN and the differences in the selections of hybrids for grain yield was interpreted. The experimental design was randomized blocks with three replications per location each year and region. The results show that SELEGEN allows selection of hybrids with high yield potential and yield stability among years and locations, and provide an easy interpretation way to unbalanced data. The use of statistical tools that enable the analysis of large amounts of data is extremely important in a hybrid rice breeding program and helps the breeder to seek genetic groups of better combining ability objectively and with focus on the constitutions of high and stable productive potential. In addition, over the years and cycles of selection the data generated can contribute to the prediction of performance saving cost and time in developing superior rice hybrids.

Abstract The aim of this study was to provide novel information on the change of cognitive performance and its predictors in early midlife between ages of 34 and 43 years. The change in verbal episodic memory between non-psychotic and schizophrenia samples was compared in the Northern Finland Birth Cohort 1966. In the non-psychotic sample, associations between primary school performance, sociodemographic factors and body mass index (BMI), and in the schizophrenia sample, between premorbid school performance and severity of illness with the change in cognitive performance were evaluated. There was no evidence of greater decline in verbal episodic memory in the schizophrenia sample, compared to the non-psychotic sample, though the schizophrenia sample had an overall lower cognitive performance at the baseline. In the non-psychotic sample, male gender, poorer school performance, increases in BMI and having no children predicted a decline in verbal episodic memory; poorer school performance and low vocational education and occupational class predicted a decline in visual episodic memory; and having children predicted a decline in executive function. In the schizophrenia sample, poorer premorbid school performance, but not the later course of illness, was related to a decline in cognitive performance. This study is one of the few studies to investigate the predictors of change in cognitive performance in the early middle-aged general population, and the first to investigate the predictors of cognitive change in early midlife schizophrenia. To summarize; poor cognitive performance in adolescence may be considered as a vulnerability marker for a later impairment in cognitive functioning. In schizophrenia, cognitive ability possibly declines mostly in a normative fashion with aging at the same rate as in the general population rather than as a result of neurodegenerative processes. These results might improve our understanding of midlife change in cognitive functioning and may also help to develop effective interventions of cognitive impairment in schizophrenia. / Tiivistelmä Tutkimuksen tavoitteena oli tuoda uutta tietoa kognitiivisen suoriutumisen muutoksesta sekä siihen liittyvistä tekijöistä varhaisessa keski-iässä ikävuosien 34 ja 43 välillä. Tutkimuksessa verrattiin kielellisessä muistisuoriutumisessa tapahtuvaa muutosta yleisväestön ja skitsofrenia-aineiston välillä Pohjois-Suomen vuoden 1966 syntymäkohortissa. Lisäksi yleisväestössä tutkittiin koulumenestyksen, sosiodemografisten tekijöiden ja painoindeksin yhteyttä ja skitsofrenia-aineistossa koulumenestyksen ja sairauden varhaisen kulun yhteyttä kognitiivisen suoriutumisen muutokseen. Kielellisen muistisuoriutumisen heikentyminen ei ollut skitsofrenia-aineistossa suurempaa verrattuna yleisväestöön, joskin kognitiivisen suoriutumisen lähtötaso oli skitsofrenia-aineistossa alempi. Yleisväestössä miessukupuoli, heikompi koulumenestys peruskoulussa, painoindeksin nousu ja lapsettomuus olivat yhteydessä kielellisen muistisuoriutumisen heikkenemiseen, heikompi koulumenestys peruskoulussa ja matala ammatillinen koulutus ja sosioekonominen asema näönvaraisen muistisuoriutumisen heikkenemiseen ja vanhemmuus toiminnanohjauksellisten taitojen laskuun. Skitsofrenia-aineistossa heikompi menestys peruskoulussa ennusti kognitiivisen suoriutumisen heikkenemistä kielellisen ja näönvaraisen muistin sekä toiminnanohjauksellisten taitojen osa-alueilla. Oireiden vakavuus ja toimintakyky sairastumisen jälkeen eivät liittyneet kognitiivisen suoriutumisen muutokseen. Tämä on yksi harvoista tutkimuksista, joissa on selvitetty kognitiivisen suoriutumisen muutosta ennustavia tekijöitä varhaisessa keski-iässä yleisväestössä, ja ensimmäinen, jossa on tutkittu kognitiivisen suoriutumisen muutosta ennustavia tekijöitä skitsofrenia-aineistossa varhaisessa keski-iässä. Yhteenvetona voidaan todeta, että heikko nuoruusiän koulumenestys voi ennustaa kognitiivisen suoriutumisen heikkenemistä varhaisessa keski-iässä. Kognitiivinen suorituskyky näyttää heikkenevän skitsofreniassa enemmänkin tavanomaisella tavalla ikääntymisen myötä kuin neurodegeneratiivisen prosessin seurauksena. Tämän tutkimuksen tulokset tuovat uutta tietoa kognitiivisen suoriutumisen muutoksesta keski-ikäisessä väestössä. Tuloksia voidaan myös hyödyntää kehitettäessä kognitiivisten häiriöiden hoitoa skitsofreniassa.

Protein palmitoylation refers to the process of adding a 16-carbon saturated fatty acid to the cysteine of a substrate protein, and this can in turn affect the substrate’s localization, stability, folding, and several other processes. This process is catalyzed by a family of 23 mammalian protein acyltransferases (PATs), a family of transmembrane enzymes that modify an estimated 10% of the proteome. At this point in time, no structure of a protein in this family has been solved, and therefore there is poor understanding about the regulation of the enzymes and their substrates. Most proteins, including palmitoylation enzymes and substrates, have some level of intrinsic disorder, and this flexibility can be important for signaling processes such as protein- protein interactions and post-translational modifications. Therefore, we assumed that examining intrinsic disorder in palmitoylation enzymes and substrates would yield insight into their regulatory mechanisms. First, we found that among other factors, utilizing intrinsic disorder predictions led to a palmitoylation predictor that significantly outperformed existing predictors. Next, we discovered a conserved region of predicted disorder-to-order transition in the disordered C-termini of the PAT family. In Erf2, the yeast Ras PAT, we developed a model where this region reversibly interacts with membranes, and we found that this region mediates interaction with Acc1, an enzyme involved in fatty acid metabolism processes. Finally, we found that an XLID-associated nonsense mutation in zDHHC9, the mammalian Ras PAT, removed a disordered region that was critical for enzyme localization. Future studies of palmitoylation utilizing the framework of intrinsic disorder may lead to additional insights about this important regulatory process.