I/D 32 -- Decisions of the Enlarged General Council, 1982 -- Supplemental to I/D No. 32 -- The New Constitutions -- (pg. 1) -- Community Life -- (pg. 1) -- Priorities and Urgent Situations (Superior General’s Report) -- (pg. 1) -- Finances -- (pg. 2) -- Planning -- (pg. 2) -- New Forms of Collaboration -- (pg. 2)

A crescente prevalência de hipertensão arterial na população mundial e os riscos por ela apresentados nas doenças coronarianas eleva a importância de seu controle. Sendo sua causa, frequentemente multifatorial, o tratamento da patologia é dificultado. Fatores ambientais associados à predisposição genética levam o indivíduo a apresentar índices pressóricos elevados de pressão arterial quando comparados a indivíduos que não apresentam tal predisposição. Identificar a predisposição genética seria ideal para amenizar ou, até mesmo, evitar o desenvolvimento da patologia. As nanopartículas estão cada vez mais associadas com biomoléculas, uma vez que suas propriedades associadas às questões médicas podem criar novos métodos potencialmente eficientes, tanto no diagnóstico como na terapêutica. O presente trabalho teve como objetivo a conjugação de nanopartículas de ouro, estabilizadas com dendrímero poli(amidoamina) de geração 4, com oligonucleotídeo para obtenção de genossensores capazes de detectar o polimorfismo de inserção e deleção do gene da enzima conversora de angiotensina I, o qual está intimamente relacionado com a predisposição à hipertensão arterial sistêmica. As nanopartículas foram caracterizadas por Microscopia Eletrônica de Transmissão (TEM), potencial zeta e Espectroscopia no Ultravioleta-Visível (UV-VIS). A formação do conjugado entre a nanopartícula e o oligonucleotídeo foi confirmada por UV-VIS, Espalhamento Dinâmico de Luz (DLS) e Espectroscopia no Infravermelho com Transformada de Fourier (FTIR). Foram construídos três sistemas de detecção diferentes, nos quais as técnicas empregadas foram Espectroscopia de Impedância Elétrica, Espectroscopia de Impedância Eletroquímica e Transistor de Efeito de Campo de Porta Estendida e Separada (SEGFET). O polimorfismo foi detectado em concentrações da ordem de 1 nM. Com destaque para aqueles em que o emprego do conjugado amplificou o sinal pelas propriedades das nanopartículas de ouro. Os genossensores propostos são promissores e futuramente poderão contribuir com a medicina preventiva. / The increasing prevalence of hypertension in the world population and the risks presented by it in coronary heart disease reveals the importance of their control. Due to its multifactorial causes, the treatment of this disease is difficult. Environmental factors associated with genetic predisposition lead the individual to present high indexes of blood pressure when compared to individuals who do not have a predisposition. To identify the genetic predisposition would be ideal to minimize or even to prevent the pathology development. Nanoparticles are increasingly associated with biomolecules, their properties added with medical questions, can create new methods potentially efficient, both in diagnosis and therapy. This study aims at developing of poly(amidoamine) dendrimer-stabilized gold nanoparticles, conjugated with oligonucleotides to obtain genosensors able to detect the polymorphism of insertion and deletion of angiotensin I converting enzyme (ACE) gene, which is closely related with the predisposition to systemic blood hypertension. The nanoparticles were characterized by Transmission Electronic Microscopy (TEM), Zeta potential and Ultraviolet-Visible Spectroscopy (UV-VIS). The formation of the conjugate formed by the nanoparticle and the oligonucleotide was confirmed by UV-VIS, Dynamic Light Scattering (DLS) and Fourier Transform Infrared Spectroscopy (FTIR). Three different detection systems were built, in which the following techniques were applied: Electrical Impedance Spectroscopy, Electrochemical Impedance Spectroscopy and Separative Extended Gate Field Effect Transitor (SEGFET). For all systems polymorphism - related sequences were detected at concentrations down to nanomolar. The use of the conjugate amplified the signal of the genosensor due to the nanoparticles. The proposed genosensors may contribute to preventative medicine.

Η στεφανιαία νόσος (ΣΝ) αποτελεί τη συχνότερη πάθηση του καρδιαγγειακού συστήματος. Κύρια αιτία της νόσου είναι η αθηροσκλήρυνση, που σήμερα θεωρείται πλέον μια χρόνια φλεγμονώδης αντίδραση του αγγειακού τοιχώματος. Η λειτουργικότητα του ενδοθηλίου του αγγειακού τοιχώματος που αποτελεί προγνωστικό δείκτη καρδιαγγειακών συμβαμάτων και μέθοδο ελέγχου της ανταπόκρισης σε φάρμακα μπορεί να προσδιοριστεί με μέτρηση της αγγειοδιαστολής που διαμεσολαβείται από τη ροή (Flow-Mediated Dilation, FMD) στη βραχιόνιο αρτηρία. Σημαντικό ρόλο στην παθοφυσιολογία της αθηροσκλήρυνσης ασκεί το σύστημα Ρενίνης-Αγγειοτενσίνης-Αλδοστερόνης (Renin-Angiotensin-Aldosterone System – RAAS) που διακρίνεται σε ενδοκρινές και ιστικό. Κεντρικά σημεία του συστήματος RAAS που αποτελούν και φαρμακευτικούς στόχους είναι η μετατροπή της Αγγειοτενσίνης Ι (ΑΤ Ι) σε Αγγειοτενσίνη ΙΙ ( ΑΤ ΙΙ ) με τη δράση του μετατρεπτικού ενζύμου της ΑT Ι (Angiotensin Converting Enzyme-ACE) και η επίδραση της ΑΤΙΙ στους υποδοχείς της. Στο ιντρόνιο 16 του γονιδίου του ενζύμου ACE(17q23) έχει βρεθεί ο πολυμορφισμός I/D που προκύπτει από την παρουσία ( Insertion– I) ή την απουσία (Deletion–D) μιας Αlu αλληλουχίας μήκους 287 bp, δημιουργώντας τρείς διακριτούς γονότυπους: II, ID και DD. Οι ομοζυγώτες DD παρουσιάζουν αύξηση κατά 50% των επιπέδων του ACE στον ορό σε σχέση με τους ομοζυγώτες II. Οι ετεροζυγώτες ID εμφανίζουν ενδιάμεσα επίπεδα. Με δεδομένο το ρόλο του συστήματος RAAS στη ΣΝ, ο ρόλος του πολυμορφισμού ACE I/D έχει καταστεί αντικείμενο μελέτης ως προς την εκδήλωση στεφανιαίας νόσου και την ανταπόκριση στεφανιαίων ασθενών στα διάφορα θεραπευτικά σχήματα αποκλεισμού του συστήματος RAAS. Στην παρούσα μελέτη προσδιορίστηκε ο πολυμορφισμός ACE I/D σε 100 φυσιολογικά άτομα και σε 100 στεφανιαίους ασθενείς. Το συμπέρασμα μετά τη στατιστική ανάλυση ήταν ότι ο γονότυπος DD δεν συνδέεται στατιστικώς σημαντικά με στεφανιαία νόσο στον ελληνικό πληθυσμό που εξετάστηκε (p>0,05). Επιπλέον προσδιορίστηκε ο πολυμορφισμός ACE I/D σε 30 στεφανιαίους ασθενείς που έλαβαν διάφορα θεραπευτικά σχήματα αποκλεισμού του συστήματος RAAS. Η ανταπόκριση των ασθενών στην αγωγή εκτιμήθηκε μέσω της μεταβολής της FMD. Ο μικρός αριθμός των ασθενών και η μεγάλη τυπική απόκλιση στις μεταβολές της FMD δεν επέτρεψε την εξαγωγή ασφαλών συμπερασμάτων για το ρόλο του πολυμορφισμού στην ανταπόκριση των ασθενών στην φαρμακευτική αγωγή. / The Renin-Angiotensin-Aldosterone System (RAAS) is an important factor for the pathogenesis of Coronary Artery Disease (CAD). The key component of RAAS is the Angiotensin Converting Enzyme (ACE). An Insertion/Deletion polymorphism (I/D) has been identified in ACE gene which accounts for half the variance of serum ACE levels (1). Subsequent reports investigated the relationship between the D allele and cardiovascular diseases, icluding CAD, with conflicting results (2). We determine ACE I/D polymorphism genotype in 100 normal individuals and 100 patients with CAD of greek origin. No association was found between D allele and CAD. Moreover, we determine ACE I/D polymorphism in 30 patients with CAD who were in treatment inhibiting RAAS. No association was found between ACE I/D polymorphism and respond.

A crescente prevalência de hipertensão arterial na população mundial e os riscos por ela apresentados nas doenças coronarianas eleva a importância de seu controle. Sendo sua causa, frequentemente multifatorial, o tratamento da patologia é dificultado. Fatores ambientais associados à predisposição genética levam o indivíduo a apresentar índices pressóricos elevados de pressão arterial quando comparados a indivíduos que não apresentam tal predisposição. Identificar a predisposição genética seria ideal para amenizar ou, até mesmo, evitar o desenvolvimento da patologia. As nanopartículas estão cada vez mais associadas com biomoléculas, uma vez que suas propriedades associadas às questões médicas podem criar novos métodos potencialmente eficientes, tanto no diagnóstico como na terapêutica. O presente trabalho teve como objetivo a conjugação de nanopartículas de ouro, estabilizadas com dendrímero poli(amidoamina) de geração 4, com oligonucleotídeo para obtenção de genossensores capazes de detectar o polimorfismo de inserção e deleção do gene da enzima conversora de angiotensina I, o qual está intimamente relacionado com a predisposição à hipertensão arterial sistêmica. As nanopartículas foram caracterizadas por Microscopia Eletrônica de Transmissão (TEM), potencial zeta e Espectroscopia no Ultravioleta-Visível (UV-VIS). A formação do conjugado entre a nanopartícula e o oligonucleotídeo foi confirmada por UV-VIS, Espalhamento Dinâmico de Luz (DLS) e Espectroscopia no Infravermelho com Transformada de Fourier (FTIR). Foram construídos três sistemas de detecção diferentes, nos quais as técnicas empregadas foram Espectroscopia de Impedância Elétrica, Espectroscopia de Impedância Eletroquímica e Transistor de Efeito de Campo de Porta Estendida e Separada (SEGFET). O polimorfismo foi detectado em concentrações da ordem de 1 nM. Com destaque para aqueles em que o emprego do conjugado amplificou o sinal pelas propriedades das nanopartículas de ouro. Os genossensores propostos são promissores e futuramente poderão contribuir com a medicina preventiva. / The increasing prevalence of hypertension in the world population and the risks presented by it in coronary heart disease reveals the importance of their control. Due to its multifactorial causes, the treatment of this disease is difficult. Environmental factors associated with genetic predisposition lead the individual to present high indexes of blood pressure when compared to individuals who do not have a predisposition. To identify the genetic predisposition would be ideal to minimize or even to prevent the pathology development. Nanoparticles are increasingly associated with biomolecules, their properties added with medical questions, can create new methods potentially efficient, both in diagnosis and therapy. This study aims at developing of poly(amidoamine) dendrimer-stabilized gold nanoparticles, conjugated with oligonucleotides to obtain genosensors able to detect the polymorphism of insertion and deletion of angiotensin I converting enzyme (ACE) gene, which is closely related with the predisposition to systemic blood hypertension. The nanoparticles were characterized by Transmission Electronic Microscopy (TEM), Zeta potential and Ultraviolet-Visible Spectroscopy (UV-VIS). The formation of the conjugate formed by the nanoparticle and the oligonucleotide was confirmed by UV-VIS, Dynamic Light Scattering (DLS) and Fourier Transform Infrared Spectroscopy (FTIR). Three different detection systems were built, in which the following techniques were applied: Electrical Impedance Spectroscopy, Electrochemical Impedance Spectroscopy and Separative Extended Gate Field Effect Transitor (SEGFET). For all systems polymorphism - related sequences were detected at concentrations down to nanomolar. The use of the conjugate amplified the signal of the genosensor due to the nanoparticles. The proposed genosensors may contribute to preventative medicine.

Long range dependent processes occur in many fields, it is important to monitor these processes to early detect their shifts. This paper considers the problem of detecting changes in an I(d) process or an ARFIMA(p,d,q) process by statistical control charts. The control limits of EWMA and EWRMS control charts of I(d) processes are established and analytic forms are derived. The average run lengths of these control charts are estimated by Monte Carlo simulations. In addition, we illustrate the performance of the control charts by empirical examples of I(d) processes and ARFIMA(1,d,1) processes.

An recent finding shows that heart rate data possess self-similar property, which is characterized by a parameter H, as well as a long range dependent parameter d. We estimate H by the EBP(Embedded Branching Process) method to derive the fractional parameter d in the first part. The heart rate and R-R interval data are found to have high differencing parameter(d=0.8 ~0.9) and against the normality assumption. Thus the heart rate and R-R interval data are first fractionally differenced of order 0.5 to achieve stationarity. In the second part, we analyze the RR-interval data on the physionet and obtain the long range parameters. After fractionally differencing 0.5 order, the EBP method is adapted to estimate the long range parameter d. The EWMA and EWRMS control charts of the I(d) processes are constructed to monitor the heart rate mean level and variability, respectively for the 18 RR-interval data sets from the physionet. For the EWMA control chart the out of control percentages are chosen to the nominal probability. However, the out of control percentages are affected by the skewness and kurtosis of the process distribution for the EWRMS control carts. Generally speaking, the I(d)-EWMA and I(d)-EWRMS control charts provide a proper monitor system for heart rate mean level and variability.

Made available in DSpace on 2017-07-21T19:59:45Z (GMT). No. of bitstreams: 1 Rubia Caldas.pdf: 1293952 bytes, checksum: 52cae77ba14b2beb72e4443c324cd16c (MD5) Previous issue date: 2013-02-28 / High blood pressure (HBP) is a multifactorial clinical condition characterized by high and sustained levels of blood pressure (BP). The renin-angiotensin system is involved in the control of the BP, and has as a component the angiotensin converting enzyme (ACE). Recent studies that relate gene variants of Angiotensin Converting Enzyme (ACE) gene, increase the risk of hypertension, compared with the presence of the allele D. Thus, it becomes necessary studies aimed at investigating the relationship of the polymorphism in intron 16 of the ACE gene with hypertension. The aim of the study was to verify the relationship between I / D polymorphism of the ACE gene and genotypic variants with the installation of HBP in four distinct groups. Participants were 112 individuals arranged in the following groups: normotensive (control), hypertensive and non-obese, hypertensive and obese and hypertensive and with type II diabetes mellitus. We evaluated the possible relationship between I/D polymorphism of the ACE gene in different groups of hypertensive patients, but there was no significant difference between the genotypes in different groups in the sample. Regarding the epidemiology higher the body mass index (BMI), waist circumference, triglycerides and cholesterol levels and physical inactivity, was greater incidence of hypertension in the population. The data obtained in this study reinforce environmental interference that are prevalent in the evolution of the framework of HBP and not related to the frequency of the D allele in the population studied. / A hipertensão arterial sistêmica (HAS) é uma condição clínica multifatorial caracterizada por níveis elevados e sustentados de pressão arterial (PA). O sistema renina-angiotensina está envolvido no controle da PA, e tem como um dos componentes a enzima conversora de angiotensina (ECA). Estudos recentes relacionam que variantes do gene da Enzima Conversora de Angiotensina (ECA) aumentam o risco de HAS, com relação à presença do alelo D. Com isso, se fazem necessários estudos voltados à investigação da relação do polimorfismo no íntron 16 do gene da ECA com a HAS. O objetivo do estudo foi verificar a existência de relação do polimorfismo I/D do gene da ECA e suas variantes genotípicas com a instalação da HAS, em quatro grupos distintos. Participaram da pesquisa 112 indivíduos arranjados nos seguintes grupos: normotenso (controle), hipertenso e não obeso, hipertenso e obeso, e hipertenso e com diabetes mellitus tipo II. Foi avaliada a possível relação do polimorfismo I/D do gene da ECA, em diferentes grupos de hipertensos, porém não foi encontrada diferença significativa quanto aos genótipos nos diferentes grupos na amostra analisada. Em relação à epidemiologia, quanto maior o índice de massa corporal (IMC), cintura abdominal, valores de colesterol e triglicerídeos e sedentarismo, maior foi a incidência de HAS na população. Os dados obtidos no presente estudo reforçam que interferências ambientais são prevalentes na evolução do quadro de HAS, e não relacionado à frequência do alelo D na população analisada.

I den här uppsatsen analyseras Henryk Wieniawskis violinkonsert i d-moll, Op. 22, sats 1. Syftet med studien är en djupdykning i satsens grundstruktur: funktionsanalys, formanalys, motivanalys, sonatform samt en beskrivning av min instuderingsprocess. Jag guidar läsaren genom verket och kommenterar parallellt mina konstnärliga val. Studien påvisar att verket genomsyras av en kammarmusikalisk dominans såväl som det innehåller en genomgående violinistisk naturlighet som tydligt återspeglar Wieniawskis gedigna personliga violinkännedom.

Tesis para optar al grado de Magíster en Estudios Internacionales / El objetivo general de esta investigación es determinar de qué manera el gasto en investigación y desarrollo (I+D) influye sobre el nivel de ingreso, desarrollo y equidad. La primera parte del trabajo consiste en una descripción de las distintas teorías existentes acerca de las relaciones entre el crecimiento económico y la innovación tecnológica. A continuación, se considera el caso de la OCDE y se presentan datos macroeconómicos de los 35 países integrantes entre 1967 y 2016, enfocándose en el crecimiento económico, el desarrollo humano y la repartición de la renta. En la segunda parte del trabajo, para estos mismos países se presentan los datos de evolución de la innovación y de sus resultados. La última parte del trabajo busca estimar, para los países de la OCDE, la relación que existe por una parte entre el PIB por habitante, el IDH y el coeficiente de GINI con el gasto en I+D. Para ello se recurrió a una regresión lineal con datos para los 35 miembros de la OCDE de 1990 a 2016. En los modelos se consideran otras variables explicativas como el nivel de ahorro, el gasto en capital humano, el nivel de regulación, el grado de apertura económica y el nivel de infraestructura existente. Los resultados mostraron que existe una relación de dependencia entre el PIB/habitante y el gasto en I+D, además de que otras variables como el nivel de ahorro y el capital humano, tenía una influencia significativa. En el caso del IDH, también se identificó una influencia positiva con el gasto en I+D, junto con la tasa de ahorro, el capital humano y el nivel de regulación. Y finalmente para el GINI, el gasto en I+D contribuye a disminuir las desigualdades, junto con la tasa de ahorro, el capital humano, la apertura comercial y el nivel de regulación. Por tanto, se puede concluir que el gasto en I+D contribuye de forma positiva tanto al crecimiento económico, como al desarrollo humano y para mejorar la repartición de la renta.

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