In this thesis we discuss deterministic compartmental epidemic models. We study the asymp- totic stability of the disease-free solution of models with pulse vaccination campaigns. The main contributions of this thesis are to extend the literature of pulse vaccination models with delay. We take results for ordinary differential equation models and extend them to models with delay differential equations. Model generalizations include the use of a general incidence term as an upper bound for the actual incidence, and the use of switch parameters to approximate time-varying parameters. In particular, we look at contact rate parameters which are piecewise constant or time-varying. We extend literature results for non-delay general incidence models to find uniform asymptotic stability of the disease-free solution which helps us to add delay. We find an upper bound for the susceptible population under pulse vaccination and use this bound to tighten results for eradication thresholds: that is, we use this upper bound to find sufficient conditions for the uniform asymptotic stability of the disease-free solution of delayed pulse vaccination models. We extend literature results for constant contact rate bilinear incidence delay models to models with periodic time-varying contact rate, and determine conditions under which the disease-free solution is uniformly asymptotically stable for small delay. We also find conditions for disease permanence in the corresponding non-delay, time-varying-parameter pulse vaccination model. For piecewise- constant contact rate bilinear incidence models we again find thresholds which guarantee uniform asymptotic stability under small delay. We additionally discuss the effects of time-varying total population on our results, through a change of variables to population fractions. The total population is commonly held constant in the literature, for analytical simplicity, so we survey the methods for time-varying total population and the effects of such variation on the pulse vaccination schemes. We retain thresholds for eradication by considering the compartment populations as fractions of the total, instead of population numbers. The result is also applied to constant-population delay systems. When changing from standard incidence to bilinear incidence in delay systems, we discuss a way to estimate the effect of time-varying N. We support our theory with simulation results.

Η ραγδαία ανάπτυξη του Διαδικτύου τόσο σε επίπεδο πλήθους χρηστών όσο και σε επίπεδο παρεχόμενων υπηρεσιών αποτελεί χαρακτηριστικό της σύγχρονης κοινωνίας. Η ανάγκη λοιπόν προστασίας των υπολογιστικών και δικτυακών συστημάτων από απειλές που μπορούν να τα καταστήσουν τρωτά είναι επιτακτική!Η προστασία των υπολογιστικών συστημάτων και δικτύων απαιτεί σε προηγούμενο στάδιο την κατανόηση και ανάλυση του είδους, της ταυτότητας και του τρόπου διάδοσης της απειλής. Η ανάπτυξη και η αναζήτηση αξιόπιστων μοντέλων ικανών να περιγράψουν τον τρόπο διάδοσης μίας απειλής αποδεικνύεται ιδιαίτερα χρήσιμη και ωφέλιμη με πολλαπλούς τρόπους , όπως το να προβλέψει μελλοντικές απειλές ή να αναπτύξει νέες μεθόδους αναχαίτισης. Η αναζήτηση μοντέλων αποτελεί πλέον ένα σημαντικό τομέα έρευνας στην ακαδημαϊκή και όχι μόνο κοινότητα. Σκοπός της παρούσας εργασίας είναι η παρουσίαση κάποιων βασικών επιδημιολογικών μοντέλων και η προσομοίωση του επισημιολογικού μοντέλου SI. Τα μοντέλα αυτά χρησιμοποιούνται σήμερα ευρέως για τη μοντελοποίηση της διάδοσης αρκετών απειλών στα δίκτυα υπολογιστών, όπως είναι για παράδειγμα οι ιοί και τα σκουλήκια ( viruses and worms). Τα επιδημιολογικά αυτά μοντέλα είναι εμπνευσμένα από την επιστήμη της βιολογίας, όπου περιγράφουν την εξάπλωση μολυσματικών ασθενειών σε ανθρώπινους πληθυσμούς. Παρουσιάζοντας πιο αναλύτικά τη δομή της παρούσας εργασίας περιγράφουμε συνοπτικά το περιεχόμενο των πέντε κεφαλαίων που ακολουθούν: Στο πρώτο κεφάλαιο γίνεται μια σύντομη ιστορική αναδρομή στον πρόγωνο του Διαδικτύου, το APRAnet. Παρουσιάζονται κάποιες βασικές έννοιες των δικτύων καθώς και τα ευρέως γνωστά μοντέλα δόμησης του Διαδικτύου, το μοντέλο αναφοράς OSI και το μοντέλο TCP/IP. Ακολουθεί μία σύντομη ιστορική αναδρομή στο κακόβουλου λογισμικού και συνοπτική αναφορά στους βασικούς τύπους κακόβουλου λογισμικού. Παρουσιάζοναι τα χαρακρηριστικά του κακόβουλου λογισμικού που επηρεάζουν την εξάπλωση του, καθώς και κάποιες τεχνικές περιορισμού της. Το τρίτο κεφάλαιο επιχειρεί να παρουσιάσει κάποιες βασικές τοπολογίες σύνθετων δικτύων που συναντάμε σήμερα και κάποια βασικά μεγέθη που χαρακτηρίζουν τα δίκτυα αυτά. Η γνώση αυτή, που αφορά στην τοπολογία και στα χαρακτηριστικά μεγέθη των σύνθετων δικτύων, είναι απαραίτητη για τη μελέτη της διάδοσης μολύνσεων στα δίκτυα. Το τέταρτο κεφάλαιο αφιερώνεται στην παρουσίαση κάποιων βασικών επιδημιολογικών μοντέλων. Στο πέμπτο κεφάλαιο παρουσιάζεται η προσομοίωση του βασικού επιδημιολογικού μοντέλου SI (Susceptible-Infectious) συναρτήση διαφόρων τοπολογιών σύνθετων δικτύων, διαφορετικού πλήθους κόμβων και μεταβλητού αριθμού συνδέσεων ανά κόμβο ή μεταβλητή πιθανότητα σύνδεσης κόμβων. Το μέγεθος το οποίο μετράται είναι μία σταθερά «T», η οποία είναι ενδεικτική για να αποφανθούμε αν μια τοπολογία σύνθετου δικτύου είναι «ανθεκτικη» ή όχι έναντι μολύνσεων… Η σταθερά αυτή περιγράφει τα βήματα που απαιτούνται, ώστε μία μόλυνση η οποία ακολουθεί το επιδημιολογικό μοντέλο διάδοσης SI, να εξελιχθεί σε επιδημία έχοντας μολύνει όλους τους κόμβους του δικτύου….Η σταθερά αυτή μπορεί να ερμηνευτεί ως μία σταθερά χρόνου. Η σταθερά αυτή αποτελεί ένα μέτρο μέτρησης των μονάδων χρόνου που απαιτούνται για να μολυνθεί ένα ολόκληρο το δίκτυο και ένα μέσο ώστε να αποκτήσουμε μία σαφή εικόνα για το ποιές τοπολογίες είναι ανθεκτικές σε μολύνσεις και ποιες όχι. / -

Made available in DSpace on 2015-07-22T20:49:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-03-30 / A idéia central desta dissertação de mestrado foi contribuir para a modernização do sistema de vigilância epidemiológica por meio do desenvolvimento de um modelo para o estudo da evolução da Tuberculose (TB) no tempo, disponibilizando este modelo em um ambiente computacional. O modelo citado foi desenvolvido para suportar experimentos controlados com estimativas realísticas, parametrizado segundo a mobilidade e interação da tuberculose com a população, bem como pelo seu desenvolvimento entre os hospedeiros. O modelo de disseminação da tuberculose foi baseado em um autômato celular probabilístico, projetado para explorar explicitamente o comportamento espaço-temporal de uma população heterogênea. As regras de transição mimetizaram os tipos de interação relacionados ao desenvolvimento da doença nessa população. Os resultados obtidos indicaram que a vacina, no que diz respeito à tuberculose, não influencia no seu desaparecimento e que apesar de apresentar um impacto muito grande na tuberculose primária, não tem poder relevante sobre a tuberculose secundária (pulmonar), sendo essa, a forma que transporta a doença de um individuo para outro. Apenas com tratamentos completamente realizados será possível o ver recrudescimento da TB. / TEDE / BV UNIFESP: Teses e dissertações

Resumo: Com objetivo de analisar aspectos epidemiológicos da Mancha de Phaeosphaeria (Phaeosphaeria maydis) e da Cercosporiose (Cercospora zeae - maydis) do milho (Zea mays) no município de Capão Bonito/SP de março a agosto de 2002 a 2006, sendo que a primeira ocorreu em todo período de estudo, enquanto a Cercosporiose (Cercospora zeae-maydis) ocorreu em dois anos (2002 e 2004), foram feitos ensaios em Blocos Casualizados com 3 repetições com 42 a 54 cultivares dependendo do ano. Quatro avaliações em todos os ensaios em intervalos semanais utilizando-se escala diagramática proposta pela Agroceres em 1993. Foi calculada a Curva de Progresso da Doença e a Área abaixo da mesma (AACPD), a qual foi analisada pelo teste F e as médias comparadas pelo teste de Scott-Knott. Com base neste teste os cultivares foram divididos em 4 grupos: Resistentes, Moderadamente Resistentes, Moderadamente Suscetíveis e Suscetíveis. Dados climáticos foram correlacionados com a doença. Foram testados os modelos matemáticos: Logístico, Exponencial, de Gompertz e Monomolecular. Sendo que este último foi o que melhor se ajustou aos dados em todos os anos para as duas doenças, tomando por base o R*2 (coeficiente de determinação entre os valores previstos e os observados). O ano de maior severidade para a Mancha de Phaeosphaeria foi o de 2005, enquanto para a Cercosporiose foi de 2002; isto provavelmente é devido às condições climáticas. A maioria dos cultivares se comportou como moderadamente resistente e resistente à Mancha de Phaeosphaeria e a Cercosporiose. Nota-se que nos anos onde a Mancha de Phaeosphaeria e Cercosporiose ocorreram concomitantemente (2002 e 2004), a primeira apresentou em todos os grupos (R, MR, MS e S) maiores severidades e inicio da epidemia mais tardia que a Cercosporiose. Em ambas a diferença de severidade deve-se principalmente à taxa de progresso de doença (r). / Abstract: With the aim to analyze epidemiological aspects the Phaeosphaeria spot (Phaeosphaeria maydis) and gray leaf spot (Cercospora zeae-maydis) of maize (Zea mays) at Capão Bonito city, from march to august of 2002 to 2006, were studied, as the first occurred in all the period of study, while the gray leaf spot occurred in 2 years (2002 and 2004). The experimental design was casualized blocks with 3 repetitions each and 42 to 54 treatments, depending on the year. Four evaluations were made in weekly intervals using Agroceres diagrammatic scale. The disease progress curve (AUDPC) and its area under it was calculated and submitted to variance analysis (ANAVA) by F test, which averages were compared by Scott-Knott. Based on the results, the cultivars were grouped in resistant, moderately resistant, moderately susceptible and susceptible. Climate data were related to the disease. The logistic, exponential, Gompertz and monomolecular mathematic models were tested, being the monolecular model which better suited the data in all years, for both diseases, based in R*2. The year with higher Phaeosphaeria spot severity was 2005, while for Cercospora leaf spot was 2002, probably caused by climatic conditions. Most varieties were moderately resistant or resistant for Phaeosphaeria spot and Cercospora leaf spot. It was observed that on the years where Phaeosphaeria spot and Cercospora leaf spot occurred concomitantly (2002 and 2004); the first presented in all groups (R, MR, MS and S) higher levels of severity and the delay on the begining of the epidemy compared to Cercospora leaf spot. For both diseases, the difference on the disease progress occured mainly beause of the disease progress rate (r). / Orientador: Modesto Barreto / Coorientador: Giséle Maria Fantin / Banca: Rita de Cássia Panizzi / Banca: Érica Auxiliadora Giacheto Scaloppi / Mestre

abstract: In contemporary society, sustainability and public well-being have been pressing challenges. Some of the important questions are:how can sustainable practices, such as reducing carbon emission, be encouraged? , How can a healthy lifestyle be maintained?Even though individuals are interested, they are unable to adopt these behaviors due to resource constraints. Developing a framework to enable cooperative behavior adoption and to sustain it for a long period of time is a major challenge. As a part of developing this framework, I am focusing on methods to understand behavior diffusion over time. Facilitating behavior diffusion with resource constraints in a large population is qualitatively different from promoting cooperation in small groups. Previous work in social sciences has derived conditions for sustainable cooperative behavior in small homogeneous groups. However, how groups of individuals having resource constraint co-operate over extended periods of time is not well understood, and is the focus of my thesis. I develop models to analyze behavior diffusion over time through the lens of epidemic models with the condition that individuals have resource constraint. I introduce an epidemic model SVRS ( Susceptible-Volatile-Recovered-Susceptible) to accommodate multiple behavior adoption. I investigate the longitudinal effects of behavior diffusion by varying different properties of an individual such as resources,threshold and cost of behavior adoption. I also consider how behavior adoption of an individual varies with her knowledge of global adoption. I evaluate my models on several synthetic topologies like complete regular graph, preferential attachment and small-world and make some interesting observations. Periodic injection of early adopters can help in boosting the spread of behaviors and sustain it for a longer period of time. Also, behavior propagation for the classical epidemic model SIRS (Susceptible-Infected-Recovered-Susceptible) does not continue for an infinite period of time as per conventional wisdom. One interesting future direction is to investigate how behavior adoption is affected when number of individuals in a network changes. The affects on behavior adoption when availability of behavior changes with time can also be examined. / Dissertation/Thesis / M.S. Computer Science 2013

The heat shock protein-70 (Hsp70) family of molecular chaperones are ubiquitous highly conserved proteins that are critical for the viability of cellular homeostasis. The ATPase activity of Hsp70 proteins is critical to their function as the affinity of a given Hsp70 for non-native substrate is modulated by ATP binding and hydrolysis. When bound to ATP, Hsp70s possess a low affinity for a given substrate protein, while the hydrolysis of ATP to ADP causes a conformational change that results in a high affinity for substrate proteins. The basal ATPase activity of Hsp70s is too low to facilitate their function in vivo, and co-chaperones are essential to modulate the efficient protein folding by Hsp70. Heat shock protein-40 (Hsp40) heat shock proteins are essential for the in vivo function of Hsp70s by stimulating the ATPase activity of these proteins and facilitating transfer of substrates. The Type III class of Hsp40 proteins have not been well characterised due to their poor levels of conservation at the primary sequence level. This is due to the fact that Type III Hsp40s only contain a J-domain and a poorly conserved C-terminal region. The newly identified Type IV class of Hsp40s, contain an abrogated HPD tripeptide motif in the J-domain and have also not been extensively studied. Trypanosoma brucei (T. brucei) is a unicellular flagellated protozoan parasite. It is the causative agent of Human African Trypansomiasis (HAT) which results in thousands of deaths and devastating agricultural losses in many parts of Africa. T. brucei undergoes a complex lifecycle that is characterised by the transition from an insect vector to a mammalian host in markedly different conditions of temperature, pH, nutrient availability and respiratory requirements. It has been proposed that molecular chaperones may enhance the survival of these parasites due to their cytoprotective effect in combating cellular stress. Due to the fact that T. brucei infection is invariably fatal if left untreated, and that no novel treatment regimens have been developed recently, the identification of potential novel drug targets among proteins essential to the parasite’s survival in the host organism is an attractive aspect of T. brucei research. Because Type III Hsp40s are poorly conserved with respect to Hsp40s found in the human host, the identification of any of these proteins found to be essential to T. brucei survival in humans could potentially make attractive novel drug targets. An in depth in silico investigation into the Type III Hsp40 complement as well as partner Hsp70 proteins in T.brucei was performed. T. brucei possesses 65 Hsp40 proteins, of which 47 were classed as Type III and 6 of which were identified as being putative Type IV Hsp40s. A small but significant number (5) of Type III TbHsp40s contained tetratricopeptide (TPR) domains in addition to the J-domain. The J-domains of the Type III TbHsp40 complement were found to be conserved with respect to those of canonical Hsp40 proteins, although the mutation of certain residues that play a key role in Hsp40-Hsp70 interaction was noted. Potential partnerships of these proteins in the parasite was also investigated. The coding regions of three previously uncharacterised TbHsp40s were successfully amplified from T. brucei TREU927 genomic DNA and cloned into an expression vector. Tbj1, a Tcj1 ortholog, was selected for further study and successfully expressed and biochemically characterised. Tbj1 expressed in E. coli was found to be insoluble, but large amounts were recovered with the aid of a denaturing purification followed by refolding elution strategies, and the bulk of the protein recovered was in compact monomeric form as determined by size-exclusion chromatography fast protein liquid chromatography (SEC-FPLC). The addition of Tbj1 to a thermally aggregated substrate resulted in increased levels of aggregation, although Tbj1 was able to assist two Hsp70 proteins in the suppression of aggregation. Tbj1 proved unable to stimulate the ATPase activity of these same Hsp70s, and could not rescue temperature sensitive cells when replacing E.coli DnaJ and CbpA. It was concluded that Tbj1 does not possess independent chaperone activity, but could display Hsp40 co-chaperone properties under certain circumstances. This could allude to a specialised function in the T. brucei parasite. The lack of human orthologues to Tbj1 could result in the attractiveness of this protein as a novel drug target.

京都大学 / 0048 / 新制・課程博士 / 博士(医科学) / 甲第18185号 / 医科博第50号 / 新制||医科||4(附属図書館) / 31043 / 京都大学大学院医学研究科医科学専攻 / (主査)教授 朝長 啓造, 教授 松岡 雅雄, 教授 小柳 義夫 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Master of Public Health - MPH / Adequate levels of adherence to treatment for tuberculosis (TB) and HIV at the same time poses a problem for public health in South Africa. TB/HIV co-infected patients face many potential barriers to adherence to treatment for both conditions. There is a need for more knowledge about factors influencing treatment adherence in co-infected patients on concomitant treatment. The aim of this study was to explore the barriers and facilitators to treatment adherence among people co-infected with TB/HIV living in the Alfred Nzo District, Eastern Cape, in order to identify the barriers and facilitators to adherence.

In the absence of an effective vaccine, vector control and surveillance of dengue fever (DF) and dengue hemorrhagic fever (DHF) are the most important strategies currently used to reduce the impact of these diseases in affected population. The objectives of this study were to estimate the incidence of symptomatic and asymptomatic dengue cases, the prevalence of antidengue antibodies, and to evaluate the laboratory and clinical aspects related to an active surveillance of dengue cases. In this study, active surveillance was incorporated as a part of the study design. At total of 3,255 people from four high risk neighborhoods were followed in a two years prospective study whereby the participants' houses were visited three times a week. During these visits, dengue cases were characterized by identifying patients with fever as well as other symptoms that were compatible with dengue disease. In addition, a biannual blood sample was taken for each study participants, to establish the prevalence and six month incidence of dengue infection. We found a crude incidence density (ID) of 3.24 by 100,000 person/days (p/d) which changed from 5.69 by 100,000 p/d for the first year of the study to 1.45 by 100.000 p/d in the second year. In both years, the months from July through September had the highest ID of 8.81 by 100,000 p/d. Children displayed higher ID when compared to adults, RR: 3.92 (2.38 - 6.48). The Plaque Reduction Neutralization Test was used to assay for the presence of antidengue antibody in 2,125 study participants (65.3% of total). The prevalence of anti dengue antibodies was found to be 86.6% (1,840 positives). The prevalence of anti DENV-1 was 74%, while 65.2 % of the participants had anti- DENV-1 and anti- DENV-2 simultaneously. The cumulative incidence of anti IgG dengue antibody in the negative participants (283 at the start of the study) was 30% in the first 6 months period, 29.6% in the second 6 months, and 23.8 in the third one. The difference between the numbers of participants detected in the active surveillance, (270 confirmed and non confirmed dengue cases) with the numbers of people who showed sero-conversion to anti-IgG dengue antibody within a relatively short period of time suggested that there was a high number of asymptomatic dengue infections present in the population. Transmissibility of the virus, the surveillance of dengue, and vaccine implementation in the near future would all be affected by the large number of asymptomatic people in hyperendemic countries.

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