Structured deterministic models applied to malaria and other endemic diseases

This thesis includes modeling studies on three structured deterministic models. These models are used to study the disease dynamics of malaria or the joint disease dynamics of HIV and HSV-2. Each of the models includes multiple components containing individuals in various epidemiological classes for the purpose of addressing questions that are of interests to biologists and epidemiologists. Some of the compartments have a continuous age-structure, which is necessary for studying the specific biological questions under investigation.^ In Chapter 2 a chronological-age structured deterministic model for malaria is presented. The model includes the human and mosquito populations with the human population structured by chronological age. The model consists of both PDEs and ODEs. The infected human population is divided into symptomatic infectious, asymptomatic infectious and asymptomatic chronic infected individuals. The original PDE model is reduced to an ODE model with aging. The basic reproduction number R0 is derived for both settings of the model. A novel assumption of the model based on biological evidence is that the infectiousness of chronic infected individuals can be triggered by bites from even susceptible mosquitoes. The model analysis indicates that this assumption contributes greatly to the R0 and therefore needs to be further studied and understood. Numerical simulations for n =2 age groups and a sensitivity/uncertainty analysis show that it is important to both asymptomatic infectious individuals and asymptomatic chronic infections. Age-targeted control strategies are also discussed.^ In Chapter 3 a deterministic malaria model is presented to study the effects of a pre-erythrocytic vaccine on malaria dynamics. The model includes two vaccinated classes, the first for initial vaccination dose(s) and the second for a booster dose. Vaccinated individuals in both compartments are structured by vaccine-age. A vaccine-age dependent transition between vaccinated classes makes it possible to model a minimum vaccine-age required for receiving the booster vaccination. The control reproduction number R is derived and shown to determine the local stability of the disease free equilibrium. Global stability of the disease free equilibrium is shown analytically under certain assumptions and conditions for the existence of endemic equilibria are identified. Numerical results suggest that the incorporation of two vaccination classes, as opposed to only one, allows for a greater accuracy in predicting threshold vaccination coverages for disease eradication. The model also exhibits backward bifurcation, indicating thatR=1 is no longer the threshold value for disease eradication. The effect of waning vaccine efficacy (vaccine-age dependent) on disease prevalence is also investigated. ^ Chapter 4 presents a deterministic model for the joint dynamics of HIV and HSV-2 to study the effect that the presence of HSV-2 may have on the prevalence of HIV. An infection-age is used to incorporate the epidemiological characteristic of HSV-2 that infected individuals change between the acute and the latent stages, and treatment may affect the lengths of these stages. The model is also structured by gender and includes one male and two female populations with different activity levels. The basic reproduction number for each disease, as well as the invasion reproduction numbers are derived. Due to the model complexity, the derivation of these reproduction numbers and their biological interpretations are very challenging, which is one of the novel aspects of this study. Numerical simulations are performed to confirm and extend the analytical results. A sensitivity analysis is also conducted. Model results demonstrate that strategies for reducing co-infections with HIV and HSV-2, particularly treating the high-risk group of females may have an important impact on the HIV disease dynamics

Molecular and Device Engineering Towards the Study of Potential Anti-MRSA Agents

At the intersection of bio-device engineering and bio-pharmaceutical studies, our project involved the design of a hydraulic manifold to be used in isothermal titration calorimetry (ITC), with the ultimate goal of using ITC to study the thermodynamic binding parameters of potential anti-Methicillin Resistant Staphylococcus aureus (MRSA) agents to our drug target, Sortase A. The hydraulic manifold redesign included the analysis of materials such as high density polyethylene (HDPE), polytetrafluorethylene (PTFE, ‘Teflon’), and polycarbonate as well as the implementation of a new construct of the manifold itself. Sortase A is a transpeptidase found in Gram-positive bacteria and catalyses the attachment of virulent surface proteins to the cell wall by recognizing a specific amino acid motif (LPXTG). The ability of the bacterium to communicate with and infect host cells is linked to the Sortase A mechanism. We have identified pyridostigmine bromide as the primary drug target based upon the analysis of ITC data

Das Computerprogramm als Erfahrungsgegenstand

Was ist eigentlich ein Computerprogramm? Technikphilosophische Überlegungen deuten darauf hin, dass unter diesen Begriff sehr unterschiedliche Gegenstände fallen können. Bisherige ontologische Analysen zergliedern aus diesem Grund den Begriff, um beispielsweise zwischen der Semantik eines Programms und greifbaren technischen Artefakten zu unterscheiden. Derartige Analysen bieten eine große Klarheit und Präzision bei der Begriffsverwendung, da die Unterscheidungen der zuvor zergliederten Begriffsanteile in den Vordergrund treten. Gleichzeitig führt dieses Vorgehen jedoch dazu, dass die Zusammenhänge, Verbindungen und wechselseitigen Beeinflussungen der einzelnen Bedeutungen, welche im "Programm"-Begriff gebündelt sind verdeckt werden können. Um diesem Nachteil zu begegnen, wird in dieser Arbeit ein mehrdimensionaler Programmbegriff entwickelt, der eine Unterscheidung zwischen verschiedenen Bedeutungsebenen des Programmbegriffs vornimmt, gleichzeitig aber deren Zusammenhang herausarbeitet. Dafür werden der Begriffsbestimmung epistemologische Überlegungen vorangestellt, die der Frage nachgehen, wie Computerprogramme überhaupt von Menschen wahrgenommen werden können, wie Programme Gegenstände menschlicher Erfahrung werden. Ausgehend von Immanuel Kants Transzendentalphilosophie und Edmund Husserls Grundlegung der Phänomenologie wird ein Zugang zu dieser Erfahrung von Computerprogrammen entwickelt. Dabei wird herausgearbeitet, dass die Programme auf vier voneinander unterscheidbare Arten als Gegenstand konstituiert werden. Die daraus resultierenden Bedeutungsebenen des vorgestellten Programmbegriffs sind jeweils Programme als räumlich-zeitliche, syntaktische, semantische und eingebettete Gegenstände. Der Zusammenhang zwischen diesen Begriffsdimensionen zeigt sich dabei als Eigenschaft der Wahrnehmung von Programmen: Je nachdem, als was ein Programm konstituiert wird, können die jeweils anderen Begriffbedeutungen von "Programm" appräsentiert, also mitgegeben, sein. Dieser Zusammenhang ist in hohem Maße gesellschaftlich und technisch bedingt. Um diese Bedingtheit zu untersuchen wird dies anschließend als Assoziation im Sinne von Bruno Latours Akteur-Netzwerk-Theorie untersucht. Der hier entwickelte Programmbegriff eignet sich, um die Bedeutung von Computerprogrammen im Rahmen technikphilosophischer und techniksoziologischer Forschung zu analysieren. Die Anwendbarkeit des mehrdimensionalen Programmbegriffs zur Analyse menschlicher Bezüge zur Computertechnologie wird in der vorliegenden Arbeit an drei Fallbeispielen im Umfeld der Softwareentwicklung aufgezeigt. Im Mittelpunkt dieser Überlegungen stehen die wechselseitigen Verhältnisse von Mensch, Technik und Gesellschaft zueinander. Abschließend zeigt ein Ausblick weitere Bereiche, in denen mithilfe des entwickelten Begriffs aussichtsreiche Untersuchungen durchgeführt werden können

Kvantifikacija fragmentacije zemljišta u Slovačkoj

During the era of socialist reconstruction the land use was intended to reach large scale agriculture – collectivization. In this period land and land ownership were separated. This situation persisted up to the present day even after the development of socio-economic circumstances. The separation of use and ownership of land, high proportion of land fragmentation and high proportion of state-held agricultural land presents acute issues in regard to land tenure in Slovakia. Current circumstances are forcing the land owner to lend their land. This paper explains that the progress of land tenure situation can be observed via measurement of changes of land fragmentation after processes such as land consolidation. It is imperative to explicitly quantify the scope of land fragmentation. Current methods of land fragmentation calculation in relation to land consolidation are rigid, ad hoc and needlessly complicated. New unified complete yet variable calculation will have wide utilization capabilities in practice. The calculation will enable monitoring of land fragmentation status as well as statistical comparisons correlating with land tenure state in Slovakia.Tijekom razdoblja socijalističke obnove, korištenje zemljišta bilo je usmjereno na postizanje poljoprivrede velikih razmjera – kolektivizacije. U tom je razdoblju bilo odvojeno zemljište od vlasništva nad zemljištem. Takvo je stanje potrajalo sve do danas, čak i nakon nastanka socioekonomskih čimbenika. Odvajanje korištenja zemljišta od vlasništva zemljišta te visoki udio fragmentacije zemljišta i visoki udio državnoga poljoprivrednog zemljišta predstavljaju ozbiljne probleme vezane uz vlasništvo nad zemljištem u Slovačkoj. Trenutne okolnosti prisiljavaju vlasnika zemljišta unajmiti zemljište. Ovaj rad objašnjava kako se napredak stanja s vlasništvom nad zemljištem može promatrati putem praćenja promjena fragmentacije zemljišta nakon postupaka kao što je komasacija zemljišta. Neophodno je eksplicitno kvantificirati opseg fragmentacije zemljišta. Suvremene metode izračunavanja fragmentacije zemljišta vezane uz komasaciju su nefleksibilne i suvišno komplicirane. Novi jedinstveni i cjeloviti izračun s varijablama imat će široku mogućnost primjene u praksi. Izračun će omogućiti praćenje stanja fragmentacije zemljišta, kao i statističke usporedbe, koje su u skladu sa stanjem posjedovanja zemljišta u Slovačkoj

El estado actual de la población en Chile

The contribution explores in the current population's condition, mainly observing in the period 1950-2000. The study includes aspects such Volume and Growth, Birthrate, Mortality, Demographic Transition, and Population Structure according to Age and Sex. The review shows that the population studied is found in evolution as any other national group over the World.La contribución explora en las condiciones actuales de la población, observándola principalmente en el período 1950-2000. El estudio incluye aspectos tales como Volumen y Crecimiento, Natalidad, Mortalidad, Transición Demográfica, y Estructura de la Población según Edad y Sexo. La revisión muestra que la población estudiada se encuentra en evolución como cualquier otro grupo nacional en el mundo