Mathematical Modelling of Spread of Vector Borne Disease In Germany

Ziel dieser Doktorarbeit ist ein mathematisches Modell zu entwickeln, um eine mögliche Ausbreitung des West-Nil-Virus (WNV) in Deutschland zu simulieren und zu bewerten. Das entwickelte Werkzeug soll auch auf eine weitere, durch Zecken übertragene Krankheit, dem Krim-Kongo-Hämorrhagischen Fieber (CCHFV) angewendet werden. Die durch den Klimawandel verursachte globalen Erwärmung unterstützt auch die Verbreitung und Entwicklung verschiedener Vektorpopulationen. Dabei hat eine Temperaturerhöhung einen positiven Einfluss auf den Lebenszyklus des Vektors und die Zunahme der Vektoraktivität. In dieser Arbeit haben wir ein Differentialgleichungsmodell (ODE) entwickelt, um den Einfluss eines regelmäßigen Eintrags von Infektionserregern auf die empfängliche Population unter Berücksichtigung des Temperatureinflusses zu verstehen. Als Ergebnis haben wir einen analytischen Ausdruck der Basisreproduktionszahl und deren Wechselwirkung mit der Temperatur gefunden. Eine Sensitivitätsanalyse zeigt, wie wichtig das Verhältnis der anfälligen Mücken zur lokalen Wirtspopulation ist. Als ein zentrales Ergebnis haben wir den zukünftigen Temperaturverlauf auf Basis der Modellergebnisse des IPCC in unser Modell integriert und Bedingungen gefunden, unter denen es zu einer dauerhaften Etablierung des West-Nil-Virus in Deutschland kommt. Darüber hinaus haben wir die entwickelten mathematischen Modelle verwendet, um verschiedene Szenarien zu untersuchen, unter denen sich CCHFV möglicherweise in einer naiven Population etablieren kann, und wir haben verschiedene Kontrollszenarien mathematisch abgeleitet, um die Belastung von einer Infektion durch Zecken zu bewältigen.The objective of this thesis is to develop the necessary mathematical model to assess the potential spread of West Nile Virus (WNV) in Germany and employ the developed tool to analyse another tick-borne disease Crimean- Congo Hemorrhagic Fever (CCHFV). Given the backdrop of global warming and the climate change, increasing temperature has benefitted the vector population. The increase in the temperature has a positive influence in the life cycle of the vector and the increase in its activities. In this thesis, we have developed an Ordinary Differential Equation (ODE) model system to understand the influence of the periodic introduction of infectious agents into the local susceptible population while taking account of influence of temperature. As results, we have found an analytic expression of the basic reproduction number and its interplay with the temperature. The sensitivity analysis shows us the importance of the ratio between the susceptible mosquitoes to the local host population. As a central result we have extrapolated the temperature trend under different IPCC conditions and found the condition under which the circulation of West Nile Virus will be permanent in Germany. Furthermore, we have utilised the developed mathematical models to examine different scenarios under which CCHFV can potentially establish in a naive population along with we mathematically derived different control scenarios to manage the burden of tick infection

Host-feeding preferences and temperature shape the dynamics of West Nile virus: a mathematical model of assessing the abatement planning

West Nile virus (WNV) is prevalent in the United States but it shows considerable divergence in transmission patterns and spatio-temporal intensity.It is to be noted that the mechanism that drives the transmission potential of WNV is described by the abilities of host species to maintain and disseminate the pathogens pertinent with different eco-epidemiological factors that have an influence on the contact rates amongst the interacting species.There is growing evidence that several vectors exhibit strong feeding preferences towards different host communities.We construct a process based weather driven ordinary differential equation (ODE) model to understand the impact of one vector species Culex pipiens, preferred avian and non-preferred human hosts and compared it surveillance data for the Culex pipiens complex collected in Cook County, Illinois, USA.In our mechanistic model, we also demonstrate that adulticide treatments produced significant reductions in the Culex pipiens population.We take into account the feeding index that can be described as the ratio between observed frequency of mosquitoes feeding on one host compared to another host, divided by the expected frequency of mosquitoes feeding on these two hosts based on the presence of the particular hosts to develop this transmission model for WNV. Our findings demonstrate that the interplay between the feeding index and mosquito abatement strategy is rather a complex phenomenon and it induces a heterogeneous contact rates that should be included while modelling multi-host, multi-vector transmission model

Development of Novel Dual Inhibitor of Chemokine Receptor 4 and Mcl-1 Against Multiple Myeloma

Multiple myeloma (MM) is a neoplastic plasma-cell disorder. This is characterized by clonal proliferation of malignant plasma cells in the bone-marrow (BM) microenvironment, monoclonal protein in blood or urine, and associated organ dysfunction. The treatment options approved by FDA are immune-modulatory agents, proteasome inhibitors, and autologous stem cell transplantation (ASCT). Unfortunately, MM remains uniformly fatal owing to intrinsic or acquired drug resistance and the median survival time is 3 to 5 years. Thus, there is a great need for novel strategies to combat MM. The intimate relationship of myeloma cells to BM microenvironment is “hallmark of myeloma”. The homing of MM cells to the BM, mediated by the chemokine stromal cell-derived factor-1α (SDF-1α) and its receptor CXCR4 has important functional sequelae. The BM microenvironment constituting cells secrete chemokines, cytokines, and growth factors such as interleukin 6 (IL6), vascular endothelial growth factor (VEGF), SDF-1α, and tumor necrosis factor α (TNFα) etc. These growth factors either secreted by MM or BM microenvironment cells (e.g. stromal cells) contribute in activation of several signaling pathways including nuclear factor-κB (NF-κB); phosphatidylinositol 3-kinase (PI3K)-Akt; Ras-Raf-MAPK kinase (MEK)-extracellular signal regulated kinase (ERK); and the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3). Activation of these pathways has been associated with increased expression of several anti-apoptotic proteins such as Bcl-2, Bcl-xL, Mcl-1, and XIAP. Collectively, these discoveries highlight that interaction of MM cells to BM microenvironment not only promote growth, survival and migration of MM cells, but also confer resistance to conventional chemotherapy. We hypothesized that an agent capable of inhibiting the migration of myeloma cells to bone marrow and suppressing the expression of survival protein Mcl-1 would be a better option for MM treatment.We have synthesized a novel dual inhibitor of CXCR4 and Mcl-1. Our data suggests that this molecule inhibits the expression of CXCR4 and Mcl-1 and survival of MM cells

Impact of DC link control strategies on the power-flow convergence of integrated AC–DC systems

For the power-flow solution of integrated AC–DC systems, five quantities are required to be solved per converter, against three independent equations available. These three equations consist of two basic converter equations and one DC network equation, corresponding to each converter. Thus, for solution, two additional equations are required. These two equations are derived from the control specifications adopted for the DC link. Depending on the application, several combinations of valid control specifications are possible. A set of valid control specifications constitutes a control strategy. It is observed that the control strategy adopted for the DC link strongly affects the power-flow convergence of integrated AC–DC systems. This paper investigates how different control strategies affect the power flow convergence of integrated AC–DC systems. Sequential method is used to solve the DC variables in the Newton Raphson (NR) power flow model. Seven typical control strategies have been taken into consideration. This is validated by numerous case studies carried out with multiple DC links incorporated in the IEEE 118-bus and 300-bus test systems

Influence of Nanogels on Mechanical, Dynamic Mechanical, and Thermal Properties of Elastomers

Abstract Use of sulfur crosslinked nanogels to improve various properties of virgin elastomers was investigated for the first time. Natural rubber (NR) and styrene butadiene rubber (SBR) nanogels were prepared by prevulcanization of the respective rubber lattices. These nanogels were characterized by dynamic light scattering, atomic force microscopy (AFM), solvent swelling, mechanical, and dynamic mechanical property measurements. Intermixing of gel and matrix at various ratios was carried out. Addition of NR gels greatly improved the green strength of SBR, whereas presence of SBR nanogels induced greater thermal stability in NR. For example, addition of 16 phr of NR gel increased the maximum tensile stress value of neat SBR by more than 48%. Noticeable increase in glass transition temperature of the gel filled systems was also observed. Morphology of these gel filled elastomers was studied by a combination of energy dispersive X-ray mapping, transmission electron microscopy, and AFM techniques. Particulate filler composite reinforcement models were used to understand the reinforcement mechanism of these nanogels.</p

Grid-Tied Neutral Point Clamped based Centralised Photovoltaic Inverter with Improved DC Link Voltage Balancing and Harmonic Minimisation Control

This paper proposes an improved space vector pulse width modulation (SVPWM) based DC link voltage balancing control of a three-phase three-level neutral point clamped (NPC) centralised inverter supplying the generated power from photo voltaic (PV) array to a three-phase utility grid. Two possible schemes have been developed based on the power conversion stage between PV array and the utility grid namely, two-stage (three-level boost converter three-phase three-level NPC inverter) and single-stage (three-phase three-level NPC inverter alone). The comparison between these two schemes has been thoroughly discussed in terms of the control strategies employed, power loss analysis and efficiency. The performance of the centralised inverter under different modes of operation has been investigated by developing the required control strategies for smooth operation. Using the proposed control strategy, the centralised inverter can be operated as a static synchronous compensator (STATCOM) during night time, if needed. The power loss incurred in the power-electronic converters has been analysed for constant and also for variable ambient temperature. The effectiveness of the centralised inverter as an active filter (AF) has also been verified when a three-phase non-linear load is considered in the system