Probing the HIV reverse-transcriptase enzyme with novel bifunctional HIV-1 RT inhibitors of the general formula (NRTI)-spacer-(NNRTI)

Includes abstract.Includes bibliographical references (leaves 224-233).The high levels of resistance elicited by both nucleoside (NRTI) and non-nucleoside (NNRTI) reverse transcriptase inhibitors have prompted the design of double-drugs combining these two entities with the aim of addressing the emergence of resistance as well as searching for synergism between the two drug target sites on HIV reverse transcriptase (RT). The strategy involves combining two different inhibitors into a single chemical entity via a linker, with the aim of developing a mixed-site inhibitor combining the inhibitory actions of each drug. This thesis describes the rational drug-design and synthesis of nine bifunctional drugs combining a nucleos(t)ide and a non-nucleoside reverse transcriptase inhibitor linked via different non-cleavable spacers. The C-5 position of the nucleos(t)ide portion of the bifunctional was used for attachment of the spacer throughout. However, the site of attachment on the nonnucleoside drug varies according to the inhibitor type

Comparative Study and Simulation of Different Maximum Power Point Tracking (MPPT) Techniques Using Fractional Control & Grey Wolf Optimizer for Grid Connected PV System with Battery

This chapter presents the comparative analysis between perturb & observe (P&O), incremental conductance (Inc Cond), and fractional open-circuit voltage (FOCV) algorithms using fractional order control & a new meta-heuristic called Grey Wolf optimizer (GWO) for extracting the maximum power from photovoltaic (PV) array. PV array systems are equipped with maximum power point tracking controllers (MPPTCs) to maximize the output power even in the case of rapid changes of the panel’s temperature and irradiance. In this chapter, three cost effective MPPTCs are introduced: FOCV, P&O and Inc. Cond. The output voltage of the array is boosted up to a higher value so it can be interfaced to the local medium voltage distribution network

Advancing vaccine development and manufacture in Africa

Emerging and known infectious diseases pose a constant threat to the health and prosperity of Africa and its people. Africa, like other regions of the world with a high burden of vaccine preventable diseases, has benefited immensely from vaccines and Africa’s growing population means an increase in the continuing need for vaccines. By 2050, Africa’s population will be 2.5 billion and one in four people in the world will be African. However, Africa has limited capacity to produce vaccines, yet is the most in need of routine vaccines. Currently less than 1% of vaccines used in Africa is made in Africa while Unicef supplies more than 60% of its global demand for vaccines to Africa. Dependency on external vaccines supply has rendered Africa vulnerable in epidemics and pandemics, and poorly prepared to respond adequately to emergency situations during disease outbreaks. Local vaccine development and production in Africa is therefore essential to support Africa’s growing needs and specific disease burdens as well as boost socio-economic development and the development of skills in biotechnology, and positively impact industrial and life science development. However, building local capacity would require the right level of political and technical support, including a clear, well-funded and coherent regional policymaking and planning approach, allowing development of the necessary ecosystem to establish a viable, competitive and sustainable vaccine manufacturing capability. An overview of the work of the African Vaccine Manufacturing Initiative (AVMI) and its mission of advancing vaccine development and manufacturing capacity in Africa will be provided. Collaborative efforts with partners, progress to date and the need for an African vaccine manufacturing policy will be discussed. Please click Additional File below for the presentation