GATA Factors Regulate Inner Ear Development and Midbrain Neurogenesis

The zinc-finger transcription factors GATA2 and GATA3 in vertebrates belong to the six-member family that are essential regulators in the development of various organs. The aim of this study was to gain new information of the roles of GATA2 and GATA3 in inner ear morphogenesis and of the function of GATA2 in neuronal fate specification in the midbrain using genetically modified mouse and chicken embryos as models. A century ago the stepwise process of inner ear epithelial morphogenesis was described, but the molecular players regulating the cellular differentiation of the otic epithelium are still not fully resolved. This study provided novel data on GATA factor roles in several developmental processes during otic development. The expression analysis in chicken suggested that GATA2 and GATA3 possess redundant roles during otic cup and vesicle formation, but complementary cell-type specific functions during vestibular and cochlear morphogenesis. The comparative analysis between mouse and chicken Gata2 and Gata3 expression revealed many conserved aspects, especially during later stages of inner ear development, while the expression was more divergent at early stages. Namely, expression of both Gata genes was initiated earlier in chicken than mouse otic epithelium relative to the morphogenetic stages. Likewise, important differences concerning Gata3 expression in the otic cup epithelium were detected between mouse and chicken, suggesting that distinct molecular mechanisms regulate otic vesicle closure in different vertebrate species. Temporally distinct Gata2 and Gata3 expression was also found during otic ganglion formation in mouse and chicken. Targeted inactivation of Gata3 in mouse embryos caused aberrant morphology of the otic vesicle that in severe cases was disrupted into two parts, a dorsal and a ventral vesicle. Detailed analyses of Gata3 mutant embryos unveiled a crucial role for GATA3 in the initial inner ear morphogenetic event, the invagination of the otic placode. A large-scale comparative expression analysis suggested that GATA3 could control cell adhesion and motility in otic epithelium, which could be important for early morphogenesis. GATA3 was also identified as the first factor to directly regulate Fgf10 expression in the otic epithelium and could thus influence the development of the semicircular ducts. Despite the serious problems in the early inner ear development, the otic sensory fate establishment and some vestibular hair cell differentiation was observable in pharmacologically rescued Gata3-/- embryos. Cochlear sensory differentiation was, however, completely blocked so that no auditory hair cells were detected. In contrast to the early morphogenetic phenotype in Gata3-/- mutants, conditional inactivation of Gata2 in mouse embryos resulted in a relatively late growth defect of the three semicircular ducts. GATA2 was required for the proliferation of the vestibular nonsensory epithelium to support growing of the three ducts. Concurrently, with the role in epithelial semicircular ducts, GATA2 was also required for the mesenchymal cell clearance from the vestibular perilymphatic region between the membranous labyrinth and bony capsule. The gamma-aminobutyric acid-secreting (GABAergic) neurons in the midbrain are clinically relevant since they contribute to fear, anxiety, and addiction regulation. The molecular mechanisms regulating the GABAergic neuronal development, however, are largely unknown. Using tissue-specific mutagenesis in mice, GATA2 was characterized as a critical determinant of the GABAergic neuronal fate in the midbrain. In Gata2-deficient mouse midbrain, GABAergic neurons were not produced, instead the Gata2-mutant cells acquired a glutamatergic neuronal phenotype. Gain-of-function experiments in chicken also revealed that GATA2 was sufficient to induce GABAergic differentiation in the midbrain.

'South-South' Remittance - Poverty reduction nexus. The Case of 'Hadiya' immigrants in South Africa, as Agents of 'Constituence development' in Ethiopia, and the policy implications of their 'remittance instrument'

This thesis explores the link between South-South remittance and development. It attempts to establish improved understanding about the role of immigrants as agents of constituency growth and development. By doing so, it illuminates the dark corners of the policy implications that the unconventional development agency of immigrants might have for countries in the Organization ft Economic Cooperation and Development (OECD). The thesis problematises the existence of state-centric international cooperation as providing the recipe for failed Aid in the face of global poverty menace. In the last half a century, the relative shi' of focus to non-state actors brought about the proliferation of NGOs. That, intrun, helped improve international access to crisis situations; however, their long-term remedial impacts on poverty and development have been contested. Major misgivings for non-governmental organizations (NGOs) are, on one hand, low level goal-bound expenditures and lack of independence from influence of the state, on the other. Therefore, the thesis enterprises to empirically verify its fundamental question whether remitting immigrants constitute an alternative development agency to the traditional players: the State and NGOs. Its main arguments are: due to state's failures in bringing sustainable development in many countries of the South, the future of poverty reduction and development also rests in immigrants' remittances. Nonetheless, in the last decade, remittance security-nexus dominated its discourse. Because of that remittance was viewed as something requiring global regime and restrictions. These temptations to tightly regulate remittance flows carry the danger of overlooking its trans-boundary nature and its strong link with livelihood of the poor. Therefore, to avoid unintended consequences of interventions, there need to be clear policy that bases itself on a discursive knowledge on the issues of North-South and South-South remittances The study involved both literature based and empirical research. It employed Discourse Analysis (C as main method for the former and snow-balling as its approach for the latter. For the first part the thesis constructed three conceptual models, these are: metrological model, police model and ecological model on remittance development-nexus. Through this modeling, the thesis achieved better deconstruction on the concepts remittance, immigrants and development agency. The protagonists of each model, the values and interests they represent, and their main arguments along various lines of dichotomies have been discussed. For instance, the main treats of meteorological model include: it sees remittance as transitional economic variable which require constant speculations and global management; it acts as meteorological station for following up or predicting the level, direction, flow and movement of global remittance. It focuses on official lines and considers the state as legitimate recipient of advic and positive consequence of remittance. On the other hand, police model views remittance as beir at best, development neutral or as an illicit activity requiring global regulations and tight control. Both immigrants and remittance viewed as subversive to establishments. It gives primacy to state stable agent of development and a partner for international cooperation. The anti-thesis to the police model is supplied by ecological model, which this thesis is a part. Ecological model on remittance and immigrants argues that, tight global regulations alone cannot be a panacea for possible abuse of informal remittance system. Ecological model, not only links remittance to poverty reduction, the main trust of development, but also considers the development agency of immigrants as critical factor for 21st century north-south development intervention. It sees immigrants as development conscious and their remittance instrument as most stable flow of finance to the developing countries. Besides, it sees remittance as effective poverty solutions than Foreign Direct Investment and international AID. This thesis focuses on the significance of South-South remittance and investigates the South Africa - Ethiopia remittance corridor, as case study; and empirically verifies the role of Ethiopian (Kembata and Hadiya) immigrants in South Africa as agents of local development back home. The study involved techniques of interview, group discussions, observations and investigative study. It also looked into the determinants of their migration to South Africa, and their remittance to Ethiopia. The theoretical models in the first part of the thesis have been operationalised throughout the empirical part to verify if the Kembata and Hadiya immigrants played the crucial role in their household poverty and local development in comparison with the Ethiopian state and the NGOs involved in the system. As evidenced by the research the thesis has made three distinct contributions to the discourse of remittance development-nexus. Fist, it systematized the debate about linkages between remittance, immigrants, development agency and policy of international cooperation by creating three conceptual models (school of thoughts); second, it singled out remitting immigrants as new agents of development in the South; third, it deconstructed concept of remittance and established South¬South remittance as additional sphere of academic investigation. In addition to the above contributions, the thesis finds that Kembata and Hadiya immigrants have engaged in various developmental activities in their locality than usually anticipated. Hence, it concludes that Ethiopian immigrants constitute an alternative development agency to the state and other non-state actors in their country, and the lesson can be applied to poverty reduction strategies in most developing countries.

Progress in tuberculosis vaccine development and host-directed therapies-a state of the art review

Tuberculosis continues to kill 1.4 million people annually. During the past 5 years, an alarming increase in the number of patients with multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis has been noted, particularly in eastern Europe, Asia, and southern Africa. Treatment outcomes with available treatment regimens for drug-resistant tuberculosis are poor. Although substantial progress in drug development for tuberculosis has been made, scientific progress towards development of interventions for prevention and improvement of drug treatment outcomes have lagged behind. Innovative interventions are therefore needed to combat the growing pandemic of multidrug-resistant and extensively drug-resistant tuberculosis. Novel adjunct treatments are needed to accomplish improved cure rates for multidrug-resistant and extensively drug-resistant tuberculosis. A novel, safe, widely applicable, and more effective vaccine against tuberculosis is also desperately sought to achieve disease control. The quest to develop a universally protective vaccine for tuberculosis continues. So far, research and development of tuberculosis vaccines has resulted in almost 20 candidates at different stages of the clinical trial pipeline. Host-directed therapies are now being developed to refocus the anti-Mycobacterium tuberculosis-directed immune responses towards the host; a strategy that could be especially beneficial for patients with multidrug-resistant tuberculosis or extensively drug-resistant tuberculosis. As we are running short of canonical tuberculosis drugs, more attention should be given to host-directed preventive and therapeutic intervention measures.

Virus-sized colloid transport in a single pore: Model development and sensitivity analysis

A mathematical model is developed to simulate the transport and deposition of virus-sized colloids in a cylindrical pore throat considering various processes such as advection, diffusion, colloid-collector surface interactions and hydrodynamic wall effects. The pore space is divided into three different regions, namely, bulk, diffusion and potential regions, based on the dominant processes acting in each of these regions. In the bulk region, colloid transport is governed by advection and diffusion whereas in the diffusion region, colloid mobility due to diffusion is retarded by hydrodynamic wall effects. Colloid-collector interaction forces dominate the transport in the potential region where colloid deposition occurs. The governing equations are non-dimensionalized and solved numerically. A sensitivity analysis indicates that the virus-sized colloid transport and deposition is significantly affected by various pore-scale parameters such as the surface potentials on colloid and collector, ionic strength of the solution, flow velocity, pore size and colloid size. The adsorbed concentration and hence, the favorability of the surface for adsorption increases with: (i) decreasing magnitude and ratio of surface potentials on colloid and collector, (ii) increasing ionic strength and (iii) increasing pore radius. The adsorbed concentration increases with increasing Pe, reaching a maximum value at Pe = 0.1 and then decreases thereafter. Also, the colloid size significantly affects particle deposition with the adsorbed concentration increasing with increasing particle radius, reaching a maximum value at a particle radius of 100 nm and then decreasing with increasing radius. System hydrodynamics is found to have a greater effect on larger particles than on smaller ones. The secondary minimum contribution to particle deposition has been found to increase as the favorability of the surface for adsorption decreases. The sensitivity of the model to a given parameter will be high if the conditions are favorable for adsorption. The results agree qualitatively with the column-scale experimental observations available in the literature. The current model forms the building block in upscaling colloid transport from pore scale to Darcy scale using Pore-Network Modeling. (C) 2014 Elsevier By. All rights reserved.

DESIGN REQUIREMENTS FOR DIRECT SUPERCRITICAL CARBON DIOXIDE RECEIVER DEVELOPMENT AND TESTING

This paper establishes the design requirements for the development and testing of direct supercritical carbon dioxide (sCO2) solar receivers. Current design considerations are based on the ASME Boiler and Pressure Vessel Code (BPVC). Section I (BPVC) considers typical boilers/superheaters (i.e. fired pressure vessels) which work under a constant low heat flux. Section VIII (BPVC) considers pressure vessels with operating pressures above 15 psig 2 bar] (i.e. unfired pressure vessels). Section III, Division I - Subsection NH (BPVC) considers a more detailed stress calculation, compared to Section I and Section VIII, and requires a creep-fatigue analysis. The main drawback from using the BPVC exclusively is the large safety requirements developed for nuclear power applications. As a result, a new set of requirements is needed to perform detailed thermal-structural analyses of solar thermal receivers subjected to a spatially-varying, high-intensity heat flux. The last design requirements document of this kind was an interim Sandia report developed in 1979 (SAND79-8183), but it only addresses some of the technical challenges in early-stage steam and molten-salt solar receivers but not the use of sCO2 receivers. This paper presents a combination of the ASME BPVC and ASME B31.1 Code modified appropriately to achieve the reliability requirements in sCO(2) solar power systems. There are five main categories in this requirements document: Operation and Safety, Materials and Manufacturing, Instrumentation, Maintenance and Environmental, and General requirements. This paper also includes the modeling guidelines and input parameters required in computational fluid dynamics and structural analyses utilizing ANSYS Fluent, ANSYS Mechanical, and nCode Design Life. The main purpose of this document is to serve as a reference and guideline for design and testing requirements, as well as to address the technical challenges and provide initial parameters for the computational models that will be employed for the development of sCO(2) receivers.

Impact of development and dissemination of Integrated Aquaculture-Agriculture (IAA) Technologies in Malawi

Malawi is a small but densely populated country in Southern Africa. Fish is an important part of the nutrition of Malawians, providing essential protein and micronutrients. However, per capita fish consumption has halved over the ten-year period between 1988 to 1998 due to over-fishing in the lakes and doubling of the population since the 1970s, accompanied by an increase in the price of fish. This has worsened access to food insecurity, especially in rural areas, in a country where an estimated 66 per cent of the population consume less than the minimum daily calorie requirement. This paper presents an ex-post impact assessment of the development and dissemination of smallscale integrated aquaculture-agriculture technologies by The WorldFish Center and its national and international partners over more than 15 years in Malawi. The impact study measures the effects of these outputs on the degree of integrated aquaculture-agriculture (IAA) technology adoption and diffusion, the effects on farm income and health of household members, and the welfare effects of increased fish supply on the Malawian economy.

Fish for the future: Fisheries development and food security for Kiribati in an era of global climate change

The Republic of Kiribati is a vast South Pacific island group with one of the largest exclusive economic zones (EEZs) in the world. Kiribati waters support a wealth of marine fisheries activities. These activities occur in oceanic, coastal and inshore environments and range from large, foreign, industrial-scale oceanic fishing operations to small-scale, domestic, inshore subsistence fisheries, aquaculture and recreational fisheries. Kiribati has developed a framework of domestic and international governance arrangements that are designed to sustainably manage its wealth of marine resources. The report provides background information for fisheries projects in Kiribati that aim to build food security, improve artisanal livelihoods and strengthen community engagement in fisheries governance. It provides information on the current status of Kiribati fishery resources (oceanic and coastal), their current governance and future challenges. Fish and fisher alike pay little heed to maritime boundaries and bureaucratic distinctions. This report covers both sides of the oceanic/coastal boundary because of the I-Kiribati communities’ interest in oceanic fisheries such as tuna and their heavy dependence on its fisheries resources for food security and economic development. The report focuses on two potential pilot sites for community-based fisheries management projects: North Tarawa and Butaritari.

Development and storage characteristics of dehydrated salt mince from low priced fish

The study showed that less initial moisture with high salt content will be the best condition for enhanced storage life of dehydrated salt mince. Between sample I (10% salt per meat weight) and sample II (15% salt per meat weight) the latter was comparatively better in colour, odour and longer shelf-life. At room temperature the dehydrated salt mince has not showed any increase in total bacterial count. It is also found that the storage life of the salt mince can be enhanced to a significant extent by lowering the moisture content to below 10% and increasing the salt content to above 30%. Peroxide value, free fatty acid value, total volatile nitrogen and trimethylamine registered gradual increase during storage at room temperature for all the three samples. Among the three samples, the sample treated with 0.1% citric acid and 0.125% butylated hydroxy anisole was comparatively better in appearance and showed less rancidity as indicated by TBA values, up to a period of 15 weeks and thereafter all the three samples were almost similar in storage characteristics. Hence, the treatment with citric acid and B.H.A. has apparently not much significance in improving shelf-life and quality of salted dehydrated fish mince.

DEVELOPMENT OF CURRENT-BASED MICROSCOPIC DEFECT ANALYSIS-METHODS AND ASSOCIATED OPTICAL FILLING TECHNIQUES FOR THE INVESTIGATION ON HIGHLY IRRADIATED HIGH-RESISTIVITY SILICON DETECTORS

Current based microscopic defect analysis methods such as current deep level transient spectroscopy (I-DLTS) and thermally stimulated current (TSC) have been further developed in accordance with the need for the defect analysis of highly irradiated (Phi(n) > 10(13) n/cm(2)) high resistivity silicon detectors. The new I-DLTS/TSC system has a temperature range of 8 K less than or equal to T less than or equal to 450 K and a high sensitivity that can detect a defect concentration of less than 10(10)/cm(3) (background noise as low as 10 fA). A new filling method using different wavelength laser illumination has been applied, which is more efficient and suitable than the traditional voltage pulse filling. It has been found that the filling of a defect level depends on such factors as the total concentration of free carriers generated or injected, the penetration length of the laser (laser wavelength), the temperature at which the filling is taking place, as well as the decay time after the filling (but before the measurement). The mechanism of the defect filling can be explained by the competition between trapping and detrapping of defect levels, possible capture cross section temperature dependence, and interaction among various defect levels in terms of charge transferring. Optimum defect filling conditions have been suggested for highly irradiated high resistivity silicon detectors.

Industrial development and land use/cover change and their effects on local environment: a case study of Changshu in eastern coastal China

The interactions among industrial development, land use/cover change (LUCC), and environmental effects in Changshu in the eastern coastal China were analyzed using high-resolution Landsat TM data in 1990, 1995, 2000, and 2006, socio-economic data and water environmental quality monitoring data from research institutes and governmental departments. Three phases of industrial development in Changshu were examined (i.e., the three periods of 1990 to 1995, 1995 to 2000, and 2000 to 2006). Besides industrial development and rapid urbanization, land use/cover in Changshu had changed drastically from 1990 to 2006. This change was characterized by major replacements of farmland by urban and rural settlements, artificial ponds, forested and constructed land. Industrialization, urbanization, agricultural structure adjustment, and rural housing construction were the major socio-economic driving forces of LUCC in Changshu. In addition, the annual value of ecosystem services in Changshu decreased slightly during 1990-2000, but increased significantly during 2000-2006. Nevertheless, the local environmental quality in Changshu, especially in rural areas, has not yet been improved significantly. Thus, this paper suggests an increased attention to fully realize the role of land supply in adjustment of environment-friendly industrial structure and urban-rural spatial restructuring, and translating the land management and environmental protection policies into an optimized industrial distribution and land-use pattern.

Origin, development and evolutionary model of shelf desertization environment in late stage of Upper Pleistocene

Based on the study of palaeo-environmental evolution in the shelves of the Eastern China Seas, the concept of ''shelf desertization'' in the late stage of Upper Pleistocene is defined; the environmental background and evolutionary process of shelf desertization are analysed. Study on the records of subbottom profiling and the data of core samples from shelf areas revealed that during low sea-level stages, the sedimentary environment in the exposed shelf plains was dominated by aeolian depositional process under cold and dry climatic conditions, i.e. under the action of strong winter-monsoon winds. Parts of the exposed marine strata were disintegrated, and aeolian sand dunes were formed on the disintegrated marine deposits, from which the finer sediment grains were blown away by wind and deposited in the downwind areas to form the derivative loess deposits. Thus a desertization environmental system was formed in the exposed shelf plains of the Eastern China Seas.