Development of a co-culture model of the human lungs for toxicity testing and identification of biomarkers of inhalation toxicity

The airway epithelium is the first point of contact in the lung for inhaled material, including infectious pathogens and particulate matter, and protects against toxicity from these substances by trapping and clearance via the mucociliary escalator, presence of a protective barrier with tight junctions and initiation of a local inflammatory response. The inflammatory response involves recruitment of phagocytic cells to neutralise and remove and invading materials and is oftern modelled using rodents. However, development of valid in vitro airway epithelial models is of great importance due to the restrictions on animal studies for cosmetic compound testing implicit in the 7th amendment to the European Union Cosmetics Directive. Further, rodent innate immune responses have fundamental differences to human. Pulmonary endothelial cells and leukocytes are also involved in the innate response initiated during pulmonary inflammation. Co-culture models of the airways, in particular where epithelial cells are cultured at air liquid interface with the presence of tight junctions and differentiated mucociliary cells, offer a solution to this problem. Ideally validated models will allow for detection of early biomarkers of response to exposure and investigation into inflammatory response during exposure. This thesis describes the approaches taken towards developing an in vitro epithelial/endothelial cell model of the human airways and identification biomarkers of response to exposure to xenobiotics. The model comprised normal human primary microvascular endothelial cells and the bronchial epithelial cell line BEAS-2B or normal human bronchial epithelial cells. BEAS-2B were chosen as their characterisation at air liquid interface is limited but they are robust in culture, thereby predicted to provide a more reliable test system. Proteomics analysis was undertaken on challenged cells to investigate biomarkers of exposure. BEAS-2B morphology was characterised at air liquid interface compared with normal human bronchial epithelial cells. The results indicate that BEAS-2B cells at an air liquid interface form tight junctions as shown by expression of the tight junction protein zonula occludens-1. To this author’s knowledge this is the first time this result has been reported. The inflammatory response of BEAS-2B (measured as secretion of the inflammatory mediators interleukin-8 and -6) air liquid interface mono-cultures to Escherichia coli lipopolysaccharide or particulate matter (fine and ultrafine titanium dioxide) was comparable to published data for epithelial cells. Cells were also exposed to polymers of “commercial interest” which were in the nanoparticle range (and referred to particles hereafter). BEAS-2B mono-cultures showed an increased secretion of inflammatory mediators after challenge. Inclusion of microvascular endothelial cells resulted in protection against LPS- and particle- induced epithelial toxicity, measured as cell viability and inflammatory response, indicating the importance of co-cultures for investigations into toxicity. Two-dimensional proteomic analysis of lysates from particle-challenged cells failed to identify biomarkers of toxicity due to assay interference and experimental variability. Separately, decreased plasma concentrations of serine protease inhibitors, and the negative acute phase proteins transthyretin, histidine-rich glycoprotein and alpha2-HS glycoprotein were identified as potential biomarkers of methyl methacrylate/ethyl methacrylate/butylacrylate treatment in rats.

Determinants of entry mode choice of MNCs in emerging markets:evidence from South Africa and Egypt

It is now stylized that the importance of foreign direct investment for developing countries and emerging markets arises from the impact of the presence of multinational corporations (MNCs) in the host country on the productivity of local firms, by way of technology diffusion and competition. There is also general agreement that the extent of technology transfer by an MNC to a developing country affiliate depends on the extent of its control on the local affiliate and that, in turn, the extent of this control depends on the mode of entry of the MNC into the host country. However, the existing literature is based on the experience of developed countries and as such does not contribute to the literature on development economics. This article addresses this lacuna using unique firm-level data from South Africa and Egypt. Our results indicate that the determinants of entry mode choice not only differ between developed and developing countries, but also among developing countries. They also bring into question the role of MNCs in fostering productivity growth in developing countries.

FDI horizontal and vertical effects on local firm technical efficiency

Differencing from previous studies on foreign direct investment (FDI) spillovers to domestic enterprises which mainly focus on productivity, in this paper we take a different perspective by analysing the impacts of FDI to technical efficiency of domestic firms. The paper goes beyond the current literature to shed some light on the spillover effects of FDI to technical efficiency of small and medium enterprises in a developing country. By exploiting a firm-level panel dataset and using SFA models following Battese and Coelli (1995), the paper is able to analyse horizontal spillovers through imitation and competition and labour mobility as well as vertical spillovers through backward and forward linkages on technical efficiency. The paper contributes to the understanding of potential effects on foreign invested enterprises on domestic economy in general and local enterprises performance in particular. Thus it importantly assists policy making by the government of developing countries, where FDI is believed to create technical spillovers on domestic enterprises.

Did they ‘Read before burning’? The Coalition and quangos

Attitudes to quangos are paradoxical. On the one hand they are perceived to be undemocratic, unaccountable organisations, while on the other they are seen to improve effectiveness, limit political interference and increase public confidence in government. This paradox is reflected in the behaviour of political parties, which generally adopt a harsh line towards quangos in opposition, but come to rely on these bodies in office. Ahead of the 2010 general election it was, however, noticeable that the Conservative party rejected this dynamic by promising to pursue ‘a more sophisticated approach’. This article explores the Coalition government's subsequent ‘public bodies reform programme’, assessing its progress against recommendations contained within the Institute for Government's Read before Burning report of July 2010. It concludes that while the Coalition has addressed long-standing concerns about the day-to-day governance of public bodies, it has failed to resolve a set of broader and strategic (metagovernance) issues.

Recursive Methods for Construction of Balanced N-ary Block Designs

2000 Mathematics Subject Classification: Primary 05B05; secondary 62K10.

Rotor retaining sleeve design for a 1.12-MW high-speed PM machine

Permanent-magnet (PM) synchronous machines (PMSMs) can provide excellent performance in terms of torque density, energy efficiency, and controllability. However, PMs on the rotor are prone to centrifugal force, which may break their physical integrity, particularly at high-speed operation. Typically, PMs are bound with carbon fiber or retained by alloy sleeves on the rotor surface. This paper is concerned with the design of a rotor retaining sleeve for a 1.12-MW 18-kr/min PM machine; its electromagnetic performance is investigated by the 2-D finite-element method (FEM). Theoretical and numerical analyses of the rotor stress are carried out. For the carbon fiber protective measure, the stresses of three PM configurations and three pole filler materials are compared in terms of operating temperature, rotor speed, retaining sleeve thickness, and interference fit. Then, a new hybrid protective measure is proposed and analyzed by the 2-D FEM for operational speeds up to 22 kr/min (1.2 times the rated speed). The rotor losses and machine temperatures with the carbon fiber retaining sleeve and the hybrid retaining sleeve are compared, and the sleeve design is refined. Two rotors using both designs are prototyped and experimentally tested to validate the effectiveness of the developed techniques for PM machines. The developed retaining sleeve makes it possible to operate megawatt PM machines at high speeds of 22 kr/min. This opens doors for many high-power high-speed applications such as turbo-generator, aerospace, and submarine motor drives.

Lichenometric dating (lichenometry) and the biology of the lichen genus rhizocarpon:challenges and future directions

Lichenometric dating (lichenometry) involves the use of lichen measurements to estimate the age of exposure of various substrata. Because of low radial growth rates and considerable longevity, species of the crustose lichen genus Rhizocarpon have been the most useful in lichenometry. The primary assumption of lichenometry is that colonization, growth and mortality of Rhizocarpon are similar on surfaces of known and unknown age so that the largest thalli present on the respective faces are of comparable age. This review describes the current state of knowledge regarding the biology of Rhizocarpon and considers two main questions: (1) to what extent does existing knowledge support this assumption; and (2) what further biological observations would be useful both to test its validity and to improve the accuracy of lichenometric dates? A review of the Rhizocarpon literature identified gaps in knowledge regarding early development, the growth rate/size curve, mortality, regeneration, competitive effects, colonization, and succession on rock surfaces. The data suggest that these processes may not be comparable on different rock surfaces, especially in regions where growth rates and thallus turnover are high. In addition, several variables could differ between rock surfaces and influence maximum thallus size, including rate and timing of colonization, radial growth rates, environmental differences, thallus fusion, allelopathy, thallus mortality, colonization and competition. Comparative measurements of these variables on surfaces of known and unknown age may help to determine whether the basic assumptions of lichenometry are valid. Ultimately, it may be possible to take these differences into account when interpreting estimated dates.

The impact of external market factors on operational practices and performance of companies

The links between operational practices and performance are well studied in the literature, both theoretically and empirically. However, mostly internal factors are inspected more closely as the basis of operational performance, even if the impact of external, environmental factors is often emphasized. Our research fills a part of this existing gap in the literature. We examine how two environmental factors, market dynamism and competition impact the use of some operational practices (such as quality improvement, product development, automation, etc.) and the resulting operations and business performance. The method of path analysis is used. Data were acquired through an international survey (IMSS – International Manufacturing Strategy Survey), which was executed in 2005, in 23 participating countries in so called "innovative" industries (ISIC 28-35) with a sample of 711 firms. Results show that both market dynamism and competition have large impact on business performance, but the indirect effects, through operations practices are rather weak compared to direct ones. The most influential practices are from the area of process and control, and quality management.

Effect of blood flow patterns on localized platelet adhesion under physiologic flow conditions using two-dimensional and three-dimensional stent models: An experimental and computational approach

This dissertation presents dynamic flow experiments with fluorescently labeled platelets to allow for spatial observation of wall attachment in inter-strut spacings, to investigate their relationship to flow patterns. Human blood with fluorescently labeled platelets was circulated through an in vitro system that produced physiologic pulsatile flow in (1) a parallel plate blow chamber that contained two-dimensional (2D) stents that feature completely recirculating flow, partially recirculating flow, and completely reattached flow, and (2) a three-dimensional (3D) cylindrical tube that contained stents of various geometric designs. ^ Flow detachment and reattachment points exhibited very low platelet deposition. Platelet deposition was very low in the recirculation regions in the 3D stents unlike the 2D stents. Deposition distal to a strut was always high in 2D and 3D stents. Spirally recirculating regions were found in 3D unlike in 2D stents, where the deposition was higher than at well-separated regions of recirculation. ^

Lions and roses: An interpretive history of Israeli-Iranian relations

This multi-disciplinary research project explores the religious and cultural foundations within the "master commemorative narratives" that frame Israeli and Iranian political discourse. In articulating their grievances against one another, Israeli and Iranian leaders express the tensions between religion, nationalism, and modernity in their own societies. The theoretical and methodological approach of this dissertation is constructivist-interpretivist. The concept of "master commemorative narratives" is adapted from Yael Zerubavel's study of ritualized remembrance in Israeli political culture, and applied to both Israeli and Iranian foreign policy. Israel’s master commemorative narrative draws heavily upon the language of the Hebrew Bible, situating foreign policy discourse within a paradigm of covenantal patrimony, exile, and return, despite the unrelenting hostility of eternal enemies and "the nations." Iran’s master commemorative narrative expresses Iranian suspicion of foreign encroachment and interference, and of the internal corruption that they engender, sacralizing resistance to the forces of evil in the figurative language and myths of pre-Islamic tradition and of Shi'a Islam. Using a constructivist-interpretive methodological approach, this research offers a unique interpretive analysis of the parallels between these narratives, where they intersect, and where they come into conflict. It highlights both the broad appeal and the diverse challenges to the components of these "master" narratives within Israeli and Iranian politics and society. The conclusion of this study explains the ways in which the recognition of religious and cultural conflicts through the optic of master commemorative narratives can complement the perspectives of other theoretical approaches and challenge the conventions of Security Studies. It also suggests some of the potential practical applications of this research in devising more effective international diplomacy.

Essays on openness, economic integration, and *growth

This dissertation examines the relationship between the degree of openness to international trade and the level of growth experienced by a country. More precisely, it explores how trade liberalization and economic integration can lead to specialization in production, affect national levels of welfare, productivity, and competition and at the same time reinforce deflationary efforts. A large part of this investigation is carried out using industry-level data from Spain. ^

A novel method for rapid and selective extraction of male DNA from rape kits using alkaline lysis and pressure cycling technology (PCT)

There is an increasing demand for DNA analysis because of the sensitivity of the method and the ability to uniquely identify and distinguish individuals with a high degree of certainty. But this demand has led to huge backlogs in evidence lockers since the current DNA extraction protocols require long processing time. The DNA analysis procedure becomes more complicated when analyzing sexual assault casework samples where the evidence contains more than one contributor. Additional processing to separate different cell types in order to simplify the final data interpretation further contributes to the existing cumbersome protocols. The goal of the present project is to develop a rapid and efficient extraction method that permits selective digestion of mixtures. ^ Selective recovery of male DNA was achieved with as little as 15 minutes lysis time upon exposure to high pressure under alkaline conditions. Pressure cycling technology (PCT) is carried out in a barocycler that has a small footprint and is semi-automated. Typically less than 10% male DNA is recovered using the standard extraction protocol for rape kits, almost seven times more male DNA was recovered from swabs using this novel method. Various parameters including instrument setting and buffer composition were optimized to achieve selective recovery of sperm DNA. Some developmental validation studies were also done to determine the efficiency of this method in processing samples exposed to various conditions that can affect the quality of the extraction and the final DNA profile. ^ Easy to use interface, minimal manual interference and the ability to achieve high yields with simple reagents in a relatively short time make this an ideal method for potential application in analyzing sexual assault samples.^

Lions and Roses: An Interpretive History of Israeli-Iranian Relations

This multi-disciplinary research project explores the religious and cultural foundations within the “master commemorative narratives” that frame Israeli and Iranian political discourse. In articulating their grievances against one another, Israeli and Iranian leaders express the tensions between religion, nationalism, and modernity in their own societies. The theoretical and methodological approach of this dissertation is constructivist-interpretivist. The concept of “master commemorative narratives” is adapted from Yael Zerubavel’s study of ritualized remembrance in Israeli political culture, and applied to both Israeli and Iranian foreign policy. Israel’s master commemorative narrative draws heavily upon the language of the Hebrew Bible, situating foreign policy discourse within a paradigm of covenantal patrimony, exile, and return, despite the unrelenting hostility of eternal enemies and “the nations.” Iran’s master commemorative narrative expresses Iranian suspicion of foreign encroachment and interference, and of the internal corruption that they engender, sacralizing resistance to the forces of evil in the figurative language and myths of pre-Islamic tradition and of Shi‘a Islam. Using a constructivist-interpretive methodological approach, this research offers a unique interpretive analysis of the parallels between these narratives, where they intersect, and where they come into conflict. It highlights both the broad appeal and the diverse challenges to the components of these “master” narratives within Israeli and Iranian politics and society. The conclusion of this study explains the ways in which the recognition of religious and cultural conflicts through the optic of master commemorative narratives can complement the perspectives of other theoretical approaches and challenge the conventions of Security Studies. It also suggests some of the potential practical applications of this research in devising more effective international diplomacy.

Physical therapy recruitment and retention strategies of hospitals in the US

Hospitals are seeing a reduction of physical therapy (PT) staff due to increased opportunities and competition. Planning effective recruitment and retention strategies for PTs in hospital settings may play an important role in reducing the problem. The primary purpose of this descriptive research was to compile information on recruitment and retention strategies used for physical therapists working in hospital settings. Four hundred surveys were mailed nationwide to hospital-based physical therapy managers. Strategies most commonly used were: attractive benefit package, interdisciplinary teams, competitive salaries, and student employment. The least used strategies used were: sign-on bonus, incentive pay programs, recruitment and retention committee and temporary staffing. It was concluded that hospital administrators need to analyze current strategies used and future recruitment and retention staffing trends, in order to institute successful strategies appropriate to their departments to effectively recruit and retain their staff.

Automatic and adaptable registration of live RGBD video streams sharing partially overlapping views

In this thesis, we introduce DeReEs-4v, an algorithm for unsupervised and automatic registration of two video frames captured depth-sensing cameras. DeReEs-4V receives two RGBD video streams from two depth-sensing cameras arbitrary located in an indoor space that share a minimum amount of 25% overlap between their captured scenes. The motivation of this research is to employ multiple depth-sensing cameras to enlarge the field of view and acquire a more complete and accurate 3D information of the environment. A typical way to combine multiple views from different cameras is through manual calibration. However, this process is time-consuming and may require some technical knowledge. Moreover, calibration has to be repeated when the location or position of the cameras change. In this research, we demonstrate how DeReEs-4V registration can be used to find the transformation of the view of one camera with respect to the other at interactive rates. Our algorithm automatically finds the 3D transformation to match the views from two cameras, requires no human interference, and is robust to camera movements while capturing. To validate this approach, a thorough examination of the system performance under different scenarios is presented. The system presented here supports any application that might benefit from the wider field-of-view provided by the combined scene from both cameras, including applications in 3D telepresence, gaming, people tracking, videoconferencing and computer vision.