Development of test-based wind-driven rain intrusion model for hurricane-induced building interior and contents damage

Major portion of hurricane-induced economic loss originates from damages to building structures. The damages on building structures are typically grouped into three main categories: exterior, interior, and contents damage. Although the latter two types of damages, in most cases, cause more than 50% of the total loss, little has been done to investigate the physical damage process and unveil the interdependence of interior damage parameters. Building interior and contents damages are mainly due to wind-driven rain (WDR) intrusion through building envelope defects, breaches, and other functional openings. The limitation of research works and subsequent knowledge gaps, are in most part due to the complexity of damage phenomena during hurricanes and lack of established measurement methodologies to quantify rainwater intrusion. This dissertation focuses on devising methodologies for large-scale experimental simulation of tropical cyclone WDR and measurements of rainwater intrusion to acquire benchmark test-based data for the development of hurricane-induced building interior and contents damage model. Target WDR parameters derived from tropical cyclone rainfall data were used to simulate the WDR characteristics at the Wall of Wind (WOW) facility. The proposed WDR simulation methodology presents detailed procedures for selection of type and number of nozzles formulated based on tropical cyclone WDR study. The simulated WDR was later used to experimentally investigate the mechanisms of rainwater deposition/intrusion in buildings. Test-based dataset of two rainwater intrusion parameters that quantify the distribution of direct impinging raindrops and surface runoff rainwater over building surface — rain admittance factor (RAF) and surface runoff coefficient (SRC), respectively —were developed using common shapes of low-rise buildings. The dataset was applied to a newly formulated WDR estimation model to predict the volume of rainwater ingress through envelope openings such as wall and roof deck breaches and window sill cracks. The validation of the new model using experimental data indicated reasonable estimation of rainwater ingress through envelope defects and breaches during tropical cyclones. The WDR estimation model and experimental dataset of WDR parameters developed in this dissertation work can be used to enhance the prediction capabilities of existing interior damage models such as the Florida Public Hurricane Loss Model (FPHLM).^

Development and Application of Covalent-Labeling Strategies for the Large-Scale Thermodynamic Analysis of Protein Folding and Ligand Binding

Thermodynamic stability measurements on proteins and protein-ligand complexes can offer insights not only into the fundamental properties of protein folding reactions and protein functions, but also into the development of protein-directed therapeutic agents to combat disease. Conventional calorimetric or spectroscopic approaches for measuring protein stability typically require large amounts of purified protein. This requirement has precluded their use in proteomic applications. Stability of Proteins from Rates of Oxidation (SPROX) is a recently developed mass spectrometry-based approach for proteome-wide thermodynamic stability analysis. Since the proteomic coverage of SPROX is fundamentally limited by the detection of methionine-containing peptides, the use of tryptophan-containing peptides was investigated in this dissertation. A new SPROX-like protocol was developed that measured protein folding free energies using the denaturant dependence of the rate at which globally protected tryptophan and methionine residues are modified with dimethyl (2-hydroxyl-5-nitrobenzyl) sulfonium bromide and hydrogen peroxide, respectively. This so-called Hybrid protocol was applied to proteins in yeast and MCF-7 cell lysates and achieved a ~50% increase in proteomic coverage compared to probing only methionine-containing peptides. Subsequently, the Hybrid protocol was successfully utilized to identify and quantify both known and novel protein-ligand interactions in cell lysates. The ligands under study included the well-known Hsp90 inhibitor geldanamycin and the less well-understood omeprazole sulfide that inhibits liver-stage malaria. In addition to protein-small molecule interactions, protein-protein interactions involving Puf6 were investigated using the SPROX technique in comparative thermodynamic analyses performed on wild-type and Puf6-deletion yeast strains. A total of 39 proteins were detected as Puf6 targets and 36 of these targets were previously unknown to interact with Puf6. Finally, to facilitate the SPROX/Hybrid data analysis process and minimize human errors, a Bayesian algorithm was developed for transition midpoint assignment. In summary, the work in this dissertation expanded the scope of SPROX and evaluated the use of SPROX/Hybrid protocols for characterizing protein-ligand interactions in complex biological mixtures.

CLARITY and PACT-based imaging of adult zebrafish and mouse for whole-animal analysis of infections.

Visualization of infection and the associated host response has been challenging in adult vertebrates. Owing to their transparency, zebrafish larvae have been used to directly observe infection in vivo; however, such larvae have not yet developed a functional adaptive immune system. Cells involved in adaptive immunity mature later and have therefore been difficult to access optically in intact animals. Thus, the study of many aspects of vertebrate infection requires dissection of adult organs or ex vivo isolation of immune cells. Recently, CLARITY and PACT (passive clarity technique) methodologies have enabled clearing and direct visualization of dissected organs. Here, we show that these techniques can be applied to image host-pathogen interactions directly in whole animals. CLARITY and PACT-based clearing of whole adult zebrafish and Mycobacterium tuberculosis-infected mouse lungs enables imaging of mycobacterial granulomas deep within tissue to a depth of more than 1 mm. Using established transgenic lines, we were able to image normal and pathogenic structures and their surrounding host context at high resolution. We identified the three-dimensional organization of granuloma-associated angiogenesis, an important feature of mycobacterial infection, and characterized the induction of the cytokine tumor necrosis factor (TNF) within the granuloma using an established fluorescent reporter line. We observed heterogeneity in TNF induction within granuloma macrophages, consistent with an evolving view of the tuberculous granuloma as a non-uniform, heterogeneous structure. Broad application of this technique will enable new understanding of host-pathogen interactions in situ.

Design, analysis and evaluation of sigma-delta based beamformers for medical ultrasound imaging applications

The inherent analogue nature of medical ultrasound signals in conjunction with the abundant merits provided by digital image acquisition, together with the increasing use of relatively simple front-end circuitries, have created considerable demand for single-bit  beamformers in digital ultrasound imaging systems. Furthermore, the increasing need to design lightweight ultrasound systems with low power consumption and low noise, provide ample justification for development and innovation in the use of single-bit  beamformers in ultrasound imaging systems. The overall aim of this research program is to investigate, establish, develop and confirm through a combination of theoretical analysis and detailed simulations, that utilize raw phantom data sets, suitable techniques for the design of simple-to-implement hardware efficient  digital ultrasound beamformers to address the requirements for 3D scanners with large channel counts, as well as portable and lightweight ultrasound scanners for point-of-care applications and intravascular imaging systems. In addition, the stability boundaries of higher-order High-Pass (HP) and Band-Pass (BP) Σ−Δ modulators for single- and dual- sinusoidal inputs are determined using quasi-linear modeling together with the describing-function method, to more accurately model the  modulator quantizer. The theoretical results are shown to be in good agreement with the simulation results for a variety of input amplitudes, bandwidths, and modulator orders. The proposed mathematical models of the quantizer will immensely help speed up the design of higher order HP and BP Σ−Δ modulators to be applicable for digital ultrasound beamformers. Finally, a user friendly design and performance evaluation tool for LP, BP and HP  modulators is developed. This toolbox, which uses various design methodologies and covers an assortment of  modulators topologies, is intended to accelerate the design process and evaluation of  modulators. This design tool is further developed to enable the design, analysis and evaluation of  beamformer structures including the noise analyses of the final B-scan images. Thus, this tool will allow researchers and practitioners to design and verify different reconstruction filters and analyze the results directly on the B-scan ultrasound images thereby saving considerable time and effort.

The Antibiotic Resistance and Prescribing in European Children Project: A Neonatal and Pediatric Antimicrobial Web-based Point Prevalence Survey in 73 Hospitals Worldwide

BACKGROUND: The neonatal and pediatric antimicrobial point prevalence survey (PPS) of the Antibiotic Resistance and Prescribing in European Children project (http://www.arpecproject.eu/) aims to standardize a method for surveillance of antimicrobial use in children and neonates admitted to the hospital within Europe. This article describes the audit criteria used and reports overall country-specific proportions of antimicrobial use. An analytical review presents methodologies on antimicrobial use.

METHODS: A 1-day PPS on antimicrobial use in hospitalized children was organized in September 2011, using a previously validated and standardized method. The survey included all inpatient pediatric and neonatal beds and identified all children receiving an antimicrobial treatment on the day of survey. Mandatory data were age, gender, (birth) weight, underlying diagnosis, antimicrobial agent, dose and indication for treatment. Data were entered through a web-based system for data-entry and reporting, based on the WebPPS program developed for the European Surveillance of Antimicrobial Consumption project.

RESULTS: There were 2760 and 1565 pediatric versus 1154 and 589 neonatal inpatients reported among 50 European (n = 14 countries) and 23 non-European hospitals (n = 9 countries), respectively. Overall, antibiotic pediatric and neonatal use was significantly higher in non-European (43.8%; 95% confidence interval [CI]: 41.3-46.3% and 39.4%; 95% CI: 35.5-43.4%) compared with that in European hospitals (35.4; 95% CI: 33.6-37.2% and 21.8%; 95% CI: 19.4-24.2%). Proportions of antibiotic use were highest in hematology/oncology wards (61.3%; 95% CI: 56.2-66.4%) and pediatric intensive care units (55.8%; 95% CI: 50.3-61.3%).

CONCLUSIONS: An Antibiotic Resistance and Prescribing in European Children standardized web-based method for a 1-day PPS was successfully developed and conducted in 73 hospitals worldwide. It offers a simple, feasible and sustainable way of data collection that can be used globally.

Nanostructuring Ferroelectrics via Focused Ion Beam Methodologies

As we reach the physical limit of Moore’s law and silicon based electronics, alternative schemes for memory and sensor devices are being proposed on
a regular basis. The properties of ferroelectric materials on the nanoscale are key to developing device applications of this intriguing material class, and nanostructuring has been readily pursued in recent times. Focused ion beam (FIB) microscopy is one of the most signi cant techniques for achieving
this. When applied in tandem with the imaging and nanoscale manipulation afforded by proximal scanning force microscopy tools, FIB-driven nanoscale characterization has demonstrated the power and ability which simply may not be possible by other fabrication techniques in the search for innovative and novel ferroic phenomena. At the same time the process is not without pitfalls; it is time-consuming and success is not always guaranteed thus often being the bane in progress. This balanced review explores a brief history of the relationship between the FIB and ferroelectrics, the fascinating properties it has unveiled, the challenges associated with FIB that have led to alterna- tive nanostructuring techniques and nally new ideas that should be explored using this exciting technique.

A graph-based hyper heuristic for timetabling problems

This paper presents an investigation of a simple generic hyper-heuristic approach upon a set of widely used constructive heuristics (graph coloring heuristics) in timetabling. Within the hyperheuristic framework, a Tabu Search approach is employed to search for permutations of graph heuristics which are used for constructing timetables in exam and course timetabling problems. This underpins a multi-stage hyper-heuristic where the Tabu Search employs permutations upon a different number of graph heuristics in two stages. We study this graph-based hyper-heuristic approach within the context of exploring fundamental issues concerning the search space of the hyper-heuristic (the heuristic space) and the solution space. Such issues have not been addressed in other hyper-heuristic research. These approaches are tested on both exam and course benchmark timetabling problems and are compared with the fine-tuned bespoke state-of-the-art approaches. The results are within the range of the best results reported in the literature. The approach described here represents a significantly more generally applicable approach than the current state of the art in the literature. Future work will extend this hyper-heuristic framework by employing methodologies which are applicable on a wider range of timetabling and scheduling problems.

A graph-based hyper heuristic for timetabling problems

This paper presents an investigation of a simple generic hyper-heuristic approach upon a set of widely used constructive heuristics (graph coloring heuristics) in timetabling. Within the hyperheuristic framework, a Tabu Search approach is employed to search for permutations of graph heuristics which are used for constructing timetables in exam and course timetabling problems. This underpins a multi-stage hyper-heuristic where the Tabu Search employs permutations upon a different number of graph heuristics in two stages. We study this graph-based hyper-heuristic approach within the context of exploring fundamental issues concerning the search space of the hyper-heuristic (the heuristic space) and the solution space. Such issues have not been addressed in other hyper-heuristic research. These approaches are tested on both exam and course benchmark timetabling problems and are compared with the fine-tuned bespoke state-of-the-art approaches. The results are within the range of the best results reported in the literature. The approach described here represents a significantly more generally applicable approach than the current state of the art in the literature. Future work will extend this hyper-heuristic framework by employing methodologies which are applicable on a wider range of timetabling and scheduling problems.

Fluorine-18-labeled estrogens, progestins and corticosteroids for receptor-based imaging of breast tumors and target areas of the brain

Estrogens can be labeled with the positron-emitting radionuclide fluorine-18 (t$\sb{1/2}$ = 110 min) by fluoride ion (n-Bu$\sb4$N$\sp{18}$F) displacement of a 16$\beta$-trifluoromethanesulfonate (triflate) derivative of the corresponding estrone 3-triflate, and purification by HPLC. That sequence has been used to synthesize the 11$\beta$-methoxy 1 and 11$\beta$-ethyl 2 analogues of the breast tumor imaging agent, 16$\alpha$-($\sp{18}$F) fluoro-17$\beta$-estradiol (FES). Tissue distribution studies of 1 and 2 in immature female rats show high selectivity for target tissue (T, uterus) vs non-target (NT, muscle and lung), with T/NT ratios being 43 and 17 at one hour after injection for 1 and 2, respectively. The parent estrogen FES has previously been shown to display an intermediate value for tissue selectivity.

An Estimation of Distribution Algorithm with Intelligent Local Search for Rule-based Nurse Rostering

This paper proposes a new memetic evolutionary algorithm to achieve explicit learning in rule-based nurse rostering, which involves applying a set of heuristic rules for each nurse's assignment. The main framework of the algorithm is an estimation of distribution algorithm, in which an ant-miner methodology improves the individual solutions produced in each generation. Unlike our previous work (where learning is implicit), the learning in the memetic estimation of distribution algorithm is explicit, i.e. we are able to identify building blocks directly. The overall approach learns by building a probabilistic model, i.e. an estimation of the probability distribution of individual nurse-rule pairs that are used to construct schedules. The local search processor (i.e. the ant-miner) reinforces nurse-rule pairs that receive higher rewards. A challenging real world nurse rostering problem is used as the test problem. Computational results show that the proposed approach outperforms most existing approaches. It is suggested that the learning methodologies suggested in this paper may be applied to other scheduling problems where schedules are built systematically according to specific rules.

Public firm sponsorship of open source software: A knowledge-based approach to open innovation

As an emerging innovation paradigm gaining momentum in recent years, the open innovation paradigm is calling for greater theoretical depth and more empirical research. This dissertation proposes that open innovation in the context of open source software sponsorship may be viewed as knowledge strategies of the firm. Hence, this dissertation examines the performance determinants of open innovation through the lens of knowledge-based perspectives. Using event study and regression methodologies, this dissertation found that these open source software sponsorship events can indeed boost the stock market performance of US public firms. In addition, both the knowledge capabilities of the firms and the knowledge profiles of the open source projects they sponsor matter for performance. In terms of firm knowledge capabilities, internet service firms perform better than other firms owing to their advantageous complementary capabilities. Also, strong knowledge exploitation capabilities of the firm are positively associated with performance. In terms of the knowledge profile of sponsored projects, platform projects perform better than component projects. Also, community-originated projects outperform firm-originated projects. Finally, based on these findings, this dissertation discussed the important theoretical implications for the strategic tradeoff between knowledge protection and sharing.

From the human rights-based approach to an ecological approach on how to achieve successful inclusion in international disability education

The barriers that people with disabilities face around the world are not only inherent to the limitations resulting from the disability itself, but, more importantly, these barriers rest with the societal technologies of exclusion. Using a mixed methodology approach, I conduct a quest to revealing several societal factors that limit full participation of people with disabilities in their communities, which will contribute to understanding and developing a more comprehensive framework for full inclusion of people with disabilities into the society. First, I conduct a multiple regression analysis to seek whether there is a statistical relationship between the national level of development, the level of democratization, and the level of education within a country’s population on one hand, and expressed concern for and preparedness to improve the quality of life for people of disabilities on another hand. The results from the quantitative methodology reveal that people without disabilities are more prepared to take care of people with disabilities when the level of development of the country is higher, when the people have more freedom of expression and hold the government accountable for its actions, and when the level of corruption is under control. However, a greater concern for the well-being of people with disabilities is correlated with a high level of country development, a decreased value of political stability and absence of violence, a decreased level of government effectiveness, and a greater level of law enforcement. None of the dependent variables are significantly correlated with the level of education from a given country. Then, I delve into an interpretive analysis to understand multiple factors that contribute to the construction of attitudes and practices towards people with disabilities. In doing this, I build upon the four main principles outlined by the United Nations as strongly recommended to be embedded in all international programmes: (1) identification of claims of human rights and the corresponding obligations of governments, hence, I assess and analyze disability rights in education, looking at United Nation, United States, and European Union Perspectives Educational Rights Provisions for People with Disabilities (Ch. 3); (2) estimated capacity of individuals to claim their rights and of governments to fulfill their obligations, hence, I look at the people with disabilities as rights-holders and duty-bearers and discuss the importance of investing in special capital in the context of global development (Ch. 4); (3) programmes monitor and evaluate the outcomes and the processes under the auspices of human rights standards, hence, I look at the importance of evaluating the UN World Programme of Action Concerning People with Disabilities from multiple perspectives, as an example of why and how to monitor and evaluate educational human rights outcomes and processes (Ch. 5); and (4) programming should reflect the recommendations of international human rights bodies and mechanisms, hence, I focus on programming that fosters development of the capacity of people with disabilities, that is, planning for an ecology of disabilities and ecoducation for people with disabilities (Ch. 6). Results from both methodologies converge to a certain point, and they further complement each other. One common result for the two methodologies employed is that disability is an evolving concept when viewed in a broader context, which integrates the four spaces that the ecological framework incorporates. Another common result is that factors such as economic, social, legal, political, and natural resources and contexts contribute to the health, education and employment opportunities, and to the overall well-being of people with disabilities. The ecological framework sees all these factors from a meta-systemic perspective, where bi-directional interactions are expected and desired, and also from a human rights point of view, where the inherent value of people is upheld at its highest standard.

An Estimation of Distribution Algorithm with Intelligent Local Search for Rule-based Nurse Rostering

This paper proposes a new memetic evolutionary algorithm to achieve explicit learning in rule-based nurse rostering, which involves applying a set of heuristic rules for each nurse's assignment. The main framework of the algorithm is an estimation of distribution algorithm, in which an ant-miner methodology improves the individual solutions produced in each generation. Unlike our previous work (where learning is implicit), the learning in the memetic estimation of distribution algorithm is explicit, i.e. we are able to identify building blocks directly. The overall approach learns by building a probabilistic model, i.e. an estimation of the probability distribution of individual nurse-rule pairs that are used to construct schedules. The local search processor (i.e. the ant-miner) reinforces nurse-rule pairs that receive higher rewards. A challenging real world nurse rostering problem is used as the test problem. Computational results show that the proposed approach outperforms most existing approaches. It is suggested that the learning methodologies suggested in this paper may be applied to other scheduling problems where schedules are built systematically according to specific rules.

Improving drug discovery using a neural networks based parallel scoring function

Virtual Screening (VS) methods can considerably aid clinical research, predicting how ligands interact with drug targets. Most VS methods suppose a unique binding site for the target, but it has been demonstrated that diverse ligands interact with unrelated parts of the target and many VS methods do not take into account this relevant fact. This problem is circumvented by a novel VS methodology named BINDSURF that scans the whole protein surface to find new hotspots, where ligands might potentially interact with, and which is implemented in massively parallel Graphics Processing Units, allowing fast processing of large ligand databases. BINDSURF can thus be used in drug discovery, drug design, drug repurposing and therefore helps considerably in clinical research. However, the accuracy of most VS methods is constrained by limitations in the scoring function that describes biomolecular interactions, and even nowadays these uncertainties are not completely understood. In order to solve this problem, we propose a novel approach where neural networks are trained with databases of known active (drugs) and inactive compounds, and later used to improve VS predictions.

Councellors' Experience During Training and Home Based HIV Councelling and Testing in Zomba District, Malawi

Introduction In 2007, St Luke’s Mission Hospital initiated a district-wide Door to Door HIV counselling and testing (HCT) programme in Zomba district. The intent of the programme was to provide quality HCT services to people in their homes and effectively those found to be HIV positive referred to appropriate services. Methodology This was a cross sectional study using a questionnaire consecutively administered to a sample of 105 counsellors who had resided in the community for a period of over one year. The questionnaire sought to establish, knowledge gained, experiences and recommendations on how the programme has been implemented and assist running of similar future programmes. Data analysis was done manually using both qualitative and quantitative methodologies. Results We report that nearly 23% of the counsellors thought that during their training as a door to door HTC councelor they had benefited in learning to working with communities; an aspect they found to be highly applicable in discharge of their duties. The major setbacks during the training were lack daily allowances, less amount of time spent on understanding child councelling and the manual used was diffucult to follow. Over 32% of the councellors were satisfied with the participation of their clients during pre-test counselling sessions, however, the major challenge they had was the misconception that they were blood suckers, a view reported by nearly 17% of the counsellors. Close to 72% reported not to have met any problems during post-test counselling compared to 24% who reported to have found challenges. Conclusion The study has revealed that there is a need to re-look child children counselling especially in training door to door HCT counsellors. It has also revealed the prevalent allowance culture despite the benefits of training. The common challenges were refusal of test Results and failure to understand discordance. Misconceptions may still exist in the community regarding anything dealing with removing blood. There is still need for more information regarding discordance especially among couples in the community.