This dissertation presents a collection of mathematical models for cellular response to the most common forms of anti-cancer therapy (radiation and chemotherapy) and the role of the cell cycle in this response. These models have application to improving cancer therapy through: optimization of dose and scheduling of agents already in clinical use; better predictive methods for selecting the most promising among new drug candidates or candidate combinations; and combination therapy with newer agents that target the cell cycle or cellular metabolism. The cellular pharmacodynamic models are based on the key concept of "cellular damage" that results from exposure to therapy and has distinct kinetics from cell kill. Damage is lethal only if it exceeds a cell's tolerance threshold at one or more checkpoints in the cell cycle (for apoptosis) or at any time point (for necrosis). This is the "peak damage" model. Each mechanism of cell kill, each agent in combination therapy, and each cycle in fractionated therapy increases the damage function (the "additive damage" model). The overall framework is termed the "peak additive damage model." This model framework is first tested on 128 independent in vitro dose-response data sets for radiation alone. It outperforms previously proposed models, including the widely-used linear-quadratic model. The peak additive damage model is then applied to radiochemotherapy. Its performance is superior to the previously proposed independent cell kill model when tested with 218 data sets for fixed-schedule exposure against. For varying-schedule exposures, cell heterogeneity and cycle asynchrony necessitate a cell-cycle-phase-structured model that divides the population into cohorts with different responses, still determined for each cohort by the peak additive damage model, that are then averaged. This model simultaneously predicts dose-response and cell cycle distribution data, and is tested with such data from the literature. Finally, a first step is taken towards allowing for microenvironmental input into cellular response, by developing a model for the cell cycle that is driven by metabolic inputs and external growth factors. Overall, the models presented here have great flexibility to be extended to complex schedules, any number of agents, and agents with metabolic or cell-cycle targets.

有感於國內投資者對於連動債券了解有限，以及投資後發現名不符實的情況普遍，故為讓大多數一般非專業投資人更清楚了解連動債券的本質，以及發行商在產品設計時是如何去挑選連結標的資產，故本論文特別選取三檔國內目前當紅的滿息提前到期連動債券(Target Redemption Structured Note)，並利用寶來證券新金融商品研究部在Matlab System中內建的多資產蒙地卡羅模擬法來評價，以了解這類型連動債券所連結標的資產的結構與特性，並進一步分析這類連動債券的報酬率與其所標榜的提前滿息到期的可能性。 本論文研究發現 一. 滿息提前到期連動債券在發行後第二年提前到期機率低於30%，第三年起更陡降至個位數，可見要在連動債券存續期間提前到期機率並不高，反而持有到連動債券期滿(本論文探討三檔皆是十年期產品)機率偏高。 二. 本論文用多資產蒙地卡羅模擬法計算發現，要在第二年滿息提前到期機率並不高，此大大有別於銀行倒流試算(simulation)結果，主要是銀行倒流測試時間與樣本數較小，甚至是經過篩選，只將較好數據納入樣本數中，以美化測試結果。 三. 所連結一籃子標的資產之相關係數愈高將會提高產品設計商發行成本與提前到期機率，而本論文所探討的三檔滿息提前到期連動債券所連結的股權標的物都是分散在各個不同產業或是不同國家，所追求的是低相關係數，相關係數最高都不超過0.7，也因此三檔產品經分析後要在前幾年累積配息而達到滿息提前到期之機率普遍不高。 四. 所連結標的資產波動度提高可降低產品設計商發行成本，但同時也減低提前到期機率；本論文所探討三檔產品的連動標的資產波動度多處於半年以來相對低檔區，未來波動度升高機率高，故有利產品設計商但不利投資人。 五. 本論文研究還發現利率上揚可降低產品設計商發行成本，故預計在全球升息趨勢下，此類型產品仍有機會設計出更具吸引力的配息與額外紅利機制，以繼續吸引投資者眼光。 六. 滿息提前到期連動債券結構愈複雜，例如提供提前到期額外紅利補償、配息只升不降等，那麼發行商成本愈高，因此在連結標的物選擇上會傾向於股票檔數多、個股波動度高且相關係數愈低的一籃子股票。

<p>Optical microscopy plays a crucial role in the biological sciences for its ability to enable visualization of biological samples at sub-cellular levels. Many imaging subdivisions exist under this umbrella of general microscopy, and each are tailored towards specific design, contrast, and visualization constraints. Standard examples that have found widespread use include dark-field, phase-contrast, holographic, and fluorescent microscopies. However, a critical factor that physically limits the optical resolution of general microscopy is diffraction. Unfortunately, this “diffraction-limit” can prevent visualization of significant biologically relevant structures, which in turn can limit biological insights. In response to such a limit, several works have advanced the field of sub-diffraction resolution imaging, which consist of optical imaging techniques that seek to achieve imaging resolutions beyond that which is allowed by the diffraction-limit. This set of techniques can largely be divided into two classes. The first class of sub-diffraction techniques is targeted towards cases where the sample is coherently illuminated and diffracts into the imaging system’s aperture. For such cases, synthetic aperture (SA) is a popular choice and operates by using oblique illuminations to spatiotemporally synthesize a wider frequency support into the image than allowed by the diffraction limit. The second class of sub-diffraction techniques, often referred to as "super-resolution" techniques, typically utilize specialized fluorophores with either photoswitching or depletion capabilities. Photoactivated localization microscopy (PALM) is a super-resolution example that localizes photoswitchable fluorophores to sub-diffraction resolutions per acquisition, before combining into a final super-resolved image. Stimulated emission depletion (STED) is another super-resolution example that spatially modulates its excitation to narrow its optical point-spread-function. Unfortunately, SA and fluorescent super-resolution techniques are generally incompatible for sub-diffraction resolution fluorescent and coherent imaging, respectively – thus, a multimodal sub-diffraction imaging solution compatible with both coherent and fluorescent imaging has remained elusive. </p><p> In this dissertation, we demonstrate that structured illumination (SI) is a sub-diffraction technique compatible with both diffractive and fluorescent imaging. We first develop the theoretical framework that extends SI to coherent imaging and experimentally demonstrate SI’s capabilities for 2D sub-diffraction resolution imaging of coherently diffractive samples. Sub-diffraction resolution imaging based on scattering intensity and transmission-based quantitative-phase (QP) are shown. In addition, we show extend SI to 3D coherent imaging, and show applications of this towards 3D QP and refractive-index (RI) tomography. Finally, we show multimodal applications of SI that allow sub-diffraction resolution fluorescent and coherent imaging, which has great potential utility for the biological sciences.</p> / Dissertation

Empirically based methods of detecting retrospective malingering (i.e., the false assertion or exaggeration of physical or psychological symptoms reportedly experienced during a prior time period) are needed given that retrospective evaluations are commonplace in forensic assessments. This study's main objective was to develop and validate a focused, standardized measure of retrospective malingering. This objective was addressed by revising the Structured Interview of Reported Symptoms (SIRS), an established measure of current feigning. The SIRS' strategies were retained and its items modified to produce two new SIRS versions: The Retrospective Structured Interview of Reported Symptoms (R-SIRS) and The Concurrent-Time Structured Interview of Reported Symptoms (CT-SIRS). Forensic inpatients were used to test the R-SIRS (n = 25) and CT-SIRS (n = 26) which both showed good internal consistency and interrater reliability. The overall effectiveness of the R-SIRS and the CT-SIRS in the classification of malingerers and genuine patients was established in this initial validation study. Moreover, their classification rates were similar to those obtained by the SIRS. Pending additional validation, these measures are expected to increase the quality of forensic evaluations by providing the first standardized methods of assessing retrospective malingering.

This study aims to investigate the determinants of capital structure in small and medium-sized enterprises (SMEs) in Malaysia and their effect on firms’ performance. The study addresses the following primary question: What are the factors that influence the capital structure of SMEs in Malaysia? The sample of this research is SMEs in the east coast region of Malaysia. Adopting a positivist paradigm, the research design includes a preliminary study comprising 25 interviews with the owner-managers of SMEs, which is analysed using thematic analysis. The results are used to finalise the conceptual framework for the main study, which takes the form of a self-completion questionnaire survey. Usable responses were received from 384 firms, giving a response rate of 75.3%. The survey data is analysed using a series of binomial logistic regression models. Results reveal that there was no indication for the impact of owner’s education and experience on capital structure decisions. Other owner-related factors, firm characteristics, management performance and environment were found to relate to all types of capital structure. Both complete and partial mediating effects are also discovered in this study. The results provide evidence to support the pecking order hypothesis (Myers, 1984; Myers and Majluf, 1984), agency theory (Jensen and Meckling, 1976) and culture model of Schwartz (1994). It appeared that owner-managers in Malaysia do not strive to adjust their capital structure towards some optimal debt ratio, which is contrary to the static trade-off theory (DeAngelo and Masulis, 1980) of capital structure. This study makes several important contributions to the existing studies of capital structure. This research led to the development of a model of capital structure determinants by integrating factors related to owner-managers, firms, culture, and environment. This study incorporates methodological triangulation that may mitigate the problem of the difficulties in accessing financial data of SMEs in Malaysia. This study also provides meaningful insight into the financing preferences of the owner-managers with relevant implementations to academics, business practitioners, financial providers and policymakers. The research findings should assist owner-managers in making optimal capital structure decisions as well as help the policymaker in making an appropriate policy on the financing.

Two proposed models will be used to help answer a long observed question in the dynamics of \textit{Manduca sexta} and its related parasitoid wasps-Why is there a large difference in diversity in hyperparasitoid species between tobacco and other related plants such as tomato? Two stage structured differential equation models are presented. The first is a single patch model to study the changes in dynamics that occur between hosts, parasitoids, and hyperparasitoids as the amount of nicotine in the plant increases. The second is a two patch model that allows hyperparasitoids to choose between patches that are nicotine negative (i.e. tomato plants) and nicotine positive (i.e. tobacco plants). Both models will be used to investigate how host nicotine sequestration may impact hyperparasitoid diversity.

Thesis advisor: Michelle M. Meyer / Bacteria commonly utilize cis-acting mRNA structures that bind specific molecules to control gene expression in response to changing cellular conditions. Examples of these ligand-sensing RNA cis-regulators are found throughout the bacterial world and include riboswitches, which interact with small metabolites to modulate the expression of fundamental metabolic genes, and the RNA structures that bind select ribosomal proteins to regulate entire ribosomal protein operons. Despite advances in both non-coding RNA discovery and validation, many predicted regulatory RNA motifs remain uncharacterized and little work has examined how RNA cis-regulators behave within their physiological context in the cell. Furthermore, it is not well understood how structured RNA regulators emerge and are maintained within bacterial genomes. In this thesis, I validate the biological function of a conserved RNA cis-regulator of ribosomal protein synthesis previously discovered by my group using bioinformatic approaches. I then investigate how bacteria respond to the loss of two different cis-regulatory RNA structures. Using Bacillus subtilis as a model organism, I introduce point mutations into the native loci of the ribosomal protein L20-interacting RNA cis-regulator and the tandem glycine riboswitch and assay the strains for fitness defects. I find that disrupting these regulatory RNA structures results in severe mutant phenotypes, especially under harsh conditions such as low temperatures or high glycine concentrations. Together, this body of work highlights the advantages of examining RNA behavior within its biological context and emphasizes the important role RNA cis-regulators play in overall organismal viability. My studies shed light on the selective pressures that impact structured RNA evolution in vivo and reinforce the potential of cis-regulatory RNAs as novel antimicrobial targets. / Thesis (PhD) — Boston College, 2017. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Background. A central role of mental health professionals within the criminal justice and forensic mental health system is the assessment, management and communication of an individual's risk of future violence (Webster & Hucker, 2007). The current methodology favoured by clinicians is the structured professional judgement (SPJ) approach (Farrington, Joliffe & Johnstone, 2008). These instruments act as guides in clinical practice in that practitioners are encouraged to apply clinical judgement on the relevance of empirically validated risk factors to each client. In this way, identified risk factors can be directly used to inform individual care and treatment, i.e. risk management. Yet, research on SPJ tools is typically based on retrospective or pseudo-prospective designs, which lack in ecological validity. Furthermore, findings are based on risk assessments completed by researchers rather than clinicians. This is an issue as risk ratings differ significantly depending on professional background (de Ruiter & de Vogel, 2004). Aims. This thesis presents five studies with the aim of examining the link between violence risk assessment and management in vivo. This includes two studies focussing on the predictive validity of SPJ tools following clinical implementation; a description of the implementation procedure; a traditional research study on the predictive power of dynamic risk factors and a pilot evaluation of a short term risk assessment tool for imminent inpatient violence. Methodology. The primary research site was the State Hospital, the high secure psychiatric facility for mentally disordered offenders in Scotland and Northern Ireland. The research population consisted of 115 male forensic patients who were followed up across different risk settings for a mean of 31 months. The SPJ instruments under investigation were the HCR-20 (Webster et al, 1997), the SVR-20 (Boer, Hart, Kropp et al, 1997) and the RSVP (Hart et al, 2003). All assessments were exclusively completed by clinicians and resulted in active risk management strategies. Additionally, the predictive validity of dynamic risk factors was examined through psychometric measures of anger, impulsivity, psychiatric symptoms, unmet needs and imagined violence. The risk of imminent violence was assessed with the Dynamic Appraisal Situational Appraisal - Inpatient Version (DASA-IV, Ogloff & Daffern, 2006). Results and Conclusions. Findings indicate that clinically implemented SPJ tools are not predictive of future violence, both within and outwith secure settings. Comparison with a previous study at the State Hospital implies that the implementation process of the HCR- 20 facilitated the knowledge transfer from assessment to management, and therefore incidents were prevented. This noted the results also highlight that clinicians may accept risk tools into practice when these have not been scientifically scrutinised. This was the case with the RSVP in that there is little published data on the psychometric properties of this tool, yet its introduction replaced the SVR-20 across the State Hospital. With regards to dynamic risk factors, the severity and chronicity of psychiatric symptoms were the strongest predictors of violence. This is further corroborated by the finding that the DASA-IV predicted violence within 24 hours of ratings provided. All findings are discussed in the context of previous research and the experienced obstacles of implementing changes within NHS settings. Clinical implications and recommendations for violence assessment and management are provided in the light of acknowledged limitations.

The purpose of this research was to determine if a structured intervention program could assist individuals in adjusting to some of the disruption associated with divorce. A secondary purpose was to determine if identity status would mediate the effects of the intervention program upon divorce adjustment. The components of the intervention program were modeled on previous research. It was hypothesized that individuals participating in a structured treatment program would manifest greater gains in areas of divorce adjustment than the control group. However, results show that while there was greater gain for the experimental group than the control group in several areas, such gain was not a level of significance sufficient to support the primary hypothesis. In addition, support was not generated for the mediational role of identity. Indeed, identity appeared as a rather stable construct, showing very little change from treatment effects and not seeming to influence treatment outcome. It was found that those individuals high in identity status reported less adjustment problems from the divorce than those individuals with low identity statuses. However, this was not a factor of treatment with the control group reporting the same finding. Implications for future research suggest studies in divorce adjustment focus on symptomology and problems in day-to-day living, with objective measuring devices rather than the subjective self-report instruments currently in use. Research on identity status as it relates to divorce adjustment should be longitudinal in nature tracking identity prior to divorce, and allowing for longer intervention periods.

The fast pace of development in the Mobile Data Services area means innovators have to remain vigilant to stay in the market. There is not time to undertake the usual market development cycles. As a consequence, researchers are looking at various ways to predict the adoption rate of a new product and ways to better forecast adoption in different niche contexts. Rogers’ (2003) provides a review of historical trends in innovation and diffusion studies, and the foundational (1962) model he developed. In the context of the most recent literature, it is found that Rogers’ generic model still works well, but variations built on his model need to be considered. In particular, the ‘Chasm’ model, developed by Moore (1999), adapts Rogers’s model to cope well with the 21st century business environment. Gilbert (2005) has taken the work of both Rogers and Moore and applied the learning to research into adoption rates and characteristics in cross-cultural situations. In New Zealand the past consumer behaviour when new mobile services have been introduced has shown a number of characteristics and specific problems. Vodafone New Zealand provides mobile services only and they now claim 54% market share (Vodafone 2005`). An early success was to significantly lower the cost of sending text messages (SMS), followed by promotion of that service to the teenage market sector. In contrast to the popularity of SMS, introduction of the WAP mobile Internet protocol was not successful in New Zealand, as was the case elsewhere. The failure is commonly attributed to a lack of services being offered to use the technology. Near the end of 2004 Telecom New Zealand launched a new product, branded ‘T3G’. Vodafone New Zealand released ‘Vodafone 3G’ during the middle of 2005. The technologies behind these products is generally called ‘3G Mobile’, or Third Generation Mobile technology. Operators in Singapore also have 3G networks, commissioned during 2004. Authors such as Salz et el (2004) find evidence to suggest that US network operators need to speed up the adoption of this technology to meet predicted demand. There are unique factors likely to affect in the New Zealand market. The OECD has repeatedly found evidence that broadband Internet adoption in New Zealand is lower than other countries. Introduction of 3G technology provides another way to access broadband Internet. The OECD indicates that pricing is one of the barriers to broadband adoption. Telephone companies will have to consider pricing 3G to appeal as an option to having a fixed Internet option. The key question to be addressed in this research is: Do the adoption intensions of New Zealanders match those of Malaysia and Singapore for expected data services use? A related question is: What other factors effect New Zealand's current relatively slow rate of adoption? Product positioning of mobile data products is going to become more critical, given that some telephone operators are ‘expecting to get 25% of revenues from mobile data within five years’ (Molony, 2001). This Thesis will provide information to assist Mobile Service Providers to predict adoption rates of new services. It will also provide a comparative reference for researchers in other countries to replicate the study, and contribute to an exciting body of international literature. The New Zealand market is characterised by high cost of broadband Internet in general (OECD, TUANZ, and others), proprietary knowledge capture, and regulation, but these issues do not stop research into the intensions of potential adopters. This thesis will fill part of that research void, by comparing emergent demand for mobile data with existing models, which have previously been used, to predict future demand. New Zealand has a reputation as an earlier adopter of new technologies (Min Economic Dev & others). This thesis will contribute evidence to indicate how New Zealanders plan to adopt mobile data services, and how intensions of adoption compare with parallel studies in Singapore, and other countries.