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Yes / Personalized medicine through Pharmacogenomics: choosing the right drug, and the right dose, for the right patients based on patient’s genetic makeup-is gradually being realised in Western countries. Yet, the practice of pharmacogenomics in Asian countries lags behind that of the West, but the medical needs for pharmacogenomics are expected to surge as better patient care is demanded in Asia. As next-generation sequencing technology advances quickly, previous technical challenges for performing pharmacogenomic studies or practices in Asia have been mostly resolved. What is lacking in Asia is an effective model of community-wide pharmacogenomics. On the delivery front, pharmacists, the drug and dosing professionals, can potentially be the main healthcare providers for pharmacogenomic services in Asia. The first large “Genomics for Precision Drug Therapy in the Community Pharmacy” in Canada, which is close to its completion, has successfully identified community pharmacists as key contact professionals for smooth facilitation and implementation of pharmacogenomics for personalized medication. It is anticipated that Asian pharmacists, with appropriate training, can have the capacity to provide expert pharmacogenomic supports for both physicians and patients in Asia. / The School of Biomedical Sciences Start-up Fund, the Chinese University of Hong Kong, the General Research Fund (#17114814; #17121616), the Theme-based Research Scheme (T12-401/13-R), Research Grant Council, Hong Kong, as well as the Hong Kong Cancer Fund, Hong Kong.

Thesis advisor: Tim Van Opijnen / Exposure to antibiotics has previously been shown to induce morphological changes to bacterial cells in Escherichia coli and Staphylococcus aureus . Response profiles to antibiotics representing various mechanisms of action provides as quick, reliable and cheap means of identifying the mechanism of action of novel antimicrobials. We evaluated whether similar cytological profiling was possible in the pathogenic bacteria Streptococcus pneumoniae and whether there were any strain specific differences in morphological changes resulting from antibiotic exposure. We evaluated antibiotics from various classes and with different mechanisms of action to develop strain specific models of phenotypic responses in order to identify clustering associated with particular mechanisms of action. Various antibiotics belonging to, cell wall synthesis inhibitors, protein synthesis inhibitors, and DNA synthesis inhibitors were evaluated using S. pneumoniae strains TIGR4 and 19F. Following exposure to high doses of antibiotics, cells were imaged for DNA and cell wall components and analyzed. Our data shows that antibiotics of the same mechanism of action induce similar morphological changes. While TIGR4 and 19F show similar changes there are strain specific differences between them. Our data shows that cytological profiling effectively indicates the mechanism of action through imaging in S. pneumoniae allowing this technique to be used to study novel antimicrobials as well as better understand bacterial responses to antibiotic stress. / Thesis (BS) — Boston College, 2019. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Biology.

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no / The prevalence of micromoulded components has steadily increased over recent years. The production of such components is extremely sensitive to a number of variables that may potentially lead to significant changes in the surface geometry, often regarded as a crucial determinant of the product¿s functionality and quality. So far, traditional large-scale quality assessment techniques have been used in micromoulding. However, these techniques are not entirely suitable for small scales . Techniques such as Atomic Force Mi- croscopy (AFM) or White Light Interferometry (WLI) have been used for obtaining full three-dimensional profiles of micromoulded components, pro- ducing large data sets that are very difficult to manage. This work presents a method of characterizing surface features of micro and nano scale based on the use of the Biharmonic equation as means of describing surface profiles whilst guaranteeing tangential (C1) continuity. Thus, the problem of rep- resenting surface features of micromoulded components from massive point clouds is transformed into a boundary-value problem, reducing the amount of data required to describe any given surface feature.The boundary condi- tions needed for finding a particular solution to the Biharmonic equation are extracted from the data set and the coefficients associated with a suitable analytic solution are used to describe key design parameters or geometric properties of a surface feature. Moreover, the expressions found for describ- ing key design parameters in terms of the analytic solution to the Biharmonic equation may lead to a more suitable quality assessment technique for micromoulding than the criteria currently used. In summary this technique provides a means for compressing point clouds representing surface features whilst providing an analytic description of such features. The work is applicable to many other instances where surface topography is in need of efficient representation. / EPSRC

Software applications’ performance is hindered by a variety of factors, but most notably by the well-known CPU-memory speed gap (often known as the memory wall). This results in the CPU sitting idle waiting for data to be brought from memory to processor caches. The addressing used by caches cause non-uniform accesses to various cache sets. The non-uniformity is due to several reasons, including how different objects are accessed by the code and how the data objects are located in memory. Memory allocators determine where dynamically created objects are placed, thus defining addresses and their mapping to cache locations. It is important to evaluate how different allocators behave with respect to the localities of the created objects. Most allocators use a single attribute, the size, of an object in making allocation decisions. Additional attributes such as the placement with respect to other objects, or specific cache area may lead to better use of cache memories. In this dissertation, we proposed and implemented a framework that allows for the development and evaluation of new memory allocation techniques. At the root of the framework is a memory tracing tool called Gleipnir, which provides very detailed information about every memory access, and relates it back to source level objects. Using the traces from Gleipnir, we extended a commonly used cache simulator for generating detailed cache statistics: per function, per data object, per cache line, and identify specific data objects that are conflicting with each other. The utility of the framework is demonstrated with a new memory allocator known as equivalence class allocator. The new allocator allows users to specify cache sets, in addition to object size, where the objects should be placed. We compare this new allocator with two well-known allocators, viz., Doug Lea and Pool allocators.

This study compared the accuracy for the two general approaches to criminal profiling, inductive and deductive. Participants were 213 college students who participated in a 1-hour training session. Participants in the experimental groups were trained in either the inductive or deductive approach to profiling. Participants in the control group were trained in a crime topic unrelated to profiling (rape and sexual assault prevention). Following the training session, participants were asked to review a double sexual homicide case and then profile the offender by completing the Profiling Offender characteristics Questionnaire. Participants trained in the inductive profiling approach were more accurate when profiling the offender’s physical characteristics. Furthermore, the inductive profiling approach led to higher overall accuracy scores compared to the control condition. These results suggest that training naïve profilers to use the inductive approach may improve the accuracy of offender profiles in sexual homicide cases.

This study compared the accuracy of criminal profiles produced by individuals versus profiles produced by teams of two. Participants were 239 college students who were randomly assigned to work alone or in a team. Participants were asked to read a double sexual homicide case, profile the offender, and answer the Profiling Offender Characteristics Questionnaire. The results indicate that although novice profiler teams only slightly outperformed individuals on overall profile accuracy, teamwork significantly improved profiling accuracy for the cognitive characteristics of the offender. In contrast, teams and individuals showed similar profile accuracy for all other facets of the offender. These results may reflect the type of reasoning used by teams and individuals to profile different offender characteristics.

Analysis of urinary hormone levels can be used to identify sex and breeding patterns in amphibians. This is especially important for ensuring the survival of endangered species. The most common way to determine hormone levels is enzyme-linked immunosorbent assay (ELISA); however, there is the possibility of cross-reactivity with this technique, and only one hormone can be monitored per plate, limiting efficiency. In this study, the effectiveness of liquid chromatography coupled to mass spectrometry (LC-MS/MS) was evaluated in terms of sensitivity, repeatability, and through-put in monitoring hormone levels in Anaxyrus boreas boreas (boreal toads). Urine samples were collected from ten different female Boreal toads over a three-year period and monitored for estrone, â-estradiol, estriol, 17á-ethinylestradiol, corticosterone, testosterone, and progesterone. To account for differences in urine concentration, creatinine (a metabolic breakdown product) was used to normalize all samples as it is typically present at a constant concentration. Prior to chromatographic analysis, all samples underwent a solid phase extraction (SPE) clean-up. Hormones in the estrogen class were derivatized via dansylation prior to analysis to enhance detection sensitivity. An Agilent 1290 Liquid Chromatograph coupled to an Agilent 6460 Triple Quadrupole Mass Spectrometer was used to quantitate hormone levels. The extraction method developed proved to be reliable and reproducible with percent recoveries in quality control samples ranging from 80%-120%. Using LC-MS/MS and derivatization, limits of quantitation as low as 0.001 parts-per-billion (ppb) were achieved for estrogens and 0.100 ppb for androgens. Ultimately, the method optimized for hormone analysis using LC-MS/MS showed to be as reliable as ELISA while also being less expensive per sample and more robust.

No description available.