Most dynamic program analysis techniques such as profile-driven compiler optimizations, software testing and runtime property checking infer program properties by profiling one or more executions of a program. Unfortunately, program profiling does not come for free. For example, even the most efficient techniques for profiling acyclic, intra-procedural paths can slow down program execution by a factor of 2. In this thesis, we propose techniques that significantly lower the overheads of profiling paths, enabling the use of path-based dynamic analyzes in cost-sensitive environments. Preferential path profiling (PPP) is a novel software-only path profiling scheme that efficiently profiles given subsets of paths, which we refer to as interesting paths. The algorithm is based on the observation that most consumers of path profiles are only interested in profiling a small set of paths known a priori. Our algorithm can be viewed as a generalization of the Ball-Larus path profiling algorithm. Whereas the Ball-Larus algorithm assigns weights to the edges of a given CFG such that the sum of the weights of the edges along each path through the CFG is unique, our algorithm assigns weights to the edges such that the sum of the weights along the edges of interesting paths is unique. Furthermore, our algorithm attempts to achieve a minimal and compact encoding of the interesting paths; such an encoding significantly reduces the overheads of path profiling by eliminating expensive hash operations during profiling. Interestingly, we find that both the Ball-Larus algorithm and PPP are essentially a form of arithmetic coding. We use this connection to prove that the numbering produced by PPP is optimal. We also propose a programmable, non-intrusive hardware path profiler (HPP). The hardware profiler consists of a path detector that detects paths by monitoring the stream of retiring branch instructions emanating from the processor pipeline. The path detector can be programmed to detect various types of paths and track architectural events that occur along paths. The second component of the hardware profiling infrastructure is a Hot Path Table (HPT), that collects accurate hot path profiles. Our experimental evaluation shows that PPP reduces the overheads of profiling paths to 15% on average (with a maximum of 26%). The algorithm can be easily extended to profile inter-procedural paths at minimal additional overheads (average of 26%). We modeled HPP using a cycle-accurate superscalar processor simulator and find that HPP generates accurate path profiles at extremely low overheads (0.6% on average) with a moderate hardware budget. We also evaluated the use of PPP and HPP in a realistic profiling scenarios. We find that the profiles generated by HPP can effectively replace expensive profiles used in profile-driven optimizations. We also find that even well-tested programs tend to exercise a large number of untested paths in the field, emphasizing the need for efficient profiling schemes that can be deployed in production environments.

As Neoplasias endócrinas múltiplas (NEMs) são síndromes herdadas de modo dominante e causadas por mutações germinativas em genes específicos. Caracterizam-se pela presença de tumores em um conjunto de glândulas endócrinas, conjunto este típico de cada tipo-específico de NEM. Dentre os diferentes tipos de NEMs, há a neoplasia endócrina múltipla tipo 2 (NEM2) que envolve os fenótipos, carcinoma medular de tireóide (CMT), hiperparatiroidismo primário (HPT), feocromocitoma (FEO) e megacólon congênito (doença de Hirschsprung, HSCR). Apesar da prevalência da NEM2 na população em geral ser baixa (~ 1:30.000), o número de casos afetados por família pode ser expressivo, uma vez que sua penetrância é praticamente completa (~100%). A doença de HSCR ou aganglionose intestinal congênita quando ocorre está geralmente associada à mutações RET nos códons 609, 618 e 620; apresenta ampla variação fenotípica, padrão de herança complexa e baixa penetrancia. Poucos casos de HSCR podem apresentar mutações em outros genes. Mutações no gene RET são responsáveis por aproximadamente metade (~50%) dos casos familiares de HSCR e alguns casos esporádicos (~10-20%), sugerindo fortemente que a HSCR seja doença poligenica. Tem-se também sugerido que polimorfismos genéticos no RET podem influenciar o fenotipo da NEM2/HSCR. No presente estudo, analisamos o gene RET no sentido de investigar se o desenvolvimento de megacólon em pacientes com a mutação germinativa RET p.C620R estaria associado à presença de ou a) a uma segunda mutação germinativa ou b) a um SNP, ou c) a um haplótipo informativo, que possivelmente poderia estar potencialmente interagindo genicamente com a mutação RET principal e eventualmente modulando o fenótipo HSCR / The multiple endocrine neoplasias (MENs) are inherited multi-tumoral conditions caused by germline mutations in specific genes. Specifically, the multiple endocrine neoplasia type 2 (NEM2) is a hereditary endocrine disorder transmitted dominantly and involving three main tumors, medullary thyroid carcinoma (CMT), primary hyperparathyroidism (HPT) and pheochromocytoma (PHEO). Despite the low prevalence of MEN2 in general population, the number of affected individuals per family can be significant as the penetrance of MEN2 is almost complete (~100%). In addition to CMT, PHEO and HPT, other conditions as congenital megacólon (Hirschsprung disease, HSCR or congenital intestinal aganglionosis) may occur in MEN2 (HSCR/MEN2). HSCR/MEN2 usually is due to RET mutations in codons 609, 618 and 620. HSCR has a wide phenotypic variation; is a complex multigenic disease; and has a low penetrance. Mutations in the RET gene are responsible for approximately 50% of the familial HSCR cases and ~10% of the sporadic HSCR cases, supporting that HSCR is a polygenic disease and this is confirmed by a few HSCR cases associated with mutations in the EDNRB and EDN3 genes. In the present study, we focused in the analysis of the RET gene in order to investigate whether the development of congenital megacólon in patients with RET mutation p.C620R is associated with the presence of, a) a second RET germline mutation, b) a SNP, or with a haplotype that co-segregate with the disease

This thesis is focused on processing of pure magnesium by high pressure torsion method (HPT). This process belongs to the group of intensive plastic deformation methods (SPD). SPD methods are in the centre of scientific interest for several decades. Theoretical part of this thesis puts an effort to summarize basic knowledge and principles of SPD methods with extra focus on method HPT. As theoretical part continues magnesium as technical material is presented. Influence of SPD on use and properties of pure magnesium is then presented. This trend is further developed in effort to describe the effect of individual HPT process variables on the properties of pure magnesium and its alloys. Focus of practical part of this thesis is in influence of number of revolutions. Samples were processed at 1/8, 1/4, 1/2, 1, 4 and 8 turns at room temperature. Speed of process was 1rpm and applied pressure was 6 GPa. The structure of commercially pure magnesium prepared by casting and moulding were observed with focus on differences caused by input material. The structure was observed by both light microscopy and back scattered electron diffraction (EBSD), focusing on structure development, grain size and grain orientation. Compared to other works on similar topic, the emphasis here is on observing the microhardness on the vertical edge of the sample. The hardness shows a steep increase right after 1/8 of a turn. With increasing number of turns gradual homogenization of microhardness is presented accompanied by slight decrease in microhardness. No trend in microhardness relative to the distance from anvil has occurred. Structure observed with EBSD shows a bimodal character with larger grains oriented in the same direction. The three-point bending test didn’t end up as expected, and the approach to evaluation of magnesium-based HPT needs to be re-evaluated for future work. A three-point bending test was designed for the initial assessment of the basic mechanical properties of the material.

Do you remember the first time you used an Automatic Teller Machine (ATM)? Or a pay-at-the-pump gas station? Or an airline e-ticket kiosk? How did you know what to do? Although you never received any formal instruction in how to interact with the self-service technology, you were likely able to accomplish your task (e.g., withdrawing or depositing money) as successfully as an experienced user. However, not so long ago, to accomplish that same task, you needed the direct mediation of a service professional who had been trained how to use the required complex technology. What has changed? In short, the technology is now able to compensate for the average consumer's lack of experience with the transactional system. The technology itself bridges the performance gap, allowing a novice to accomplish the same task as an experienced professional. This shift to a self-service paradigm is completely changing the dynamics of the consumer relationship with the capitalist enterprise, resulting in what is rapidly becoming the default consumer interface of the postmodern era. The recognition that the entire performance support apparatus now revolves around the end user/consumer rather than the employee represents a tectonic shift in the workforce training industry. What emerges is a homogenized consumer culture enabled by self-service technologies--a kiosk culture. No longer is the ability to interact with complex technology confined to a privileged workforce minority who has access to expensive and time-consuming training. The growth of the kiosk culture is being driven equally by business financial pressures, consumer demand for more efficient transactions, and the improved sophistication of compensatory technology that allows a novice to perform a task with the same competence as an expert. "The Kiosk Culture" examines all aspects of self-service technology and its ascendancy. Beyond the milieu of business, the kiosk culture is also infiltrating all corners of society, including medicine, athletics, and the arts, forcing us to re-examine our definitions of knowledge, skills, performance, and even humanity. The current ubiquity of self-service technology has already impacted our society and will continue to do so as we ride the rising tide of the kiosk culture.