Doctor of Philosophy

dissertationAlmost all high performance computing applications are written in MPI, which will continue to be the case for at least the next several years. Given the huge and growing importance of MPI, and the size and sophistication of MPI codes, scalable and incisive MPI debugging tools are essential. Existing MPI debugging tools have, despite their strengths, many glaring de ficiencies, especially when it comes to debugging under the presence of nondeterminism related bugs, which are bugs that do not always show up during testing. These bugs usually become manifest when the systems are ported to di fferent platforms for production runs. This dissertation focuses on the problem of developing scalable dynamic verifi cation tools for MPI programs that can provide a coverage guarantee over the space of MPI nondeterminism. That is, the tools should be able to detect diff erent outcomes of nondeterministic events in an MPI program and enforce all those di fferent outcomes through repeated executions of the program with the same test harness. We propose to achieve the coverage guarantee by introducing efficient distributed causality tracking protocols that are based on the matches-before order. The matches-before order is introduced to address the shortcomings of the Lamport happens-before order [40], which is not sufficient to capture causality for MPI program executions due to the complexity of the MPI semantics. The two protocols we propose are the Lazy Lamport Clocks Protocol (LLCP) and the Lazy Vector Clocks Protocol (LVCP). LLCP provides good scalability with a small possibility of missing potential outcomes of nondeterministic events while LVCP provides full coverage guarantee with a scalability tradeoff . In practice, we show through our experiments that LLCP provides the same coverage as LVCP. This thesis makes the following contributions: •The MPI matches-before order that captures the causality between MPI events in an MPI execution. • Two distributed causality tracking protocols for MPI programs that rely on the matches-before order. • A Distributed Analyzer for MPI programs (DAMPI), which implements the two aforementioned protocols to provide scalable and modular dynamic verifi cation for MPI programs. • Scalability enhancement through algorithmic improvements for ISP, a dynamic verifi er for MPI programs

Problem Management Plus: An Evidence-Based Approach to Expanding Access to Community-Based Mental Health Supports

Problem Management Plus (PM+) is a proven, scalable, and cost-effective low-intensity mental health intervention that can be delivered by trained non-clinical workers for people who are experiencing common mental health conditions, such as anxiety or depression, or stressful life problems. PM+ fills a gap in the behavioral health services system by providing early intervention and potential prevention of more acute behavioral health service needs. As a model that relies on building the capacity and diversity of the behavioral health workforce, it holds promise for enhancing access to community-based mental health supports. This issue brief is designed to define and describe the PM+ intervention and its origins and identify preliminary considerations for implementing it in the United States

Providing Insight into the Performance of Distributed Applications Through Low-Level Metrics

The field of high-performance computing (HPC) has always dealt with the bleeding edge of computational hardware and software to achieve the maximum possible performance for a wide variety of workloads. When dealing with brand new technologies, it can be difficult to understand how these technologies work and why they work the way they do. One of the more prevalent approaches to providing insight into modern hardware and software is to provide tools that allow developers to access low-level metrics about their performance. The modern HPC ecosystem supports a wide array of technologies, but in this work, I will be focusing on two particularly influential technologies: The Message Passing Interface (MPI), and Graphical Processing Units (GPUs).For many years, MPI has been the dominant programming paradigm in HPC. Indeed, over 90% of applications that are a part of the U.S. Exascale Computing Project plan to use MPI in some fashion. The MPI Standard provides programmers with a wide variety of methods to communicate between processes, along with several other capabilities. The high-level MPI Profiling Interface has been the primary method for profiling MPI applications since the inception of the MPI Standard, and more recently the low-level MPI Tool Information Interface was introduced.Accelerators like GPUs have been increasingly adopted as the primary computational workhorse for modern supercomputers. GPUs provide more parallelism than traditional CPUs through a hierarchical grid of lightweight processing cores. NVIDIA provides profiling tools for their GPUs that give access to low-level hardware metrics.In this work, I propose research in applying low-level metrics to both the MPI and GPU paradigms in the form of an implementation of low-level metrics for MPI, and a new method for analyzing GPU load imbalance with a synthetic efficiency metric. I introduce Software-based Performance Counters (SPCs) to expose internal metrics of the Open MPI implementation along with a new interface for exposing these counters to users and tool developers. I also analyze a modified load imbalance formula for GPU-based applications that uses low-level hardware metrics provided through nvprof in a hierarchical approach to take the internal load imbalance of the GPU into account

Evaluation of Property Management Agent Performance: A Novel Empirical Model

For many different reasons, property management agents (PMAs) are appointed for managing housing developments in both public and private housing sectors in many different cities. While third-party housing management eases the burdens of property owners and tenants in taking care of their properties, it may lead to agency problems. In fact, cases of mismanagement of multi-owned properties are common in Hong Kong and other Asian cities, leading to accelerated urban decay and augmented confrontations between property owners, users and PMAs. To promote better property management services, the performance of PMAs should be evaluated so market players can benchmark the performance of different PMAs for better-informed decision-making. This study reviews previous and existing measures for evaluating PMA performance and proposes a new evaluation model which is built upon the residual concept proposed by William Sharpe. The ideas underpinning the framework and how a PMA’s performance is evaluated using the framework are detailed. Using this new model, 217 housing developments in Hong Kong are studied and the performance of the respective PMAs is evaluated and benchmarked. The evaluation outcomes are validated with the SERVQUAL scores of these 217 housing developments. Practical implications of the research findings follow

07341 Abstracts Collection -- Code Instrumentation and Modeling for Parallel Performance Analysis

From 20th to 24th August 2007, the Dagstuhl Seminar 07341 ``Code Instrumentation and Modeling for Parallel Performance Analysis\u27\u27 was held in the International Conference and Research Center (IBFI), Schloss Dagstuhl. During the seminar, several participants presented their current research, and ongoing work and open problems were discussed. Abstracts of the presentations given during the seminar as well as abstracts of seminar results and ideas are put together in this paper. The first section describes the seminar topics and goals in general. Links to extended abstracts or full papers are provided, if available

A new generation of pPRIG-based retroviral vectors

<p>Abstract</p> <p>Background</p> <p>Retroviral vectors are valuable tools for gene transfer. Particularly convenient are IRES-containing retroviral vectors expressing both the protein of interest and a marker protein from a single bicistronic mRNA. This coupled expression increases the relevance of tracking and/or selection of transduced cells based on the detection of a marker protein. pAP2 is a retroviral vector containing eGFP downstream of a modified IRES element of EMCV origin, and a CMV enhancer-promoter instead of the U3 region of the 5'LTR, which increases its efficiency in transient transfection. However, pAP2 contains a limited multicloning site (MCS) and shows weak eGFP expression, which previously led us to engineer an improved version, termed pPRIG, harboring: i) the wild-type ECMV IRES sequence, thereby restoring its full activity; ii) an optimized MCS flanked by T7 and SP6 sequences; and iii) a HA tag encoding sequence 5' of the MCS (pPRIG HAa/b/c).</p> <p>Results</p> <p>The convenience of pPRIG makes it a good basic vector to generate additional derivatives for an extended range of use. Here we present several novel pPRIG-based vectors (collectively referred to as PRIGs) in which : i) the HA tag sequence was inserted in the three reading frames 3' of the MCS (3'HA PRIGs); ii) a functional domain (ER, VP16 or KRAB) was inserted either 5' or 3' of the MCS (« modular » PRIGs); iii) eGFP was replaced by either eCFP, eYFP, mCherry or puro-R (« single color/resistance » PRIGs); and iv) mCherry, eYFP or eGFP was inserted 5' of the MCS of the IRES-eGFP, IRES-eCFP or IRES-Puro-R containing PRIGs, respectively (« dual color/selection » PRIGs). Additionally, some of these PRIGs were also constructed in a pMigR MSCV background which has been widely used in pluripotent cells.</p> <p>Conclusion</p> <p>These novel vectors allow for straightforward detection of any expressed protein (3'HA PRIGs), for functional studies of chimeric proteins (« modular » PRIGs), for multiple transductions and fluorescence analyses of transduced cells (« single color/resistance » PRIGs), or for quantitative detection of studied proteins in independently identified/selected transduced cells (« dual color/selection » PRIGs). They maintain the original advantages of pPRIG and provide suitable tools for either transient or stable expression and functional studies in a large range of experimental settings.</p

Possible evidence of near transfer effects after adaptive working memory training in persons with multiple sclerosis

Background: Cognitive deficits, especially in working memory (WM) and information processing (IP) efficiency, are common in people with multiple sclerosis (PwMS). Few studies have examined the efficacy of n-back training in improving these two cognitive functions in PwMS. In the present study, we examined the effects of an intensive n-back training program by measuring the gains on the trained task (2- and 3-back tasks), but we also studied possible near transfer effects to other tests that assess WM and IP, as well as far transfer effects or improvements in other cognitive functions. Methods: A sample consisting of 35 PwMS with different cognitive statuses. All the participants underwent an adaptive n-back training for 10 days (60 min/day), and they were neuropsychologically assessed at baseline (D1) and after training (D10). The effectiveness of the training was tested: (1) by using mean-based comparisons and Cohen's d values; (2) by estimating and comparing the quartile values of the D1 and D10 distributions. Two indexes of improvement in individual performance were calculated, the net score improvement index (NSI) and the percent of maximum possible individualized improvement (PMPI). Results: Repeat practice improves 2- and 3-back performance, showing more correct responses (CR) and lower reaction times (RT) on D10 compared to D1. These results were corroborated by the NSI and PMPI scores, but the gains after training were more statistically significant for the 3-back (observing higher CR and lower RT after training) than for the 2-back (observing gains in CR, but not in RT). We also observed a possible transference of this improvement on the n-back task to other WM/IPS tests. Specifically, statistically significant pre-post training differences were found in the values in three quartiles of the Paced Auditory Serial Addition Test (PASAT; q25, p < 0.03; q50, p < 0.001; q75, p < 0.002) and of the Symbol Digit Modalities Test (SDMT; q25, p < 0.03; q50, p < 0.001; q75, p < 0.001) as well as in two quartiles of the Letter-Number Sequencing Task (LNST; q50, p < 0.004; q75 p < 0.001), and in one quartile of the Digit Backwards Span Test (DSBT; q75, p < 0.001). Reliable change analyses confirmed these performance improvements on the PASAT, SDMT, and LNST. Conclusions: This study confirmed that the intensive and adaptive n-back training produced improvements in the trained task in PwMS with different cognitive statuses. Furthermore, these gains were not only observed on the trained task, but they seemed to be also transferred to other tests that measured WM and IP functions

Novel targeted siRNA-loaded hybrid nanoparticles: preparation, characterization and in vitro evaluation.

BACKGROUND: siRNAs have a high potential for silencing critical molecular pathways that are pathogenic. Nevertheless, their clinical application has been limited by a lack of effective and safe nanotechnology-based delivery system that allows a controlled and safe transfection to cytosol of targeted cells without the associated adverse effects. Our group recently reported a very effective and safe hybrid nanoparticle delivery system composing human IgG and poloxamer-188 for siRNA delivery to cancer cells. However, these nanoparticles need to be optimized in terms of particle size, loading capacity and encapsulation efficiency. In the present study, we explored the effects of certain production parameters on particle size, loading capacity and encapsulation efficiency. Further, to make these nanoparticles more specific in their delivery of siRNA, we conjugated anti-NTSR1-mAb to the surface of these nanoparticles to target NTSR1-overexpressing cancer cells. The mechanism of siRNA release from these antiNTSR1-mAb functionalized nanoparticles was also elucidated. RESULTS: It was demonstrated that the concentration of human IgG in the starting nanoprecipitation medium and the rotation speed of the magnetic stirrer influenced the encapsulation efficiency, loading capacity and the size of the nanoparticles produced. We also successfully transformed these nanoparticles into actively targeted nanoparticles by functionalizing with anti-NTSR1-mAb to specifically target NTSR1-overexpressing cancer cells, hence able to avoid undesired accumulation in normal cells. The mechanism of siRNA release from these nanoparticles was elucidated to be by Fickian diffusion. Using flow cytometry and fluorescence microscopy, we were able to confirm the active involvement of NTSR1 in the uptake of these anti-NTSR1-mAb functionalized hybrid nanoparticles by lung adenocarcinoma cells. CONCLUSIONS: This hybrid nanoparticle delivery system can be used as a platform technology for intracellular delivery of siRNAs to NTSR1-overexpressing tumor cells

Lazy Fault Detection for Redundant MPI

As the scale of supercomputers grows, it is becoming increasingly important for software to efficiently withstand hardware and software faults. Process replication is one resilience technique, but typical implementations require replicas to stay closely synchronized with each other. We propose algorithms to lazily detect faults in replicated MPI applications, allowing for more flexibility in replica scheduling and potential power savings. Evaluation shows that, when all processes are operated at full power, this approach allows applications to complete substantially faster as compared to using a synchronized model, and often as fast as in non-replicated execution