Parallel and concurrent software sometimes exhibit incorrect behavior because of

unintended interference between different threads of execution. Common classes

of concurrency bugs include data races, deadlocks, and atomicity violations.

These bugs are often non-deterministic and hard to find without sophisticated

tools. We present Active Testing, a methodology to effectively find concurrency

bugs that scales to large distributed memory parallel systems.

Active Testing combines the coverage and predictive power of program analysis

with the familiarity of testing. It works in two phases: in the predictive

analysis phase, a program is executed and monitored for potential concurrency

bugs and in the testing phase, Active Testing re-executes the program while

controlling the thread schedules in an attempt to reproduce the bug predicted in

the first phase.

We have implemented Active Testing for multi-threaded Java programs in the

CalFuzzer framework. We have also developed UPC-Thrille, an Active Testing framework

for Unified Parallel C (UPC) programs written in the Single Program Multiple

Data (SPMD) programming model combined with the Partitioned Global Address Space

(PGAS) memory model. We explain in detail the design decisions and optimizations

that were necessary to scale Active Testing to thousands of cores. We present

extensions to UPC-Thrille that support hybrid memory models as well.

We evaluate the effectiveness of Active Testing by running our tools on several

Java and UPC benchmarks, showing that it can predict and confirm real

concurrency bugs with low overhead. We demonstrate the scalability of Active

Testing by running benchmarks with UPC-Thrille on large clusters with thousands

of cores.

The possibility of using the mesh-free method Smoothed Particle Hydrodynamics (SPH) towards analyzing modern additive manufacturing techniques, extrusion based ones in particular, is investigated in this report. The mathematical foundations and a number of corresponding topics regarding SPH is introduced, ranging from incompressible SPH and implicit timestepping methods to total Lagrangian formulations: displaying its robust capabilities for solving multiphyiscal mechanical problems. Finally, we demonstrate a swarm-intelligence based optimization scheme coupled with our SPH solver to optimize extrusion topologies for DIW (Direct Ink Writing) applications.

Tourette Syndrome (TS) is a genetic, neurodevelopmental disorder that is characterized by the juvenile-onset of chronic motor and vocal tics and is often associated with other overlapping neuropsychiatric comorbidities including OCD, ADHD, self-injurious behaviors (SIBs), and social impairments. In this dissertation, we report novel TS-like behaviors in a CNS-specific conditional knockout mouse model of Zfp521 (Zfp521-BrKO). Zfp521 is a zinc finger transcription factor first identified as enriched in striatonigral MSNs from our laboratory's FACS-array profiling of striatal MSN subtypes (and later verified by the BAC-TRAP methodology) and is known to be critical in the differentiation of ES cells into early neuronal precursors. Converging evidence from the striatal expression of Zfp521 and the neurodevelopmental roles of Zfp423 (paralog) and Ebf1 (a physically interacting transcriptional partner of Zfp521) suggests Zfp521 may be involved in striatal development. Extensive studies of the behavioral and neuropathological phenotypes show that Zfp521-BrKO mice demonstrate robust TS-like face validity, exhibiting juvenile-onset of several simple and complex tic-like motor behaviors that are exacerbated by stress or suppressed by attention, multiple TS-associated comorbidities, and select neuropathologies reported in TS patients. Pharmacological suppression of tic-like behaviors by haloperidol, a neuroleptic that is among the first-line treatments for TS, but not by fluoxetine, a SSRI used to treat OCD, reveals Zfp521-BrKO mice demonstrate selective predictive validity for tics associated with TS rather than the compulsive behaviors of OCD. Interestingly, Zfp521-BrKO mice are highly resistant to haloperidol-induced catalepsy, implicating hypofunctional indirect pathway D2-MSNs in the pathophysiology of the tic-like behaviors in the mutant mice, which was confirmed through immunohistochemical, electrophysiological, and optogenetic interrogation of the striatopallidal MSNs. Furthermore, supported by electrophysiological evidence of D1-MSN activation by haloperidol in Zfp521-BrKO, presumably by presynaptic D2-autoreceptor-mediated increase in DA release, we show that Zfp521-BrKO mice demonstrate unique predictive validity for tic-suppression by DA-agonism with pergolide and selective D1-receptor agonism. Our studies not only establish Zfp521-BrKO mice as a comprehensive animal model of TS with a distinct underlying BG circuitry dysfunction, but also highlights the potential of these mice as a powerful tool for TS drug discovery. Elucidating the molecular mechanisms of Zfp521, in both the normal and TS brain, will provide critical insights into the fundamental processes of striatal development and have significant implications for human genetic studies of TS.

Background

Results

Conclusion

Xanthomonas oryzae pv. oryzae, the causal agent of bacterial blight disease, is a serious pathogen of rice. Here we describe a fluorescent marker system to study virulence and pathogenicity of X. oryzae pv. oryzae.

A fluorescent X. oryzae pv. oryzae Philippine race 6 strain expressing green fluorescent protein (GFP) (PXO99GFP) was generated using the gfp gene under the control of the neomycin promoter in the vector, pPneo-gfp. The PXO99GFPstrain displayed identical virulence and avirulence properties as the wild type control strain, PXO99. Using fluorescent microscopy, bacterial multiplication and colonization were directly observed in rice xylem vessels. Accurate and rapid determination of bacterial growth was assessed using fluoremetry and an Enzyme-Linked ImmunoSorbant Assay (ELISA).

Our results indicate that the fluorescent marker system is useful for assessing bacterial infection and monitoring bacterial multiplication in planta.

Xanthomonas oryzae pv. oryzae, the causal agent of bacterial blight disease, is a serious pathogen of rice. Here we describe a fluorescent marker system to study virulence and pathogenicity of X. oryzae pv. oryzae.

A fluorescent X. oryzae pv. oryzae Philippine race 6 strain expressing green fluorescent protein (GFP) (PXO99GFP) was generated using the gfp gene under the control of the neomycin promoter in the vector, pPneo-gfp. The PXO99GFPstrain displayed identical virulence and avirulence properties as the wild type control strain, PXO99. Using fluorescent microscopy, bacterial multiplication and colonization were directly observed in rice xylem vessels. Accurate and rapid determination of bacterial growth was assessed using fluoremetry and an Enzyme-Linked ImmunoSorbant Assay (ELISA).

Our results indicate that the fluorescent marker system is useful for assessing bacterial infection and monitoring bacterial multiplication in planta.