Garbage collection optimization for non uniform memory access architectures

Cache-coherent non uniform memory access (ccNUMA) architecture is a standard design pattern for contemporary multicore processors, and future generations of architectures are likely to be NUMA. NUMA architectures create new challenges for managed runtime systems. Memory-intensive applications use the system’s distributed memory banks to allocate data, and the automatic memory manager collects garbage left in these memory banks. The garbage collector may need to access remote memory banks, which entails access latency overhead and potential bandwidth saturation for the interconnection between memory banks. This dissertation makes five significant contributions to garbage collection on NUMA systems, with a case study implementation using the Hotspot Java Virtual Machine. It empirically studies data locality for a Stop-The-World garbage collector when tracing connected objects in NUMA heaps. First, it identifies a locality richness which exists naturally in connected objects that contain a root object and its reachable set— ‘rooted sub-graphs’. Second, this dissertation leverages the locality characteristic of rooted sub-graphs to develop a new NUMA-aware garbage collection mechanism. A garbage collector thread processes a local root and its reachable set, which is likely to have a large number of objects in the same NUMA node. Third, a garbage collector thread steals references from sibling threads that run on the same NUMA node to improve data locality. This research evaluates the new NUMA-aware garbage collector using seven benchmarks of an established real-world DaCapo benchmark suite. In addition, evaluation involves a widely used SPECjbb benchmark and Neo4J graph database Java benchmark, as well as an artificial benchmark. The results of the NUMA-aware garbage collector on a multi-hop NUMA architecture show an average of 15% performance improvement. Furthermore, this performance gain is shown to be as a result of an improved NUMA memory access in a ccNUMA system. Fourth, the existing Hotspot JVM adaptive policy for configuring the number of garbage collection threads is shown to be suboptimal for current NUMA machines. The policy uses outdated assumptions and it generates a constant thread count. In fact, the Hotspot JVM still uses this policy in the production version. This research shows that the optimal number of garbage collection threads is application-specific and configuring the optimal number of garbage collection threads yields better collection throughput than the default policy. Fifth, this dissertation designs and implements a runtime technique, which involves heuristics from dynamic collection behavior to calculate an optimal number of garbage collector threads for each collection cycle. The results show an average of 21% improvements to the garbage collection performance for DaCapo benchmarks.

The experience of teaching statistics to non-specialist students in Saudi universities

Undoubtedly, statistics has become one of the most important subjects in the modern world, where its applications are ubiquitous. The importance of statistics is not limited to statisticians, but also impacts upon non-statisticians who have to use statistics within their own disciplines. Several studies have indicated that most of the academic departments around the world have realized the importance of statistics to non-specialist students. Therefore, the number of students enrolled in statistics courses has vastly increased, coming from a variety of disciplines. Consequently, research within the scope of statistics education has been able to develop throughout the last few years. One important issue is how statistics is best taught to, and learned by, non-specialist students. This issue is controlled by several factors that affect the learning and teaching of statistics to non-specialist students, such as the use of technology, the role of the English language (especially for those whose first language is not English), the effectiveness of statistics teachers and their approach towards teaching statistics courses, students’ motivation to learn statistics and the relevance of statistics courses to the main subjects of non-specialist students. Several studies, focused on aspects of learning and teaching statistics, have been conducted in different countries around the world, particularly in Western countries. Conversely, the situation in Arab countries, especially in Saudi Arabia, is different; here, there is very little research in this scope, and what there is does not meet the needs of those countries towards the development of learning and teaching statistics to non-specialist students. This research was instituted in order to develop the field of statistics education. The purpose of this mixed methods study was to generate new insights into this subject by investigating how statistics courses are currently taught to non-specialist students in Saudi universities. Hence, this study will contribute towards filling the knowledge gap that exists in Saudi Arabia. This study used multiple data collection approaches, including questionnaire surveys from 1053 non-specialist students who had completed at least one statistics course in different colleges of the universities in Saudi Arabia. These surveys were followed up with qualitative data collected via semi-structured interviews with 16 teachers of statistics from colleges within all six universities where statistics is taught to non-specialist students in Saudi Arabia’s Eastern Region. The data from questionnaires included several types, so different techniques were used in analysis. Descriptive statistics were used to identify the demographic characteristics of the participants. The chi-square test was used to determine associations between variables. Based on the main issues that are raised from literature review, the questions (items scales) were grouped and five key groups of questions were obtained which are: 1) Effectiveness of Teachers; 2) English Language; 3) Relevance of Course; 4) Student Engagement; 5) Using Technology. Exploratory data analysis was used to explore these issues in more detail. Furthermore, with the existence of clustering in the data (students within departments within colleges, within universities), multilevel generalized linear models for dichotomous analysis have been used to clarify the effects of clustering at those levels. Factor analysis was conducted confirming the dimension reduction of variables (items scales). The data from teachers’ interviews were analysed on an individual basis. The responses were assigned to one of the eight themes that emerged from within the data: 1) the lack of students’ motivation to learn statistics; 2) students' participation; 3) students’ assessment; 4) the effective use of technology; 5) the level of previous mathematical and statistical skills of non-specialist students; 6) the English language ability of non-specialist students; 7) the need for extra time for teaching and learning statistics; and 8) the role of administrators. All the data from students and teachers indicated that the situation of learning and teaching statistics to non-specialist students in Saudi universities needs to be improved in order to meet the needs of those students. The findings of this study suggested a weakness in the use of statistical software applications in these courses. This study showed that there is lack of application of technology such as statistical software programs in these courses, which would allow non-specialist students to consolidate their knowledge. The results also indicated that English language is considered one of the main challenges in learning and teaching statistics, particularly in institutions where English is not used as the main language. Moreover, the weakness of mathematical skills of students is considered another major challenge. Additionally, the results indicated that there was a need to tailor statistics courses to the needs of non-specialist students based on their main subjects. The findings indicate that statistics teachers need to choose appropriate methods when teaching statistics courses.

A III-V channel field effect transistor for non-classical CMOS: process optimisation for improved gate stack function

This thesis describes a collection of studies into the electrical response of a III-V MOS stack comprising metal/GaGdO/GaAs layers as a function of fabrication process variables and the findings of those studies. As a result of this work, areas of improvement in the gate process module of a III-V heterostructure MOSFET were identified. Compared to traditional bulk silicon MOSFET design, one featuring a III-V channel heterostructure with a high-dielectric-constant oxide as the gate insulator provides numerous benefits, for example: the insulator can be made thicker for the same capacitance, the operating voltage can be made lower for the same current output, and improved output characteristics can be achieved without reducing the channel length further. It is known that transistors composed of III-V materials are most susceptible to damage induced by radiation and plasma processing. These devices utilise sub-10 nm gate dielectric films, which are prone to contamination, degradation and damage. Therefore, throughout the course of this work, process damage and contamination issues, as well as various techniques to mitigate or prevent those have been investigated through comparative studies of III-V MOS capacitors and transistors comprising various forms of metal gates, various thicknesses of GaGdO dielectric, and a number of GaAs-based semiconductor layer structures. Transistors which were fabricated before this work commenced, showed problems with threshold voltage control. Specifically, MOSFETs designed for normally-off (VTH > 0) operation exhibited below-zero threshold voltages. With the results obtained during this work, it was possible to gain an understanding of why the transistor threshold voltage shifts as the gate length decreases and of what pulls the threshold voltage downwards preventing normally-off device operation. Two main culprits for the negative VTH shift were found. The first was radiation damage induced by the gate metal deposition process, which can be prevented by slowing down the deposition rate. The second was the layer of gold added on top of platinum in the gate metal stack which reduces the effective work function of the whole gate due to its electronegativity properties. Since the device was designed for a platinum-only gate, this could explain the below zero VTH. This could be prevented either by using a platinum-only gate, or by matching the layer structure design and the actual gate metal used for the future devices. Post-metallisation thermal anneal was shown to mitigate both these effects. However, if post-metallisation annealing is used, care should be taken to ensure it is performed before the ohmic contacts are formed as the thermal treatment was shown to degrade the source/drain contacts. In addition, the programme of studies this thesis describes, also found that if the gate contact is deposited before the source/drain contacts, it causes a shift in threshold voltage towards negative values as the gate length decreases, because the ohmic contact anneal process affects the properties of the underlying material differently depending on whether it is covered with the gate metal or not. In terms of surface contamination; this work found that it causes device-to-device parameter variation, and a plasma clean is therefore essential. This work also demonstrated that the parasitic capacitances in the system, namely the contact periphery dependent gate-ohmic capacitance, plays a significant role in the total gate capacitance. This is true to such an extent that reducing the distance between the gate and the source/drain ohmic contacts in the device would help with shifting the threshold voltages closely towards the designed values. The findings made available by the collection of experiments performed for this work have two major applications. Firstly, these findings provide useful data in the study of the possible phenomena taking place inside the metal/GaGdO/GaAs layers and interfaces as the result of chemical processes applied to it. In addition, these findings allow recommendations as to how to best approach fabrication of devices utilising these layers.

The role of non-coding RNA in the development of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease of the small pulmonary arteries, characterised by pulmonary vascular remodelling due to excessive proliferation and resistance to apoptosis of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs). The increased pulmonary vascular resistance and elevated pulmonary artery pressures result in right heart failure and premature death. Germline mutations of the bone morphogenetic protein receptor-2 (bmpr2) gene, a receptor of the transforming growth factor beta (TGF-β) superfamily, account for approximately 75%-80% of the cases of heritable form of PAH (HPAH) and 20% of sporadic cases or idiopathic PAH (IPAH). IPAH patients without known bmpr2 mutations show reduced expression of BMPR2. However only ~ 20% of bmpr2-mutation carriers will develop the disease, due to an incomplete penetrance, thus the need for a ‘second hit’ including other genetic and/or environmental factors is accepted. Diagnosis of PAH occurs most frequently when patients have reached an advanced stage of disease. Although modern PAH therapies can markedly improve a patient’s symptoms and slow the rate of clinical deterioration, the mortality rate from PAH remains unacceptably high. Therefore, the development of novel therapeutic approaches is required for the treatment of this multifaceted disease. Noncoding RNAs (ncRNAs) include microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). MiRNAs are ~ 22 nucleotide long and act as negative regulators of gene ex-pression via degradation or translational inhibition of their target mRNAs. Previous studies showed extensive evidence for the role of miRNAs in the development of PAH. LncRNAs are transcribed RNA molecules greater than 200 nucleotides in length. Similar to classical mRNA, lncRNAs are translated by RNA polymerase II and are generally alternatively spliced and polyadenylated. LncRNAs are highly versatile and function to regulate gene expression by diverse mechanisms. Unlike miRNAs, which exhibit well-defined actions in negatively regulating gene expression via the 3’-UTR of mRNAs, lncRNAs play more diverse and unpredictable regulatory roles. Although a number of lncRNAs have been intensively investigated in the cancer field, studies of the role of lncRNAs in vascular diseases such as PAH are still at a very early stage. The aim of this study was to investigate the involvement of specific ncRNAs in the development of PAH using experimental animal models and cell culture. The first ncRNA we focused on was miR-143, which is up-regulated in the lung and right ventricle tissues of various animal models of PH, as well as in the lungs and PASMCs of PAH patients. We show that genetic ablation of miR-143 is protective against the development of chronic hypoxia induced PH in mice, assessed via measurement of right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH) and pulmonary vascular remodelling. We further report that knockdown of miR-143-3p in WT mice via anti-miR-143-3p administration prior to exposure of mice to chronic hypoxia significantly decreases certain indices of PH (RVSP) although no significant changes in RVH and pulmo-nary vascular remodelling were observed. However, a reversal study using antimiR-143-3p treatment to modulate miR-143-3p demonstrated a protective effect on RVSP, RVH, and muscularisation of pulmonary arteries in the mouse chronic hypoxia induced PH model. In vitro experiments showed that miR-143-3p overexpression promotes PASMC migration and inhibits PASMC apoptosis, while knockdown miR-143-3p elicits the opposite effect, with no effects observed on cellular proliferation. Interestingly, miR-143-3p-enriched exosomes derived from PASMCs mediated cell-to-cell communication between PASMCs and PAECs, contributing to the pro-migratory and pro-angiogenic phenotype of PAECs that underlies the pathogenesis of PAH. Previous work has shown that miR-145-5p expression is upregulated in the chronic hypoxia induced mouse model of PH, as well as in PAH patients. Genetic ablation and pharmacological inhibition (subcutaneous injection) of miR-145-5p exert a protective against the de-velopment of PAH. In order to explore the potential for alternative, more lung targeted delivery strategies, miR-145-5p expression was inhibited in WT mice using intranasal-delivered antimiR-145-5p both prior to and post exposure to chronic hypoxia. The decreased expression of miR-145-5p in lung showed no beneficial effect on the development of PH compared with control antimiRNA treated mice exposed to chronic hypoxia. Thus, miR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, while the inhibition of miR-143-3p prevented the development of experimental pulmonary hypertension. We focused on two lncRNAs in this project: Myocardin-induced Smooth Muscle Long noncoding RNA, Inducer of Differentiation (MYOSLID) and non-annotated Myolnc16, which were identified from RNA sequencing studies in human coronary artery smooth muscle cells (HCASMCs) that overexpress myocardin. MYOSLID was significantly in-creased in PASMCs from patients with IPAH compared to healthy controls and increased in circulating endothelial progenitor cells (EPCs) from bmpr2 mutant PAH patients. Exposure of PASMCs to hypoxia in vitro led to a significant upregulation in MYOSLID expres-sion. MYOSLID expression was also induced by treatment of PASMC with BMP4, TGF-β and PDGF, which are known to be triggers of PAH in vitro. Small interfering RNA (siR-NA)-mediated knockdown MYOSLID inhibited migration and induced cell apoptosis without affecting cell proliferation and upregulated several genes in the BMP pathway in-cluding bmpr1α, bmpr2, id1, and id3. Modulation of MYOSLID also affected expression of BMPR2 at the protein level. In addition, MYOSLID knockdown affected the BMP-Smad and BMP-non-Smad signalling pathways in PASMCs assessed by phosphorylation of Smad1/5/9 and ERK1/2, respectively. In PAECs, MYOSLID expression was also induced by hypoxia exposure, VEGF and FGF2 treatment. In addition, MYOSLID knockdown sig-nificantly decreased the proliferation of PAECs. Thus, MYOSLID may be a novel modulator in pulmonary vascular cell functions, likely through the BMP-Smad and –non-Smad pathways. Treatment of PASMCs with inflammatory cytokines (IL-1 and TNF-α) significantly in-duced the expression of Myolnc16 at a very early time point. Knockdown of Myolnc16 in vitro decreased the expression of il-6, and upregulated the expression of il-1 and il-8 in PASMCs. Moreover, the expression levels of chemokines (cxcl1, cxcl6 and cxcl8) were sig-nificantly decreased with Myolnc16 knockdown. In addition, Myolnc16 knockdown decreased the MAP kinase signalling pathway assessed by phosphorylation of ERK1/2 and p38 MAPK and inhibited cell migration and proliferation in PASMCs. Thus, Myolnc16 may a novel modulator of PASMCs functions through anti-inflammatory signalling pathways. In summary, in this thesis we have demonstrated how miR-143-3p plays a protective role in the development of PH both in vivo animal models and patients, as well as in vitro cell cul-ture. Moreover, we have showed the role of two novel lncRNAs in pulmonary vascular cells. These ncRNAs represent potential novel therapeutic targets for the treatment of PAH with further work addressing to investigate the target genes, and the pathways modulated by these ncRNAs during the development of PAH.