Application acceleration : an investigation of automatic porting methods for application accelerators

Future HPC systems will contain both large collections of multi-core proces sors and specialist many-core co-processors. These specialised many-core co processors are typically classified as Application Accelerators. More specifically, Application Accelerations are devices such as GPUs, CELL Processors, FPGAs and custom application specific integrated circuit devices(ASICs). These devices present new challenges to overcome, including their programming difficulties, their diversity and lack of commonality of programming approach between them and the issue of selecting the most appropriate device for an application. This thesis attempts to tackle these problems by examining the suitability of automatic porting methods. In the course of this research, relevant software, both academic and com mercial, has been analysed to determine how it attempts to solve the problems relating to the use of application acceleration devices. A new approach is then constructed, this approach is an Automatic Self-Modifying Application Porting system that is able to not only port code to an acceleration device, but, using performance data, predict the appropriate device for the code being ported. Additionally, this system is also able to use the performance data that are gathered by the system to modify its own decision making model and improve its future predictions. Once the system has been developed, a series of applications are trialled and their performance, both in terms of execution time and the accuracy of the systems predictions, are analysed. This analysis has shown that, although the system is not able to flawlessly predict the correct device for an unseen application, it is able to achieve an accuracy of over 80% and, just as importantly, the code it produces is within 15% of that produced by an experienced human programmer. This analysis has also shown that while automatically ported code performs favourably in nearly all cases when compared to a single-core CPU, automatically ported code only out performs a quad-core CPU in three out of seven application case studies. From these results, it is also shown that the system is able to utilise this performance data and build a decision model allowing the users to determine if an automatically ported version of their application will provide performance improvement compared to both CPU types considered. The availability of such a system may prove valuable in allowing a diverse range of users to utilise the performance supplied by many-core devices within next generation HPC systems

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

A novel Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Application acceleration : an investigation of automatic porting methods for application accelerators

Future HPC systems will contain both large collections of multi-core proces sors and specialist many-core co-processors. These specialised many-core co processors are typically classified as Application Accelerators. More specifically, Application Accelerations are devices such as GPUs, CELL Processors, FPGAs and custom application specific integrated circuit devices(ASICs). These devices present new challenges to overcome, including their programming difficulties, their diversity and lack of commonality of programming approach between them and the issue of selecting the most appropriate device for an application. This thesis attempts to tackle these problems by examining the suitability of automatic porting methods. In the course of this research, relevant software, both academic and com mercial, has been analysed to determine how it attempts to solve the problems relating to the use of application acceleration devices. A new approach is then constructed, this approach is an Automatic Self-Modifying Application Porting system that is able to not only port code to an acceleration device, but, using performance data, predict the appropriate device for the code being ported. Additionally, this system is also able to use the performance data that are gathered by the system to modify its own decision making model and improve its future predictions. Once the system has been developed, a series of applications are trialled and their performance, both in terms of execution time and the accuracy of the systems predictions, are analysed. This analysis has shown that, although the system is not able to flawlessly predict the correct device for an unseen application, it is able to achieve an accuracy of over 80% and, just as importantly, the code it produces is within 15% of that produced by an experienced human programmer. This analysis has also shown that while automatically ported code performs favourably in nearly all cases when compared to a single-core CPU, automatically ported code only out performs a quad-core CPU in three out of seven application case studies. From these results, it is also shown that the system is able to utilise this performance data and build a decision model allowing the users to determine if an automatically ported version of their application will provide performance improvement compared to both CPU types considered. The availability of such a system may prove valuable in allowing a diverse range of users to utilise the performance supplied by many-core devices within next generation HPC systems

An intelligent semi-automatic application porting system for application accelerators

Work involving the use of application acceleration devices is showing great promise, however, there are still major obstacles preventing their widespread adoption. Currently the process of porting applications to an accelerator requires expertise in both the computer science and application domains, due to the lack of abstraction available. We present our work associated with the development of a novel solution to this abstraction problem; an intelligent semi-automatic application porting system, that will allow a higher level of abstraction, to be presented to the end user, while maintaining reasonable performance levels. A prototype system has been constructed that can successfully port applications to Graphics Processing Units (GPUs) and shows promising results in terms of performance comparisons between CPU and GPU. We are presently extending our prototype to other application acceleration devices and to allow the automatic selection of the most appropriate device for an application using Machine Learning techniques. We expect our work and results will be of widespread interest to the increasing community involved in porting code to application accelerators

Towards automated compliance checking in the construction industry

The Construction industry has a complex structure of regulatory compliance, consisting of statutory requirements and performance based regulations. The increasing importance of sustainability has further intensified this, with a new building’s compliance against sustainability assessment methodologies now often an important contractual requirement. Automatic compliance checking against these requirements has been long sought after within this industry and several approaches have attempted to achieve this goal. The key improvement that can be made to many existing approaches is enabling the development and maintenance of the regulations by those who are most qualified to do this the domain experts. This is illustrated by the fact that in many cases regulatory compliance systems are closed and when modifications are needed they must be made by software’s developers. This process is simply not viable in this industries rapidly changing environment. In this paper we describe our framework for compliance checking, showing the potential for utilising an integrated process to enable domain experts to create and maintain their own regulations that can then be executed by an open source rule engine. We will describe our process, the methodology and software developed to support it. We will present our initial results in the form of two case studies illustrating progress towards automation of commonly used regulations. Finally, we will also discuss how our approach could be generalised to other related sectors to enable the adoption of a similar approach towards automatic regulatory compliance

The Fundamentals : a testimony to the truth Vol. 8

Old Testament criticism and New Testament Christianity / Prof. W.H. Griffith Thomas Evolutionism in the pulpit / an occupant of the pew Decadence of Darwinism / Rev. Henry H. Beach Paul\u27s testimony to the doctrine of sin / Prof. Chas B. Williams The science of conversion / Rev. H.M. Sydenstricker The doctrinal value of the first chapters of Genesis / Rev. Dyson Hague The knowledge of God / Rev. David James Burrell Preach the Word / Howard Crosby Mormonism: its origin, characteristics, and doctrines / Rev. R.G. McNiecehttps://digitalcommons.biola.edu/the-fundamentals/1007/thumbnail.jp