Parallelism and the software-hardware interface in embedded systems

This thesis by publications addresses issues in the architecture and microarchitecture of next generation, high performance streaming Systems-on-Chip through quantifying the most important forms of parallelism in current and emerging embedded system workloads. The work consists of three major research tracks, relating to data level parallelism, thread level parallelism and the software-hardware interface which together reflect the research interests of the author as they have been formed in the last nine years. Published works confirm that parallelism at the data level is widely accepted as the most important performance leverage for the efficient execution of embedded media and telecom applications and has been exploited via a number of approaches the most efficient being vectorlSIMD architectures. A further, complementary and substantial form of parallelism exists at the thread level but this has not been researched to the same extent in the context of embedded workloads. For the efficient execution of such applications, exploitation of both forms of parallelism is of paramount importance. This calls for a new architectural approach in the software-hardware interface as its rigidity, manifested in all desktop-based and the majority of embedded CPU's, directly affects the performance ofvectorized, threaded codes. The author advocates a holistic, mature approach where parallelism is extracted via automatic means while at the same time, the traditionally rigid hardware-software interface is optimized to match the temporal and spatial behaviour of the embedded workload. This ultimate goal calls for the precise study of these forms of parallelism for a number of applications executing on theoretical models such as instruction set simulators and parallel RAM machines as well as the development of highly parametric microarchitectural frameworks to encapSUlate that functionality.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Wave-resistance computation via CFD and IGA-BEM solvers : a comparative study

This paper delivers a preliminary comparative study on the computation of wave resistance via a commercial CFD solver (STAR-CCM+®) versus an in-house developed IGA-BEM solver for a pair of hulls, namely the parabolic Wigley hull and the KRISO container ship (KCS). The CFD solver combines a VOF (Volume Of Fluid) free-surface modelling technique with alternative turbulence models, while the IGA-BEM solver adopts an inviscid flow model that combines the Boundary Element approach (BEM) with Isogeometric Analysis (IGA) using T-splines or NURBS. IGA is a novel and expanding concept, introduced by Hughes and his collaborators (Hughes et al, 2005), aiming to intrinsically integrate CAD with Analysis by communicating the CAD model of the geometry (the wetted ship hull in our case) to the solver without any approximation

Differential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer’s disease, frontotemporal dementia and progressive supranuclear palsy

OBJECTIVES: This longitudinal study compared emerging plasma biomarkers for neurodegenerative disease between controls, patients with Alzheimer's disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP). METHODS: Plasma phosphorylated tau at threonine-181 (p-tau181), amyloid beta (Αβ)42, Aβ40, neurofilament light (NfL) and glial fibrillar acidic protein (GFAP) were measured using highly sensitive single molecule immunoassays (Simoa) in a multicentre cohort of 300 participants (controls=73, amyloid positive mild cognitive impairment (MCI+) and AD dementia=63, LBD=117, FTD=28, PSP=19). LBD participants had known positron emission tomography (PET)-Aβ status. RESULTS: P-tau181 was elevated in MCI+AD compared with all other groups. Aβ42/40 was lower in MCI+AD compared with controls and FTD. NfL was elevated in all dementias compared with controls while GFAP was elevated in MCI+AD and LBD. Plasma biomarkers could classify between MCI+AD and controls, FTD and PSP with high accuracy but showed limited ability in differentiating MCI+AD from LBD. No differences were detected in the levels of plasma biomarkers when comparing PET-Aβ positive and negative LBD. P-tau181, NfL and GFAP were associated with baseline and longitudinal cognitive decline in a disease specific pattern. CONCLUSION: This large study shows the role of plasma biomarkers in differentiating patients with different dementias, and at monitoring longitudinal change. We confirm that p-tau181 is elevated in MCI+AD, versus controls, FTD and PSP, but is less accurate in the classification between MCI+AD and LBD or detecting amyloid brain pathology in LBD. NfL was elevated in all dementia groups, while GFAP was elevated in MCI+AD and LBD

Possible relationship between Seismic Electric Signals (SES) lead time and earthquake stress drop

Stress drop values for fourteen large earthquakes with MW ≥ 5.4 which occurred in Greece during the period 1983–2007 are available. All these earthquakes were preceded by Seismic Electric Signals (SES). An attempt has been made to investigate possible correlation between their stress drop values and the corresponding SES lead times. For the stress drop, we considered the Brune stress drop, ΔσB, estimated from far field body wave displacement source spectra and ΔσSB derived from the strong motion acceleration response spectra. The results show a relation may exist between Brune stress drop, ΔσB, and lead time which implies that earthquakes with higher stress drop values are preceded by SES with shorter lead time

Gene-Environment Interaction Research and Transgenic Mouse Models of Alzheimer's Disease

The etiology of the sporadic form of Alzheimer's disease (AD) remains largely unknown. Recent evidence has suggested that gene-environment interactions (GxE) may play a crucial role in its development and progression. Whereas various susceptibility loci have been identified, like the apolipoprotein E4 allele, these cannot fully explain the increasing prevalence of AD observed with aging. In addition to such genetic risk factors, various environmental factors have been proposed to alter the risk of developing AD as well as to affect the rate of cognitive decline in AD patients. Nevertheless, aside from the independent effects of genetic and environmental risk factors, their synergistic participation in increasing the risk of developing AD has been sparsely investigated, even though evidence points towards such a direction. Advances in the genetic manipulation of mice, modeling various aspects of the AD pathology, have provided an excellent tool to dissect the effects of genes, environment, and their interactions. In this paper we present several environmental factors implicated in the etiology of AD that have been tested in transgenic animal models of the disease. The focus lies on the concept of GxE and its importance in a multifactorial disease like AD. Additionally, possible mediating mechanisms and future challenges are discussed

The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: a clinical observational study

<p>Abstract</p> <p>Background</p> <p>Available iron chelation regimes in thalassaemia may achieve different changes in cardiac and hepatic iron as assessed by MR. The aim of this study was to assess the efficacy of four available iron chelator regimes in 232 thalassaemia major patients by assessing the rate of change in repeated measurements of cardiac and hepatic MR.</p> <p>Results</p> <p>For the heart, deferiprone and the combination of deferiprone and deferoxamine significantly reduced cardiac iron at all levels of iron loading. As patients were on deferasirox for a shorter time, a second analysis ("Initial interval analysis") assessing the change between the first two recorded MR results for both cardiac and hepatic iron (minimum interval 12 months) was made. Combination therapy achieved the most rapid fall in cardiac iron load at all levels and deferiprone alone was significantly effective with moderate and mild iron load. In the liver, deferasirox effected significant falls in iron load and combination therapy resulted in the most rapid decline.</p> <p>Conclusion</p> <p>With the knowledge of the efficacy of the different available regimes and the specific iron load in the heart and the liver, appropriate tailoring of chelation therapy should allow clearance of iron. Combination therapy is best in reducing both cardiac and hepatic iron, while monotherapy with deferiprone or deferasirox are effective in the heart and liver respectively. The outcomes of this study may be useful to physicians as to the chelation they should prescribe according to the levels of iron load found in the heart and liver by MR.</p

Differential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy.

OBJECTIVES: This longitudinal study compared emerging plasma biomarkers for neurodegenerative disease between controls, patients with Alzheimer's disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP). METHODS: Plasma phosphorylated tau at threonine-181 (p-tau181), amyloid beta (Αβ)42, Aβ40, neurofilament light (NfL) and glial fibrillar acidic protein (GFAP) were measured using highly sensitive single molecule immunoassays (Simoa) in a multicentre cohort of 300 participants (controls=73, amyloid positive mild cognitive impairment (MCI+) and AD dementia=63, LBD=117, FTD=28, PSP=19). LBD participants had known positron emission tomography (PET)-Aβ status. RESULTS: P-tau181 was elevated in MCI+AD compared with all other groups. Aβ42/40 was lower in MCI+AD compared with controls and FTD. NfL was elevated in all dementias compared with controls while GFAP was elevated in MCI+AD and LBD. Plasma biomarkers could classify between MCI+AD and controls, FTD and PSP with high accuracy but showed limited ability in differentiating MCI+AD from LBD. No differences were detected in the levels of plasma biomarkers when comparing PET-Aβ positive and negative LBD. P-tau181, NfL and GFAP were associated with baseline and longitudinal cognitive decline in a disease specific pattern. CONCLUSION: This large study shows the role of plasma biomarkers in differentiating patients with different dementias, and at monitoring longitudinal change. We confirm that p-tau181 is elevated in MCI+AD, versus controls, FTD and PSP, but is less accurate in the classification between MCI+AD and LBD or detecting amyloid brain pathology in LBD. NfL was elevated in all dementia groups, while GFAP was elevated in MCI+AD and LBD.b. Funding This study was funded by the Cambridge Centre for Parkinson-Plus, the National Institute for Health Research (NIHR) Biomedical Research Centre at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge and the NIHR Newcastle Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The UK Dementia Research Institute, receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the UK Dementia Research Institute at UCL, the Wellcome Trust and an anonymous donor