Tiled microprocessors

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2007.Includes bibliographical references (p. 251-258).Current-day microprocessors have reached the point of diminishing returns due to inherent scalability limitations. This thesis examines the tiled microprocessor, a class of microprocessor which is physically scalable but inherits many of the desirable properties of conventional microprocessors. Tiled microprocessors are composed of an array of replicated tiles connected by a special class of network, the Scalar Operand Network (SON), which is optimized for low-latency, low-occupancy communication between remote ALUs on different tiles. Tiled microprocessors can be constructed to scale to 100's or 1000's of functional units. This thesis identifies seven key criteria for achieving physical scalability in tiled microprocessors. It employs an archetypal tiled microprocessor to examine the challenges in achieving these criteria and to explore the properties of Scalar Operand Networks. The thesis develops the field of SONs in three major ways: it introduces the 5-tuple performance metric, it describes a complete, high-frequency SON implementation, and it proposes a taxonomy, called AsTrO, for categorizing them.(cont.) To develop these ideas, the thesis details the design, implementation and analysis of a tiled microprocessor prototype, the Raw Microprocessor, which was implemented at MIT in 180 nm technology. Overall, compared to Raw, recent commercial processors with half the transistors required 30x as many lines of code, occupied 100x as many designers, contained 50x as many pre-tapeout bugs, and resulted in 33x as many post-tapeout bugs. At the same time, the Raw microprocessor proves to be more versatile in exploiting ILP, stream, and server-farm workloads with modest to large amounts of parallelism.by Michael Bedford Taylor.Ph.D

Design decision in the implementation of a raw architecture workstation

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1999.Includes bibliographical references (p. 53).by Michael Bedford Taylor.S.M

Quality Time: A simple online technique for quantifying multicore execution efficiency

Abstract—In order to increase utilization, multicore pro-cessors share memory resources among an increasing number of cores. This sharing leads to memory interference, which in turn leads to a non-uniform degradation in the execution of concurrent applications, even in the presence of fairness mechanisms. Many utilities rely on application CPU Time both for measuring resource usage and inferring application progress. These utilities are therefore directly affected by the distorting effects of multicore interference on the representativeness of CPU Time as a proxy for progress. This makes reasoning about myriad properties from fairness, to QoS, to throughput optimality very difficult in consolidated environments, such as IaaS. We introduce the notion of Quality Time, which provides a measure of application progress analogous to CPU Time’s measure of resource usage, and we propose a simple online sampling-based technique to approximate Quality Time with high accuracy. We have implemented three user-space tools called Qtime, Qtop, and Qplacer. Qtime can attach to an application to calculate its Quality Time online, Qtop is a dashboard that monitors the Quality Times of all applications on the system, and Qplacer leverages Quality Time information to find better application placements and improve overall system quality. With Quality Time, we are able to reduce the error in inferring execution efficiency from 150.3 % to 25.1 % in the worst case and from 30.0 % to 7.5 % on average. Qplacer can increase average system throughput by 3.2 % when compared to static application placement. I

The Perioperative Quality Improvement Programme (PQIP patient study): protocol for a UK multicentre, prospective cohort study to measure quality of care and outcomes after major surgery

INTRODUCTION: Major surgery accounts for a substantial proportion of health service activity, due not only to the primary procedure, but the longer-term health implications of poor short-term outcome. Data from small studies or from outside the UK indicate that rates of complications and failure to rescue vary between hospitals, as does compliance with best practice processes. Within the UK, there is currently no system for monitoring postoperative complications (other than short-term mortality) in major non-cardiac surgery. Further, there is variation between national audit programmes, in the emphasis placed on quality assurance versus quality improvement, and therefore the principles of measurement and reporting which are used to design such programmes. METHODS AND ANALYSIS: The PQIP patient study is a multi-centre prospective cohort study which recruits patients undergoing major surgery. Patient provide informed consent and contribute baseline and outcome data from their perspective using a suite of patient-reported outcome tools. Research and clinical staff complete data on patient risk factors and outcomes in-hospital, including two measures of complications. Longer-term outcome data are collected through patient feedback and linkage to national administrative datasets (mortality and readmissions). As well as providing a uniquely granular dataset for research, PQIP provides feedback to participating sites on their compliance with evidence-based processes and their patients' outcomes, with the aim of supporting local quality improvement. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Health Research Authority in the UK. Dissemination of interim findings (non-inferential) will form a part of the improvement methodology and will be provided to participating centres at regular intervals, including near-real time feedback of key process measures. Inferential analyses will be published in the peer-reviewed literature, supported by a comprehensive multi-modal communications strategy including to patients, policy makers and academic audiences as well as clinicians

Remaking the self in John Dunton’s The Life and Errors of John Dunton (1705)

© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. John Dunton (1659–1732) is a bookseller and writer best known today as a tireless self-promoter whose I-centred and experimental work contributed to the development of the novel and autobiography in the eighteenth century. This article is the first full-length study of his own autobiographical record, The Life and Errors of John Dunton (1705). Dunton the showman is in plentiful evidence in this text, but he also presents another, more sober and serious-minded version of the self by following accounts of earlier stages of his life with their reformed versions. His coupling of religious-led self-examination with a commitment to literary novelty makes The Life a most unusual form of spiritual autobiography in its early stages. Yet The Life is a composite text in an even more obvious sense than this. For around half-way through the text Dunton abandons his close focus on the self for hundreds of cursory character sketches of his contemporaries, and in doing so swaps spiritual considerations for indirect comments on his own social activities and commercial concerns. This article studies these two main, ostensibly opposed, sections of The Life–its autobiographical and biographical material–and suggests points of contact between them

Group B <em>Streptococcus </em>engages an inhibitory siglec through sialic acid mimicry to blunt innate immune and inflammatory responses <em>in vivo</em>

Group B Streptococcus (GBS) is a common agent of bacterial sepsis and meningitis in newborns. The GBS surface capsule contains sialic acids (Sia) that engage Sia-binding immunoglobulin-like lectins (Siglecs) on leukocytes. Here we use mice lacking Siglec-E, an inhibitory Siglec of myelomonocytic cells, to study the significance of GBS Siglec engagement during in vivo infection. We found GBS bound to Siglec-E in a Sia-specific fashion to blunt NF-κB and MAPK activation. As a consequence, Siglec-E-deficient macrophages had enhanced pro-inflammatory cytokine secretion, phagocytosis and bactericidal activity against the pathogen. Following pulmonary or low-dose intravenous GBS challenge, Siglec-E KO mice produced more pro-inflammatory cytokines and exhibited reduced GBS invasion of the central nervous system. In contrast, upon high dose lethal challenges, cytokine storm in Siglec-E KO mice was associated with accelerated mortality. We conclude that GBS Sia mimicry influences host innate immune and inflammatory responses in vivo through engagement of an inhibitory Siglec, with the ultimate outcome of the host response varying depending upon the site, stage and magnitude of infection

Rad21-Cohesin Haploinsufficiency Impedes DNA Repair and Enhances Gastrointestinal Radiosensitivity in Mice

Approximately half of cancer-affected patients receive radiotherapy (RT). The doses delivered have been determined upon empirical experience based upon average radiation responses. Ideally higher curative radiation doses might be employed in patients with genuinely normal radiation responses and importantly radiation hypersensitive patients would be spared the consequences of excessive tissue damage if they were indentified before treatment. Rad21 is an integral subunit of the cohesin complex, which regulates chromosome segregation and DNA damage responses in eukaryotes. We show here, by targeted inactivation of this key cohesin component in mice, that Rad21 is a DNA-damage response gene that markedly affects animal and cell survival. Biallelic deletion of Rad21 results in early embryonic death. Rad21 heterozygous mutant cells are defective in homologous recombination (HR)-mediated gene targeting and sister chromatid exchanges. Rad21+/− animals exhibited sensitivity considerably greater than control littermates when challenged with whole body irradiation (WBI). Importantly, Rad21+/− animals are significantly more sensitive to WBI than Atm heterozygous mutant mice. Since supralethal WBI of mammals most typically leads to death via damage to the gastrointestinal tract (GIT) or the haematopoietic system, we determined the functional status of these organs in the irradiated animals. We found evidence for GIT hypersensitivity of the Rad21 mutants and impaired bone marrow stem cell clonogenic regeneration. These data indicate that Rad21 gene dosage is critical for the ionising radiation (IR) response. Rad21 mutant mice thus represent a new mammalian model for understanding the molecular basis of irradiation effects on normal tissues and have important implications in the understanding of acute radiation toxicity in normal tissues

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment