3,671 research outputs found

    Coz: Finding Code that Counts with Causal Profiling

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    Improving performance is a central concern for software developers. To locate optimization opportunities, developers rely on software profilers. However, these profilers only report where programs spent their time: optimizing that code may have no impact on performance. Past profilers thus both waste developer time and make it difficult for them to uncover significant optimization opportunities. This paper introduces causal profiling. Unlike past profiling approaches, causal profiling indicates exactly where programmers should focus their optimization efforts, and quantifies their potential impact. Causal profiling works by running performance experiments during program execution. Each experiment calculates the impact of any potential optimization by virtually speeding up code: inserting pauses that slow down all other code running concurrently. The key insight is that this slowdown has the same relative effect as running that line faster, thus "virtually" speeding it up. We present Coz, a causal profiler, which we evaluate on a range of highly-tuned applications: Memcached, SQLite, and the PARSEC benchmark suite. Coz identifies previously unknown optimization opportunities that are both significant and targeted. Guided by Coz, we improve the performance of Memcached by 9%, SQLite by 25%, and accelerate six PARSEC applications by as much as 68%; in most cases, these optimizations involve modifying under 10 lines of code.Comment: Published at SOSP 2015 (Best Paper Award

    Treatment and outcomes in necrotising autoimmune myopathy: an australian perspective

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    Necrotising Autoimmune Myopathy (NAM) presents as a subacute proximal myopathy with high creatine kinase levels. It is associated with statin exposure, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibody, connective tissue diseases, signal recognition particle (SRP) antibody and malignancy. This case series presents our Western Australian NAM patient cohort: comparing the subgroup presentations, biopsy appearance and treatment outcomes. We retrospectively collected data on patients diagnosed with NAM at the Western Australian Neuroscience Research Institute between the years 2000 and 2015. We identified 20 patients with Necrotising Autoimmune Myopathy: 14 with anti-HMGCR antibodies; two with anti-SRP antibodies; three with connective tissue disease; two as yet unspecified. Median creatine kinase level was 6047units/L (range 1000–17000). The statin naïve patients with HMGCR antibodies and patients with SRP antibodies were the most severely affected subgroups, with higher creatine kinase levels, and were more resistant to immunotherapy. Two or more immunotherapy agents were required in 90%; eight patients required IVIG and rituximab. Steroid weaning commonly precipitated relapses. Four patients had complete remission, and the remaining patients still require immunotherapy. Necrotising Autoimmune Myopathy is a potentially treatable myopathy, which can be precipitated by statin therapy and requires early, aggressive immunotherapy, usually requiring multiple steroid sparing agents for successful steroid weaning

    Sleep disordered breathing and subclinical impairment of respiratory function are common in sporadic inclusion body myositis

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    Relatively little is known about frequency and extent of respiratory problems in sporadic inclusion body myositis (IBM). To address this issue a study of peripheral muscle and respiratory function and related symptoms was performed in a cohort with biopsy-proven IBM. Dyspnoea, daytime sleepiness, dysphagia, spirometry, respiratory muscle strength, arterial blood gas tensions and ventilation during sleep were assessed. Sixteen patients were studied (10 males; age 68.1 ± 9.9 years; disease duration 11.9 ± 5.0 years; body mass index 28.5 ± 4.0 kg/m2). Four reported excessive daytime sleepiness; 8 had at least mild dysphagia; forced vital capacity was <80% predicted normal in 7; sniff nasal inspiratory pressure was reduced in 3; daytime hypoxemia was present in 9 and hypercapnia in one. Sleep study was performed in 15 and revealed sleep disordered breathing (apnoea–hypopnoea index 23.4 ± 12.8 (range 7–50.3) events/h) in all. There were no consistent relationships between respiratory function impairment, occurrence of sleep disordered breathing, and severity of peripheral muscle weakness. Thus, asymptomatic impairment of respiratory function was common and sleep disordered breathing observed in all patients tested, irrespective of daytime respiratory function. This suggests respiratory function testing, including sleep study, should be performed routinely in IBM, irrespective of peripheral muscle function or other disease severity parameters

    Rotational Evolution During Type I X-Ray Bursts

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    The rotation rates of six weakly-magnetic neutron stars accreting in low-mass X-ray binaries have most likely been measured by Type I X-ray burst observations with RXTE. The nearly coherent oscillations detected during the few seconds of thermonuclear burning are most simply understood as rotational modulation of brightness asymmetries on the neutron star surface. We show that, as suggested by Strohmayer and colleagues, the frequency changes of 1-2 Hz observed during bursts are consistent with angular momentum conservation as the burning shell hydrostatically expands and contracts. We calculate how vertical heat propagation through the radiative outer layers of the atmosphere and convection affect the coherence of the oscillation. We show that the evolution of the rotational profile depends strongly on whether the burning layers are composed of pure helium or mixed hydrogen/helium. Our results help explain the absence (presence) of oscillations from hydrogen-burning (helium-rich) bursts that was found by Muno and collaborators. We investigate angular momentum transport within the burning layers and the recoupling of the burning layers with the star. We show that the Kelvin-Helmholtz instability is quenched by the strong stratification, and that mixing between the burning fuel and underlying ashes by the baroclinic instability does not occur. However, the baroclinic instability may have time to operate within the differentially rotating burning layer, potentially bringing it into rigid rotation.Comment: To appear in The Astrophysical Journal; minor corrections made to tables and figure

    NMR-based Structural Studies of the Glycosylated MUC1 Tandem Repeat Peptide

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    MUC1 is a glycoprotein that plays an important role in cancer pathogenesis. In order to study the effect of glycosylation on the conformational propensities of the tandem repeat domain of MUC1, we have determined the structure of the MUC1 tandem repeat peptide AHGVTSAPDTRPAPGSTAPP, O-glycosylated with the trisaccharide (α-Glc-1,4-β-Glc-1,4-α-GalNAc-) at Thr5. This glycopeptide was synthesized to model a heavily Oglycosylated threonine residue in the tandem repeat domain. The NMR experiments used in this study included TOCSY, NOESY, ROESY, DQF-COSY, HSQC and 1D NMR. The peak volumes determined using the program SPARKY were converted into distance constraints using the program CALIBA. The programs FiSiNOE and HABAS were used to generate angle constraints. Using conformational restraints obtained from NMR, the program DYANA was used to determine the structures of the peptide. Finally, structural refinement was performed within the SYBYL software package using GLYCAM parameters and Kollman-all atom types. The presence of strong sequential αN connectivities suggested an extended conformation of the peptide backbone. Strong sequential αδ connectivities were indicative of a trans conformation of the Ala-Pro peptide bonds. In addition, presence of sequential NN connectivities in the peptide segments Gly3-Val4-Thr5-Ser6, Asp9-Thr10-Arg11 and Gly-Ser16 were indicative of twist-like conformations of the peptide backbone in these peptide segments
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