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Linux Kernel Co-Scheduling For Bulk Synchronous Parallel Applications

This paper describes a kernel scheduling algorithm that is based on co-scheduling principles and that is intended for parallel applications running on 1000 cores or more where inter-node scalability is key. Experimental results for a Linux implementation on a Cray XT5 machine are presented.1 The results indicate that Linux is a suitable operating system for this new scheduling scheme, and that this design provides a dramatic improvement in scaling performance for synchronizing collective operations at scale.

99 GENERAL AND MISCELLANEOUS↗

There goes the neighborhood: performance degradation due to nearby jobs

Predictable performance is important for understanding and alleviating application performance issues; quantifying the effects of source code, compiler, or system software changes; estimating the time required for batch jobs; and determining the allocation requests for proposals. Our experiments show that on a Cray XE system, the execution time of a communication-heavy parallel application ranges from 28% faster to 41% slower than the average observed performance. Blue Gene systems, on the other hand, demonstrate no noticeable run-to-run variability. In this paper, we focus on Cray machines and investigate potential causes for performance variability such as OS jitter, shape of the allocated partition, and interference from other jobs sharing the same network links. Reducing such variability could improve overall throughput at a computer center and save energy costs.

Computer Science↗

Enhancer of Zeste Homolog 2 Overexpression in Nasopharyngeal Carcinoma: An Independent Poor Prognosticator That Enhances Cell Growth

Purpose: As a key component of polycomb-repressive complex 2, enhancer of zeste homolog 2 (EZH2) represses target genes through histone methylation and is frequently overexpressed and associated with poor prognosis in common carcinomas. For the first time, we reported EZH2 expression and its biological and clinical significance in nasopharyngeal carcinoma (NPC). Methods and Materials: In NPC cell lines and specimens, endogenous expression of EZH2 mRNA and protein was determined by semiquantitative reverse transcription-polymerase chain reaction and immunoblotting, respectively. To analyze the effect on cell growth, stable silencing of EZH2 was established in EZH2-expressing TW02 NPC cells with RNA interference. EZH2 immunolabeling was assessable for 89 primary NPC biopsy samples and correlated with clinicopathological variables, disease-specific survival (DSS), and overall survival (OS). Results: Growth activity of TW02 cells was significantly suppressed (p < 0.001) with stable EZH2 silencing. Compared with normal nasopharyngeal tissue, expression levels of EZH2 transcript and protein were apparently upregulated in NPC specimens. As a continuous variable, higher EZH2 expression preferentially occurred in NPCs of T3 to T4 stages (p = 0.03) and significantly predicted inferior DSS (p = 0.0010) and OS (p = 0.004). The prognostic implications for DSS (p = 0.010) and OS (p = 0.006) still remained valid when using the median ({>=}60%) of EZH2 immunolabeling index to dichotomize the cohort. In the multivariate model, higher EZH2 expression was an independent adverse factor of both DSS (p = 0.012) and OS (p = 0.011), along with American Joint Committee on Cancer Stages III to IV (p = 0.024 for DSS, p = 0.017 for OS). Conclusion: At least partly through promoting cell growth, EZH2 implicates disease progression, confers tumor aggressiveness, and represents an independent adverse prognosticator in patients with NPC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

BlackjackBench: Portable Hardware Characterization

DARPA's AACE project aimed to develop Architecture Aware Compiler Environments that automatically characterize the hardware and optimize the application codes accordingly. We present the BlackjackBench suite, a collection of portable micro-benchmarks that automate system characterization, plus statistical analysis techniques for interpreting the results. BlackjackBench discovers the effective sizes and speeds of the hardware environment rather than the often unattainable peak values. We aim at hardware features that can be observed by running executables generated by existing compilers from standard C codes. We characterize the memory hierarchy, including cache sharing and NUMA characteristics of the system, properties of the processing cores affecting execution speed, and the length of the OS scheduler time slot. We show how these features of modern multicores can be discovered programmatically. We also show how the features could interfere with each other resulting in incorrect interpretation of the results, and how established classification and statistical analysis techniques reduce experimental noise and aid automatic interpretation of results.

99 GENERAL AND MISCELLANEOUS↗

Argobots: A Lightweight Low-Level Threading and Tasking Framework

In the past few decades, a number of user-level threading and tasking models have been proposed in the literature to address the shortcomings of OS-level threads, primarily with respect to cost and flexibility. Current state-of-the-art user-level threading and tasking models, however, are either too specific to applications or architectures or are not as powerful or flexible. In this paper, we present Argobots, a lightweight, low-level threading and tasking framework that is designed as a portable and performant substrate for high-level programming models or runtime systems. Argobots offers a carefully designed execution model that balances generality of functionality with providing a rich set of controls to allow specialization by the user or high-level programming model. We describe the design, implementation, and optimization of Argobots and present integrations with three example high-level models: OpenMP, MPI, and co-located I/O service. Evaluations show that (1) Argobots outperforms existing generic threading runtimes; (2) our OpenMP runtime offers more efficient interoperability capabilities than production OpenMP runtimes do; (3) when MPI interoperates with Argobots instead of Pthreads, it enjoys reduced synchronization costs and better latency hiding capabilities; and (4) I/O service with Argobots reduces interference with co-located applications, achieving performance competitive with that of the Pthreads version.

Seo, Sangmin (ORCID:0000000295159836)↗

Results of apparent atomic oxygen reactions on Ag, C, and Os exposed during the Shuttle STS-4 orbits

Films selected for anticipated reaction with atomic oxygen, namely carbon, silver, and osmium, were exposed during the Shuttle STS-4 mission. A silver film within 5 nm of 225 nm thick was converted to a transparent blue-green interference film within 5 nm of 355 nm thick. Both carbon and osmium films 10-30 nm thick apparently formed volatile oxides and disappeared, except where well shielded. A calculated total of approximately 7 x 10 to the 19th oxygen atoms per sq cm struck the surfaces, which could have removed on the order of 3 microns of material if only 10 percent reacted. The absence of apparent effects on adjacent thin and thick gold films is offered as evidence that sputtering is not responsible.

Peters, P. N.↗

RECK is not an independent prognostic marker for breast cancer

Background The REversion-inducing Cysteine-rich protein with Kazal motif (RECK) is a well-known inhibitor of matrix metalloproteinases (MMPs) and cellular invasion. Although high expression levels of RECK have already been correlated with a better clinical outcome for several tumor types, its main function, as well as its potential prognostic value for breast cancer patients, remain unclear. Methods The RECK expression profile was investigated in a panel of human breast cell lines with distinct aggressiveness potential. RECK functional analysis was undertaken using RNA interference methodology. RECK protein levels were also analyzed in 1040 cases of breast cancer using immunohistochemistry and tissue microarrays (TMAs). The association between RECK expression and different clinico-pathological parameters, as well as the overall (OS) and disease-free (DFS) survival rates, were evaluated. Results Higher RECK protein expression levels were detected in more aggressive breast cancer cell lines (T4-2, MDA-MB-231 and Hs578T) than in non-invasive (MCF-7 and T47D) and non-tumorigenic (S1) cell lines. Indeed, silencing RECK in MDA-MB-231 cells resulted in elevated levels of pro-MMP-9 and increased invasion compared with scrambled (control) cells, without any effect on cell proliferation. Surprisingly, by RECK immunoreactivity analysis on TMAs, we found no association between RECK positivity and survival (OS and DFS) in breast cancer patients. Even considering the different tumor subtypes (luminal A, luminal B, Her2 type and basal-like) or lymph node status, RECK remained ineffective for predicting the disease outcome. Moreover, by multivariate Cox regression analysis, we found that RECK has no prognostic impact for OS and DFS, relative to standard clinical variables. Conclusions Although it continues to serve as an invasion and MMP inhibitor in breast cancer, RECK expression analysis is not useful for prognosis of these patients.

60 APPLIED LIFE SCIENCES↗

Elemental ratio measurements of organic compounds using aerosol mass spectrometry: characterization, improved calibration, and implications

Elemental compositions of organic aerosol (OA) particles provide useful constraints on OA sources, chemical evolution, and effects. The Aerodyne high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) is widely used to measure OA elemental composition. This study evaluates AMS measurements of atomic oxygen-to-carbon (O : C), hydrogen-to-carbon (H : C), and organic mass-to-organic carbon (OM : OC) ratios, and of carbon oxidation state ( OS C ) for a vastly expanded laboratory data set of multifunctional oxidized OA standards. For the expanded standard data set, the method introduced by Aiken et al. (2008), which uses experimentally measured ion intensities at all ions to determine elemental ratios (referred to here as "Aiken-Explicit"), reproduces known O : C and H : C ratio values within 20% (average absolute value of relative errors) and 12%, respectively. The more commonly used method, which uses empirically estimated H 2 O + and CO + ion intensities to avoid gas phase air interferences at these ions (referred to here as "Aiken-Ambient"), reproduces O : C and H : C of multifunctional oxidized species within 28 and 14% of known values. The values from the latter method are systematically biased low, however, with larger biases observed for alcohols and simple diacids. A detailed examination of the H 2 O + , CO + , and CO 2 + fragments in the high-resolution mass spectra of the standard compounds indicates that the Aiken-Ambient method underestimates the CO + and especially H 2 O + produced from many oxidized species. Combined AMS–vacuum ultraviolet (VUV) ionization measurements indicate that these ions are produced by dehydration and decarboxylation on the AMS vaporizer (usually operated at 600 °C). Thermal decomposition is observed to be efficient at vaporizer temperatures down to 200 °C. These results are used together to develop an "Improved-Ambient" elemental analysis method for AMS spectra measured in air. The Improved-Ambient method uses specific ion fragments as markers to correct for molecular functionality-dependent systematic biases and reproduces known O : C (H : C) ratios of individual oxidized standards within 28% (13%) of the known molecular values. The error in Improved-Ambient O : C (H : C) values is smaller for theoretical standard mixtures of the oxidized organic standards, which are more representative of the complex mix of species present in ambient OA. For ambient OA, the Improved-Ambient method produces O : C (H : C) values that are 27% (11%) larger than previously published Aiken-Ambient values; a corresponding increase of 9% is observed for OM : OC values. These results imply that ambient OA has a higher relative oxygen content than previously estimated. The OS C values calculated for ambient OA by the two methods agree well, however (average relative difference of 0.06 OS C units). This indicates that OS C is a more robust metric of oxidation than O : C, likely since OS C is not affected by hydration or dehydration, either in the atmosphere or during analysis.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Investigation of the in vitro toxicological properties of the synthetic cannabimimetic drug CP-47,497-C8

Cannabicyclohexanol (CP-47,497-C8) is a representative of a group of cannabimimetic cyclohexylphenols which is added to herbal mixtures as a cannabis substitute since 2008. Although in the beginning CP-47,497-C8 was the main ingredient of “Spice” and similar products, it was partly replaced by aminoalkylindole-type cannabinoid receptor agonists like JWH-018, JWH-073 or JWH-250, but never completely disappeared from the market. Since information on its toxicological properties is scarce, we investigated the effects of the drug in human derived cell lines. The cytotoxic effects were studied in a panel of assays (SRB, XTT, LDHe and NR tests) in a buccal derived (TR146) and a liver derived (HepG2) cell line. The strongest effects were seen in the two former assays at levels ≥ 7.5 μM indicating that the compound interferes with protein synthesis and causes membrane damage. In additional comet assays, DNA damage was detected at levels ≥ 10 μM. Experiments with lesion specific enzymes showed that these effects are not due to oxidative damage of DNA bases. The negative findings obtained in Salmonella/microsome assays and the positive results of micronucleus tests with the cell lines indicate that the compound does not cause gene mutations but acts on the chromosomal level. In contrast to other synthetic cannabinoids, no indication for estrogenic/antiestrogenic properties was seen in a luciferase assay with bone marrow derived U2-OS cells. In conclusion, our findings show that the drug has only weak cytotoxic properties. However, the induction of chromosomal damage indicates that it may cause adverse effects in users due to its impact on the stability of the genetic material. - Highlights: • We tested the toxic properties of a synthetic cannabinoid. • Acute cytotoxic effects were detected with doses ≥ 7 μM. • No hormonal effects were found. • DNA damage was detected at levels ≥ 10 μM in comet assay and micronucleus tests. • Effects in directly exposed tissues may occur in humans.

60 APPLIED LIFE SCIENCES↗

Implementation of High-Dose-Rate Brachytherapy and Androgen Deprivation in Patients With Prostate Cancer

Purpose: To evaluate outcome (overall survival [OS], the actuarial 5-year cancer-specific survival [CSS], disease-free survival [DFS], biochemical failure-free survival [BFS]), complications and morbidity in patients treated with high-dose-rate brachytherapy (HDR-BT) boost and hormonal treatment with curative aims. Methods: Between 2004 and 2009, 275 prospectively followed pN0/N0M0 patients were included: 19 patients (7%) with T2, Gleason score 7 and prostate-specific antigen (PSA) <10 and 256 patients (93%) with T3 or Gleason score 8-10 or PSA >20 received multimodal treatment with conformal four-field radiotherapy (prostate/vesiculae 2 Gy Multiplication-Sign 25) combined with HDR-BT (iridium 192; prostate 10 Gy Multiplication-Sign 2) with long-term androgen deprivation therapy (ADT). Results: After a median observation time of 44.2 months (range, 10.4-90.5 months) 12 patients had relapsed clinically and/or biochemically and 10 patients were dead, of which 2 patients died from prostate cancer. Five-year estimates of BFS, CSS, DFS, and OS rates were 98.5%, 99.3%, 95.6%, and 96.3%, respectively. None of the patients with either Gleason score <8 or with intermediate risk profile had relapsed. The number of HDR-BT treatments was not related to outcome. Despite of age (median, 65.7 years; range, 45.7-77 years) and considerable pretreatment comorbidity in 39 of 275 patients, Genitourinary treatment-related morbidity was moderate with long-lasting Radiation Therapy Oncology Group Grade 2 voiding problems in 26 patients (9.5%) and occasionally mucous discharge in 20 patients (7%), none with Grade >2 for gastrointestinal at follow-up. Complications during implantations were related to pubic arch interference (4 patients) and lithotomy time, causing 2 patients to develop compartment syndrome. Conclusion: Despite still preliminary observations, our 5-year outcome estimates favor the implementation of high-dose-rate brachytherapy in high-risk patients combined with conformal external radiotherapy and long-term ADT. High-quality implants can be achieved by a trained specialized team at a high-turnover center using transrectal ultrasound-based treatment plans with acceptable morbidity and complication rates.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Operating System Support for Fine-Grained Task Migration

With the end of clock scaling and the limited power budget available (20-30MW), future supercomputers will meet exascale performance primarily through a higher level of parallelism. Current operating (OS) and runtime (RT) systems are designed for the classical SMP model and based on the static and coarse-grained process/thread paradigm. They do not provide the required level of flexibility, especially within a single compute node, to meet the requirements imposed by exascale systems in terms of power/energy efficiency, resilience, managing concurrency and performance portability. The high level of concurrency poses new challenges specific to exascale systems that need to be addressed by novel solutions. In particular, requiring the user to manage billions of concurrent threads could easily result in poor data locality, clogged interconnection networks, unchecked propagation of soft errors, and lack of control over power/energy consumption. Equally important, managing such level of concurrency interferes with the user’s focus on the application and the algorithm. We envision that the computation will be encapsulated into fine-grained tasks that can be isolated and protected from the other tasks running in the system. Whenever a task needs to work on some data that is not stored on the local node, the OS/RT allows the task to be migrated to the node that owns the data. Each task is associated with a contained state (set or architectural registers, stack frame, running node, etc.) that describes the progress of the task and that should be moved together with the task’s code. We believe system support for task migration is a fundamental function that can ease the job of tackling several of the exascale challenges.

Gioiosa, Roberto↗