bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance driven multi-objective distributed scheduling for parallel computations
Authors: Narang Ankur , Srivastava Abhinav , Katta Naga Praveen Kumar , Shyamasundar Rudrapatna K. 
Published: July 2011

With the advent of many-core architectures and strong need for Petascale (and Exascale) performance in scientific domains and industry analytics, efficient scheduling of parallel computations for higher productivity and performance has become very important. Further, movement of massive amounts (Terabytes to Petabytes) of data is very expensive, which necessitates affinity driven computations. Therefore, distributed scheduling of parallel computations on multiple places 1 needs to optimize multiple performance objectives: follow affinity maximally and ensure efficient space, time and message complexity. Simultaneous consideration of these objectives makes distributed scheduling a particularly challenging problem. In addition, parallel computations have data dependent execution patterns which requires online scheduling to effectively optimize the computation orchestration as it unfolds.
This paper presents an online algorithm for affinity driven distributed scheduling of multi-place 2 parallel computations. To optimize multiple performance objectives simultaneously, our algorithm uses a low time and message complexity mechanism for ensuring affinity and a randomized work-stealing mechanism within places for load balancing. Theoretical analysis of the expected and probabilistic lower and upper bounds on time and message complexity of this algorithm has been provided. On multi-core clusters such as Blue Gene/P (MPP architecture) and Intel multicore cluster, we demonstrate performance close to the custom MPI+Pthreads code. Further, strong, weak and data (increasing input data size) scalability have been demonstrated on multi-core clusters. Using well known benchmarks, we demonstrate 16% to 30% performance gain as compared to Cilk [6] on multi-core Intel Xeon 5570 (NUMA) architecture. Detailed experimental analysis illustrates efficient space (main memory) utilization as well. To the best of our knowledge, this is the first time multi-objective affinity driven distributed scheduling algorithm has been designed, theoretically analyzed and experimentally evaluated in a multi-place setup for multi-core cluster architectures.
Gem #73
Authors: Kuo Dean , Wallenburg Angela 
Published: July 2011

In the previous Gem in this series, we saw how to deal with overflow errors, based on source code from Tokeneer. In this Gem, we show how to ensure secure information flow.
This Gem brings us to the end of this series on Tokeneer, and we would like to say a big thank you to the SPARK team at Praxis HIS for providing these resources.
Performance profiling of virtual machines
Authors: Du Jiaqing , Sehrawat Nipun , Zwaenepoel Willy 
Published: July 2011

Profilers based on hardware performance counters are indispensable for performance debugging of complex software systems. All modern processors feature hardware performance counters, but current virtual machine monitors (VMMs) do not properly expose them to the guest operating systems. Existing profiling tools require privileged access to the VMM to profile the guest and are only available for VMMs based on paravirtualization. Diagnosing performance problems of software running in a virtualized environment is therefore quite difficult.
This paper describes how to extend VMMs to support performance profiling. We present two types of profiling in a virtualized environment: guest-wide profiling and system-wide profiling. Guest-wide profiling shows the runtime behavior of a guest. The profiler runs in the guest and does not require privileged access to the VMM. System-wide profiling exposes the runtime behavior of both the VMM and any number of guests. It requires profilers both in the VMM and in those guests.
Not every VMM has the right architecture to support both types of profiling. We determine the requirements for each of them, and explore the possibilities for their implementation in virtual machines using hardware assistance, paravirtualization, and binary translation.
We implement both guest-wide and system-wide profiling for a VMM based on the x86 hardware virtualization extensions and system-wide profiling for a VMM based on binary translation. We demonstrate that these profilers provide good accuracy with only limited overhead.
Perfctr-Xen
Authors: Nikolaev Ruslan , Back Godmar 
Published: July 2011

Virtualization is a powerful technique used for variety of application domains, including emerging cloud environments that provide access to virtual machines as a service. Because of the interaction of virtual machines with multiple underlying software and hardware layers, the analysis of the performance of applications running in virtualized environments has been difficult. Moreover, performance analysis tools commonly used in native environments were not available in virtualized environments, a gap which our work closes.
This paper discusses the challenges of performance monitoring inherent to virtualized environments and introduces a technique to virtualize access to low-level performance counters on a per-thread basis. The technique was implemented in perfctr-xen, a framework for the Xen hypervisor that provides an infrastructure for higher-level profilers. This framework supports both accumulative event counts and interrupt-driven event sampling. It is light-weight, providing direct user mode access to logical counter values. perfctr-xen supports multiple modes of virtualization, including paravirtualization and hardware-assisted virtualization. perfctr-xen applies guest kernel-hypervisor coordination techniques to reduce virtualization overhead. We present experimental results based on microbenchmarks and SPEC CPU2006 macrobenchmarks that show the accuracy and usability of the obtained measurements when compared to native execution.
Patch auditing in infrastructure as a service clouds
Authors: Litty Lionel , Lie David 
Published: July 2011

A basic requirement of a secure computer system is that it be up to date with regard to software security patches. Unfortunately, Infrastructure as a Service (IaaS) clouds make this difficult. They leverage virtualization, which provides functionality that causes traditional security patch update systems to fail. In addition, the diversity of operating systems and the distributed nature of administration in the cloud compound the problem of identifying unpatched machines.
In this work, we propose P2, a hypervisor-based patch audit solution. P2 audits VMs and detects the execution of unpatched binary and non-binary files in an accurate, continuous and OSagnostic manner. Two key innovations make P2 possible. First, P2 uses efficient information flow tracking to identify the use of unpatched non-binary files in a vulnerable way.We performed a patch survey and discover that 64% of files modified by security updates do not contain binary code, making the audit of non-binary files crucial. Second, P2 implements a novel algorithm that identifies binaries in mid-execution to allow handling of VMs resumed from a checkpoint or migrated into the cloud. We have implemented a prototype of P2 and and our experiments show that it accurately reports the execution of unpatched code while imposing performance overhead of 4%.
HERC2 Interacts with Claspin and Regulates DNA Origin Firing and Replication Fork Progression
Authors: Izawa Naoki , Wu Wenwen , Sato Ko , Nishikawa Hiroyuki , Kato Akihiro , Boku Narikazu , Itoh Fumio , Ohta Tomohiko 
Published: July 2011

Abstract
DNA replication, recombination, and repair are highly interconnected processes the disruption of which must be coordinated in cancer. HERC2, a large HECT protein required for homologous recombination repair, is an E3 ubiquitin ligase that targets breast cancer suppressor BRCA1 for degradation. Here, we show that HERC2 is a component of the DNA replication fork complex that plays a critical role in DNA elongation and origin firing. In the presence of BRCA1, endogenous HERC2 interacts with Claspin, a protein essential for G2–M checkpoint activation and replication fork stability. Claspin depletion slowed S-phase progression and additional HERC2 depletion reduced the effect of Claspin depletion. In addition, HERC2 interacts with replication fork complex proteins. Depletion of HERC2 alleviated the slow replication fork progression in Claspin-deficient cells, suppressed enhanced origin firing, and led to a decrease in MCM2 phosphorylation. In a HERC2-dependent manner, treatment of cells with replication inhibitor aphidicolin enhanced MCM2 phosphorylation. Taken together, our results suggest that HERC2 regulates DNA replication progression and origin firing by facilitating MCM2 phosphorylation. These findings establish HERC2 as a critical function in DNA repair, checkpoint activation, and DNA replication. Cancer Res; 71(17); 5621–5. ©2011 AACR.
Using Tandem Mass Spectrometry in Targeted Mode to Identify Activators of Class IA PI3K in Cancer
Authors: Yang Xuemei , Turke Alexa B. , Qi Jie , Song Youngchul , Rexer Brent N. , Miller Todd W. , Jänne Pasi A. , Arteaga Carlos L. , Cantley Lewis C. , Engelman Jeffrey A. , Asara John M. 
Published: July 2011

Abstract
Phosphatiditylinositide-3-kinase (PI3K) is activated in some cancers by direct mutation, but it is activated more commonly in cancer by mutation of upstream acting receptor tyrosine kinases (TK). At present, there is no systematic method to determine which TK signaling cascades activate PI3K in certain cancers, despite the likely utility of such information to help guide selection of tyrosine kinase inhibitor (TKI) drug strategies for personalized therapy. Here, we present a quantitative liquid chromatography tandem mass spectrometry approach that identifies upstream activators of PI3K both in vitro and in vivo. Using non–small cell lung carcinoma to illustrate this approach, we show a correct identification of the mechanism of PI3K activation in several models, thereby identifying the most appropriate TKI to downregulate PI3K signaling. This approach also determined the molecular mechanisms and adaptors required for PI3K activation following inhibition of the mTOR kinase TORC1. We further validated the approach in breast cancer cells with mutational activation of PIK3CA, where tandem mass spectrometry detected and quantitatively measured the abundance of a helical domain mutant (E545K) of PIK3CA connected to PI3K activation. Overall, our findings establish a mass spectrometric approach to identify functional interactions that govern PI3K regulation in cancer cells. Using this technique to define the pathways that activate PI3K signaling in a given tumor could help inform clinical decision making by helping guide personalized therapeutic strategies for different patients. Cancer Res; 71(18); 5965–75. ©2011 AACR.
Cytotoxic Activity of Immunotoxin SS1P Is Modulated by TACE-Dependent Mesothelin Shedding
Authors: Zhang Yujian , Chertov Oleg , Zhang Jingli , Hassan Raffit , Pastan Ira 
Published: July 2011

Abstract
Mesothelin is a cell-surface tumor-associated antigen expressed in several human cancers. The limited expression of mesothelin on normal tissues and its high expression in many cancers make it an attractive candidate for targeted therapies using monoclonal antibodies, immunoconjugates, and immunotoxins. Mesothelin is actively shed from the cell surface and is present in the serum of patients with malignant mesothelioma, which could negatively affect the response to these therapies. We have found that mesothelin sheddase activity is mediated by a TNF-α converting enzyme (TACE), a member of the matrix metalloproteinase/a disintegrin and metalloprotease family. We showed that EGF and TIMP-3 act through TACE as endogenous regulators of mesothelin shedding. We also found that reducing shedding significantly improved the in vitro cytotoxicity of immunotoxin SS1P, which targets mesothelin and is currently in clinical trials for the treatment of patients with mesothelioma and lung cancer. Our findings provide a mechanistic understanding of mesothelin shedding and could help improve mesothelin-based targeted therapies. Cancer Res; 71(17); 5915–22. ©2011 AACR.
Breast Field Cancerization: Isolation and Comparison of Telomerase-Expressing Cells in Tumor and Tumor Adjacent, Histologically Normal Breast Tissue
Authors: Trujillo Kristina A. , Hines William C. , Vargas Keith M. , Jones Anna C. , Joste Nancy E. , Bisoffi Marco , Griffith Jeffrey K. 
Published: July 2011

AbstractTelomerase stabilizes chromosomes by maintaining telomere length, immortalizes mammalian cells, and is expressed in more than 90% of human tumors. However, the expression of human telomerase reverse transcriptase (hTERT) is not restricted to tumor cells. We have previously shown that a subpopulation of human mammary epithelial cells (HMEC) in tumor-adjacent, histologically normal (TAHN) breast tissues expresses hTERT mRNA at levels comparable with levels in breast tumors. In the current study, we first validated a reporter for measuring levels of hTERT promoter activity in early-passage HMECs and then used this reporter to compare hTERT promoter activity in HMECs derived from tumor and paired TAHN tissues 1, 3, and 5 cm from the tumor (TAHN-1, TAHN-3, and TAHN-5, respectively). Cell sorting, quantitative real-time PCR, and microarray analyses showed that the 10% of HMECs with the highest hTERT promoter activity in both tumor and TAHN-1 tissues contain more than 95% of hTERT mRNA and overexpress many genes involved in cell cycle and mitosis. The percentage of HMECs within this subpopulation showing high hTERT promoter activity was significantly reduced or absent in TAHN-3 and TAHN-5 tissues. We conclude that the field of “normal tissue” proximal to the breast tumors contains a population of HMECs similar in hTERT expression levels and in gene expression to the HMECs within the tumor mass and that this population is significantly reduced in tissues more distal to the tumor. Mol Cancer Res; 9(9); 1209–21. ©2011 AACR.
Contribution of Xanthine Oxidoreductase to Mammary Epithelial and Breast Cancer Cell Differentiation In Part Modulates Inhibitor of Differentiation-1
Authors: Fini Mehdi A. , Monks Jenifer , Farabaugh Susan M. , Wright Richard M. 
Published: July 2011

Abstract
Loss of xanthine oxidoreductase (XOR) has been linked to aggressive breast cancer in vivo and to breast cancer cell aggressiveness in vitro. In the present study, we hypothesized that the contribution of XOR to the development of the normal mammary gland may underlie its capacity to modulate breast cancer. We contrasted in vitro and in vivo developmental systems by differentiation marker and microarray analyses. Human breast cancer microarray was used for clinical outcome studies. The role of XOR in differentiation and proliferation was examined in human breast cancer cells and in a mouse xenograft model. Our data show that XOR was required for functional differentiation of mammary epithelial cells both in vitro and in vivo. Poor XOR expression was observed in a mouse ErbB2 breast cancer model, and pharmacologic inhibition of XOR increased breast cancer tumor burden in mouse xenograft. mRNA microarray analysis of human breast cancer revealed that low XOR expression was significantly associated with time to tumor relapse. The opposing expression of XOR and inhibitor of differentiation-1 (Id1) during HC11 differentiation and mammary gland development suggested a potential functional relationship. While overexpression of Id1 inhibited HC11 differentiation and XOR expression, XOR itself modulated expression of Id1 in differentiating HC11 cells. Overexpression of XOR both inhibited Id1-induced proliferation and -stimulated differentiation of Heregulin-β1–treated human breast cancer cells. These results show that XOR is an important functional component of differentiation whose diminished expression contributes to breast cancer aggressiveness, and they support XOR as both a breast cancer biomarker and a target for pharmacologic activation in therapeutic management of aggressive breast cancer. Mol Cancer Res; 9(9); 1242–54. ©2011 AACR.
Assessing constipation in palliative care within a gastroenterology framework
Authors: Clark Katherine , Currow David C 
Published: July 2011

Background: Constipation is common and distressing in palliative care. Despite this, approaches to assessment and subsequent treatment are most remarkable for the numbers who fail adequate palliation. Aim: The primary aim of this paper is to summarise the current approaches to assessing constipation in palliative care, contrasting these approaches with those recommended by gastroenterologists in the assessment of resistant constipation in non-palliative care. The secondary aim is to suggest ways that the approaches used by gastroenterologist could be modified to be tolerable to palliative care. Design: A non-systematic review of the literature was undertaken. Data sources: The electronic databases (MEDLINE, CINHAL) were searched for English language articles that explored assessment of constipation in palliative care and evidence-based gastroenterology guidelines that summarised assessment and management of constipation. Results: Currently, the assessment of constipation in palliative care is predominantly based on people’s reports, physical examination and if further imaging is deemed necessary, a plain abdominal radiograph. However, data in non-palliative care patients refutes the usefulness of self-reported symptoms to localise whether problems are due to colon dysfunction or structures of defaecation. Plain radiographs are most useful to exclude a bowel obstruction only. In cases of resistant constipation, gastroenterology guidelines recommend an assessment approach that includes measuring colon transit time and an assessment of the structures that facilitate defaecation. Conclusions: Current approaches to assessing constipation in palliative care are very different to those recommended by gastroenterology guidelines. However, modified approaches may be tolerable to palliative care patients and offer the chance of developing targeted palliation.
Gender differences in prevalence of depression among patients receiving palliative care: The role of dependency
Authors: Hayes Richard D , Lee William , Rayner Lauren , Price Annabel , Monroe Barbara , Hansford Penny , Sykes Nigel , Hotopf Matthew 
Published: July 2011

Background: in community studies the prevalence of depression is higher in women than men; however, in palliative care settings this relationship is usually less strong, absent or reversed. Aim: to identify reasons for excess depression among men receiving palliative care. Design: cross-sectional study. Setting/participants: we interviewed 300 patients recruited from a large hospice in South East London. Depression was measured using the Primary Care Evaluation of Mental Disorder. Results: the higher prevalence of depression among men was not explained by a higher prevalence of particular types of cancer nor confounding by other covariates. Possible effect modifiers were examined. Depending on others for help with basic tasks (eating, dressing, washing or using the toilet) was a risk factor for depression in men only, with 37.8% of dependent men being depressed compared to 2.4% of similarly affected women (OR = 24.3, 3.1–193.2, p = 0.003). We observed a dose-response effect between the level of dependency and depression in men ( p for trend = 0.01). Conclusion: depending on others for help with basic tasks appears to contribute to the burden of depression among men with terminal illness. This gender-specific association may explain why the usual gender differences in depression prevalence are not observed in palliative care.
Development of a driver model to study the effects of real-world driver behaviour on the fuel consumption
Authors: McGordon A , Poxon J E W , Cheng C , Jones R P , Jennings P A 
Published: July 2011

The real-world fuel economy of vehicles is becoming increasingly important to manufacturers and customers. One of the major influences in this is driver behaviour, but it is difficult to study in a controlled and repeatable manner. An assessment of driver models for studying real-world driver behaviour has been carried out. It has been found that none of the currently existing driver models has sufficient fidelity for studying the effects of real-world driver behaviour on the fuel economy of the individual vehicle. A decision-making process has been proposed which allows a driver model with a range of driving tasks to be developed. This paper reports the initial results of a driver model as applied to the conceptually straightforward scenario of high-speed cruising. Data for the driver model have been obtained through real-world data logging. It has been shown that the simulation driver model can provide a good representation of real-world driving behaviour in terms of the vehicle speed, and this is compared with a number of logged driver speed traces. A comparison of the modelled fuel economy for logged and driver model real-world drivers shows good agreement.
A dynamic model of an overhung rotor with ball bearings
Authors: Cakmak O , Sanliturk K Y 
Published: July 2011

A ball bearing comprising rolling elements, inner and outer rings, and a cage structure can be described as a multi-body system (MBS). In order to predict the dynamic behaviour and resonance characteristics of a rotor–ball bearing system, it can be modelled and analysed as a MBS with flexible and rigid parts. In this study, a ball bearing is modelled with MBS approach using MSC ADAMS commercial software. The Hertzian theory is used for modelling the contact dynamics between the balls and the rings. The ball bearing model is then assembled with the rotor model which comprised a shaft and a disc positioned at the free end of the shaft. The ball bearing model is used with both flexible and rigid shaft assumptions in order to highlight the differences between the two cases. For the flexible shaft case, the MBS model also included a finite element model of the shaft. As expected, it is necessary to include the flexibility of the shaft in the model in order to to predict the changes in the modal characteristics of the system as a function of the rotor speed. Furthermore, including the gyroscopic effects leads to observe the forward and backward travelling modes with different natural frequencies. The effects of the bearing diametral clearance and localized defects on the inner and outer rings are modelled and analysed using the model developed. Also, the effects of the rotor unbalance on the vibration level of the whole system are examined. A test rig – consisting of two ball bearings, a shaft, and a disc – is also designed and developed so as to validate the theoretical model using experimental data. Order tracking and modal analyses are carried out and Campbell diagrams are obtained. Finally, the theoretical and the experimental results are compared and a refined MBS model is obtained for further analyses.