CST (CTC1-STN1-TEN1) is a heterotrimeric, RPA-like complex that binds to single-stranded DNA (ssDNA) and functions in the replication of telomeric and non-telomeric DNA. Previous studies demonstrated ...that deletion of CTC1 results in decreased cell proliferation and telomere DNA damage signaling. However, a detailed analysis of the consequences of conditional CTC1 knockout (KO) has not been fully elucidated. Here, we investigated the effects of CTC1 KO on cell cycle progression, genome-wide replication and activation of the DNA damage response. Consistent with previous findings, we demonstrate that CTC1 KO results in decreased cell proliferation, G2 arrest and RPA-bound telomeric ssDNA. However, despite the increased levels of telomeric RPA-ssDNA, global ATR-dependent CHK1 and p53 phosphorylation was not detected in CTC1 KO cells. Nevertheless, we show that RPA-ssDNA does activate ATR, leading to the phosphorylation of RPA and autophosphorylation of ATR. Further analysis determined that inactivation of ATR, but not CHK1 or ATM, suppressed the accumulation of G2 arrested cells and phosphorylated RPA following CTC1 removal. These results suggest that ATR is localized and active at telomeres but is unable to elicit a global checkpoint response through CHK1. Furthermore, CTC1 KO inhibited CHK1 phosphorylation following hydroxyurea-induced replication stress. Additional studies revealed that this suppression of CHK1 phosphorylation, following replication stress, is caused by decreased levels of the ATR activator TopBP1. Overall, our results identify CST as a novel regulator of the ATR-CHK1 pathway.
Virtualization technologies such as Xen can be used in order to satisfy the disparate and often incompatible system requirements of different user groups in shared-use computing facilities. This ...capability is particularly important for HEP applications, which often have restrictive requirements. The use of virtualization adds flexibility, however, it is essential that the virtualization technology place little overhead on the HEP application. We present an evaluation of the practicality of running HEP applications in multiple Virtual Machines (VMs) on a single multi-core Linux system. We use the benchmark suite used by the HEPiX CPU Benchmarking Working Group to give a quantitative evaluation relevant to the HEP community. Benchmarks are packaged inside VMs and then the VMs are booted onto a single multi-core system. Benchmarks are then simultaneously executed on each VM to simulate highly loaded VMs running HEP applications. These techniques are applied to a variety of multi-core CPU architectures and VM configurations.
The Worldwide LHC Computing Grid relies on the network as a critical part of its infrastructure and therefore needs to guarantee effective network usage and prompt detection and resolution of any ...network issues, including connection failures, congestion, traffic routing, etc. The WLCG Network and Transfer Metrics project aims to integrate and combine all network-related monitoring data collected by the WLCG infrastructure. This includes FTS monitoring information, monitoring data from the XRootD federation, as well as results of the perfSONAR tests. The main challenge consists of further integrating and analyzing this information in order to allow the optimizing of data transfers and workload management systems of the LHC experiments. In this contribution, we present our activity in commissioning WLCG perfSONAR network and integrating network and transfer metrics: We motivate the need for the network performance monitoring, describe the main use cases of the LHC experiments as well as status and evolution in the areas of configuration and capacity management, datastore and analytics, including integration of transfer and network metrics and operations and support.
The WLCG infrastructure moved from a very rigid network topology, based on the MONARC model, to a more relaxed system, where data movement between regions or countries does not necessarily need to ...involve T1 centres. While this evolution brought obvious advantages, especially in terms of flexibility for the LHC experiment's data management systems, it also opened the question of how to monitor the increasing number of possible network paths, in order to provide a global reliable network service. The perfSONAR network monitoring system has been evaluated and agreed as a proper solution to cover the WLCG network monitoring use cases: it allows WLCG to plan and execute latency and bandwidth tests between any instrumented endpoint through a central scheduling configuration, it allows archiving of the metrics in a local database, it provides a programmatic and a web based interface exposing the tests results; it also provides a graphical interface for remote management operations. In this contribution we will present our activity to deploy a perfSONAR based network monitoring infrastructure, in the scope of the WLCG Operations Coordination initiative: we will motivate the main choices we agreed in terms of configuration and management, describe the additional tools we developed to complement the standard packages and present the status of the deployment, together with the possible future evolution.
The emergence of academic and commercial Infrastructure-as-a-Service (IaaS) clouds is opening access to new resources for the HEP community. In this paper we will describe a system we have developed ...for creating a single dynamic batch environment spanning multiple IaaS clouds of different types (e.g. Nimbus, OpenNebula, Amazon EC2). A HEP user interacting with the system submits a job description file with a pointer to their VM image. VM images can either be created by users directly or provided to the users. We have created a new software component called Cloud Scheduler that detects waiting jobs and boots the user VM required on any one of the available cloud resources. As the user VMs appear, they are attached to the job queues of a central Condor job scheduler, the job scheduler then submits the jobs to the VMs. The number of VMs available to the user is expanded and contracted dynamically depending on the number of user jobs. We present the motivation and design of the system with particular emphasis on Cloud Scheduler. We show that the system provides the ability to exploit academic and commercial cloud sites in a transparent fashion.
We show that distributed Infrastructure-as-a-Service (IaaS) compute clouds can be effectively used for the analysis of high energy physics data. We have designed a distributed cloud system that works ...with any application using large input data sets requiring a high throughput computing environment. The system uses IaaS-enabled science and commercial clusters in Canada and the United States. We describe the process in which a user prepares an analysis virtual machine (VM) and submits batch jobs to a central scheduler. The system boots the user-specific VM on one of the IaaS clouds, runs the jobs and returns the output to the user. The user application accesses a central database for calibration data during the execution of the application. Similarly, the data is located in a central location and streamed by the running application. The system can easily run one hundred simultaneous jobs in an efficient manner and should scale to many hundreds and possibly thousands of user jobs.
The recent increase in availability of Infrastructure-as-a-Service (IaaS) computing clouds provides a new way for researchers to run complex scientific applications. However, using cloud resources ...for a large number of research jobs requires significant effort and expertise. Furthermore, running jobs on many different clouds presents even more difficulty. In order to make it easy for researchers to deploy scientific applications across many cloud resources, we have developed a virtual machine resource manager (Cloud Scheduler) for distributed compute clouds. In response to a user's job submission to a batch system, the Cloud Scheduler manages the distribution and deployment of user-customized virtual machines across multiple clouds. We describe the motivation for and implementation of a distributed cloud using the Cloud Scheduler that is spread across both commercial and dedicated private sites, and present some early results of scientific data analysis using the system.
The deployment of HEP applications in heterogeneous grid environments can be challenging because many of the applications are dependent on specific OS versions and have a large number of complex ...software dependencies. Virtual machine monitors such as Xen could be used to package HEP applications, complete with their execution environments, to run on resources that do not meet their operating system requirements. Our previous work has shown HEP applications running within Xen suffer little or no performance penalty as a result of virtualization. However, a practical strategy is required for remotely deploying, booting, and controlling virtual machines on a remote cluster. One tool that promises to overcome the deployment hurdles using standard grid technology is the Globus Virtual Workspaces project. We describe strategies for the deployment of Xen virtual machines using Globus Virtual Workspace middleware that simplify the deployment of HEP applications.
The present paper highlights the approach used to design and implement a web services based BaBar Monte Carlo (MC) production grid using Globus Toolkit version 4. The grid integrates the resources of ...two clusters at the University of Victoria, using the ClassAd mechanism provided by the Condor-G metascheduler. Each cluster uses the Portable Batch System (PBS) as its local resource management system (LRMS). Resource brokering is provided by the Condor matchmaking process, whereby the job and resource attributes are expressed as ClassAds. The important features of the grid are automatic registering of resource ClassAds to the central registry, ClassAds extraction from the registry to the metascheduler for matchmaking, and the incorporation of input/output file staging. Web-based monitoring is employed to track the status of grid resources and the jobs for an efficient operation of the grid. The performance of this new grid for BaBar jobs, and the existing Canadian computational grid (GridX1) based on Globus Toolkit version 2 is found to be consistent.
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