Primary Copy Research Articles

Clinical characteristics and genetic analysis of a Chinese pedigree affected with Alström syndrome

To explore the clinical characteristics and genetic etiology of a Chinese pedigree affected with Alström syndrome. A pedigree with 5 members affected with Alström syndrome who had visited the First Affiliated Hospital of Zhengzhou University in February 2021 was selected as the study subject. Clinical data of the pedigree were collected, and peripheral venous blood samples were collected for the extraction of genomic DNA. Genetic testing was carried out for the eldest daughter and third son through whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. The eldest daughter (14 years old) and the third son (11 years old) both had congenital nystagmus, amblyopia, growth retardation and type 2 diabetes. WES revealed that both had harbored homozygous c.3538A>T (p.Lys1180*) variant of the ALMS1 gene. Sanger sequencing confirmed that the father, mother, and second daughter were all heterozygous carriers. Based on the Guidelines for Genetic Variation and the Technical Standards for Interpretation and Reporting of Primary Copy Number Variations, the variant was predicted as pathogenic (PVS1+PM2_Supporting+PP4). The homozygous c.3538A>T (p.Lys1180*) variant of the ALSM1 gene probably underlay the Alström syndrome in this pedigree, which has provided a reference for the clinical treatment.

Qinyah Al-‘Ārif li Ḥukm Al-Iqtidā bi Al-Mukhālif (A Property of the Knowledgeable Regarding the Ruling of Following the Opposition) By Al-Faqīh Al-Muḥaddith Muḥammad Akram bin ‘Abdir Raḥmān Al-Sindī Al-Naṣrbūrī Died in the Twelfth Hijrī Century. Investigation and Study

Research aim: Participation in reviving the Islamic heritage on Fundamentals of Jurisprudence by investigating a valuable manuscript, and presenting it to the respected reader. Research methodology: The investigation relied on two manuscripts by comparing between them, based on the text chosen for the primary copy, and relying on the other copy for the text understanding and correction, so that the text will be correctly produced as intended by its author, although with the mention of the difference between the two copies in the footnote. Research findings: The authenticity of the book’s ascription to its author, and his wide knowledge of the literature of his Ḥanafī co-scholars, and his accuracy in what he transmits from them, although with critique and rejoinder in some places. Recommendations: Giving attention to the investigation of manuscripts of Islamic heritage, most especially those authored on a particular field or a particular issue, because it contains scholarly focus and explanations that may not be easily found in the books that are comprehensive on all issues and chapters.

Rhakhis: A workflow for managing the WFO taxonomic backbone

In 2021, the World Flora Online (WFO) Council agreed that the team at the Royal Botanic Garden Edinburgh would take on the technical role of managing the WFO Taxonomic Backbone (WFO-TB). This presentation outlines the implementation of a system to manage the associated data and explores possible future developments. The WFO-TB is a global concensus checklist of plants including bryophytes, pteridophytes, gymnosperms and angiosperms. The checklist data consists of two parts: facts concerning the nomenclatural acts that establish the names under the nomenclatural code, and consensus expert opinion on the placement of those names into a single, authoritative taxonomy. WFO-TB is unique in that it is both global in scope and curated by a large team of experts from multiple institutions. There are currently around 280 specialist contributors organised into 37 Taxonomic Expert Networks (TENs). The primary function of the WFO-TB is to provide structure to the hundreds of thousands of descriptions, images and other pieces of Content that make up the WFO’s main web portal, but periodic snapshots of the taxonomic data are also made available as public downloads and published as the WFO Plant List. The WFO Plant List is unique in that it remembers each version of WFO-TB that was published and links between them thus providing a stable, citable resource. In addition, data can be released in any format that researchers may find useful including through ChecklistBank and so be potentially incorporated into the Catalogue of Life and GBIF (Global Biodiversity Information Facility). All checklist data are released with a Creative Commons (CC) license of CC0 so that others may freely build upon, enhance and reuse the works for any purposes without restriction under copyright or database law. Prior to 2022, the WFO-TB was managed as part of the main WFO data resources supporting the WFO Portal by the team at Missouri Botanical Garden. Moving responsibility for hosting the backbone to the team at Edinburgh added significant resources to the project as a whole, but created technical challenges. The first requirement of the new system (called Rhakhis, a Greek form of rachis, the ‘backbone’ of a leaf or inflorescence) was to demonstrate that it could feed data back to Missouri in a way that could be incorporated into the WFO infrastructure without causing disruption to the Content curation process. This was completed in early 2022, and, by June, the primary copy of the WFO-TB data had been entrusted to Rhakhis. The June 2022 version of the WFO Plant List and the WFO-TB was published using the previous system, switching to publication from Rhakhis in December 2022. The system architecture of Rhakhis is quite simple. A MySQL database holds all the data and is exposed via a GraphQL API to a web-based user interface written in Javascript using React and Bootstrap. User authentication is handled via a link to ORCiD (Open Researcher and Contributor ID). Authorisation for editors is delegated hierarchically down the taxonomic tree. This provides the ability for TENs and the TEN Manager to oversee and manage the live data directly and to delegate authority to colleagues. The TEN Manager has access to a plain HTML bulk loader interface that enables the ingestion of CSV and files in DwC-A (Darwin Core Archive) format supplied by TENs as well as updates from other data sources, such as IPNI (International Plant Names Index) and WCVP (RBG Kew’s World Checklist of Vascular Plants). Rhakhis is designed as a standalone data management tool for taxonomists involved in the project rather than a public website, and is hosted on a WFO server on the Google Cloud. The WFO Plant List is run on a separate system and designed to be a performant public-facing website. Periodic snapshots of the WFO-TB are imported into a Solr Index that is then exposed via another GraphQL API as well as Semantic Web-compliant HTTPS URIs. A web-based user interface to WFO Plant List is implemented as part of the Craft CMS (Content Management System) that also runs the About pages of the WFO Web Portal, but it would be possible to build other interfaces to this data. The periodic snapshots of the WFO-TB, which are published through the WFO Plant List, are archived in Zenodo and assigned a DOI (Digital Object Identifier), as well as contributed to Catalogue of Life ChecklistBank. The archive formats currently supported include: Darwin Core Archive and Catalogue of Life Data Package, but other formats will be considered in the future. We are interested in investigating the creation of data papers, e.g., through the Biodiversity Data Journal at Pensoft, to provide additional accreditation for contributors and exposure of their data.

The Insigne of the Proconsul of Africa. Maritime Shipping Depictions in the Notitia Dignitatum

The largely unstudied insigne of the proconsul Africae, governor of the late Roman province Africa, is preserved in the primary copies of Notitia Dignitatum from around 400 ce and known from copies of the lost Codex Spirensis. This article, based on a combination of legal and art historical methods, seeks to determine the meaning of the insignia’s symbolic representations, especially its references to maritime shipping. Details in the insignia, including the colors used in it, can be considered a visual statement of the proconsul Africae’s scope of competence and intended to amplify the association in the Notitia Dignitatum. The reader in antiquity of the Notitia Dignitatum possibly saw the Africa proconsularis emblem as illustrating that official’s crucial role in producing supplies for Rome and delivering them by maritime freight. It is of note that no other insignia in the Notitia Dignitatum have maritime symbols or other details relating to seafaring. The depictions’ high degree of technical detail attests to the reliability of the insignia to the Notitia Dignitatum in studies concerned with Late Antiquity.

Abstract P2-01-06: Detection of circulating tumor DNA post neoadjuvant chemotherapy using a personalized assay is associated with disease relapse

Abstract Background: Approximately 30% of patients with early breast cancer present disease relapse after surgery, and technologies that enable the detection of circulating tumor DNA (ctDNA) were shown to identify them earlier than standard imaging. In the present study, we aimed to interrogate the value of the SignateraTM personalized ctDNA assay for early detection of disease relapse. Methods: The study included 52 early breast cancer patients undergoing neoadjuvant chemotherapy from an ongoing translational, single-center study at Jules Bordet Institute, Brussels, Belgium. From each patient, primary tumor tissue sections, blood sample for normal DNA, and serial plasma samples were sent to NATERA Inc for ctDNA detection using the SignateraTM assay. Plasma samples were collected before the initiation of neoadjuvant chemotherapy (baseline), after neoadjuvant chemotherapy, before surgery (pre-surgery), and at follow-up post-surgery. Whole exome sequencing (WES) was performed on the primary tumor tissue and matched normal DNA to design a patient-specific ctDNA assay. The unique set of SNV’s identified in WES were tracked in serial plasma samples. Associations between baseline ctDNA detection and standard clinicopathological characteristics and primary tumor point mutations or copy number aberrations were evaluated. Association between ctDNA detection, pathological complete response (pCR) and event-free survival (EFS) were explored. Fisher, Mann-Whitney and Kruskal-Wallis tests were used to compare variables. Log-rank tests and Cox regressions were used for survival analyses. Hazard ratios (HRs) and confidence intervals (CIs) were obtained from Cox regressions. For multivariable tests, logistic regressions were used for binary outcomes and Cox regressions for survival outcomes. P-values were obtained by comparing models with and without the variable of interest using Chi-square test in ANOVAs. Results: Forty-four out of 52 (85%) initially selected patients had the required tumor cellularity (≥ 20%) and adequate tumor DNA quantity and quality and had personalized ctDNA assays designed. In these 44 patients, 154 plasma samples were successfully processed including 38, 41, 75, 38 at baseline, pre-surgery, follow-up (any timepoint) and last follow-up timepoint, respectively. Twenty (45%) patients had hormone receptor positive/HER2-negative, 13 (30%) triple-negative and 11 (25%) HER2-positive breast cancers. Detection of ctDNA was observed in 22 of 38 (58%) patients at baseline and was significantly associated with Ki67>20% and MYC copy number gain in the primary tumor. ctDNA detection at pre-surgery and at last follow-up was observed in 2 of 41 (5%) and 2 of 38 (5%) patients respectively. All patients who achieved pCR were ctDNA-negative at the pre-surgical time point. With a median follow-up of 3.03 years (range 0.39 - 5.85), we observed 8 relapses (7 distant and 1 local, respectively). After adjusting for pCR, ctDNA detection was associated with shorter EFS at pre-surgery and at last follow-up time points (HR: 53, 95% CI: 4.5-624, p<0.01, and HR: 31, 95% CI: 2.7-352, p<0.01, respectively), but not at baseline (HR: 1.4, 95% CI: 0.3-5.9, p=0.67). Conclusions: The detection of ctDNA post neoadjuvant chemotherapy is associated with disease relapse in early breast cancer supporting interventional trials in this setting. Citation Format: Elisa Agostinetto, Frédéric Cailleux, Matteo Lambertini, Françoise Rothé, Hsin-Ta Wu, Mustafa Balcioglu, Himanshu Sethi, Delphine Vincent, Giulia Viglietti, Andrea Gombos, Andreas Papagiannis, Isabelle Veys, Ahmad Awada, Christos Sotiriou, Ekaterina Kalashnikova, Alexey Aleshin, Denis Larsimont, David Venet, Michail Ignatiadis. Detection of circulating tumor DNA post neoadjuvant chemotherapy using a personalized assay is associated with disease relapse [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-01-06.

Main Memory Database Recovery

Many of today’s applications need massive real-time data processing. In-memory database systems have become a good alternative for these requirements. These systems maintain the primary copy of the database in the main memory to achieve high throughput rates and low latency. However, a database in RAM is more vulnerable to failures than in traditional disk-oriented databases because of the memory volatility. DBMSs implement recovery activities (logging, checkpoint, and restart) for recovery proposes. Although the recovery component looks similar in disk- and memory-oriented systems, these systems differ dramatically in the way they implement their architectural components, such as data storage, indexing, concurrency control, query processing, durability, and recovery. This survey aims to provide a thorough review of in-memory database recovery techniques. To achieve this goal, we reviewed the main concepts of database recovery and architectural choices to implement an in-memory database system. Only then, we present the techniques to recover in-memory databases and discuss the recovery strategies of a representative sample of modern in-memory databases.

Identification of primary copy number variations reveal enrichment of Calcium, and MAPK pathways sensitizing secondary sites for autism

BackgroundAutism is a neurodevelopmental condition with genetic heterogeneity. It is characterized by difficulties in reciprocal social interactions with strong repetitive behaviors and stereotyped interests. Copy number variations (CNVs) are genomic structural variations altering the genomic structure either by duplication or deletion. De novo or inherited CNVs are found in 5–10% of autistic subjects with a size range of few kilobases to several megabases. CNVs predispose humans to various diseases by altering gene regulation, generation of chimeric genes, and disruption of the coding region or through position effect. Although, CNVs are not the initiating event in pathogenesis; additional preceding mutations might be essential for disease manifestation. The present study is aimed to identify the primary CNVs responsible for autism susceptibility in healthy cohorts to sensitize secondary-hits. In the current investigation, primary-hit autism gene CNVs are characterized in 1715 healthy cohorts of varying ethnicities across 12 populations using Affymetrix high-resolution array study. Thirty-eight individuals from twelve families residing in Karnataka, India, with the age group of 13–73 years are included for the comparative CNV analysis. The findings are validated against global 179 autism whole-exome sequence datasets derived from Simons Simplex Collection. These datasets are deposited at the Simons Foundation Autism Research Initiative (SFARI) database.ResultsThe study revealed that 34.8% of the subjects carried 2% primary-hit CNV burden with 73 singleton-autism genes in different clusters. Of these, three conserved CNV breakpoints were identified with ARHGAP11B, DUSP22, and CHRNA7 as the target genes across 12 populations. Enrichment analysis of the population-specific autism genes revealed two signaling pathways—calcium and mitogen-activated protein kinases (MAPK) in the CNV identified regions. These impaired pathways affected the downstream cascades of neuronal function and physiology, leading to autism behavior. The pathway analysis of enriched genes unravelled complex protein interaction networks, which sensitized secondary sites for autism. Further, the identification of miRNA targets associated with autism gene CNVs added severity to the condition.ConclusionThese findings contribute to an atlas of primary-hit genes to detect autism susceptibility in healthy cohorts, indicating their impact on secondary sites for manifestation.

Asymmetric-partition replication for highly scalable distributed transaction processing in practice

Database replication is widely known and used for high availability or load balancing in many practical database systems. In this paper, we show how a replication engine can be used for three important practical cases that have not previously been studied very well. The three practical use cases include: 1) scaling out OLTP/OLAP-mixed workloads with partitioned replicas, 2) efficiently maintaining a distributed secondary index for a partitioned table, and 3) efficiently implementing an online re-partitioning operation. All three use cases are crucial for enabling a high-performance shared-nothing distributed database system. To support the three use cases more efficiently, we propose the concept of asymmetric-partition replication , so that replicas of a table can be independently partitioned regardless of whether or how its primary copy is partitioned. In addition, we propose the optimistic synchronous commit protocol which avoids the expensive two-phase commit without sacrificing transactional consistency. The proposed asymmetric-partition replication and its optimized commit protocol are incorporated in the production versions of the SAP HANA in-memory database system. Through extensive experiments, we demonstrate the significant benefits that the proposed replication engine brings to the three use cases.

QoS-Aware Task Placement With Fault-Tolerance in the Edge-Cloud

The geographically dispersed resources and ever-changing context incur unique heterogeneity, potential fragility, and vulnerability of an edge-cloud system. Thus, the reliability guarantee of services in the edge-cloud is critical. This paper firstly proposes a QoS-aware scheduling model with fault-tolerance in the edge-cloud, which extends the traditional primary-backup (PB) fault-tolerant model to improve the service reliability in the edge-cloud with the time constraints of tasks being satisfied. Then, a QoS-aware fault-tolerant scheduling algorithm including primary copy placement, backup copy placement and an adjustment mechanism is proposed to improve the QoS levels of tasks in the edge-cloud. The primary copy placement is to guarantee the earlier execution of the primary copy of a task to better satisfy the time requirements of tasks. The backup copy placement is to ensure the later execution of the backup copy of a task, reducing the overlapping of the two copies of a task, realizing the improvement of the resource utilization in the edge-cloud under the condition of redundancy and deadline requirements of tasks. The adjustment mechanism is triggered to rearrange the task copies of a computing node of the edge-cloud after the deallocation of a backup copy on the node, to better assist the goal-achievement of the primary and backup copy scheduling. Finally, through extensive simulation experiments with the real world taxi traces, the performance difference between the proposed method and the other four methods are evaluated. Results show that the proposed method generally outperforms the other methods in terms of guarantee ratio, average QoS level, and reliability cost.

Distribution Differences in the EPSPS Gene in Chromosomes Between Glyphosate-Resistant and -Susceptible Goosegrass (Eleusine indica)

Abstract Glyphosate is a popular herbicide used to control goosegrass [Eleusine indica (L.) Gaertn.], one of the most troublesome weeds in cotton fields. However, high selection pressure has led to some populations being difficult to control in cotton fields in China. In this study, levels of glyphosate resistance were quantified and 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) amplification was confirmed. In addition, distribution of the EPSPS gene among the chromosomes was also investigated using fluorescence in situ hybridization (FISH) methodology. One population (AHCZ) was confirmed to be glyphosate resistant with a resistance index of 3.4 and significantly reduced shikimate accumulation compared to susceptible population. All examined individuals exhibited no mutations in the EPSPS gene in AHCZ. Expression and copy numbers of EPSPS in the AHCZ population were 5.7 and 15.4 times higher, respectively, than in the susceptible population. A positive correlation was identified between signal intensities of primary anti-EPSPS antibody and copy numbers of the EPSPS protein, as indicated by immunoblot analysis. FISH results revealed that, in mitotic metaphase chromosomes, signals were observed dispersed across two sets of homologous chromosomes in a resistant individual (copy number = 31), while in susceptible individuals, signals were only partially detected in one set of homologous chromosomes. In interphase nuclei, EPSPS signals were brightest in resistant individual compared to those that were susceptible. In conclusion, one E. indica population from a cotton field in the Anhui Province has evolved resistance to glyphosate, and EPSPS gene amplification was confirmed as the resistant mechanism.

ATLAS Distributed Computing Experience and Performance During the LHC Run-2

ATLAS Distributed Computing during LHC Run-1 was challenged by steadily increasing computing, storage and network requirements. In addition, the complexity of processing task workflows and their associated data management requirements led to a new paradigm in the ATLAS computing model for Run-2, accompanied by extensive evolution and redesign of the workflow and data management systems. The new systems were put into production at the end of 2014, and gained robustness and maturity during 2015 data taking. ProdSys2, the new request and task interface; JEDI, the dynamic job execution engine developed as an extension to PanDA; and Rucio, the new data management system, form the core of Run-2 ATLAS distributed computing engine.One of the big changes for Run-2 was the adoption of the Derivation Framework, which moves the chaotic CPU and data intensive part of the user analysis into the centrally organized train production, delivering derived AOD datasets to user groups for final analysis. The effectiveness of the new model was demonstrated through the delivery of analysis datasets to users just one week after data taking, by completing the calibration loop, Tier-0 processing and train production steps promptly. The great flexibility of the new system also makes it possible to execute part of the Tier-0 processing on the grid when Tier-0 resources experience a backlog during high data-taking periods.The introduction of the data lifetime model, where each dataset is assigned a finite lifetime (with extensions possible for frequently accessed data), was made possible by Rucio. Thanks to this the storage crises experienced in Run-1 have not reappeared during Run-2. In addition, the distinction between Tier-1 and Tier-2 disk storage, now largely artificial given the quality of Tier-2 resources and their networking, has been removed through the introduction of dynamic ATLAS clouds that group the storage endpoint nucleus and its close-by execution satellite sites. All stable ATLAS sites are now able to store unique or primary copies of the datasets.ATLAS Distributed Computing is further evolving to speed up request processing by introducing network awareness, using machine learning and optimisation of the latencies during the execution of the full chain of tasks. The Event Service, a new workflow and job execution engine, is designed around check-pointing at the level of event processing to use opportunistic resources more efficiently.ATLAS has been extensively exploring possibilities of using computing resources extending beyond conventional grid sites in the WLCG fabric to deliver as many computing cycles as possible and thereby enhance the significance of the Monte-Carlo samples to deliver better physics results.The exploitation of opportunistic resources was at an early stage throughout 2015, at the level of 10% of the total ATLAS computing power, but in the next few years it is expected to deliver much more. In addition, demonstrating the ability to use an opportunistic resource can lead to securing ATLAS allocations on the facility, hence the importance of this work goes beyond merely the initial CPU cycles gained.In this paper, we give an overview and compare the performance, development effort, flexibility and robustness of the various approaches.

Abstract PR02: GPC2 is a candidate immunotherapeutic target and putative oncogene in high-risk neuroblastoma and other pediatric cancers

Abstract Background: Children with high-risk neuroblastoma have a poor prognosis despite intensive multimodal chemoradiotherapy. While monoclonal antibodies targeting the disialoganglioside GD2 improve outcomes in neuroblastoma, this therapy is associated with significant “on target-off tumor” toxicities. Thus, a major challenge remains in identifying novel cell surface molecules that meet the stringent criteria for modern immunotherapeutics, including unique tumor expression compared to normal childhood tissues, and preferably that these cell surface molecules be required for tumor sustenance and thus may be less susceptible to immune escape mechanisms. Methods: Differentially expressed genes that represent putative cell surface immunotherapeutic targets were initially identified by comparing high-risk neuroblastoma RNA sequencing data (N=126 primary tumors) to paired normal tissue data (GTEx; N=25 unique normal tissues; N=1-313 replicate samples/tissue type). For further prioritization, gene sets were filtered by in silico cell surface prediction and by absolute RNA expression, and then by assessing primary tumor DNA copy number via SNP genotyping data (N=177). For prioritized genes, protein expression and cellular localization was confirmed by Western blot, immunohistiochemistry (IHC), immunofluroescence (IF) and membrane extraction techniques in neuroblastoma cell lines and primary tumors. For functional characterization, neuroblastoma cell lines (N=12) were subjected to both gain and loss of function studies for each candidate gene. Results: The initial transcriptome-based discovery effort identified 649 significantly differentially expressed genes (log-fold change tumor vs. normal >1 for each tissue; adjusted p<0.05), 86 (13%) of which were predicted to be potential cell surface molecules. Through our analytic pipeline, we prioritized the extracellular glycosylphosphatidylinositol (GPI) anchored, signaling co-receptor Glypican-2 (GPC2) for validation given robust differential RNA expression (log-fold change tumor vs. normal tissue = 2.1-8.2; p<3 x 10-10), high-level absolute RNA expression (median FPKM=57; 85% of tumors with FPKM >25) and consistent DNA copy number gain (31% of primary neuroblastomas; N=177) associated with significantly higher GPC2 expression (p<0.0001). Immunoblot analysis confirmed ubiquitous GPC2 protein expression (N=8 high-risk neuroblastomas and 23 cell lines) and membrane extraction, IF, and IHC confirmed dense plasma membrane associated GPC2 protein expression in neuroblastoma cell lines. IHC analysis of primary neuroblastoma tumors (N=165) compared to a parallel array of pediatric normal tissues (N=41) further confirmed GPC2 protein expression to be membrane associated and tumor specific with very limited normal tissue expression. Lentiviral mediated RNAi induced GPC2 depletion in a panel of 12 neuroblastoma cell lines resulted in significant apoptosis and growth inhibition both in transient CellTiter-Glo and Caspase-Glo assays (20-87% decreased growth and 1.5-18.4-fold increased caspase 3/7 level vs. control) and with longer term real-time monitoring of cell growth (RT-CES). GPC2 overexpression resulted in significantly increased cellular proliferation (2.7-fold growth increase vs. control, p<0.0001). Finally, GPC2 was also found to be significantly differentially overexpressed in other embryonal cancers, most notably medulloblastoma. Conclusions: GPC2 is a candidate cell surface immunotherapeutic target and putative oncogene in high-risk neuroblastoma. More globally, these data show that genome-wide transcriptome analysis integrated with genomic and functional validation can identify differentially expressed cell surface oncogenes that may be attractive immunotherapeutic targets. Development of a GPC2 directed chimeric antigen receptor is ongoing, and progress will be reported. This abstract is also presented as Poster A13. Citation Format: Kristopher R. Bosse, Pichai Raman, Robyn T. Sussman, Michael Randall, Dan Martinez, Zhongyu Zhu, Bruce Pawel, Tricia Bhatti, Javed Khan, Dimiter S. Dimitrov, Crystal Mackall, John M. Maris. GPC2 is a candidate immunotherapeutic target and putative oncogene in high-risk neuroblastoma and other pediatric cancers. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr PR02.

A PSO-Optimized Real-Time Fault-Tolerant Task Allocation Algorithm in Wireless Sensor Networks

One of challenging issues for task allocation problem in wireless sensor networks (WSNs) is distributing sensing tasks rationally among sensor nodes to reduce overall power consumption and ensure these tasks finished before deadlines. In this paper, we propose a soft real-time fault-tolerant task allocation algorithm (FTAOA) for WSNs in using primary/backup (P/B) technique to support fault tolerance mechanism. In the proposed algorithm, the construction process of discrete particle swarm optimization (DPSO) is achieved through adopting a binary matrix encoding form, minimizing tasks execution time, saving node energy cost, balancing network load, and defining a fitness function for improving scheduling effectiveness and system reliability. Furthermore, FTAOA employs passive backup copies overlapping technology and is capable to determinate the mode of backup copies adaptively through scheduling primary copies as early as possible and backup copies as late as possible. To improve resource utilization, we allocate tasks to the nodes with high performance in terms of load, energy consumption, and failure ratio. Analysis and simulation results show the feasibility and effectiveness of FTAOA. FTAOA can strike a good balance between local solution and global exploration and achieve a satisfactory result within a short period of time.

기본 사본을 갖는 P2P 멀티플레이어 게임 구조의 수준별 일관성 제어 기법

A Multiplayer Online Game(MOG) is a game capable of supporting hundreds or thousands of players and is mostly played using the Internet. P2P(peer-to-peer) architectures for MOGs can potentially achieve high scalability, low cost, and good performance. The basic idea of many P2P-based games is to distribute the game state among peers and along with it processing, network, and storage tasks. In a primary-copy based replication scheme where any update to the object has to be first performed on the primary copy, this means distributing primary copies of objects among peers. Most multiplayer games use a primary-copy model in order to provide strong consistency control over an object. Games consist of various types of actions that have different levels of sensitivity and can be categorized according to their consistency requirements. With the appropriate consistency level of each action type within a game, this paper allows developers to choose the right trade-off between performance and consistency. The performance for P2P game architecture with the primary-copy model is evaluated through simulation experiments and analysis.

Abstract A72: Next-generation sequencing of disseminated tumor cells

Abstract Disseminated tumor cells (DTCs) detected in the bone marrow have been shown as an independent prognostic factor for women with breast cancer. However, the mechanisms behind the tumor cell dissemination are still unclear and more detailed knowledge is needed to fully understand why some cells remain dormant and others metastasize. Sequencing of single cells has opened for the possibility to dissect the genetic content of subclones of a primary tumor, as well as DTCs. Previous studies of genetic changes in DTCs have employed single-cell array comparative genomic hybridization which provides information about larger aberrations. To date, next generation sequencing provides the possibility to discover new, smaller and copy neutral genetic changes. In this study, we performed whole genome amplification and subsequently next generation sequencing to analyze DTCs from two breast cancer patients. We compared copy number profiles of the DTCs and the corresponding primary tumor generated from sequencing and SNP-CGH data, respectively. While one tumor revealed mostly whole arm gains and losses, the other had more complex alterations, as well as subclonal amplification and deletions. Whole arm gains or losses in the primary tumor were in general also observed in the corresponding DTC. Both primary tumors showed amplification of chromosome 1q and deletion of parts of chromosome 16q, which was recaptured in the corresponding DTCs. Interestingly, clear differences were also observed, indicating that the DTC underwent further evolution at the copy number level. This study provides a proof-of-principle for sequencing of DTCs and correlation with primary copy number profiles. The analyses allow insight into tumor cell dissemination and show ongoing copy number evolution in DTCs compared to the primary tumors. Note: This abstract was not presented at the conference. Citation Format: Elen K. Møller, Parveen Kumar, Thierry Voet, April Peterson, Peter Van Loo, Randi Mathiesen, Renate Fjelldal, Jason Grundstad, Elin Borgen, Lars O. Baumbusch, Bjørn Naume, Anne-Lise Børresen-Dale, Silje Nord, Vessela N. Kristensen. Next-generation sequencing of disseminated tumor cells. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A72. doi:10.1158/1538-7445.CHTME14-A72

Efficient Resource Management Mechanism with Fault Tolerant Model for Computational Grids

Grid computing provides a framework and deployment environment that enables resource sharing, accessing, aggregation and management. It allows resource and coordinated use of various resources in dynamic, distributed virtual organization. The grid scheduling is responsible for resource discovery, resource selection and job assignment over a decentralized heterogeneous system. In the existing system, primary-backup approach is used for fault tolerance in a single environment. In this approach, each task has a primary copy and backup copy on two different processors. For dependent tasks, precedence constraint among tasks must be considered when scheduling backup copies and overloading backups. Then, two algorithms have been developed to schedule backups of dependent and independent tasks. The proposed work is to manage the resource failures in grid job scheduling. In this method, data source and resource are integrated from different geographical environment. Faulttolerant scheduling with primary backup approach is used to handle job failures in grid environment. Impact of communication protocols is considered. Communication protocols such as Transmission Control Protocol (TCP), User Datagram Protocol (UDP) which are used to distribute the message of each task to grid resources.

Canonical and non‐canonical EcfG sigma factors control the general stress response in Rhizobium etli

A core component of the α-proteobacterial general stress response (GSR) is the extracytoplasmic function (ECF) sigma factor EcfG, exclusively present in this taxonomic class. Half of the completed α-proteobacterial genome sequences contain two or more copies of genes encoding σEcfG-like sigma factors, with the primary copy typically located adjacent to genes coding for a cognate anti-sigma factor (NepR) and two-component response regulator (PhyR). So far, the widespread occurrence of additional, non-canonical σEcfG copies has not satisfactorily been explained. This study explores the hierarchical relation between Rhizobium etli σEcfG1 and σEcfG2, canonical and non-canonical σEcfG proteins, respectively. Contrary to reports in other species, we find that σEcfG1 and σEcfG2 act in parallel, as nodes of a complex regulatory network, rather than in series, as elements of a linear regulatory cascade. We demonstrate that both sigma factors control unique yet also shared target genes, corroborating phenotypic evidence. σEcfG1 drives expression of rpoH2, explaining the increased heat sensitivity of an ecfG1 mutant, while katG is under control of σEcfG2, accounting for reduced oxidative stress resistance of an ecfG2 mutant. We also identify non-coding RNA genes as novel σEcfG targets. We propose a modified model for GSR regulation in R. etli, in which σEcfG1 and σEcfG2 function largely independently. Based on a phylogenetic analysis and considering the prevalence of α-proteobacterial genomes with multiple σEcfG copies, this model may also be applicable to numerous other species.

Next-Generation Sequencing of Disseminated Tumor Cells

Disseminated tumor cells (DTCs) detected in the bone marrow have been shown as an independent prognostic factor for women with breast cancer. However, the mechanisms behind the tumor cell dissemination are still unclear and more detailed knowledge is needed to fully understand why some cells remain dormant and others metastasize. Sequencing of single cells has opened for the possibility to dissect the genetic content of subclones of a primary tumor, as well as DTCs. Previous studies of genetic changes in DTCs have employed single-cell array comparative genomic hybridization which provides information about larger aberrations. To date, next-generation sequencing provides the possibility to discover new, smaller, and copy neutral genetic changes. In this study, we performed whole-genome amplification and subsequently next-generation sequencing to analyze DTCs from two breast cancer patients. We compared copy-number profiles of the DTCs and the corresponding primary tumor generated from sequencing and SNP-comparative genomic hybridization (CGH) data, respectively. While one tumor revealed mostly whole-arm gains and losses, the other had more complex alterations, as well as subclonal amplification and deletions. Whole-arm gains or losses in the primary tumor were in general also observed in the corresponding DTC. Both primary tumors showed amplification of chromosome 1q and deletion of parts of chromosome 16q, which was recaptured in the corresponding DTCs. Interestingly, clear differences were also observed, indicating that the DTC underwent further evolution at the copy-number level. This study provides a proof-of-principle for sequencing of DTCs and correlation with primary copy-number profiles. The analyses allow insight into tumor cell dissemination and show ongoing copy-number evolution in DTCs compared to the primary tumors.

Fault-Tolerant Scheduling for Real-Time Tasks with QoS Requirements on Heterogeneous Clusters

PDF HTML阅读 XML下载 导出引用 引用提醒 异构集群系统中具有QoS 需求的实时任务容错调度 DOI: 10.3724/SP.J.1001.2011.03833 作者: 作者单位: 作者简介: 通讯作者: 中图分类号: 基金项目: 国家安全重大基础研究计划(973)(6136101); 国家高技术研究发展计划(863)(2008AA7070412) Fault-Tolerant Scheduling for Real-Time Tasks with QoS Requirements on Heterogeneous Clusters Author: Affiliation: Fund Project: 摘要 | 图/表 | 访问统计 | 参考文献 | 相似文献 | 引证文献 | 资源附件 | 文章评论 摘要:容错调度是调度问题中一个重要的研究内容,是提高系统可靠性的有效手段.目前已有很多集群系统时任务的容错调度算法,但是这些算法都没有考虑到任务的QoS 需求问题.提出了一种异构集群系统中具有QoS 需求的实时任务容错调度算法FTQ(fault-tolerant QoS-based scheduling).该算法采用主版本/副版本(primary/backup, 简称PB)技术,综合考虑了任务的时间限制、任务的QoS 需求、系统的可靠性和系统资源的利用率,能够自适应地根据系统负载情况动态地调整任务的QoS 级别和副版本的执行模式,从而提高了系统的灵活性、可靠性、可调和资源的利用率.对系统的可靠性进行了定量分析,并将其引入到容错调度算法中,提高了系统的可靠性.同时,度过程中尽量提前主版本的开始时间,推迟副版本的开始时间,以使任务的副版本采用被动执行模式或者使任版本和副版本的重叠部分尽量少,提高了资源的利用率.此外,采用了副版本重叠技术,并分析了副版本的最晚时间及其约束条件,提高了任务的调度成功率.通过大量的模拟实验,对FTQ,NOFTQ 和DYFARS 算法进行了.实验结果表明,FTQ 算法的性能优于其他方法,具有更好的调度质量. Abstract:Fault-Tolerant scheduling, an effective means of improving a system’s performance, plays a significant role in scheduling research. Despite the fact that fault-tolerant scheduling has been extensively proposed for real-time tasks on clusters, QoS (quality of service) requirements for some tasks have not been considered. This paper proposes a fault-tolerance scheduling algorithm FTQ (fault-tolerant QoS-based scheduling) for real-time tasks with QoS needs on heterogeneous clusters. FTQ adopts the primary/backup model and takes the timing constraints of tasks, QoS requirements of tasks, reliability of systems, and system resource utilization into account. FTQ can adjust the QoS levels of real-time tasks and the execution schemes of backup copies to improve system flexibility, reliability, schedulability, and resource utilization. The system reliability is quantitatively measured and combined into FTQ, which improves the system performance. Meanwhile, FTQ strives to advance the start time of primary copies and delay the start time of backup copies to make backup copies adopt passive execution scheme, or decrease overlapping sections of primary and backup copies as much as possible to improve resource utilization. FTQ adaptively adjusts the QoS levels of tasks and the execution schemes of backup copies to attain a higher flexibility. The overlapping technology of backup copies is employed. The latest start time of backup copies and its constraints are analyzed. Compared with NOFTQ and DYFARS, FTQ shows obvious superiority with a higher scheduling quality proven by a considerable number of simulated experiments. 参考文献 相似文献 引证文献

Communication-aware Fault-tolerant Scheduling Strategy for Precedence Constrained Tasks in Heterogeneous Distributed Systems

Abstract Fault-tolerant scheduling is an important issue for optimal heterogeneous distributed systems because of a wide range of resource failures. Primary-backup approach is a common methodology used for fault tolerance wherein each task has a primary copy and a backup copy on two different processors. For independent tasks, the backup copy can overload with other backup copies on the same processor, as long as their corresponding primary copies are scheduled on different processors. Unfortunately, most of the scheduling algorithms developed on a simple model where communication contention is not taken into account. In this paper we proposed a improve list scheduling algorithm, called heterogeneous communication-aware fault-tolerant scheduling (HCFS). The new approach for computing task priority is proposed which considers the performance difference in heterogeneous systems. Simulation results show that compared with existing scheduling algorithms in the literature, our scheduling algorithm improves the reliability and performance.