Time-Optimal and Conflict-Free Mappings of Uniform Dependence Algorithms into Lower Dimensional Processor Arrays

Most existing methods of mapping algorithms into processor arrays are restricted to the case where n-dimensional algorithms or algorithms with n nested loops are mapped into (n—l)-dimensional arrays. However, in practice, it is interesting to map n-dimensional algorithms into (k —l)-dimensional arrays where k\u3c.n. For example, many algorithms at bit-level are at least 4-dimensional (matrix multiplication, convolution, LU decomposition, etc.) and most existing bit level processor arrays are 2-dimensional. A computational conflict occurs if two or more computations of an algorithm are mapped into the same processor and the same execution time. In this paper, necessary and sufficient conditions are derived to identify all mappings without computational conflicts, based on the Hermite normal form of the mapping matrix. These conditions are used to propose methods of mapping any n-dimensional algorithm into (k— l)-dimensional arrays, kn—3, optimality of the mapping is guaranteed

Partitioning of Uniform Dependency Algorithms for Parallel Execution on MIMD/ Systolic Systems

An algorithm can be modeled as an index set and a set of dependence vectors. Each index vector in the index set indexes a computation of the algorithm. If the execution of a computation depends on the execution of another computation, then this dependency is represented as the difference between the index vectors of the computations. The dependence matrix corresponds to a matrix where each column is a dependence vector. An independent partition of the index set is such that there are no dependencies between computations that belong to different blocks of the partition. This report considers uniform dependence algorithms with any arbitrary kind of index set and proposes two very simple methods to find independent partitions of the index set. Each method has advantages over the other one for certain kind of application, and they both outperform previously proposed approaches in terms of computational complexity and/or optimality. Also, lower bounds and upper bounds of the cardinality of the maximal independent partitions are given. For some algorithms it is shown that the cardinality of the maximal partition is equal to the greatest common divisor of some subdeterminants of the dependence matrix. In an MIMD/multiple systolic array computation environment, if different blocks of ail independent partition are assigned to different processors/arrays, the communications between processors/arrays will be minimized to zero. This is significant because the communications usually dominate the overhead in MIMD machines. Some issues of mapping partitioned algorithms into MIMD/systolic systems are addressed. Based on the theory of partitioning, a new method is proposed to test if a system of linear Diophantine equations has integer solutions

Detailed Modeling and Reliability Analysis of Fault-Tolerant Processor Arrays

Recent advances in VLSI/WSI technology have led to the design of processor arrays with a large number of processing elements confined in small areas. The use of redundancy to increase fault-tolerance has the effect of reducing the ratio of area dedicated to processing elements over the area occupied by other resources in the array. The assumption of fault-free hardware support (switches, buses, interconnection links, etc.,), leads at best to conservative reliability estimates. However, detailed modeling entails not only an explosive growth in the model state space but also a difficult model construction process. To address the latter problem, a systematic method to construct Markov models for the reliability evaluation of processor arrays is proposed. This method is based on the premise that the fault behavior of a processor array can be modeled by a Stochastic Petri Net (SPN). However, in order to obtain a more compact representation, a set of attributes is associated with each transition in the Petri net model. This representation is referred to as a Modified Stochastic Petri Net (MSPN) model. A MSPN allows the construction of the corresponding Markov model as the reachability graph is being generated. The Markov model generated can include the effect of failures of several different components of the array as well as the effect of a peculiar distribution of faults when the reconfiguration occurs. Specific reconfiguration schemes such as Successive Row Elimination (SRE), Alternate Row-Column Elimination (ARCE) and Direct Reconfiguration (DR), are analyze

COSMIC: A Model for Multiprocessor Performance Analysis

COSMIC, the Combined Ordering Scheme Model with Isolated Components, describes the execution of specific algorithms on multiprocessors and facilitates analysis of their performance. Building upon previous modeling efforts such as Petri nets, COSMIC structures the modeling of a system along several issues including computational and overhead costs due to sequencing of operations, synchronization between operations, and contention for limited resources. This structuring allows us to isolate the performance impact associated with each issue. Finally, studying the performance of a system while executing a specific algorithm gives insight into its performance under realistic operating conditions. The model also allows us to study realistically sized algorithms with ease, especially when they are regularly structured. During the analysis of a system modeled by COSMIC, a set timed Petri nets is produced. These Petri nets are then analyzed to determine measures of the systems performance. To facilitate the specification, manipulation, and analysis of large timed Petri nets, a set of tools has been developed. These tools take advantage of several special properties of the timed Petri nets that greatly reduce the computational resources required to calculate the required measures. From this analysis, performance measures show not only total performance, but also present a breakdown of these results into several specific categories

Destination Tag Routing Techniques Based on a State Model for the IADM Network

A state model is proposed for solving the problem of routing and rerouting messages in the Inverse Augmented Data Manipulator (IADM) network. Using this model, necessary and sufficient conditions for the reroutability of messages are established, and then destination tag schemes are derived. These schemes are simpler, more efficient and require less complex hardware than previously proposed routing schemes. Two destination tag schemes are proposed. For one of the schemes, rerouting is totally transparent to the sender of the message and any blocked link of a given type can be avoided. Compared with previous works that deal with the same type of blockage, the timeXspace complexity is reduced from O(logN) to O(1). For the other scheme, rerouting is possible for any type of link blockage. A universal rerouting algorithm is constructed based on the second scheme, which finds a blockage-free path for any combination of multiple blockages if there exists such a path, and indicates absence of such a path if there exists none. In addition, the state model is used to derive constructively a lower bound on the number of subgraphs which are isomorphic to the Indirect Binary N-Cube network in the IADM network. This knowledge can be used to characterize properties of the IADM networks and for permutation routing in the IADM networks

Archer: A Community Distributed Computing Infrastructure for Computer Architecture Research and Education

This paper introduces Archer, a community-based computing resource for computer architecture research and education. The Archer infrastructure integrates virtualization and batch scheduling middleware to deliver high-throughput computing resources aggregated from resources distributed across wide-area networks and owned by different participating entities in a seamless manner. The paper discusses the motivations leading to the design of Archer, describes its core middleware components, and presents an analysis of the functionality and performance of a prototype wide-area deployment running a representative computer architecture simulation workload.Comment: 11 pages, 2 figures. Describes the Archer project, http://archer-project.or

Down-Regulation of hsa-miR-10a in Chronic Myeloid Leukemia CD34+ Cells Increases USF2-Mediated Cell Growth

MicroRNAs (miRNA) are small noncoding, single-stranded RNAs that inhibit gene expression at a posttranscriptional level, whose abnormal expression has been described in different tumors. The aim of our study was to identify miRNAs potentially implicated in chronic myeloid leukemia (CML). We detected an abnormal miRNA expression profile in mononuclear and CD34+ cells from patients with CML compared with healthy controls. Of 157 miRNAs tested, hsa-miR-10a, hsa-miR-150, and hsa-miR-151 were down-regulated, whereas hsa-miR-96 was up-regulated in CML cells. Down-regulation of hsa-miR-10a was not dependent on BCR-ABL1 activity and contributed to the increased cell growth of CML cells. We identified the upstream stimulatory factor 2 (USF2) as a potential target of hsa-miR-10a and showed that overexpression of USF2 also increases cell growth. The clinical relevance of these findings was shown in a group of 85 newly diagnosed patients with CML in which expression of hsa-miR-10a was down-regulated in 71% of the patients, whereas expression of USF2 was up-regulated in 60% of the CML patients, with overexpression of USF2 being significantly associated with decreased expression of hsa-miR-10a (P = 0.004). Our results indicate that down-regulation of hsa-miR-10a may increase USF2 and contribute to the increase in cell proliferation of CML implicating a miRNA in the abnormal behavior of CML

Mutations in KCTD1 Cause Scalp-Ear-Nipple Syndrome

Scalp-ear-nipple (SEN) syndrome is a rare, autosomal-dominant disorder characterized by cutis aplasia of the scalp; minor anomalies of the external ears, digits, and nails; and malformations of the breast. We used linkage analysis and exome sequencing of a multiplex family affected by SEN syndrome to identify potassium-channel tetramerization-domain-containing 1 (KCTD1) mutations that cause SEN syndrome. Evaluation of a total of ten families affected by SEN syndrome revealed KCTD1 missense mutations in each family tested. All of the mutations occurred in a KCTD1 region encoding a highly conserved bric-a-brac, tram track, and broad complex (BTB) domain that is required for transcriptional repressor activity. KCTD1 inhibits the transactivation of the transcription factor AP-2 alpha (TFAP2A) via its BTB domain, and mutations in TFAP2A cause cutis aplasia in individuals with branchiooculofacial syndrome (BOFS), suggesting a potential overlap in the pathogenesis of SEN syndrome and BOFS. the identification of KCTD1 mutations in SEN syndrome reveals a role for this BTB-domain-containing transcriptional repressor during ectodermal development.National Institutes of Health National Human Genome Research InstituteLife Sciences Discovery FundWashington Research FoundationMassachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USAUniv Washington, Dept Pediat, Seattle, WA 98195 USAUniv Washington, Dept Genome Sci, Seattle, WA 98195 USAUniv Western Sydney Macarthur, Sch Med, Campbelltown, NSW 2560, AustraliaGenet Learning Disabil Serv, Newcastle, NSW 2298, AustraliaJohns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USAUniversidade Federal de São Paulo, Dept Morphol & Genet, Clin Genet Ctr, BR-04021001 São Paulo, BrazilPontificia Univ Catolica Parana, Dept Internal Med, BR-1155 Curitiba, Parana, BrazilWestern Gen Hosp, South East Scotland Clin Genet Serv, Edinburgh EH4 2XU, Midlothian, ScotlandUniv Florence, Dept Genet & Mol Med, I-50132 Florence, ItalyHop Necker Enfants Malad, Dept Genet, INSERM, U781, F-75015 Paris, FranceUniv Paris Descartes Sorbonne Paris Cite, Inst Imagine, F-75015 Paris, FranceHop Cote Nacre, CHU Caen, Serv Genet, F-14033 Caen 9, FranceUniv Connecticut, Ctr Hlth, Dept Reconstruct Sci, Farmington, CT 06030 USABoston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA 02115 USATreuman Katz Ctr Pediat Bioeth, Seattle Childrens Res Inst, Seattle, WA 98101 USAUniversidade Federal de São Paulo, Dept Morphol & Genet, Clin Genet Ctr, BR-04021001 São Paulo, BrazilNational Institutes of Health National Human Genome Research Institute: 1U54HG006493National Institutes of Health National Human Genome Research Institute: 1RC2HG005608National Institutes of Health National Human Genome Research Institute: 5RO1HG004316Life Sciences Discovery Fund: 2065508Life Sciences Discovery Fund: 0905001Web of Scienc

Prophylactic Treatment With Simvastatin Modulates the Immune Response and Increases Animal Survival Following Lethal Sepsis Infection

Chronic use of statins may have anti-inflammatory action, promoting immunomodulation and survival in patients with sepsis. This study aimed to analyze the effects of pretreatment with simvastatin in lethal sepsis induced by cecal ligation and puncture (CLP). Male Swiss mice received prophylactic treatment with simvastatin or pyrogen-free water orally in a single daily dose for 30 days. After this period, the CLP was performed. Naïve and Sham groups were performed as non-infected controls. Animal survival was monitored for 60 h after the CLP. Half of mice were euthanized after 12 h to analyze colony-forming units (CFUs); hematological parameters; production of IL-10, IL-12, IL-6, TNF-α, IFN-γ, and MCP-1; cell counts on peritoneum, bronchoalveolar lavage (BAL), bone marrow, spleen, and mesenteric lymph node; immunephenotyping of T cells and antigen presenting cells and production of hydrogen peroxide (H2O2). Simvastatin induced an increase in survival and a decrease in the CFU count on peritoneum and on BAL cells number, especially lymphocytes. There was an increase in the platelets and lymphocytes number in the Simvastatin group when compared to the CLP group. Simvastatin induced a greater activation and proliferation of CD4+ T cells, as well as an increase in IL-6 and MCP-1 production, in chemotaxis to the peritoneum and in H2O2 secretion at this site. These data suggest that simvastatin has an impact on the survival of animals, as well as immunomodulatory effects in sepsis induced by CLP in mice

Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia

Clonal evolution in acute myeloid leukemia (AML) originates long before diagnosis and is a dynamic process that may affect survival. However, it remains uninvestigated during routine diagnostic workups. We hypothesized that the mutational status of bone marrow dysplastic cells and leukemic blasts, analyzed at the onset of AML using integrated multidimensional flow cytometry (MFC) immunophenotyping and fluorescence-activated cell sorting (FACS) with next-generation sequencing (NGS), could reconstruct leukemogenesis. Dysplastic cells were detected by MFC in 285 of 348 (82%) newly diagnosed patients with AML. Presence of dysplasia according to MFC and World Health Organization criteria had no prognostic value in older adults. NGS of dysplastic cells and blasts isolated at diagnosis identified 3 evolutionary patterns: stable (n = 12 of 21), branching (n = 4 of 21), and clonal evolution (n = 5 of 21). In patients achieving complete response (CR), integrated MFC and FACS with NGS showed persistent measurable residual disease (MRD) in phenotypically normal cell types, as well as the acquisition of genetic traits associated with treatment resistance. Furthermore, whole-exome sequencing of dysplastic and leukemic cells at diagnosis and of MRD uncovered different clonal involvement in dysplastic myelo-erythropoiesis, leukemic transformation, and chemoresistance. Altogether, we showed that it is possible to reconstruct leukemogenesis in ∼80% of patients with newly diagnosed AML, using techniques other than single-cell multiomics.This work was supported by grants from the Área de Oncología del Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red (CIBER-ONC) (CB16/12/00369, CB16/12/00233, CB16/12/00489, and CB16/12/00284), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS numbers PI16/01661, PI16/00517, and PI19/01518), and the Plan de Investigación de la Universidad de Navarra (PIUNA 2014-18). This work was supported internationally by the Cancer Research UK, FCAECC, and AIRC under the Accelerator Award Program (EDITOR)