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At least 19 records

Identification and characterization of novel NuMA isoforms

Highlights: • Seven NuMA isoforms generated by alternative splicing were categorized into 3 groups: long, middle and short. • Both exons 15 and 16 in long NuMA were “hotspot” for alternative splicing. • Lower expression of short NuMA was observed in cancer cells compared with nonneoplastic controls. • Distinct localization pattern of short isoforms indicated different function from that of long and middle NuMA. - Abstract: The large nuclear mitotic apparatus (NuMA) has been investigated for over 30 years with functions related to the formation and maintenance of mitotic spindle poles during mitosis. However, the existence and functions of NuMA isoforms generated by alternative splicing remains unclear. In the present work, we show that at least seven NuMA isoforms (categorized into long, middle and short groups) generated by alternative splicing from a common NuMA mRNA precursor were discovered in HeLa cells and these isoforms differ mainly at the carboxyl terminus and the coiled-coil domains. Two “hotspot” exons with molecular mass of 3366-nt and 42-nt tend to be spliced during alternative splicing in long and middle groups. Furthermore, full-length coding sequences of long and middle NuMA obtained by using fusion PCR were constructed into GFP-tagged vector to illustrate their cellular localization. Long NuMA mainly localized in the nucleus with absence from nucleoli during interphase and translocated to the spindle poles in mitosis. Middle NuMA displayed the similar cell cycle-dependent distribution pattern as long NuMA. However, expression of NuMA short isoforms revealed a distinct subcellular localization. Short NuMA were present in the cytosol during the whole cycle, without colocalization with mitotic apparatus. These results have allowed us tentatively to explore a new research direction for NuMA’s various functions.

60 APPLIED LIFE SCIENCES↗

A chimeric protein composed of NuMA fused to the DNA binding domain of LANA is sufficient for the ori-P-dependent DNA replication

The Kaposi's sarcoma-associated herpesvirus (KSHV) genome is stably maintained in KSHV-infected PEL cell lines during cell division. We previously showed that accumulation of LANA in the nuclear matrix fraction could be important for the latent DNA replication, and that the functional significance of LANA should be its recruitment of ori-P to the nuclear matrix. Here, we investigated whether the forced localization of the LANA-DNA binding domain (DBD) to the nuclear matrix facilitated ori-P-containing plasmid replication. We demonstrated that chimeric proteins constructed by fusion of LANA DBD with the nuclear mitotic apparatus protein (NuMA), which is one of the components of the nuclear matrix, could bind with ori-P and enhance replication of an ori-P-containing plasmid, compared with that in the presence of DBD alone. These results further suggested that the ori-P recruitment to the nuclear matrix through the binding with DBD is important for latent viral DNA replication. - Highlights: •KSHV replication in latency depends on LANA localization to the nuclear matrix. •LANA DBD was fused with NuMA, a nuclear matrix protein, at the N- and C-terminus. •NuMA-DBD was in the nuclear matrix and supported the ori-P dependent replication. •LANA in the nuclear matrix should be important for the KSHV replication in latency.

60 APPLIED LIFE SCIENCES↗

High-content image informatics of the structural nuclear protein NuMA parses trajectories for stem/progenitor cell lineages and oncogenic transformation

Stem and progenitor cells that exhibit significant regenerative potential and critical roles in cancer initiation and progression remain difficult to characterize. Cell fates are determined by reciprocal signaling between the cell microenvironment and the nucleus; hence parameters derived from nuclear remodeling are ideal candidates for stem/progenitor cell characterization. Here we applied high-content, single cell analysis of nuclear shape and organization to examine stem and progenitor cells destined to distinct differentiation endpoints, yet undistinguishable by conventional methods. Nuclear descriptors defined through image informatics classified mesenchymal stem cells poised to either adipogenic or osteogenic differentiation, and oligodendrocyte precursors isolated from different regions of the brain and destined to distinct astrocyte subtypes. Nuclear descriptors also revealed early changes in stem cells after chemical oncogenesis, allowing the identification of a class of cancer-mitigating biomaterials. To capture the metrology of nuclear changes, we developed a simple and quantitative “imaging-derived” parsing index, which reflects the dynamic evolution of the high-dimensional space of nuclear organizational features. A comparative analysis of parsing outcomes via either nuclear shape or textural metrics of the nuclear structural protein NuMA indicates the nuclear shape alone is a weak phenotypic predictor. In contrast, variations in the NuMA organization parsed emergent cell phenotypes and discerned emergent stages of stem cell transformation, supporting a prognosticating role for this protein in the outcomes of nuclear functions. - Highlights: • High-content analysis of nuclear shape and organization classify stem and progenitor cells poised for distinct lineages. • Early oncogenic changes in mesenchymal stem cells (MSCs) are also detected with nuclear descriptors. • A new class of cancer-mitigating biomaterials was identified based on image informatics. • Textural metrics of the nuclear structural protein NuMA are sufficient to parse emergent cell phenotypes.

60 APPLIED LIFE SCIENCES↗

NUMA-Aware Thread Scheduling for Big Data Transfers over Terabits Network Infrastructure

The evergrowing trend of big data has led scientists to share and transfer the simulation and analytical data across the geodistributed research and computing facilities. However, the existing data transfer frameworks used for data sharing lack the capability to adopt the attributes of the underlying parallel file systems (PFS). LADS (Layout-Aware Data Scheduling) is an end-to-end data transfer tool optimized for terabit network using a layout-aware data scheduling via PFS. However, it does not consider the NUMA (Nonuniform Memory Access) architecture. In this paper, we propose a NUMA-aware thread and resource scheduling for optimized data transfer in terabit network. First, we propose distributed RMA buffers to reduce memory controller contention in CPU sockets and then schedule the threads based on CPU socket and NUMA nodes inside CPU socket to reduce memory access latency. We design and implement the proposed resource and thread scheduling in the existing LADS framework. Experimental results showed from 21.7% to 44% improvement with memory-level optimizations in the LADS framework as compared to the baseline without any optimization.

97 MATHEMATICS AND COMPUTING↗

Data and Thread Placement in NUMA Architectures: A Statistical Learning Approach

Nowadays, NUMA architectures are common in compute-intensive systems. Achieving high performance for multi-threaded application requires both a careful placement of threads on computing units and a thorough allocation of data in memory. Finding such a placement is a hard problem to solve, because performance depends on complex interactions in several layers of the memory hierarchy. In this paper we propose a black-box approach to decide if an application execution time can be impacted by the placement of its threads and data, and in such a case, to choose the best placement strategy to adopt. We show that it is possible to reach near-optimal placement policy selection. Furthermore, solutions work across several recent processor architectures and decisions can be taken with a single run of low overhead profiling.

data↗

Affinity-aware checkpoint restart

Current checkpointing techniques employed to overcome faults for HPC applications result in inferior application performance after restart from a checkpoint for a number of applications. This is due to a lack of page and core affinity awareness of the checkpoint/restart (C/R) mechanism, i.e., application tasks originally pinned to cores may be restarted on different cores, and in case of non-uniform memory architectures (NUMA), quite common today, memory pages associated with tasks on a NUMA node may be associated with a different NUMA node after restart. Here, this work contributes a novel design technique for C/R mechanisms to preserve task-to-core maps and NUMA node specific page affinities across restarts. Experimental results with BLCR, a C/R mechanism, enhanced with affinity awareness demonstrate significant performance benefits of 37%-73% for the NAS Parallel Benchmark codes and 6-12% for NAMD with negligible overheads instead of up to nearly four times longer an execution times without affinity-aware restarts on 16 cores.

97 MATHEMATICS AND COMPUTING↗

Exploring Architectural-Aware Affinity Policies in Modern HPC Runtimes

Modern commodity and High-Performance Computing (HPC) systems are evolving with complex CPU architectures. These architectures now feature higher core and NUMA domain counts and implement features such as hyperthreading. When considering significant differences in hardware configurations, library availability, and hardware-tailored system/software stacks, which could substantially vary from one system to another, performance portability is hard to achieve. Throughout the years, this trend resulted in an increasingly high burden on application developers to fine-tune their workloads for each architecture. This work explores how hardware-dependent aspects such as locality/process/thread affinity affect performance in modern CPU architectures. We focus our study on the Global Memory and Threading (GMT) distributed runtime system as a representative of Partitioned Global Address Space (PGAS) software stacks commonly adopted for productivity. In particular, to appreciate performance implications, we evaluate GMT’s thread affinity policies, and, introduce two new ones which exploit architectural awareness. Finally, we explore alternative NUMA configurations via different process bindings and perform a scalability study on three HPC clusters with varying CPU architectures and NUMA layouts. Our analysis indicates that more complex architectures are more affected by affinity and binding policies and highlights the importance of setting proper runtime configurations to achieve superior performance.

Di Dio Lavore, Ian↗

Energy-aware Thread and Data Management in Heterogeneous Multi-core, Multi-memory Systems

By 2004, microprocessor design focused on multicore scaling—increasing the number of cores per die in each generation—as the primary strategy for improving performance. These multicore processors typically equip multiple memory subsystems to improve data throughput. In addition, these systems employ heterogeneous processors such as GPUs and heterogeneous memories like non-volatile memory to improve performance, capacity, and energy efficiency. With the increasing volume of hardware resources and system complexity caused by heterogeneity, future systems will require intelligent ways to manage hardware resources. Early research to improve performance and energy efficiency on heterogeneous, multi-core, multi-memory systems focused on tuning a single primitive or at best a few primitives in the systems. The key limitation of past efforts is their lack of a holistic approach to resource management that balances the tradeoff between performance and energy consumption. In addition, the shift from simple, homogeneous systems to these heterogeneous, multicore, multi-memory systems requires in-depth understanding of efficient resource management for scalable execution, including new models that capture the interchange between performance and energy, smarter resource management strategies, and novel low-level performance/energy tuning primitives and runtime systems. Tuning an application to control available resources efficiently has become a daunting challenge; managing resources in automation is still a dark art since the tradeoffs among programming, energy, and performance remain insufficiently understood. In this dissertation, I have developed theories, models, and resource management techniques to enable energy-efficient execution of parallel applications through thread and data management in these heterogeneous multi-core, multi-memory systems. I study the effect of dynamic concurrent throttling on the performance and energy of multi-core, non-uniform memory access (NUMA) systems. I use critical path analysis to quantify memory contention in the NUMA memory system and determine thread mappings. In addition, I implement a runtime system that combines concurrent throttling and a novel thread mapping algorithm to manage thread resources and improve energy efficient execution in multi-core, NUMA systems.

97 MATHEMATICS AND COMPUTING↗

CLOMP v1.5

CLOMP is the C version of the Livermore OpenMP benchmark developed to measure OpenMP overheads and other performance impacts due to threading. For simplicity, it does not use MPI by default but it is expected to be run on the resources a threaded MPI task would use (e.g., a portion of a shared memory compute node). Compiling with -DWITH_MPI allows packing one or more nodes with CLOMP tasks and having CLOMP report OpenMP performance for the slowest MPI task. On current systems, the strong scaling performance results for 4, 8, or 16 threads are of the most interest. Suggested weak scaling inputs are provided for evaluating future systems. Since MPI is often used to place at least one MPI task per coherence or NUMA domain, it is recommended to focus OpenMP runtime measurements on a subset of node hardware where it is most possible to have low OpenMP overheads (e.g., within one coherence domain or NUMA domain).

97 MATHEMATICS AND COMPUTING↗

Performance Analysis of Scientific Computing Workloads on Trusted Execution Environments

Scientific computing sometimes involves computation on sensitive data. Depending on the data and the execution environment, the HPC (high-performance computing) user or data provider may require confidentiality and/or integrity guarantees. To study the applicability of hardware-based trusted execution environments (TEEs) to enable secure scientific computing, we deeply analyze the performance impact of AMD SEV and Intel SGX for diverse HPC benchmarks including traditional scientific computing, machine learning, graph analytics, and emerging scientific computing workloads. We observe three main findings: 1) SEV requires careful memory placement on large scale NUMA machines (1x -3.4x slowdown without and 1x -1.15x slowdown with NUMA aware placement), 2) virtualization - a prerequisite for SEV - results in performance degradation for workloads with irregular memory accesses and large working sets (1x -4x slowdown compared to native execution for graph applications) and 3) SGX is inappropriate for HPC given its limited secure memory size and inflexible programming model (1.2x -126x slowdown over unsecure execution). Finally, we discuss forthcoming new TEE designs and their potential impact on scientific computing.

97 MATHEMATICS AND COMPUTING↗

Evaluating Modern GPU Interconnect: PCIe, NVLink, NV-SLI, NVSwitch and GPUDirect

High performance multi-GPU computing becomes an inevitable trend due to the ever-increasing demand on computation capability in emerging domains such as deep learning, big data and planet-scale simulations. However, the lack of deep understanding on how modern GPUs can be connected and the real impact of state-of-the-art interconnect technology on multi-GPU application performance become a hurdle. In this paper, we fill the gap by conducting a thorough evaluation on five latest types of modern GPU interconnects: PCIe, NVLink-V1, NVLink-V2, NVLink-SLI and NVSwitch, from six high-end servers and HPC platforms: NVIDIA P100-DGX-1, V100-DGX-1, DGX-2, OLCF’s SummitDev and Summit supercomputers, as well as an SLI-linked system with two NVIDIA Turing RTX-2080 GPUs. Based on the empirical evaluation, we have observed four new types of GPU communication network NUMA effects: three are triggered by NVLink’s topology, connectivity and routing, while one is caused by PCIe chipset design issue. These observations indicate that, for a multi-GPU application running in a multi-GPU node, choosing the right GPU combination can impose considerable impact on GPU communication efficiency, as well as an application’s overall performance. Our evaluation can be leveraged in building practical multi-GPU performance models, which are vital for GPU task allocation, scheduling and migration in a shared environment (e.g., AI cloud and HPC centers), as well as communication-oriented performance tuning.

Performance Evaluation, GPU, Interconnect, NUMA, P↗

Multiscale Modeling Framework Using Element‐Based Galerkin Methods for Moist Atmospheric Limited‐Area Simulations

This paper presents a multiscale modeling framework (MMF) to model moist atmospheric limited-area weather. The MMF resolves large-scale convection using a coarse grid while simultaneously resolving local features through numerous fine local grids and coupling them seamlessly. Both large- and small-scale processes are modeled using the compressible Navier-Stokes equations within the Nonhydrostatic Unified Model of the Atmosphere (NUMA), and are discretized using a continuous element-based Galerkin method (spectral elements) with high-order basis functions. Consequently, the large-scale and small-scale models share the same dynamical core but have the flexibility to be adjusted individually. The proposed MMF method is tested in 2D and 3D idealized limited-area weather problems involving storm clouds produced by squall line and supercell simulations. Numerical results from the MMF showed enhanced representation of cloud processes compared to the coarse model.

Kang, Soonpil [Naval Postgraduate School, Monterey↗

Tartan: Evaluating Modern GPU Interconnect via a Multi-GPU Benchmark Suite

In this paper, we fill the gap by proposing a multi-GPU benchmark suite named Tartan, which contains microbenchmarks, scale-up and scale-out applications. We then apply Tartan to evaluate the four latest types of modern GPU interconnects, i.e., PCI- e, NVLink-V1, NVLink-V2 and InfiniBand with GPUDirect- RDMA from two recently released NVIDIA super AI platforms as well as ORNL’s exascale prototype system. Based on empirical evaluation, we observe four new types of NUMA effects: three types are triggered by NVLink’s topology, connectivity and routing, while one type is caused by PCI-e (i.e., anti-locality). They are very important for performance tuning in multi-GPU environment. Our evaluation results show that, unless the current CPU-GPU master-slave programming model can be replaced, it is difficult for scale-up multi-GPU applications to really benefit from faster intra-node interconnects such as NVLinks; while for inter-node scale-out applications, although interconnect is more crucial to the overall performance, GPUDirect-RDMA appears to be not always the optimal choice.

HPC↗

Argo NodeOS: Toward Unified Resource Management for Exascale

Exascale systems are expected to feature hundreds of thousands of compute nodes with hundreds of hardware threads and complex memory hierarchies with a mix of on-package and persistent memory modules. In this context, the Argo project is developing a new operating system for exascale machines. Targeting production workloads using workflows or coupled codes, we improve the Linux kernel on several fronts. We extend the memory management of Linux to be able to subdivide NUMA memory nodes, allowing better resource partitioning among processes running on the same node. We also add support for memory-mapped access to node- local, PCIe-attached NVRAM devices and introduce a new scheduling class targeted at parallel runtimes supporting user- level load balancing.

Perarnau, Swann↗