Latency, Power and Performance Trade-offs in Network-on-Chips by Link Microarchitecture Exploration

This paper presents a power, latency and throughput trade-off study on NoCs by varying microarchitectural (e.g. pipelining) and circuit level (e.g. frequency and voltage) parameters. We change pipelining depth, operating frequency and supply voltage for 3 example NoCs - 16 node 2D Torus, Tree network and Reduced 2D Torus. We use an in-house NoC exploration framework capable of topology generation and comparison using parameterized models of Routers and links developed in SystemC. The framework utilizes interconnect power and delay models from a low-level modelling tool called Intacte[1]1. We find that increased pipelining can actually reduce latency. We also find that there exists an optimal degree of pipelining which is the most energy efficient in terms of minimizing energy-delay product.

Acetylation of Transition Protein 2 (TP2) by KAT3B (p300) Alters Its DNA Condensation Property and Interaction with Putative Histone Chaperone NPM3

The hallmark of mammalian spermiogenesis is the dramatic chromatin remodeling process wherein the nucleosomal histones are replaced by the transition proteins TP1, TP2, and TP4. Subsequently these transition proteins are replaced by the protamines P1 and P2. Hyperacetylation of histone H4 is linked to their replacement by transition proteins. Here we report that TP2 is acetylated in vivo as detected by anti-acetylated lysine antibody and mass spectrometric analysis. Further, recombinant TP2 is acetylated in vitro by acetyltransferase KAT3B (p300) more efficiently than by KAT2B (PCAF). In vivo p300 was demonstrated to acetylate TP2. p300 acetylates TP2 in its C-terminal domain, which is highly basic in nature and possesses chromatin-condensing properties. Mass spectrometric analysis showed that p300 acetylates four lysine residues in the C-terminal domain of TP2. Acetylation of TP2 by p300 leads to significant reduction in its DNA condensation property as studied by circular dichroism and atomic force microscopy analysis. TP2 also interacts with a putative histone chaperone, NPM3, wherein expression is elevated in haploid spermatids.Interestingly, acetylation of TP2 impedes its interaction with NPM3. Thus, acetylation of TP2 adds a new dimension to its role in the dynamic reorganization of chromatin during mammalian spermiogenesis.

A System-C based Micro architectural Exploration Framework for Latency, Power and Performance Trade-offs of On-Chip Interconnection

We describe a System-C based framework we are developing, to explore the impact of various architectural and microarchitectural level parameters of the on-chip interconnection network elements on its power and performance. The framework enables one to choose from a variety of architectural options like topology, routing policy, etc., as well as allows experimentation with various microarchitectural options for the individual links like length, wire width, pitch, pipelining, supply voltage and frequency. The framework also supports a flexible traffic generation and communication model. We provide preliminary results of using this framework to study the power, latency and throughput of a 4x4 multi-core processing array using mesh, torus and folded torus, for two different communication patterns of dense and sparse linear algebra. The traffic consists of both Request-Response messages (mimicing cache accesses)and One-Way messages. We find that the average latency can be reduced by increasing the pipeline depth, as it enables higher link frequencies. We also find that there exists an optimum degree of pipelining which minimizes energy-delay product.

Probing p300/CBP associated Factor (PCAF)-dependent pathways with a small molecule inhibitor

PCAF (KAT2B) belongs to the GNAT family of lysine acetyltransferases (KAT) and specifically acetylates the histone H3K9 residue and several nonhistone proteins. PCAF is also a transcriptional coactivator. Due to the lack of a PCAF KAT-specific small molecule inhibitor, the exclusive role of the acetyltransferase activity of PCAF is not well understood. Here, we report that a natural compound of the hydroxybenzoquinone class, embelin, specifically inhibits H3Lys9 acetylation in mice and inhibits recombinant PCAF-mediated acetylation with near complete specificity in vitro. Furthermore, using embelin, we have identified the gene networks that are regulated by PCAF during muscle differentiation, further highlighting the broader regulatory functions of PCAF in muscle differentiation in addition to the regulation via MyoD acetylation.

Progressive fusion of reconstruction algorithms for low latency applications in compressed sensing

Recently, it has been shown that fusion of the estimates of a set of sparse recovery algorithms result in an estimate better than the best estimate in the set, especially when the number of measurements is very limited. Though these schemes provide better sparse signal recovery performance, the higher computational requirement makes it less attractive for low latency applications. To alleviate this drawback, in this paper, we develop a progressive fusion based scheme for low latency applications in compressed sensing. In progressive fusion, the estimates of the participating algorithms are fused progressively according to the availability of estimates. The availability of estimates depends on computational complexity of the participating algorithms, in turn on their latency requirement. Unlike the other fusion algorithms, the proposed progressive fusion algorithm provides quick interim results and successive refinements during the fusion process, which is highly desirable in low latency applications. We analyse the developed scheme by providing sufficient conditions for improvement of CS reconstruction quality and show the practical efficacy by numerical experiments using synthetic and real-world data. (C) 2013 Elsevier B.V. All rights reserved.

High Throughput, Low Latency, Memory Optimized 64K Point FFT Architecture using Novel Radix-4 Butterfly Unit

In this paper we propose a fully parallel 64K point radix-4(4) FFT processor. The radix-4(4) parallel unrolled architecture uses a novel radix-4 butterfly unit which takes all four inputs in parallel and can selectively produce one out of the four outputs. The radix-4(4) block can take all 256 inputs in parallel and can use the select control signals to generate one out of the 256 outputs. The resultant 64K point FFT processor shows significant reduction in intermediate memory but with increased hardware complexity. Compared to the state-of-art implementation 5], our architecture shows reduced latency with comparable throughput and area. The 64K point FFT architecture was synthesized using a 130nm CMOS technology which resulted in a throughput of 1.4 GSPS and latency of 47.7 mu s with a maximum clock frequency of 350MHz. When compared to 5], the latency is reduced by 303 mu s with 50.8% reduction in area.

Bi-Modal DRAM Cache: Improving Hit Rate, Hit Latency and Bandwidth

In this paper, we present Bi-Modal Cache - a flexible stacked DRAM cache organization which simultaneously achieves several objectives: (i) improved cache hit ratio, (ii) moving the tag storage overhead to DRAM, (iii) lower cache hit latency than tags-in-SRAM, and (iv) reduction in off-chip bandwidth wastage. The Bi-Modal Cache addresses the miss rate versus off-chip bandwidth dilemma by organizing the data in a bi-modal fashion - blocks with high spatial locality are organized as large blocks and those with little spatial locality as small blocks. By adaptively selecting the right granularity of storage for individual blocks at run-time, the proposed DRAM cache organization is able to make judicious use of the available DRAM cache capacity as well as reduce the off-chip memory bandwidth consumption. The Bi-Modal Cache improves cache hit latency despite moving the metadata to DRAM by means of a small SRAM based Way Locator. Further by leveraging the tremendous internal bandwidth and capacity that stacked DRAM organizations provide, the Bi-Modal Cache enables efficient concurrent accesses to tags and data to reduce hit time. Through detailed simulations, we demonstrate that the Bi-Modal Cache achieves overall performance improvement (in terms of Average Normalized Turnaround Time (ANTT)) of 10.8%, 13.8% and 14.0% in 4-core, 8-core and 16-core workloads respectively.

Inhibition of p300 lysine acetyltransferase activity by luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model

Chromatin acetylation is attributed with distinct functional relevance with respect to gene expression in normal and diseased conditions thereby leading to a topical interest in the concept of epigenetic modulators and therapy. We report here the identification and characterization of the acetylation inhibitory potential of an important dietary flavonoid, luteolin. Luteolin was found to inhibit p300 acetyltransferase with competitive binding to the acetyl CoA binding site. Luteolin treatment in a xenografted tumor model of head and neck squamous cell carcinoma (HNSCC), led to a dramatic reduction in tumor growth within 4 weeks corresponding to a decrease in histone acetylation. Cells treated with luteolin exhibit cell cycle arrest and decreased cell migration. Luteolin treatment led to an alteration in gene expression and miRNA profile including up-regulation of p53 induced miR-195/215, let7C; potentially translating into a tumor suppressor function. It also led to down regulation of oncomiRNAs such as miR-135a, thereby reflecting global changes in the microRNA network. Furthermore, a direct correlation between the inhibition of histone acetylation and gene expression was established using chromatin immunoprecipitation on promoters of differentially expressed genes. A network of dysregulated genes and miRNAs was mapped along with the gene ontology categories, and the effects of luteolin were observed to be potentially at multiple levels: at the level of gene expression, miRNA expression and miRNA processing.

Regulation of extracellular matrix genes by arecoline in primary gingival fibroblasts requires epithelial factors

Background and Objective: Oral submucous fibrosis, a disease of collagen disorder, has been attributed to arecoline present in the saliva of betel quid chewers. However, the molecular basis of the action of arecoline in the pathogenesis of oral submucous fibrosis is poorly understood. The basic aim of our study was to elucidate the mechanism underlying the action of arecoline on the expression of genes in oral fibroblasts. Material and Methods: Human keratinocytes (HaCaT cells) and primary human gingival fibroblasts were treated with arecoline in combination with various pathway inhibitors, and the expression of transforming growth factor-beta isoform genes and of collagen isoforms was assessed using reverse transcription polymerase chain reaction analysis. Results: We observed the induction of transforming growth factor-beta2 by arecoline in HaCaT cells and this induction was found to be caused by activation of the M-3 muscarinic acid receptor via the induction of calcium and the protein kinase C pathway. Most importantly, we showed that transforming growth factor-beta2 was significantly overexpressed in oral submucous fibrosis tissues (p = 0.008), with a median of 2.13 (n = 21) compared with 0.75 (n = 18) in normal buccal mucosal tissues. Furthermore, arecoline down-regulated the expression of collagens 1A1 and 3A1 in human primary gingival fibroblasts; however these collagens were induced by arecoline in the presence of spent medium of cultured human keratinocytes. Treatment with a transforming growth factor-beta blocker, transforming growth factor-beta1 latency-associated peptide, reversed this up-regulation of collagen, suggesting a role for profibrotic cytokines, such as transforming growth factor-beta, in the induction of collagens. Conclusion: Taken together, our data highlight the importance of arecoline-induced epithelial changes in the pathogenesis of oral submucous fibrosis.

A Petri net model for evaluating packet buffering strategies in a network processor

Previous studies have shown that buffering packets in DRAM is a performance bottleneck. In order to understand the impediments in accessing the DRAM, we developed a detailed Petri net model of IP forwarding application on IXP2400 that models the different levels of the memory hierarchy. The cell based interface used to receive and transmit packets in a network processor leads to some small size DRAM accesses. Such narrow accesses to the DRAM expose the bank access latency, reducing the bandwidth that can be realized. With real traces up to 30% of the accesses are smaller than the cell size, resulting in 7.7% reduction in DRAM bandwidth. To overcome this problem, we propose buffering these small chunks of data in the on chip scratchpad memory. This scheme also exploits greater degree of parallelism between different levels of the memory hierarchy. Using real traces from the internet, we show that the transmit rate can be improved by an average of 21% over the base scheme without the use of additional hardware. Further, the impact of different traffic patterns on the network processor resources is studied. Under real traffic conditions, we show that the data bus which connects the off-chip packet buffer to the micro-engines, is the obstacle in achieving higher throughput.

RECONNECT: A NoC for polymorphic ASICs using a low overhead single cycle router

A polymorphic ASIC is a runtime reconfigurable hardware substrate comprising compute and communication elements. It is a ldquofuture proofrdquo custom hardware solution for multiple applications and their derivatives in a domain. Interoperability between application derivatives at runtime is achieved through hardware reconfiguration. In this paper we present the design of a single cycle Network on Chip (NoC) router that is responsible for effecting runtime reconfiguration of the hardware substrate. The router design is optimized to avoid FIFO buffers at the input port and loop back at output crossbar. It provides virtual channels to emulate a non-blocking network and supports a simple X-Y relative addressing scheme to limit the control overhead to 9 bits per packet. The 8times8 honeycomb NoC (RECONNECT) implemented in 130 nm UMC CMOS standard cell library operates at 500 MHz and has a bisection bandwidth of 28.5 GBps. The network is characterized for random, self-similar and application specific traffic patterns that model the execution of multimedia and DSP kernels with varying network loads and virtual channels. Our implementation with 4 virtual channels has an average network latency of 24 clock cycles and throughput of 62.5% of the network capacity for random traffic. For application specific traffic the latency is 6 clock cycles and throughput is 87% of the network capacity.

Stress responses in mycobacteria

Mycobacterium tuberculosis is a successful pathogen that overcomes numerous challenges presented by the immune system of the host. This bacterium usually establishes a chronic infection in the host where it may silently persist inside a granuloma until, a failure in host defenses, leads to manifestation of the disease. None of the conventional anti-tuberculosis drugs are able to target these persisting bacilli. Development of drugs against such persisting bacilli is a constant challenge since the physiology of these dormant bacteria is still not understood at the molecular level. Some evidence suggests that the in vivo environment encountered by the persisting bacteria is anoxic and nutritionally starved. Based on these assumptions, anaerobic and starved cultures are used as models to study the molecular basis of dormancy. This review outlines the problem of persistence of M. tuberculosis and the various in vitro models used to study mycobacterial latency. The basis of selecting the nutritional starvation model has been outlined here. Also, the choice of M. smegmatis as a model suitable for studying mycobacterial latency is discussed. Lastly, general issues related to oxidative stress and bacterial responses to it have been elaborated. We have also discussed general control of OxyR-mediated regulation and emphasized the processes which manifest in the absence of functional OxyR in the bacteria. Lastly, a new class of protein called Dps has been reviewed for its important role in protecting DNA under stress.

A cost effective pipelined divider for double precision floating point number

he growth of high-performance application in computer graphics, signal processing and scientific computing is a key driver for high performance, fixed latency; pipelined floating point dividers. Solutions available in the literature use large lookup table for double precision floating point operations.In this paper, we propose a cost effective, fixed latency pipelined divider using modified Taylor-series expansion for double precision floating point operations. We reduce chip area by using a smaller lookup table. We show that the latency of the proposed divider is 49.4 times the latency of a full-adder. The proposed divider reduces chip area by about 81% than the pipelined divider in [9] which is based on modified Taylor-series.

Voluntary Control of Multisaccade Gaze Shifts During Movement Preparation and Execution

Ramakrishnan A, Chokhandre S, Murthy A. Voluntary control of multisaccade gaze shifts during movement preparation and execution. J Neurophysiol 103: 2400-2416, 2010. First published February 17, 2010; doi: 10.1152/jn.00843.2009. Although the nature of gaze control regulating single saccades is relatively well documented, how such control is implemented to regulate multisaccade gaze shifts is not known. We used highly eccentric targets to elicit multisaccade gaze shifts and tested the ability of subjects to control the saccade sequence by presenting a second target on random trials. Their response allowed us to test the nature of control at many levels: before, during, and between saccades. Although the saccade sequence could be inhibited before it began, we observed clear signs of truncation of the first saccade, which confirmed that it could be inhibited in midflight as well. Using a race model that explains the control of single saccades, we estimated that it took about 100 ms to inhibit a planned saccade but took about 150 ms to inhibit a saccade during its execution. Although the time taken to inhibit was different, the high subject-wise correlation suggests a unitary inhibitory control acting at different levels in the oculomotor system. We also frequently observed responses that consisted of hypometric initial saccades, followed by secondary saccades to the initial target. Given the estimates of the inhibitory process provided by the model that also took into account the variances of the processes as well, the secondary saccades (average latency similar to 215 ms) should have been inhibited. Failure to inhibit the secondary saccade suggests that the intersaccadic interval in a multisaccade response is a ballistic stage. Collectively, these data indicate that the oculomotor system can control a response until a very late stage in its execution. However, if the response consists of multiple movements then the preparation of the second movement becomes refractory to new visual input, either because it is part of a preprogrammed sequence or as a consequence of being a corrective response to a motor error.

A Parallel Progressive Refinement Image Rendering Algorithm on a Scalable Multithreaded VLSI Processor Array

In this paper we develop a multithreaded VLSI processor linear array architecture to render complex environments based on the radiosity approach. The processing elements are identical and multithreaded. They work in Single Program Multiple Data (SPMD) mode. A new algorithm to do the radiosity computations based on the progressive refinement approach[2] is proposed. Simulation results indicate that the architecture is latency tolerant and scalable. It is shown that a linear array of 128 uni-threaded processing elements sustains a throughput close to 0.4 million patches/sec.