Scalable Hierarchical Instruction Cache for Ultralow-Power Processors Clusters

High performance and energy efficiency are critical requirements for Internet of Things (IoT) end-nodes. Exploiting tightly coupled clusters of programmable processors (CMPs) has recently emerged as a suitable solution to address this challenge. One of the main bottlenecks limiting the performance and energy efficiency of these systems is the instruction cache architecture due to its criticality in terms of timing (i.e., maximum operating frequency), bandwidth, and power. We propose a hierarchical instruction cache tailored to ultralow-power (ULP) tightly coupled processor clusters where a relatively large cache (L1.5) is shared by L1 private (PR) caches through a two-cycle latency interconnect. To address the performance loss caused by the L1 capacity misses, we introduce a next-line prefetcher with cache probe filtering (CPF) from L1 to L1.5. We optimize the core instruction fetch (IF) stage by removing the critical core-to-L1 combinational path. We present a detailed comparison of instruction cache architectures' performance and energy efficiency for parallel ULP (PULP) clusters. Focusing on the implementation, our two-level instruction cache provides better scalability than existing shared caches, delivering up to 20% higher operating frequency. On average, the proposed two-level cache improves maximum performance by up to 17% compared to the state-of-the-art while delivering similar energy efficiency for most relevant applications

Caffeic Acid Phenethyl Ester and Its Amide Analogue Are Potent Inhibitors of Leukotriene Biosynthesis in Human Polymorphonuclear Leukocytes

BACKGROUND: 5-lipoxygenase (5-LO) catalyses the transformation of arachidonic acid (AA) into leukotrienes (LTs), which are important lipid mediators of inflammation. LTs have been directly implicated in inflammatory diseases like asthma, atherosclerosis and rheumatoid arthritis; therefore inhibition of LT biosynthesis is a strategy for the treatment of these chronic diseases. METHODOLOGY/PRINCIPAL FINDINGS: Analogues of caffeic acid, including the naturally-occurring caffeic acid phenethyl ester (CAPE), were synthesized and evaluated for their capacity to inhibit 5-LO and LTs biosynthesis in human polymorphonuclear leukocytes (PMNL) and whole blood. Anti-free radical and anti-oxidant activities of the compounds were also measured. Caffeic acid did not inhibit 5-LO activity or LT biosynthesis at concentrations up to 10 µM. CAPE inhibited 5-LO activity (IC(50) 0.13 µM, 95% CI 0.08-0.23 µM) more effectively than the clinically-approved 5-LO inhibitor zileuton (IC(50) 3.5 µM, 95% CI 2.3-5.4 µM). CAPE was also more effective than zileuton for the inhibition of LT biosynthesis in PMNL but the compounds were equipotent in whole blood. The activity of the amide analogue of CAPE was similar to that of zileuton. Inhibition of LT biosynthesis by CAPE was the result of the inhibition of 5-LO and of AA release. Caffeic acid, CAPE and its amide analog were free radical scavengers and antioxidants with IC(50) values in the low µM range; however, the phenethyl moiety of CAPE was required for effective inhibition of 5-LO and LT biosynthesis. CONCLUSIONS: CAPE is a potent LT biosynthesis inhibitor that blocks 5-LO activity and AA release. The CAPE structure can be used as a framework for the rational design of stable and potent inhibitors of LT biosynthesis

Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome

There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV‐6) and Epstein–Barr virus (EBV) have been proposed as infectious triggers. Thirty CFS patients with elevated IgG antibody titers against HHV‐6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double‐blind, placebo‐controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI‐20) and Fatigue Severity Scale (FSS) scores, self‐reported cognitive function, and physician‐determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels. VGCV patients experienced a greater improvement by MFI‐20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI‐20 mental fatigue subscore ( P  = 0.039), FSS score ( P  = 0.006), and cognitive function ( P  = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders ( P  = 0.029). In the VGCV arm, monocyte counts decreased ( P  < 0.001), neutrophil counts increased ( P  = 0.037) and cytokines were more likely to evolve towards a Th1‐profile ( P  < 0.001). Viral IgG antibody titers did not differ between arms. VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted. J. Med. Virol. 85:2101–2109, 2013 . © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100139/1/jmv23713.pd

A Many-body Problem with Point Interactions on Two Dimensional Manifolds

A non-perturbative renormalization of a many-body problem, where non-relativistic bosons living on a two dimensional Riemannian manifold interact with each other via the two-body Dirac delta potential, is given by the help of the heat kernel defined on the manifold. After this renormalization procedure, the resolvent becomes a well-defined operator expressed in terms of an operator (called principal operator) which includes all the information about the spectrum. Then, the ground state energy is found in the mean field approximation and we prove that it grows exponentially with the number of bosons. The renormalization group equation (or Callan-Symanzik equation) for the principal operator of the model is derived and the $\beta$ function is exactly calculated for the general case, which includes all particle numbers.Comment: 28 pages; typos are corrected, three figures are adde

Vega: A Ten-Core SoC for IoT Endnodes with DNN Acceleration and Cognitive Wake-Up from MRAM-Based State-Retentive Sleep Mode

The Internet-of-Things (IoT) requires endnodes with ultra-low-power always-on capability for a long battery lifetime, as well as high performance, energy efficiency, and extreme flexibility to deal with complex and fast-evolving near-sensor analytics algorithms (NSAAs). We present Vega, an IoT endnode system on chip (SoC) capable of scaling from a 1.7- μW fully retentive cognitive sleep mode up to 32.2-GOPS (at 49.4 mW) peak performance on NSAAs, including mobile deep neural network (DNN) inference, exploiting 1.6 MB of state-retentive SRAM, and 4 MB of non-volatile magnetoresistive random access memory (MRAM). To meet the performance and flexibility requirements of NSAAs, the SoC features ten RISC-V cores: one core for SoC and IO management and a nine-core cluster supporting multi-precision single instruction multiple data (SIMD) integer and floating-point (FP) computation. Vega achieves the state-of-the-art (SoA)-leading efficiency of 615 GOPS/W on 8-bit INT computation (boosted to 1.3 TOPS/W for 8-bit DNN inference with hardware acceleration). On FP computation, it achieves the SoA-leading efficiency of 79 and 129 GFLOPS/W on 32- and 16-bit FP, respectively. Two programmable machine learning (ML) accelerators boost energy efficiency in cognitive sleep and active states

The opposite of Dante's hell? The transfer of ideas for social housing at international congresses in the 1850s–1860s

With the advent of industrialization, the question of developing adequate housing for the emergent working classes became more pressing than before. Moreover, the problem of unhygienic houses in industrial cities did not stop at the borders of a particular nation-state; sometimes literally as pandemic diseases spread out 'transnationally'. It is not a coincidence that in the nineteenth century the number of international congresses on hygiene and social topics expanded substantially. However, the historiography about social policy in general and social housing in particular, has often focused on individual cases because of the different pace of industrial and urban development and is thus dominated by national perspectives. In this paper, I elaborate on transnational exchange processes and local adaptations and transformations. I focus on the transfer of the housing model of SOMCO in Mulhouse, (a French house building association) during social international congresses. I examine whether cross-national networking enabled and facilitated the implementation of ideas on the local scale. I will elaborate on the transmission and the local adaptation of the Mulhouse-model in Belgium. Convergences, divergences, and different factors that influenced the local transformations (personal choice, political situation, socioeconomic circumstances) will be taken into accoun

Phase II study of olaparib in patients with refractory Ewing sarcoma following failure of standard chemotherapy

Background: Preclinical studies have documented antitumor activity of PARP inhibition both in vitro and in vivo, against Ewing sarcoma cells. This study aimed to translate that observation into a clinical trial to assess the efficacy and tolerability of olaparib, a PARP inhibitor, in patients with advanced Ewing sarcoma (EWS) progressing after prior chemotherapy. Methods: In this nonrandomized phase II trial, adult participants with radiographically measureable metastatic EWS received olaparib tablets, 400 mg orally twice daily, until disease progression or drug intolerance. Tumor measurements were determined by CT or MRI at 6 and 12 weeks after starting olaparib administration, and then every 8 weeks thereafter. Tumor response determinations were made according to RECIST 1.1, and adverse event determinations were made according to CTCAE, version 4.0. A total of 22 participants were planned to be enrolled using a conventional 2-step phase II study design. If no objective responses were observed after 12 participants had been followed for at least 3 months, further accrual would be stopped. Results: 12 participants were enrolled, and all were evaluable. There were no objective responses (PR/CR), 4 SD (duration 10.9, 11.4, 11.9, and 17.9 wks), and 8 PD as best response. Of the SD, 2 had minor responses (−9% and −11.7% by RECIST 1.1). The median time to disease progression was 5.7 weeks. Further enrollment was therefore discontinued. No significant or unexpected toxicities were observed with olaparib, with only a single case each of grade 3 anemia and grade 3 thrombocytopenia observed. Conclusions: This study is the first report of a prospective phase II trial to evaluate the safety and efficacy of a PARP inhibitor in patients with advanced Ewing sarcoma after failure of standard chemotherapy. Olaparib administration was safe and well tolerated when administered to this small heavily pre-treated cohort at the 400 mg BID dose, although the median duration of dosing was for only 5.7 weeks. No significant responses or durable disease control was seen, and the short average interval to disease progression underscores the aggressiveness of this disease. Other studies to combine cytotoxic chemotherapy with PARP inhibition in EWS are actively ongoing. Trial registration ClinicalTrials.gov Identifier: NCT0158354

Aconitate decarboxylase 1 participates in the control of pulmonary Brucella infection in mice

Brucellosis is one of the most widespread bacterial zoonoses worldwide. Here, our aim was to identify the effector mechanisms controlling the early stages of intranasal infection with Brucella in C57BL/6 mice. During the first 48 hours of infection, alveolar macrophages (AMs) are the main cells infected in the lungs. Using RNA sequencing, we identified the aconitate decarboxylase 1 gene ( Acod1 ;also known as Immune responsive gene 1), as one of the genes most upregulated in murine AMs in response to B .melitensis infection at 24 hours post-infection. Upregulation of Acod1 was confirmed by RT-qPCR in lungs infected with B .melitensis and B .abortus .We observed that Acod1 -/- C57BL/6 mice display a higher bacterial load in their lungs than wild-type (wt) mice following B .melitensis or B .abortus infection, demonstrating that Acod1 participates in the control of pulmonary Brucella infection. The ACOD1 enzyme is mostly produced in mitochondria of macrophages, and converts cis-aconitate, a metabolite in the Krebs cycle, into itaconate. Dimethyl itaconate (DMI), a chemically-modified membrane permeable form of itaconate, has a dose-dependent inhibitory effect on Brucella growth in vitro .Interestingly, structural analysis suggests the binding of itaconate into the binding site of B .abortus isocitrate lyase. DMI does not inhibit multiplication of the isocitrate lyase deletion mutant Δ aceA B .abortus in vitro .Finally, we observed that, unlike the wt strain, the Δ aceA B .abortus strain multiplies similarly in wt and Acod1 -/- C57BL/6 mice. These data suggest that bacterial isocitrate lyase might be a target of itaconate in AMs.info:eu-repo/semantics/publishe

Induced pseudoscalar coupling of the proton weak interaction

The induced pseudoscalar coupling $g_p$ is the least well known of the weak coupling constants of the proton's charged--current interaction. Its size is dictated by chiral symmetry arguments, and its measurement represents an important test of quantum chromodynamics at low energies. During the past decade a large body of new data relevant to the coupling $g_p$ has been accumulated. This data includes measurements of radiative and non radiative muon capture on targets ranging from hydrogen and few--nucleon systems to complex nuclei. Herein the authors review the theoretical underpinnings of $g_p$, the experimental studies of $g_p$, and the procedures and uncertainties in extracting the coupling from data. Current puzzles are highlighted and future opportunities are discussed.Comment: 58 pages, Latex, Revtex4, prepared for Reviews of Modern Physic