bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Length of Cultivation Time for Isolation of Propionibacterium acnes in Suspected Bone and Joint Infections Is More than 7 Days
Authors: Bossard Daniel A. , Ledergerber Bruno , Zingg Patrick O. , Gerber Christian , Zinkernagel Annelies S. , Zbinden Reinhard , Achermann Yvonne
Published: October 2016

Diagnosis of
Propionibacterium acnes
bone and joint infection is challenging due to the long cultivation time of up to 14 days. We retrospectively studied whether reducing the cultivation time to 7 days allows accurate diagnosis without losing sensitivity. We identified patients with at least one positive
P. acnes
sample between 2005 and 2015 and grouped them into “infection” and “no infection.” An infection was defined when at least two samples from the same case were positive. Clinical and microbiological data, including time to positivity for different cultivation methods, were recorded. We found 70 cases of proven
P. acnes
infection with a significant faster median time to positivity of 6 days (range, 2 to 11 days) compared to 9 days in 47 cases with
P. acnes
identified as a contamination (
P
< 0.0001). In 15 of 70 (21.4%) patients with an infection, tissue samples were positive after day 7 and in 6 patients (8.6%) after day 10 when a blind subculture of the thioglycolate broth was performed. The highest sensitivity was detected for thioglycolate broth (66.3%) and the best positive predictive values for anaerobic agar plates (96.5%). A prolonged transportation time from the operating theater to the microbiological laboratory did not influence time to positivity of
P. acnes
growth. By reducing the cultivation time to 7 days, false-negative diagnoses would increase by 21.4%; thus, we recommend that biopsy specimens from bone and joint infections be cultivated to detect
P. acnes
for 10 days with a blind subculture at the end.
Exploiting Bacterial Whole-Genome Sequencing Data for Evaluation of Diagnostic Assays: Campylobacter Species Identification as a Case Study
Authors: Jansen van Rensburg Melissa J. , Swift Craig , Cody Alison J. , Jenkins Claire , Maiden Martin C. J.
Published: October 2016

The application of whole-genome sequencing (WGS) to problems in clinical microbiology has had a major impact on the field. Clinical laboratories are now using WGS for pathogen identification, antimicrobial susceptibility testing, and epidemiological typing. WGS data also represent a valuable resource for the development and evaluation of molecular diagnostic assays, which continue to play an important role in clinical microbiology. To demonstrate this application of WGS, this study used publicly available genomic data to evaluate a duplex real-time PCR (RT-PCR) assay that targets
mapA
and
ceuE
for the detection of
Campylobacter jejuni
and
Campylobacter coli
, leading global causes of bacterial gastroenteritis.
In silico
analyses of
mapA
and
ceuE
primer and probe sequences from 1,713 genetically diverse
C. jejuni
and
C. coli
genomes, supported by RT-PCR testing, indicated that the assay was robust, with 1,707 (99.7%) isolates correctly identified. The high specificity of the
mapA-ceuE
assay was the result of interspecies diversity and intraspecies conservation of the target genes in
C. jejuni
and
C. coli
. Rare instances of a lack of specificity among
C. coli
isolates were due to introgression in
mapA
or sequence diversity in
ceuE
. The results of this study illustrate how WGS can be exploited to evaluate molecular diagnostic assays by using publicly available data, online databases, and open-source software.
In Vivo
Efficacy of Measles Virus Fusion Protein-Derived Peptides Is Modulated by the Properties of Self-Assembly and Membrane Residence
Authors: Figueira T. N. , Palermo L. M. , Veiga A. S. , Huey D. , Alabi C. A. , Santos N. C. , Welsch J. C. , Mathieu C. , Horvat B. , Niewiesk S. , Moscona A. , Castanho M. A. R. B. , Porotto M.
Published: October 2016

Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad repeat (HR) regions of F can inhibit MV infection at the entry stage. In previous work, we have generated potent MV fusion inhibitors by dimerizing the F-derived peptides and conjugating them to cholesterol. We have shown that prophylactic intranasal administration of our lead fusion inhibitor efficiently protects from MV infection
in vivo
. We show here that peptides tagged with lipophilic moieties self-assemble into nanoparticles until they reach the target cells, where they are integrated into cell membranes. The self-assembly feature enhances biodistribution and the half-life of the peptides, while integration into the target cell membrane increases fusion inhibitor potency. These factors together modulate
in vivo
efficacy. The results suggest a new framework for developing effective fusion inhibitory peptides.

IMPORTANCE
Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. We show here that specific biophysical properties regulate the
in vivo
efficacy of MV F-derived peptides.
High Epstein-Barr Virus Load and Genomic Diversity Are Associated with Generation of gp350-Specific Neutralizing Antibodies following Acute Infectious Mononucleosis
Authors: Weiss Eric R. , Alter Galit , Ogembo Javier Gordon , Henderson Jennifer L. , Tabak Barbara , Bakiş Yasin , Somasundaran Mohan , Garber Manuel , Selin Liisa , Luzuriaga Katherine
Published: October 2016

The Epstein-Barr virus (EBV) gp350 glycoprotein interacts with the cellular receptor to mediate viral entry and is thought to be the major target for neutralizing antibodies. To better understand the role of EBV-specific antibodies in the control of viral replication and the evolution of sequence diversity, we measured EBV gp350-specific antibody responses and sequenced the gp350 gene in samples obtained from individuals experiencing primary EBV infection (acute infectious mononucleosis [AIM]) and again 6 months later (during convalescence [CONV]). EBV gp350-specific IgG was detected in the sera of 17 (71%) of 24 individuals at the time of AIM and all 24 (100%) individuals during CONV; binding antibody titers increased from AIM through CONV, reaching levels equivalent to those in age-matched, chronically infected individuals. Antibody-dependent cell-mediated phagocytosis (ADCP) was rarely detected during AIM (4 of 24 individuals; 17%) but was commonly detected during CONV (19 of 24 individuals; 79%). The majority (83%) of samples taken during AIM neutralized infection of primary B cells; all samples obtained at 6 months postdiagnosis neutralized EBV infection of cultured and primary target cells. Deep sequencing revealed interpatient gp350 sequence variation but conservation of the CR2-binding site. The levels of gp350-specific neutralizing activity directly correlated with higher peripheral blood EBV DNA levels during AIM and a greater evolution of diversity in gp350 nucleotide sequences from AIM to CONV. In summary, we conclude that the viral load and EBV gp350 diversity during early infection are associated with the development of neutralizing antibody responses following AIM.

IMPORTANCE
Antibodies against viral surface proteins can blunt the spread of viral infection by coating viral particles, mediating uptake by immune cells, or blocking interaction with host cell receptors, making them a desirable component of a sterilizing vaccine. The EBV surface protein gp350 is a major target for antibodies. We report the detection of EBV gp350-specific antibodies capable of neutralizing EBV infection
in vitro
. The majority of gp350-directed vaccines focus on glycoproteins from lab-adapted strains, which may poorly reflect primary viral envelope diversity. We report some of the first primary gp350 sequences, noting that the gp350 host receptor binding site is remarkably stable across patients and time. However, changes in overall gene diversity were detectable during infection. Patients with higher peripheral blood viral loads in primary infection and greater changes in viral diversity generated more efficient antibodies. Our findings provide insight into the generation of functional antibodies, necessary for vaccine development.
Slow net sediment accumulation sets snowball Earth apart from all younger glacial episodes
Authors: Partin Camille A. , Sadler Peter M.
Published: October 2016

During the Sturtian and Marinoan “snowball Earth” episodes, ice cover is thought to have extended from polar to tropical latitudes. We test the supposition that such an extreme glacial climate, not repeated in the subsequent ∼635 m.y. of Earth history, would have reduced the vigor of the hydrologic cycle and thus diminished sediment flux to the oceans. With >500 sediment accumulation rates to characterize Sturtian and Marinoan deposits, we find median accumulation rates at least four to 15 times slower than expected for Phanerozoic glaciomarine deposits as characterized by >10,000 rates. Our comparison is conservative with respect to time span, latitude, and distance from the ice margin. Phanerozoic accumulation rates decrease systematically when averaged over longer time spans. Comparisons were drawn, therefore, at 5 and 57 m.y. time spans to match minimum Marinoan and Sturtian durations, respectively. Cenozoic glaciomarine accumulation also slows with increasing latitude from temperate to polar climates and with increasing distance from the ice margin. After accounting for time span, snowball Earth deposits at low latitude are found to be thinner than would be expected either for high-latitude Cenozoic glacial deposits or for very distal glaciomarine abyssal muds with ice-rafted debris. The rate discrepancy is not readily attributed to overestimates of the total Marinoan or Sturtian durations. If sediment fluxes during warm melt intervals did approach Phanerozoic rates, these intervals must have occupied a much smaller proportion of snowball Earth episodes than in younger glacial climates.
Dalteparin-sodium induced drug fever in a neonate
Authors: Wackernagel Dirk , Obaya Sami , Nydert Per
Published: October 2016

Drug fever caused by dalteparin-sodium (DS), a low-molecular-weight derivative of heparin, is neither listed in the official drug information and nor published as a case report until today. A preterm infant, born at 26 weeks of gestation, developed fever 2 days after starting a treatment with DS for an intracardial thrombus. The fever reverses soon after changing the treatment to unfractionated heparin and reappeared after reintroduction of DS. Once again, after discontinuing DS, the infant regained normothermia. Bacterial and viral infections, tissue damage, impaired liver or kidney function, preservative agents and comedications could be ruled out as fever origin. By using the Naranjo adverse drug reaction (ADR) probability scale and the Liverpool ADR causality assessment tool, this case can be classified as ‘probable ADR’ and ‘definite ADR’. This is the first case report of a drug fever caused by the low-molecular-weight heparin DS in a preterm infant.
Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion
Authors: Weersink Rianne A , Bouma Margriet , Burger David M , Drenth Joost P H , Hunfeld Nicole G M , Kranenborg Minke , Monster-Simons Margje H , van Putten Sandra A W , Metselaar Herold J , Taxis Katja , Borgsteede Sander D
Published: October 2016

Introduction

Liver cirrhosis can have a major impact on drug pharmacokinetics and pharmacodynamics. Patients with cirrhosis often suffer from potentially preventable adverse drug reactions. Guidelines on safe prescribing for these patients are lacking. The aim of this study is to develop a systematic method for evaluating the safety and optimal dosage of drugs in patients with liver cirrhosis.

Methods and analysis

For each drug, a six-step evaluation process will be followed. (1) Available evidence on the pharmacokinetics and safety of a drug in patients with liver cirrhosis will be collected from the Summary of Product Characteristics (SmPC) and a systematic literature review will be performed. (2) Data regarding two outcomes, namely pharmacokinetics and safety, will be extracted and presented in a standardised assessment report. (3) A safety classification and dosage suggestion will be proposed for each drug. (4) An expert panel will discuss the validity and clinical relevance of this suggested advice. (5) Advices will be implemented in all relevant Clinical Decision Support Systems in the Netherlands and published on a website for patients and healthcare professionals. (6) The continuity of the advices will be guaranteed by a yearly check of new literature and comments on the advices. This protocol will be applied in the evaluation of a selection of drugs: (A) drugs used to treat (complications of) liver cirrhosis, and (B) drugs frequently prescribed to the general population.

Ethics and dissemination

Since this study does not directly involve human participants, it does not require ethical clearance. Besides implementation on a website and in clinical decision support systems, we aim to publish the generated advices of one or two drug classes in a peer-reviewed journal and at conference meetings.
Virtual touch quantification (VTq) elastography for non-invasive assessment of liver disease and its complications: what the clinician needs to know
Authors: Sherman David , Lung Phillip , Shorvon Philip
Published: October 2016

Liver stiffness measurement (LSM) is the most widely used non-invasive alternative to biopsy for assessing liver fibrosis in the UK. Virtual touch quantification (VTq, also known as acoustic radiation force impulse) is the principal available alternative to transient elastography (Fibroscan) and is delivered via software enhancements to standard ultrasound (US) machines. It has recently been endorsed by National Institute for Health and Care Excellence in terms of both accuracy and cost-effectiveness for use in viral hepatitis. However, while an increasing proportion of radiologists use VTq, familiarity among gastroenterologists and trainees with LSM techniques is variable and implementation is patchy. This review considers the background, evidence for and practical use of VTq elastography in clinical practice in the UK. Potential future developments in this rapidly evolving field are also highlighted.
Influences of root-induced soil suction and root geometry on slope stability: a centrifuge study
Authors: Leung A.K. , Kamchoom V. , Ng C.W.W.
Published: October 2016

Soil bioengineering using vegetation has been recognised as an environmentally friendly solution for shallow slope stabilization. Plant transpiration induces suction in the soil, but its effects on slope stability are often ignored. This study investigates the influences of transpiration-induced suction and mechanical reinforcement of different root geometries (i.e., tap- and heart-shaped) to the slope stability subjected to an intense rainfall with an intensity of 70 mm/h (prototype scale; corresponding to a return period of 1000 years), via centrifuge modelling. New model roots that have scaled mechanical properties close to real roots were used to simulate transpiration-induced suction in the centrifuge. Transient seepage analyses were performed using SEEP/W to back-analyse the suction responses due to transpiration and rainfall. Subsequently, the back-analysed suction was used to assess the factor of safety of the slopes using SLOPE/W. It is revealed that heart-shaped roots provided greater stabilization effects to a 60° clayey sand slope than tap-shaped roots. The heart-shaped roots induced higher suction, leading to 14% reduction of rainfall infiltration and 6% increase in shear strength. Although transpiration-induced suction in a 45° slope was reduced to zero after the rainfall, mechanical root reinforcement was found to be sufficient to maintain slope stability.
Effects of soil structure on the shear behaviour of an unsaturated loess at different suctions and temperatures
Authors: Ng C.W.W. , Mu Q.Y. , Zhou C.
Published: October 2016

Previous studies of shear behaviour at different suctions and temperatures focused mainly on recompacted soils. Limited attention has been paid to intact soil. In this paper, the shear behaviour of intact and recompacted loess was studied using a suction- and temperature-controlled direct shear apparatus. A scanning electron microscope and mercury intrusion porosimeter were used to evaluate the microstructure of both intact and recompacted loess. For a given suction and temperature, intact specimens exhibit a higher shear stiffness and larger dilatancy than recompacted specimens. This is mainly because clay particles in intact specimens accumulate near grain contacts and stick to the grain surfaces, as revealed in scanning electron microscopy and mercury intrusion porosimetry tests. This type of clay particle distribution in intact specimens results in a more resistant structure and higher yield stress. At suctions of 0 and 200 kPa, the shear stiffness and dilatancy of recompacted specimens increase with temperature. The shear stiffness and maximum dilatancy increase by as much as 47% and 63% at suctions of 0 and 200 kPa, respectively. These increases in shear stiffness and dilatancy are attributed mainly to the continuous plastic volumetric contraction during heating, which induced strain-hardening effects. On the contrary, thermal effects on the stress–strain behaviour of intact specimens are negligible at zero suction. At a suction of 200 kPa, as soil temperature rises from 20 to 60 °C, the shear stiffness and maximum dilatancy of intact specimens decrease by 35% and 68%, respectively. It is evident that intact specimens and recompacted specimens experience opposite thermal effects.
Synthesis and photophysical properties of expanded dehydrobenzoannulene macrotricycles
Authors: Takeda Takashi , Haley Michael M.
Published: October 2016

A sequential Sonogashira cross-coupling/Pd-mediated oxidative homocoupling strategy affords two expanded dehydrobenzoannulene (DBA) structures containing two [14]DBAs fused to an [18]DBA core. Noticeable differences in the absorption and emission spectra are observed in comparison with a structurally related [18]DBA-centered trefoil containing three fused [14]DBAs.
A new family of links topologically, but not smoothly, concordant to the Hopf link
Authors: Davis Christopher W. , Ray Arunima
Published: October 2016

We give new examples of 2-component links with linking number one and unknotted components that are topologically concordant to the positive Hopf link, but not smoothly so – in addition, they are not smoothly concordant to the positive Hopf link with a knot tied in the first component. Such examples were previously constructed by Cha–Kim–Ruberman–Strle; we show that our examples are distinct in smooth concordance from theirs.
Khovanov homology and knot Floer homology for pointed links
Authors: Baldwin John A. , Levine Adam Simon , Sarkar Sucharit
Published: October 2016

A well-known conjecture states that for any [Formula: see text]-component link [Formula: see text] in [Formula: see text], the rank of the knot Floer homology of [Formula: see text] (over any field) is less than or equal to [Formula: see text] times the rank of the reduced Khovanov homology of [Formula: see text]. In this paper, we describe a framework that might be used to prove this conjecture. We construct a modified version of Khovanov homology for links with multiple basepoints and show that it mimics the behavior of knot Floer homology. We also introduce a new spectral sequence converging to knot Floer homology whose [Formula: see text] page is conjecturally isomorphic to our new version of Khovanov homology; this would prove that the conjecture stated above holds over the field [Formula: see text].
Realization of plucking polynomials
Authors: Cheng Zhiyun , Mukherjee Sujoy , Przytycki Józef H. , Wang Xiao , Yang Seung Yeop
Published: October 2016

We give necessary and sufficient conditions for a given polynomial to be a plucking polynomial of a rooted tree. We discuss the fact that different rooted trees can have the same polynomial.
A Decision Support Methodology for Locating Bank Branches: A Case Study in Turkey
Authors: Basar Ayfer , Kabak Özgür , Ilker Topcu Y.
Published: October 2016

This paper presents an integrated decision support methodology for locating bank branches. The methodology is composed of two stages: problem structuring, and modeling. In the first stage, initially, a number of criteria are selected with the help of a detailed literature review and expert opinions. Subsequently, importance weights of these criteria for different types of bank branches are identified based on judgments of experts for pairwise comparison questions. At the modeling stage, considering the characteristics and importance of the criteria, a novel multi-objective mathematical programming model is proposed to find specific locations of bank branches. The proposed methodology is applied in locating branches of a Turkish bank. In order to test the validity of the results and robustness, a sensitivity analysis is conducted and the solutions are found to be robust.
Frequency-Aware ESL Power Estimation for ARM Cortex-A9 Using a Black Box Processor Model
Authors: Schürmans Stefan , Onnebrink Gereon , Leupers Rainer , Ascheid Gerd , Chen Xiaotao
Published: October 2016

Power estimation has become a strongly desired feature in Electronic System Level (ESL) simulations. Most existing power estimation approaches for this abstraction level require component models with observable internals. However, most ESL models of modern processors are delivered as black box components. This work presents a tool-based ESL power estimation methodology for black box models and its extension for multiple clock frequencies. The evaluation uses hardware measurements of the ARM Cortex-A9 subsystem of the OMAP4460 chip for reference. The achieved estimation error is 5% on average for fixed-frequency power models and 7% for multifrequency power models.
Asymmetry-aware work-stealing runtimes
Authors: Torng Christopher , Wang Moyang , Batten Christopher
Published: October 2016

Amdahl's law provides architects a compelling reason to introduce system asymmetry to optimize for both serial and parallel regions of execution. Asymmetry in a multicore processor can arise statically (e.g., from core microarchitecture) or dynamically (e.g., applying dynamic voltage/frequency scaling). Work stealing is an increasingly popular approach to task distribution that elegantly balances task-based parallelism across multiple worker threads. In this paper, we propose asymmetry-aware work-stealing (AAWS) runtimes, which are carefully designed to exploit both the static and dynamic asymmetry in modern systems. AAWS runtimes use three key hardware/software techniques: work-pacing, work-sprinting, and work-mugging. Work-pacing and work-sprinting are novel techniques that combine a marginal-utility-based approach with integrated voltage regulators to improve performance and energy efficiency in high- and low-parallel regions. Work-mugging is a previously proposed technique that enables a waiting big core to preemptively migrate work from a busy little core. We propose a simple implementation of work-mugging based on lightweight user-level interrupts. We use a vertically integrated research methodology spanning software, architecture, and VLSI to make the case that holistically combining static asymmetry, dynamic asymmetry, and work-stealing runtimes can improve both performance and energy efficiency in future multicore systems.
Back to the future
Authors: Jain Akanksha , Lin Calvin
Published: October 2016

Belady's algorithm is optimal but infeasible because it requires knowledge of the future. This paper explains how a cache replacement algorithm can nonetheless learn from Belady's algorithm by applying it to past cache accesses to inform future cache replacement decisions. We show that the implementation is surprisingly efficient, as we introduce a new method of efficiently simulating Belady's behavior, and we use known sampling techniques to compactly represent the long history information that is needed for high accuracy. For a 2MB LLC, our solution uses a 16KB hardware budget (excluding replacement state in the tag array). When applied to a memory-intensive subset of the SPEC 2006 CPU benchmarks, our solution improves performance over LRU by 8.4%, as opposed to 6.2% for the previous state-of-the-art. For a 4-core system with a shared 8MB LLC, our solution improves performance by 15.0%, compared to 12.0% for the previous state-of-the-art.
LAP
Authors: Cheng Hsiang-Yun , Zhao Jishen , Sampson Jack , Irwin Mary Jane , Jaleel Aamer , Lu Yu , Xie Yuan
Published: October 2016

Emerging non-volatile memory (NVM) technologies, such as spin-transfer torque RAM (STT-RAM), are attractive options for replacing or augmenting SRAM in implementing last-level caches (LLCs). However, the asymmetric read/write energy and latency associated with NVM introduces new challenges in designing caches where, in contrast to SRAM, dynamic energy from write operations can be responsible for a larger fraction of total cache energy than leakage. These properties lead to the fact that no single traditional inclusion policy being dominant in terms of LLC energy consumption for asymmetric LLCs.

We propose a novel selective inclusion policy, Loop-block-Aware Policy (
LAP
), to reduce energy consumption in LLCs with asymmetric read/write properties. In order to eliminate redundant writes to the LLC, LAP incorporates advantages from both non-inclusive and exclusive designs to selectively cache only part of upper-level data in the LLC. Results show that LAP outperforms other variants of selective inclusion policies and consumes 20% and 12% less energy than non-inclusive and exclusive STT-RAM-based LLCs, respectively. We extend LAP to a system with SRAM/STT-RAM hybrid LLCs to achieve energy-efficient data placement, reducing the energy consumption by 22% and 15% over non-inclusion and exclusion on average, with average-case performance improvements, small worst-case performance loss, and minimal hardware overheads.
Efficient synonym filtering and scalable delayed translation for hybrid virtual caching
Authors: Park Chang Hyun , Heo Taekyung , Huh Jaehyuk
Published: October 2016

Conventional translation look-aside buffers (TLBs) are required to complete address translation with short latencies, as the address translation is on the critical path of all memory accesses even for L1 cache hits. Such strict TLB latency restrictions limit the TLB capacity, as the latency increase with large TLBs may lower the overall performance even with potential TLB miss reductions. Furthermore, TLBs consume a significant amount of energy as they are accessed for every instruction fetch and data access. To avoid the latency restriction and reduce the energy consumption, virtual caching techniques have been proposed to defer translation to after L1 cache misses. However, an efficient solution for the synonym problem has been a critical issue hindering the wide adoption of virtual caching.

Based on the virtual caching concept, this study proposes a hybrid virtual memory architecture extending virtual caching to the entire cache hierarchy, aiming to improve both performance and energy consumption. The hybrid virtual caching uses virtual addresses augmented with address space identifiers (ASID) in the cache hierarchy for common non-synonym addresses. For such non-synonyms, the address translation occurs only after last-level cache (LLC) misses. For uncommon synonym addresses, the addresses are translated to physical addresses with conventional TLBs before L1 cache accesses. To support such hybrid translation, we propose an efficient synonym detection mechanism based on Bloom filters which can identify synonym candidates with few false positives. For large memory applications, delayed translation alone cannot solve the address translation problem, as fixed-granularity delayed TLBs may not scale with the increasing memory requirements. To mitigate the translation scalability problem, this study proposes a delayed many segment translation designed for the hybrid virtual caching. The experimental results show that our approach effectively lowers accesses to the TLBs, leading to significant power savings. In addition, the approach provides performance improvement with scalable delayed translation with variable length segments.
ARM virtualization
Authors: Dall Christoffer , Li Shih-Wei , Lim Jin Tack , Nieh Jason , Koloventzos Georgios
Published: October 2016

ARM servers are becoming increasingly common, making server technologies such as virtualization for ARM of growing importance. We present the first study of ARM virtualization performance on server hardware, including multicore measurements of two popular ARM and x86 hypervisors, KVM and Xen. We show how ARM hardware support for virtualization can enable much faster transitions between VMs and the hypervisor, a key hypervisor operation. However, current hypervisor designs, including both Type 1 hypervisors such as Xen and Type 2 hypervisors such as KVM, are not able to leverage this performance benefit for real application workloads. We discuss the reasons why and show that other factors related to hypervisor software design and implementation have a larger role in overall performance. Based on our measurements, we discuss changes to ARM's hardware virtualization support that can potentially bridge the gap to bring its faster VM-to-hypervisor transition mechanism to modern Type 2 hypervisors running real applications. These changes have been incorporated into the latest ARM architecture.
Cambricon
Authors: Liu Shaoli , Du Zidong , Tao Jinhua , Han Dong , Luo Tao , Xie Yuan , Chen Yunji , Chen Tianshi
Published: October 2016

Neural Networks (NN) are a family of models for a broad range of emerging machine learning and pattern recondition applications. NN techniques are conventionally executed on general-purpose processors (such as CPU and GPGPU), which are usually not energy-efficient since they invest excessive hardware resources to flexibly support various workloads. Consequently, application-specific hardware accelerators for neural networks have been proposed recently to improve the energy-efficiency. However, such accelerators were designed for a small set of NN techniques sharing similar computational patterns, and they adopt complex and informative instructions (control signals) directly corresponding to high-level functional blocks of an NN (such as layers), or even an NN as a whole. Although straightforward and easy-to-implement for a limited set of similar NN techniques, the lack of agility in the instruction set prevents such accelerator designs from supporting a variety of different NN techniques with sufficient flexibility and efficiency.

In this paper, we propose a novel domain-specific Instruction Set Architecture (ISA) for NN accelerators, called Cambricon, which is a load-store architecture that integrates scalar, vector, matrix, logical, data transfer, and control instructions, based on a comprehensive analysis of existing NN techniques. Our evaluation over a total of ten representative yet distinct NN techniques have demonstrated that Cambricon exhibits strong descriptive capacity over a broad range of NN techniques, and provides higher code density than general-purpose ISAs such as ×86, MIPS, and GPGPU. Compared to the latest state-of-the-art NN accelerator design DaDianNao [5] (which can only accommodate 3 types of NN techniques), our Cambricon-based accelerator prototype implemented in TSMC 65nm technology incurs only negligible latency/power/area overheads, with a versatile coverage of 10 different NN benchmarks.
Accelerating dependent cache misses with an enhanced memory controller
Authors: Hashemi Milad , Khubaib  , Ebrahimi Eiman , Mutlu Onur , Patt Yale N.
Published: October 2016

On-chip contention increases memory access latency for multicore processors. We identify that this additional latency has a substantial efect on performance for an important class of latency-critical memory operations: those that result in a cache miss and are dependent on data from a prior cache miss. We observe that the number of instructions between the frst cache miss and its dependent cache miss is usually small. To minimize dependent cache miss latency, we propose adding just enough functionality to dynamically identify these instructions at the core and migrate them to the memory controller for execution as soon as source data arrives from DRAM. This migration allows memory requests issued by our new Enhanced Memory Controller (EMC) to experience a 20% lower latency than if issued by the core. On a set of memory intensive quad-core workloads, the EMC results in a 13% improvement in system performance and a 5% reduction in energy consumption over a system with a Global History Bufer prefetcher, the highest performing prefetcher in our evaluation.
Treadmill
Authors: Zhang Yunqi , Meisner David , Mars Jason , Tang Lingjia
Published: October 2016

Managing tail latency of requests has become one of the primary challenges for large-scale Internet services. Data centers are quickly evolving and service operators frequently desire to make changes to the deployed software and production hardware configurations. Such changes demand a confident understanding of the impact on one's service, in particular its effect on tail latency (e.g., 95th- or 99th-percentile response latency of the service). Evaluating the impact on the tail is challenging because of its inherent variability. Existing tools and methodologies for measuring these effects suffer from a number of deficiencies including poor load tester design, statistically inaccurate aggregation, and improper attribution of effects. As shown in the paper, these pitfalls can often result in misleading conclusions.

In this paper, we develop a methodology for statistically rigorous performance evaluation and performance factor attribution for server workloads. First, we find that careful design of the server load tester can ensure high quality performance evaluation, and empirically demonstrate the inaccuracy of load testers in previous work. Learning from the design flaws in prior work, we design and develop a modular load tester platform, Treadmill, that overcomes pitfalls of existing tools. Next, utilizing Treadmill, we construct measurement and analysis procedures that can properly attribute performance factors. We rely on statistically-sound performance evaluation and quantile regression, extending it to accommodate the idiosyncrasies of server systems. Finally, we use our augmented methodology to evaluate the impact of common server hardware features with Facebook production workloads on production hardware. We decompose the effects of these features on request tail latency and demonstrate that our evaluation methodology provides superior results, particularly in capturing complicated and counter-intuitive performance behaviors. By tuning the hardware features as suggested by the attribution, we reduce the 99th-percentile latency by 43% and its variance by 93%.
Rescuing uncorrectable fault patterns in on-chip memories through error pattern transformation
Authors: Duwe Henry , Jian Xun , Petrisko Daniel , Kumar Rakesh
Published: October 2016

Voltage scaling can effectively reduce processor power, but also reduces the reliability of the SRAM cells in on-chip memories. Therefore, it is often accompanied by the use of an error correcting code (ECC). To enable reliable and efficient memory operation at low voltages, ECCs for on-chip memories must provide both high error coverage and low correction latency. In this paper, we propose error pattern transformation, a novel low-latency error correction technique that allows on-chip memories to be scaled to voltages lower than what has been previously possible. Our technique relies on the observation that the number of on-chip memory errors that many ECCs can correct differs widely depending on the error patterns in the logical words they protect. We propose adaptively rearranging the logical bit to physical bit mapping per word according to the BIST-detectable fault pattern in the physical word. The adaptive logical bit to physical bit mapping transforms many uncorrectable error patterns in the logical words into correctable error patterns and, therefore, improving on-chip memory reliability. This reduces the minimum voltage at which on-chip memory can run by 70mV over the best low-latency ECC baseline, leading to a 25.7% core-wide power reduction for an ARM Cortex-A7-like core. Energy per instruction is reduced by 15.7% compared to the best baseline.
Using multiple input, multiple output formal control to maximize resource efficiency in architectures
Authors: Pothukuchi Raghavendra Pradyumna , Ansari Amin , Voulgaris Petros , Torrellas Josep
Published: October 2016

As processors seek more resource efficiency, they increasingly need to target multiple goals at the same time, such as a level of performance, power consumption, and average utilization. Robust control solutions cannot come from heuristic-based controllers or even from formal approaches that combine multiple single-parameter controllers. Such controllers may end-up working against each other. What is needed is control-theoretical MIMO (multiple input, multiple output) controllers, which actuate on multiple inputs and control multiple outputs in a coordinated manner.

In this paper, we use MIMO control-theory techniques to develop controllers to dynamically tune architectural parameters in processors. To our knowledge, this is the first work in this area. We discuss three ways in which a MIMO controller can be used. We develop an example of MIMO controller and show that it is substantially more effective than controllers based on heuristics or built by combining single-parameter formal controllers. The general approach discussed here is likely to be increasingly relevant as future processors become more resource-constrained and adaptive.
miR-11 regulates pupal size of Drosophila melanogaster via directly targeting Ras85D
Authors: Li Yao , Li Shengjie , Jin Ping , Chen Liming , Ma Fei
Published: October 2016

MicroRNAs play diverse roles in various physiological processes during Drosophila development. In the present study, we reported that miR-11 regulates pupal size during Drosophila metamorphosis via targeting Ras85D with the following evidences: pupal size was increased in the miR-11 deletion mutant; restoration of miR-11 in the miR-11 deletion mutant rescued the increased pupal size phenotype observed in the miR-11 deletion mutant; ectopic expression of miR-11 in brain insulin-producing cells (IPCs) and whole body shows consistent alteration of pupal size; Dilps and Ras85D expressions were negatively regulated by miR-11 in vivo; miR-11 targets Ras85D through directly binding to Ras85D 3′-untranslated region in vitro; removal of one copy of Ras85D in the miR-11 deletion mutant rescued the increased pupal size phenotype observed in the miR-11 deletion mutant. Thus, our current work provides a novel mechanism of pupal size determination by microRNAs during Drosophila melanogaster metamorphosis.
Effects of dietary iron intake and chronic kidney disease on fibroblast growth factor 23 metabolism in wild-type and hepcidin knockout mice
Authors: Hanudel Mark R. , Chua Kristine , Rappaport Maxime , Gabayan Victoria , Valore Erika , Goltzman David , Ganz Tomas , Nemeth Elizabeta , Salusky Isidro B.
Published: October 2016

In the setting of normal kidney function, iron deficiency is associated with increased FGF23 production and cleavage, altering circulating FGF23 levels. Our objective was to determine how chronic kidney disease (CKD) and dietary iron intake affect FGF23 production and metabolism in wild-type (WT) and hepcidin knockout (HKO) mice. For 8 wk, the mice were fed diets that contained adenine (to induce CKD) or no adenine (control group), with either low-iron (4 ppm) or standard-iron (335 ppm) concentrations. The low-iron diet induced iron deficiency anemia in both the WT and HKO mice. Among the WT mice, in both the control and CKD groups, a low-iron compared with a standard-iron diet increased bone Fgf23 mRNA expression, C-terminal FGF23 (cFGF23) levels, and FGF23 cleavage as manifested by a lower percentage intact FGF23 (iFGF23). Independent of iron status, CKD was associated with inhibition of FGF23 cleavage. Similar results were observed in the HKO control and CKD groups. Dietary iron content was more influential on FGF23 parameters than the presence or absence of hepcidin. In the CKD mice (WT and HKO, total n = 42), independent of the effects of serum phosphate, iron deficiency was associated with increased FGF23 production but also greater cleavage, whereas worse kidney function was associated with increased FGF23 production but decreased cleavage. Therefore, in both the WT and HKO mouse models, dietary iron content and CKD affected FGF23 production and metabolism.
Seeing a straight line on a curved surface: decoupling of patterns from surfaces by single IT neurons
Authors: Ratan Murty N. Apurva , Arun S. P.
Published: October 2016

We have no difficulty seeing a straight line drawn on a paper even when the paper is bent, but this inference is in fact nontrivial. Doing so requires either matching local features or representing the pattern after factoring out the surface shape. Here we show that single neurons in the monkey inferior temporal (IT) cortex show invariant responses to patterns across rigid and nonrigid changes of surfaces. We recorded neuronal responses to stimuli in which the pattern and the surrounding surface were varied independently. In a subset of neurons, we found pattern-surface interactions that produced similar responses to stimuli across congruent pattern and surface transformations. These interactions produced systematic shifts in curvature tuning of patterns when overlaid on convex and flat surfaces. Our results show that surfaces are factored out of patterns by single neurons, thereby enabling complex perceptual inferences.

NEW & NOTEWORTHY We have no difficulty seeing a straight line on a curved piece of paper, but in fact, doing so requires decoupling the shape of the surface from the pattern itself. Here we report a novel form of invariance in the visual cortex: single neurons in monkey inferior temporal cortex respond similarly to congruent transformations of patterns and surfaces, in effect decoupling patterns from the surface on which they are overlaid.
An Unusual Case of Paraganglioma of the Broad Ligament Presenting as Cystic Mass
Authors: Sinai Khandeparkar Siddhi Gaurish , Kulkarni Maithili Mandar , Gaopande Vandana , Joshi Avinash , Naphade Pushpalata
Published: October 2016

In clinical practice, broad ligament (BL) tumors are seldom encountered. Paraganglioma of the BL is exceedingly rare entity. Here we present an unusual case of broad ligament paraganglioma, presenting as a cystic mass, in a 50-year-old postmenopausal female. A high degree of suspicion along with detailed immunohistopathological work-up is needed for arriving at an accurate diagnosis.
Measurement of Mobile Switching Centres Throughput in GSM Network Integrating Sliding Window Algorithm with a Single Server Finite Queuing Model
Authors: Babu Bollini Dinaker , Muniratnam Naidu Mannava , Rao Nuka Mallikharjuna
Published: October 2016

The sliding window algorithm proposed for determining an optimal sliding window does not consider the waiting times of call setup requests of a mobile station in queue at a Mobile Switching Centre (MSC) in the Global System for Mobile (GSM) Communication Network. This study proposes a model integrating the sliding window algorithm with a single server finite queuing model, referred to as integrated model for measurement of realistic throughput of a MSC considering the waiting times of call setup requests. It assumes that a MSC can process one call setup request at a time. It is useful in determining an optimal sliding window size that maximizes the realistic throughput of a MSC. Though the model assumes that a MSC can process one call setup request at a time, its scope can be extended for measuring the realistic throughput of a MSC that can process multiple call setup requests at a time.
Rapid and Quantitative Determination of S-Adenosyl-L-Methionine in the Fermentation Process by Surface-Enhanced Raman Scattering
Authors: Ren Hairui , Chen Zhaoyang , Zhang Xin , Zhao Yongmei , Wang Zheng , Wu Zhenglong , Xu Haijun
Published: October 2016

Concentrations of S-Adenosyl-L-Methionine (SAM) in aqueous solution and fermentation liquids were quantitatively determined by surface-enhanced Raman scattering (SERS) and verified by high-pressure liquid chromatography (HPLC). The Ag nanoparticle/silicon nanowire array substrate was fabricated and employed as an active SERS substrate to indirectly measure the SAM concentration. The linear relationship between the integrated intensity of peak centered at ~2920 cm−1in SERS spectra and the SAM concentration was established, and the limit of detections of SAM concentrations was analyzed to be ~0.1 g/L. The concentration of SAM in real solution could be predicted by the linear relationship and verified by the HPLC detection method. The relative deviations (δ) of the predicted SAM concentration are less than 13% and the correlation coefficient is 0.9998. Rolling-Circle Filter was utilized to subtract fluorescence background and the optimal results were obtained when the radius of the analyzing circle is 650 cm−1.
Application of Cerium (IV) as an Oxidimetric Agent for the Determination of Ethionamide in Pharmaceutical Formulations
Authors: Basavaiah Kanakapura , Qarah Nagib A. S. , Abdulrahman Sameer A. M.
Published: October 2016

Two simple methods are described for the determination of ethionamide (ETM) in bulk drug and tablets using cerium (IV) sulphate as the oxidimetric agent. In both methods, the sample solution is treated with a measured excess of cerium (IV) solution in H2SO4 medium, and after a fixed standing time, the residual oxidant is determined either by back titration with standard iron (II) solution to a ferroin end point in titrimetry or by reacting with o-dianisidine followed by measurement of the absorbance of the orange-red coloured product at 470 nm in spectrophotometry. In titrimetry, the reaction proceeded with a stoichiometry of 1 : 2 (ETM : Ce (IV)) and the amount of cerium (IV) consumed by ETM was related to the latter’s amount, and the method was applicable over 1.0–8.0 mg of drug. In spectrophotometry, Beer’s law was obeyed over the concentration range of 0.5–5.0 μg/mL ETM with a molar absorptivity value of 2.66 × 104 L/(mol·cm). The limits of detection (LOD) and quantification (LOQ) calculated according to ICH guidelines were 0.013 and 0.043 μg/mL, respectively. The proposed titrimetric and spectrophotometric methods were found to yield reliable results when applied to bulk drug and tablets analysis, and hence they can be applied in quality control laboratories.