bluuebunny/crossref_metadata_2025_split 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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACT
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

Abstract
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 &gt;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 &gt;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.
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

IntroductionLiver 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 analysisFor 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 disseminationSince 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.
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.
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.
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%.
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.
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.