bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilization of Variant and Fusion Proteins To Functionally Map the Aggregatibacter actinomycetemcomitans Trimeric Autotransporter Protein ApiA
Authors: Cugini Carla , Mei Yongyi , Furgang David , George Nisha , Ramasubbu Narayanan , Fine Daniel H.
Published: December 2017

The Gram-negative bacterium
Aggregatibacter actinomycetemcomitans
is a causative agent of localized aggressive periodontitis. Critical to its infection process is the first and essential step of attachment, which is related to the coordinated functions of surface components comprised of proteins and extracellular polysaccharides. One such protein is the outer membrane trimeric autotransporter protein ApiA, a versatile virulence factor with numerous functions, including cell binding, invasion, serum resistance, autoaggregation, and induction of cytokine release. Here we report on the use of
Escherichia coli
strains expressing protein variants to define the separate functions ascribed to the N terminus and those related to the C terminus. Importantly, a hybrid protein that comprised the N terminus of trimeric ApiA and the β-barrel domain of monomeric autotransporter Aae was constructed, which allowed the expression of a monomer surface-exposed domain of ApiA. Functional and phenotypic analyses demonstrated that the C terminus of ApiA forms an independent domain that is crucial for general stability and trimer formation, which appears to be associated with autoaggregation, biofilm formation, and surface expression. Importantly, the results show that the monomeric form of the N-terminal passenger domain of ApiA, while surface exposed, is sufficient for binding to buccal epithelial cells; however, it is not sufficient to allow aggregation and biofilm formation, strengthening the importance of the role of trimerization in these phenotypes.
CdtC-Induced Processing of Membrane-Bound CdtA Is a Crucial Step in Aggregatibacter actinomycetemcomitans Cytolethal Distending Toxin Holotoxin Formation
Authors: Tsuruda Keiko , Matangkasombut Oranart , Ohara Masaru , Sugai Motoyuki
Published: December 2017

Aggregatibacter actinomycetemcomitans
is an oral pathogen causing periodontal disease and bacterial endocarditis. It produces cytolethal distending toxin (CDT) that could damage mammalian cells and tissues. CDT is a tripartite protein toxin composed of CdtA, CdtB, and CdtC. We have previously indicated that CdtA is a lipoprotein and that the proteolytic processing of CdtA is important for biogenesis and secretion of CDT holotoxin. Here, we established an
in vitro
processing assay of CdtA and investigated the interactions of CdtA with other Cdt subunits. This assay demonstrated that incubation of membrane-bound CdtA (MCdtA), CdtB, and CdtC immediately generated a processed form of CdtA (CdtA′), which is recovered from the soluble fraction. In contrast, incubation of soluble membrane-unbound CdtA with CdtB and CdtC did not yield any CdtA′. Furthermore, incubation of CdtC with MCdtA was enough to induce rapid processing of MCdtA, whereas CdtB alone was unable to induce the processing. Coimmunoprecipitation demonstrated that CdtA′ and CdtC formed a complex. Furthermore, subsequent addition of CdtB to this reaction mixture resulted in complete CDT holotoxin complex. The cytolethal distending activity assay demonstrated that CDT complex containing CdtA′ showed far stronger cytotoxicity than that containing CdtA. Collectively, our data suggest that CDT holotoxin formation
in vivo
is a sequential event: interaction of MCdtA and CdtC induces proteolytic processing of MCdtA, and the released CdtA′ forms a complex with CdtC. Subsequent binding of CdtB to the CdtA′/CdtC complex results in CDT holotoxin formation.
The Superantigen Toxic Shock Syndrome Toxin 1 Alters Human Aortic Endothelial Cell Function
Authors: Kulhankova Katarina , Kinney Kyle J. , Stach Jessica M. , Gourronc Françoise A. , Grumbach Isabella M. , Klingelhutz Aloysius J. , Salgado-Pabón Wilmara
Published: December 2017

Staphylococcus aureusinfective endocarditis (IE) is a fast-progressing and tissue-destructive infection of the cardiac endothelium. The superantigens (SAgs) toxic shock syndrome toxin 1 (TSST-1), staphylococcal enterotoxin C (SEC), and the toxins encoded by the enterotoxin gene cluster (egc) play a novel and essential role in the etiology ofS. aureusIE. Recent studies indicate that SAgs act at the infection site to cause tissue pathology and promote vegetation growth. The underlying mechanism of SAg involvement has not been clearly defined. In SAg-mediated responses, immune cell priming is considered a primary triggering event leading to endothelial cell activation and altered function. Utilizing immortalized human aortic endothelial cells (iHAECs), we demonstrated that TSST-1 directly activates iHAECs, as documented by upregulation of vascular and intercellular adhesion molecules (VCAM-1 and ICAM-1). TSST-1-mediated activation results in increased monolayer permeability and defects in vascular reendothelialization. Yet stimulation of iHAECs with TSST-1 fails to induce interleukin-8 (IL-8) and IL-6 production. Furthermore, simultaneous stimulation of iHAECs with TSST-1 and lipopolysaccharide (LPS) inhibits LPS-mediated IL-8 and IL-6 secretion, even after pretreatment with either of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and IL-1β. IL-8 suppression is not mediated by TSST-1 binding to its canonical receptor major histocompatibility complex class II (MHC-II), supporting current evidence for a nonhematopoietic interacting site on SAgs. Together, the data suggest that TSST-1 differentially regulates cell-bound and secreted markers of endothelial cell activation that may result in dysregulated innate immune responses duringS. aureusIE. Endothelial changes resulting from the action of SAgs can therefore directly contribute to the aggressive nature ofS. aureusIE and development of life-threatening complications.
Macrophage Polarization Alters Postphagocytosis Survivability of the Commensal Streptococcus gordonii
Authors: Croft Andrew J. , Metcalfe Sarah , Honma Kiyonobu , Kay Jason G.
Published: December 2017

Oral streptococci are generally considered commensal organisms; however, they are becoming recognized as important associate pathogens during the development of periodontal disease as well as being associated with several systemic diseases, including as a causative agent of infective endocarditis. An important virulence determinant of these bacteria is an ability to evade destruction by phagocytic cells, yet how this subversion occurs is mostly unknown. UsingStreptococcus gordoniias a model commensal oral streptococcus that is also associated with disease, we find that resistance to reactive oxygen species (ROS) with an active ability to damage phagosomes allows the bacterium to avoid destruction within macrophages. This ability to survive relies not only on the ROS resistance capabilities of the bacterium but also on ROS production by macrophages, with both being required for maximal survival of internalized bacteria. Importantly, we also show that this dependence on ROS production by macrophages for resistance has functional significance:S. gordoniiintracellular survival increases when macrophages are polarized toward an activated (M1) profile, which is known to result in prolonged phagosomal ROS production compared to that of alternatively (M2) polarized macrophages. We additionally find evidence of the bacterium being capable of both delaying the maturation of and damaging phagosomes. Taken together, these results provide essential insights regarding the mechanisms through which normally commensal oral bacteria can contribute to both local and systemic inflammatory disease.
Galactosylation of the Secondary Cell Wall Polysaccharide of Bacillus anthracis and Its Contribution to Anthrax Pathogenesis
Authors: Chateau Alice , Lunderberg Justin Mark , Oh So Young , Abshire Teresa , Friedlander Arthur , Quinn Conrad P. , Missiakas Dominique M. , Schneewind Olaf
Published: December 2017

Bacillus anthracis
, the causative agent of anthrax disease, elaborates a secondary cell wall polysaccharide (SCWP) that is essential for bacterial growth and cell division.
B. anthracis
SCWP is comprised of trisaccharide repeats with the structure, [→4)-β-ManNAc-(1→4)-β-GlcNAc(
O
3-α-Gal)-(1→6)-α-GlcNAc(
O
3-α-Gal,
O
4-β-Gal)-(1→]
6-12
. The genes whose products promote the galactosylation of
B. anthracis
SCWP are not yet known. We show here that the expression of
galE1
, encoding a UDP-glucose 4-epimerase necessary for the synthesis of UDP-galactose, is required for
B. anthracis
SCWP galactosylation. The
galE1
mutant assembles surface (S) layer and S layer-associated proteins that associate with ketal-pyruvylated SCWP via their S layer homology domains similarly to wild-type
B. anthracis
, but the mutant displays a defect in γ-phage murein hydrolase binding to SCWP. Furthermore, deletion of
galE1
diminishes the capsulation of
B. anthracis
with poly-
d
-γ-glutamic acid (PDGA) and causes a reduction in bacterial virulence. These data suggest that SCWP galactosylation is required for the physiologic assembly of the
B. anthracis
cell wall envelope and for the pathogenesis of anthrax disease.

IMPORTANCE
Unlike virulent
Bacillus anthracis
isolates,
B. anthracis
strain CDC684 synthesizes secondary cell wall polysaccharide (SCWP) trisaccharide repeats without galactosyl modification, exhibits diminished growth
in vitro
in broth cultures, and is severely attenuated in an animal model of anthrax. To examine whether SCWP galactosylation is a requirement for anthrax disease, we generated variants of
B. anthracis
strains Sterne 34F2 and Ames lacking UDP-glucose 4-epimerase by mutating the genes
galE1
and
galE2
. We identified
galE1
as necessary for SCWP galactosylation. Deletion of
galE1
decreased the poly-
d
-γ-glutamic acid (PDGA) capsulation of the vegetative form of
B. anthracis
and increased the bacterial inoculum required to produce lethal disease in mice, indicating that SCWP galactosylation is indeed a determinant of anthrax disease.
Flexible Hinges in Bacterial Chemoreceptors
Authors: Akkaladevi Narahari , Bunyak Filiz , Stalla David , White Tommi A. , Hazelbauer Gerald L.
Published: December 2017

Transmembrane bacterial chemoreceptors are extended, rod-shaped homodimers with ligand-binding sites at one end and interaction sites for signaling complex formation and histidine kinase control at the other. There are atomic-resolution structures of chemoreceptor fragments but not of intact, membrane-inserted receptors. Electron tomography of
in vivo
signaling complex arrays lack distinct densities for chemoreceptor rods away from the well-ordered base plate region, implying structural heterogeneity. We used negative staining, transmission electron microscopy, and image analysis to characterize the molecular shapes of intact homodimers of the
Escherichia coli
aspartate receptor Tar rendered functional by insertion into nanodisc-provided
E. coli
lipid bilayers. Single-particle analysis plus tomography of particles in a three-dimensional matrix revealed two bend loci in the chemoreceptor cytoplasmic domain, (i) a short, two-strand gap between the membrane-proximal, four-helix-bundle HAMP (histidine kinases, adenylyl cyclases, methyl-accepting chemoreceptors, and phosphatases) domain and the membrane-distal, four-helix coiled coil and (ii) aligned glycines in the extended, four-helix coiled coil, the position of a bend noted in the previous X-ray structure of a receptor fragment. Our images showed HAMP bends from 0° to ∼13° and glycine bends from 0° to ∼20°, suggesting that the loci are flexible hinges. Variable hinge bending explains indistinct densities for receptor rods outside the base plate region in subvolume averages of chemotaxis arrays. Bending at flexible hinges was not correlated with the chemoreceptor signaling state. However, our analyses showed that chemoreceptor bending avoided what would otherwise be steric clashes between neighboring receptors that would block the formation of core signaling complexes and chemoreceptor arrays.

IMPORTANCE
This work provides new information about the shape of transmembrane bacterial chemoreceptors, crucial components in the molecular machinery of bacterial chemotaxis. We found that intact, lipid-bilayer-inserted, and thus functional homodimers of the
Escherichia coli
chemoreceptor Tar exhibited bends at two flexible hinges along their ∼200-Å, rod-like, cytoplasmic domains. One hinge was at the short, two-strand gap between the membrane-proximal, four-helix-bundle HAMP (histidine kinases, adenylyl cyclases, methyl-accepting chemoreceptors, and phosphatases) domain and the membrane-distal, four-helix coiled coil. The other hinge was at aligned glycines in the extended, four-helix coiled coil, where a bend had been identified in the X-ray structure of a chemoreceptor fragment. Our analyses showed that flexible hinge bending avoided structural clashes in chemotaxis core complexes and their arrays.
Effectiveness of acupuncture for cancer pain: protocol for an umbrella review and meta-analyses of controlled trials
Authors: He Yihan , Liu Yihong , May Brian H , Zhang Anthony Lin , Zhang Haibo , Lu ChuanJian , Yang Lihong , Guo Xinfeng , Xue Charlie Changli
Published: December 2017

Introduction

The National Comprehensive Cancer Network guidelines for adult cancer pain indicate that acupuncture and related therapies may be valuable additions to pharmacological interventions for pain management. Of the systematic reviews related to this topic, some concluded that acupuncture was promising for alleviating cancer pain, while others argued that the evidence was insufficient to support its effectiveness.

Methods and analysis

This review will consist of three components: (1) synthesis of findings from existing systematic reviews; (2) updated meta-analyses of randomised clinical trials and (3) analyses of results of other types of clinical studies. We will search six English and four Chinese biomedical databases, dissertations and grey literature to identify systematic reviews and primary clinical studies. Two reviewers will screen results of the literature searches independently to identify included reviews and studies. Data from included articles will be abstracted for assessment, analysis and summary. Two assessors will appraise the quality of systematic reviews using Assessment of Multiple Systematic Reviews; assess the randomised controlled trials using the Cochrane Collaboration’s risk of bias tool and other types of studies according to the Newcastle-Ottawa Scale. We will use ‘summary of evidence’ tables to present evidence from existing systematic reviews and meta-analyses. Using the primary clinical studies, we will conduct meta-analysis for each outcome, by grouping studies based on the type of acupuncture, the comparator and the specific type of pain. Sensitivity analyses are planned according to clinical factors, acupuncture method, methodological characteristics and presence of statistical heterogeneity as applicable. For the non-randomised studies, we will tabulate the characteristics, outcome measures and the reported results of each study. Consistencies and inconsistencies in evidence will be investigated and discussed. Finally, we will use the Grading of Recommendations Assessment, Development and Evaluation approach to evaluate the quality of the overall evidence.

Ethics and dissemination

There are no ethical considerations associated with this review. The findings will be disseminated in peer-reviewed journals or conference presentations.

PROSPERO registration number

CRD42017064113.
Vacuolar processing enzymes, AmVPE1 and AmVPE2, as potential executors of ethylene regulated programmed cell death in the lace plant (Aponogeton madagascariensis)
Authors: Rantong Gaolathe , Gunawardena Arunika H.L.A.N.
Published: December 2017

Perforation formation in Aponogeton madagascariensis (Mirb.) H.Bruggen (lace plant) is an excellent model for studying developmentally regulated programmed cell death (PCD). In this study, we isolated and identified two lace plant vacuolar processing enzymes (VPEs) and investigated their involvement in PCD and throughout leaf development. Lace plant VPE transcript levels were determined during seven different stages of leaf development. PCD and non-PCD cells from “window” stage leaves (in which perforations are forming) were separated through laser-capture microscopy and their transcript levels were also determined. VPE activity was also studied between the cell types, through a VPE activity-based probe JOPD1. Additionally, VPE transcript levels were studied in plants treated with an ethylene biosynthesis inhibitor, aminoethoxyvinylglycine (AVG). The two isolated VPEs, AmVPE1 and AmVPE2, are vegetative type VPEs. AmVPE1 had higher transcript levels during a pre-perforation developmental stage, immediately prior to visible signs of PCD. AmVPE2 transcript levels were higher later during window and late window stages. Both VPEs had higher transcript and activity levels in PCD compared with the non-PCD cells. AVG treatment inhibited PCD and associated increases in VPE transcript levels. Our results suggested that VPEs are involved in the execution of the ethylene-related PCD in the lace plant.
Adaptive control of structural balance for complex dynamical networks based on dynamic coupling of nodes
Authors: Gao Zilin , Wang Yinhe , Zhang Lili
Published: December 2017

In the existing research results of the complex dynamical networks controlled, the controllers are mainly used to guarantee the synchronization or stabilization of the nodes’ state, and the terms coupled with connection relationships may affect the behaviors of nodes, this obviously ignores the dynamic common behavior of the connection relationships between the nodes. In fact, from the point of view of large-scale system, a complex dynamical network can be regarded to be composed of two time-varying dynamic subsystems, which can be called the nodes subsystem and the connection relationships subsystem, respectively. Similar to the synchronization or stabilization of the nodes subsystem, some characteristic phenomena can be also emerged in the connection relationships subsystem. For example, the structural balance in the social networks and the synaptic facilitation in the biological neural networks. This paper focuses on the structural balance in dynamic complex networks. Generally speaking, the state of the connection relationships subsystem is difficult to be measured accurately in practical applications, and thus it is not easy to implant the controller directly into the connection relationships subsystem. It is noted that the nodes subsystem and the relationships subsystem are mutually coupled, which implies that the state of the connection relationships subsystem can be affected by the controllable state of nodes subsystem. Inspired by this observation, by using the structural balance theory of triad, the controller with the parameter adaptive law is proposed for the nodes subsystem in this paper, which may ensure the connection relationship matrix to approximate a given structural balance matrix in the sense of the uniformly ultimately bounded (UUB). That is, the structural balance may be obtained by employing the controlling state of the nodes subsystem. Finally, the simulations are used to show the validity of the method in this paper.
SURFACE MODIFICATIONS OF ACTIVATED CARBON AND ITS IMPACT ON APPLICATION
Authors: PEGO MATHEUS , CARVALHO JANAÍNA , GUEDES DAVID
Published: December 2017

The main and new surface modification methods of activated carbon (AC) and their influence on application (adsorption capacity) were reviewed. Adsorption capacity is an important issue, contributing to hazardous substances environment management. According to literature, it is true that surface chemistry strongly affects adsorption capacity. Surface chemistry can be modified by several methods that lead to different activated carbon properties. Furthermore, adsorbate properties, and their relationships with surface structure, can impact adsorption properties. Surface modifications can be conducted by adding some atoms to the surface structure, making the surface more acidic or basic. Introduction of oxygen and ammonia atoms (chemical modification) are the main processes to make the surface more acidic and basic, respectively, although may bring chemical wastes to environment. Surface modification is done by chemical and physical modifications that lead activated carbons to present different properties. The main and new methods of chemical and physical modifications are compared and presented in this paper. Some new physical methods, like corona treatment, plasma discharge and microwave radiation, can be applied to cause surface modifications. Corona treatment can be a practical and new way to cause surface modification on an activated carbon surface.
Maximin and Minimax Strategies in Two-Players Game with Two Strategic Variables
Authors: Satoh Atsuhiro , Tanaka Yasuhito
Published: December 2017

We examine maximin and minimax strategies for players in a two-players game with two strategic variables, [Formula: see text] and [Formula: see text]. We consider two patterns of game; one is the [Formula: see text]-game in which the strategic variables of players are [Formula: see text]’s, and the other is the [Formula: see text]-game in which the strategic variables of players are [Formula: see text]’s. We call two players Players A and B, and will show that the maximin strategy and the minimax strategy in the [Formula: see text]-game, and the maximin strategy and the minimax strategy in the [Formula: see text]-game are all equivalent for each player. However, the maximin strategy for Player A and that for Player B are not necessarily equivalent, and they are not necessarily equivalent to their Nash equilibrium strategies in the [Formula: see text]-game nor the [Formula: see text]-game. But, in a special case, where the objective function of Player B is the opposite of the objective function of Player A, the maximin strategy for Player A and that for Player B are equivalent, and they constitute the Nash equilibrium both in the [Formula: see text]-game and the [Formula: see text]-game.
H∞ Constraint Pareto Optimal Strategy for Stochastic LPV Systems
Authors: Ahmed Mostak , Mukaidani Hiroaki , Shima Tadashi
Published: December 2017

[Formula: see text] constraint Pareto optimal strategy for stochastic linear parameter varying (LPV) systems with multiple decision makers is investigated. The modified stochastic bounded real lemma and linear quadratic control (LQC) for the stochastic LPV systems are reformulated by means of linear matrix inequalities (LMIs). In order to decide the strategy set of multiple decision makers, Pareto optimal strategy is considered for each player and the [Formula: see text] constraint is imposed. The solvability conditions of the problem are established from cross-coupled matrix inequalities (CCMIs). The efficiency of the proposed strategy set is demonstrated using a numerical example.
Micromechanical Modeling of Flexural Strength for Epoxy Polymer Concrete
Authors: Ma Dongpeng , Liu Yiping , Zhang Nanli , Jiang Zhenyu , Tang Liqun , Xi Huifeng
Published: December 2017

Epoxy polymer concrete (EPC) has been widely used in civil engineering nowadays due to its excellent mechanical properties and advantages in processing. In this paper, a modeling study has been carried out on the flexural performance of EPC. Two classic micromechanics models, i.e. rule of mixture and Mori-Tanaka method, are introduced to predict the flexural strength of EPC with various epoxy resin contents. The comparison shows that the parallel model based on the rule of mixture attains a good agreement with the measured results when the epoxy resin content is sufficiently high to achieve strong adhesion between the aggregate and the epoxy resin. In contrast, the Mori–Tanaka method with the failure criterion dominated by the weakest phase fails to give acceptable prediction due to the unsuitability of its basic assumptions to EPC, particularly when the epoxy resin content is at relatively high levels.
Sharing the Benefits of China’s Growth by Providing Opportunities to All
Authors: Westmore Ben
Published: December 2017

Living standards in China have greatly improved over the past few decades. Both sustained economic growth and an expansion of the social security system have contributed to a sharp reduction in the number of people in poverty. However, urban–rural inequalities remain large, and some of the poorest households are being left behind. Further reforms are needed to ensure that the benefits of future growth are shared and that marginalized groups have the opportunity to actively participate in the economy. In particular, policy settings should be adjusted to increase access to good quality education and healthcare for rural and migrant workers and to improve the portability of social security benefits. Changes to the social assistance system that raise work incentives and protect low-income households in poorer locations are also a priority. New spending measures can be funded by adjustments to the tax system which will, in themselves, benefit inclusiveness.
Credit Rating Downgrades and Sudden Stops of Capital Flows in the Eurozone
Authors: Ioannou Stefanos
Published: December 2017

The current paper investigates the impact of sovereign ratings on sudden stops of capital in the context of the Eurozone. Our analysis focuses on the qualitative aspect of ratings on the hypothesis that such aspect has a concrete impact on capital movements. A panel probit model is utilized for our purposes. We distinguish between net and gross capital inflows, while we also draw a distinction between long-term and short-term oriented capital. Our results confirm the influence of sovereign ratings for the majority of our model specifications. They also appear to be most significant in the case of short-term flows.
The 2015/16 “Super” El Niño Event and Its Climatic Impact
Authors: ZHOU Bing , SHAO Xie
Published: December 2017

Climatic monitoring shows that 2015 has been the warmest year around the globe since the first modern observation was conducted in1880. Asia has witnessed its average land surface temperature reaching the highest level since 1901; China has seen the warmest year since 1951 when it had completed the meteorological records; the CO2 concentration in the atmosphere exceeds 400[Formula: see text]ppm; the ocean thermal capacity sets a new record high; and the global sea surface temperature has also been the highest since 1870. Against the backdrop of global warming, the incidence of strong El Niño and the duration of El Niño in the central and eastern equatorial Pacific Ocean have both significantly increased, while the time interval between El Niño and La Niña has shortened. The 2015/16 “Super” El Niño event exceeds previous two “Super” El Niño events in several indexes (e.g. durative event and peak intensity), although the 1982/83 El Niño event keeps the record in terms of the intensity of atmospheric response to the ocean. Influenced by the 2015/16 “Super” El Niño event, the general atmospheric circulation was significantly abnormal with extreme climate events frequently occurring in many places worldwide.
Mass Digitization of Early Modern Texts With Optical Character Recognition
Authors: Christy Matthew , Gupta Anshul , Grumbach Elizabeth , Mandell Laura , Furuta Richard , Gutierrez-Osuna Ricardo
Published: December 2017

Optical character recognition (OCR) engines work poorly on texts published with premodern printing technologies. Engaging the key technological contributors from the IMPACT project, an earlier project attempting to solve the OCR problem for early modern and modern texts, the Early Modern OCR Project (eMOP) of Texas A8M received funding from the Andrew W. Mellon Foundation to improve OCR outputs for early modern texts from the Eighteenth Century Collections Online (ECCO) and Early English Books Online (EEBO) proprietary database products—or some 45 million pages. Added to print problems are the poor quality of the page images in these collections, which would be too time consuming and expensive to reimage. This article describes eMOP's attempts to OCR 307,000 documents digitized from microfilm to make our cultural heritage available for current and future researchers. We describe the reasoning behind our choices as we undertook the project based on other relevant studies; discoveries we made; the data and the system we developed for processing it; the software, algorithms, training procedures, and tools that we developed; and future directions that should be taken for further work in developing OCR engines for cultural heritage materials.
Modeling Drive-Managed SMR Performance
Authors: Shafaei Mansour , Hajkazemi Mohammad Hossein , Desnoyers Peter , Aghayev Abutalib
Published: December 2017

Accurately modeling drive-managed Shingled Magnetic Recording (SMR) disks is a challenge, requiring an array of approaches including both existing disk modeling techniques as well as new techniques for inferring internal translation layer algorithms. In this work, we present the first predictive simulation model of a generally available drive-managed SMR disk. Despite the use of unknown proprietary algorithms in this device, our model that is derived from external measurements is able to predict mean latency within a few percent, and with an Root Mean Square (RMS) cumulative latency error of 25% or less for most workloads tested. These variations, although not small, are in most cases less than three times the drive-to-drive variation seen among seemingly identical drives.
Effective Verification for Low-Level Software with Competing Interrupts
Authors: Liang Lihao , Melham Tom , Kroening Daniel , Schrammel Peter , Tautschnig Michael
Published: December 2017

Interrupt-driven software is difficult to test and debug, especially when interrupts can be nested and subject to priorities. Interrupts can arrive at arbitrary times, leading to an exponential blow-up in the number of cases to consider. We present a new formal approach to verifying interrupt-driven software based on symbolic execution. The approach leverages recent advances in the encoding of the execution traces of interacting, concurrent threads. We assess the performance of our method on benchmarks drawn from embedded systems code and device drivers, and experimentally compare it to conventional approaches that use source-to-source transformations. Our results show that our method significantly outperforms these techniques. To the best of our knowledge, our work is the first to demonstrate effective verification of low-level embedded software with nested interrupts.
UDLF
Authors: Valem Lucas Pascotti , Guimarães Pedronette Daniel Carlos
Published: December 2017

The Unsupervised Distance Learning Framework (UDLF) [1] is a software developed to facilitate the general use and evaluation of novel unsupervised learning methods. These methods aim at post-processing the ranking information for different tasks, being especially useful for multimedia retrieval. The major advantage of UDLF is that it provides a unified and extensive model for implementing different unsupervised methods. Any execution or experiment can be easily conducted by setting a configuration file, no recompilation is required. To evaluate the retrieval results, the framework computes different effectiveness and efficiency measures and it allows for exporting visual output results to external files. UDLF is written in C++, works out of the box, does not require external libraries, and is compatible with different operating systems including Linux, MacOS, and Windows. The source code is publicly available on GitHub under the terms of the GPLv2 license.
Study on Quality Standard of Processed Curcuma Longa Radix
Authors: Chen Zhimin , Zhao Yongfeng , Quan Liang , Zhou Haiting , Cao Dong , Hu Changjiang , Li Wenbing , Yang Zhuo
Published: December 2017

To control the quality of Curcuma Longa Radix by establishing quality standards, this paper increased the contents of extract and volatile oil determination. Meanwhile, the curcumin was selected as the internal marker, and the relative correlation factors (RCFs) of demethoxycurcumin and bisdemethoxycurcumin were established by high performance liquid chromatography (HPLC). The contents of multicomponents were calculated based on their RCFs. The rationality and feasibility of the methods were evaluated by comparison of the quantitative results between external standard method (ESM) and quantitative analysis of multicomponents by single‐marker (QAMS). Ethanol extracts ranged from 9.749 to 15.644% and the mean value was 13.473%. The volatile oil ranged from 0.45 to 0.90 mL/100 g and the mean value was 0.66 mL/100 g. This method was accurate and feasible and could provide a reference for further comprehensive and effective control of the quality standard of Curcuma Longa Radix and its processed products.
Ultrasound in Infertility Setting: Optimal Strategy to Evaluate the Assessment of Tubal Patency
Authors: Mandia Luca , Personeni Carlo , Antonazzo Patrizio , Angileri Salvatore Alessio , Pinto Antonio , Savasi Valeria
Published: December 2017

Tubal patency is a key element in women who are undergoing assisted reproductive techniques (ART), in order to attempt or exclude intrauterine insemination (IUI) cycles. Amongst the different procedures that can be used, without resorting to laparoscopy that remains the gold standard, hystero-salpingo-contrast sonography (HyCoSy) is an acceptable, time-efficient, and well tolerated option; it can be performed with administration of saline and air simultaneously or alternately (air/saline-HyCoSy), or with some other contrast agents, like SonoVue (sulfur hexafluoride microbubbles). In this paper, we describe two different studies: in the first one, our aim is to compare the efficiency of air/saline-HyCoSy with HyCoSy performed with contrast media (SonoVue), considering hysterosalpingography (HSG) and laparoscopy (LPS) as reference tests; in the second one, we estimate the pregnancy rate of a cohort of infertile women selected to undergo IUI cycles after tubal bilateral patency demonstration with air/saline-HyCoSy, to understand if this technique can be used as an efficient screening procedure in a Reproductive Unit.
Optic Neuritis in the Older Chinese Population: A 5-Year Follow-Up Study
Authors: Wang Junqing , Zhou Huanfen , Qin Limin , Peng Chunxia , Zhao Jie , Teng Da , Lin Dahe , Ai Nanping , Xu Quangang , Wei Shihui
Published: December 2017

Objective. This study aims to describe the clinical manifestations and outcomes in a cohort of older Chinese patients.Method. A retrospective study of patients aged ≥ 45 years who had a first episode of optic neuritis (ON) between May 2008 and November 2012. Clinical features at onset and last follow-up were analyzed within subgroups (age 45–65 years and age ≥ 65 years).Results. 76 patients (99 eyes) were included, of which 58% were females. The mean age at presentation was 55.53 ± 8.29 years (range: 45–83 years). Vision loss was severe at presentation, with initial best corrected vision activity (BCVA) < 20/200 in 93% and final BCVA < 20/200 in 53% of patients at 5-year follow-up. Final BCVA significantly correlated with the initial BCVA and peripapillary retinal nerve fiber layer. At last follow-up, 14.5% were diagnosed with neuromyelitis optica spectrum disorder (NMOSD), 1.3% were diagnosed with multiple sclerosis (MS), 5.2% with chronic relapsing inflammatory optic neuropathy, 1.3% with infectious ON, and 19.7% with autoimmune ON. None of the elderly group (≥65 years) developed NMOSD or MS.Conclusion. Chinese patients in the age group ≥ 65 years with ON are less likely to develop NMOSD or MS. Notwithstanding, they had more severe visual loss at onset and poor recovery.
Nuclear Translocation of SGPP-1 and Decrease of SGPL-1 Activity Contribute to Sphingolipid Rheostat Regulation of Inflammatory Dendritic Cells
Authors: Schwiebs Anja , Thomas Dominique , Kleuser Burkhard , Pfeilschifter Josef M. , Radeke Heinfried H.
Published: December 2017

A balanced sphingolipid rheostat is indispensable for dendritic cell function and survival and thus initiation of an immune response. Sphingolipid levels are dynamically maintained by the action of sphingolipid enzymes of which sphingosine kinases, S1P phosphatases (SGPP-1/2) and S1P lyase (SGPL-1), are pivotal in the balance of S1P and sphingosine levels. In this study, we present that SGPP-1 and SGPL-1 are regulated in inflammatory dendritic cells and contribute to S1P fate. TLR-dependent activation caused SGPL-1 protein downregulation with subsequent decrease of enzymatic activity by two-thirds. In parallel, confocal fluorescence microscopy revealed that endogenous SGPP-1 was expressed in nuclei of naive dendritic cells and was translocated into the cytoplasmatic compartment upon inflammatory stimulation resulting in dephosphorylation of S1P. Mass spectrometric determination showed that a part of the resulting sphingosine was released from the cell, increasing extracellular levels. Another route of diminishing intracellular S1P was possibly taken by its export via ATP-binding cassette transporter C1 which was upregulated in array analysis, while the S1P transporter, spinster homolog 2, was not relevant in dendritic cells. These investigations newly describe the sequential expression and localization of the endogenous S1P regulators SGPP-1 and SGPL-1 and highlight their contribution to the sphingolipid rheostat in inflammation.
Prediction of Flow and Temperature Distributions in a High Flux Research Reactor Using the Porous Media Approach
Authors: Huang Shanfang , Gong Daxin , Li Chao , Guo Xiaoyu , Wang Guanbo , Yin Huaqiang , Wang Kan
Published: December 2017

High thermal neutron fluxes are needed in some research reactors and for irradiation tests of materials. A High Flux Research Reactor (HFRR) with an inverse flux trap-converter target structure is being developed by the Reactor Engineering Analysis Lab (REAL) at Tsinghua University. This paper studies the safety of the HFRR core by full core flow and temperature calculations using the porous media approach. The thermal nonequilibrium model is used in the porous media energy equation to calculate coolant and fuel assembly temperatures separately. The calculation results show that the coolant temperature keeps increasing along the flow direction, while the fuel temperature increases first and decreases afterwards. As long as the inlet coolant mass flow rate is greater than 450 kg/s, the peak cladding temperatures in the fuel assemblies are lower than the local saturation temperatures and no boiling exists. The flow distribution in the core is homogeneous with a small flow rate variation less than 5% for different assemblies. A large recirculation zone is observed in the outlet region. Moreover, the porous media model is compared with the exact model and found to be much more efficient than a detailed simulation of all the core components.
An Anatomical Study of Maxillary-Zygomatic Complex Using Three-Dimensional Computerized Tomography-Based Zygomatic Implantation
Authors: Xu Xiangliang , Zhao Shijie , Liu Hui , Sun Zhipeng , Wang Jianwei , Zhang Weiguang
Published: December 2017

Objective. To obtain anatomical data of maxillary-zygomatic complex based on simulating the zygomatic implantation using cadaver heads and three-dimensional computerized tomography (3D-CT). Methods. Simulating zygomatic implantation was performed using seven cadaver heads and 3D-CT images from forty-eight adults. After measuring the maxillary-zygomatic complex, we analyzed the position between the implantation path and the maxillary sinus cavity as well as the distance between the implantation path and the zygomatic nerve. Results. The distance from the starting point to the endpoint of the implant was 56.85 ± 5.35 mm in cadaver heads and 58.15 ± 7.37 mm in 3D-CT images. For the most common implantation path (80.20%), the implant went through the maxillary sinus cavity completely. The projecting points of the implant axis (IA) on the surface of zygoma were mainly located in the region of frontal process of zygomatic bone close to the lateral orbital wall. The distances between IA and zygomatic nerve in 53 sides were shorter than 2 mm. Conclusion. The simulating zygomatic implantation on cadaver skulls and 3D-CT imaging provided useful anatomical data of the maxillary-zygomatic complex. It is necessary to take care to avoid the zygomatic nerve injury during implantation, because it frequently appears on the route of implantation.
Nonlinear System Identification Using Quasi-ARX RBFN Models with a Parameter-Classified Scheme
Authors: Wang Lan , Cheng Yu , Hu Jinglu , Liang Jinling , Dobaie Abdullah M.
Published: December 2017

Quasi-linear autoregressive with exogenous inputs (Quasi-ARX) models have received considerable attention for their usefulness in nonlinear system identification and control. In this paper, identification methods of quasi-ARX type models are reviewed and categorized in three main groups, and a two-step learning approach is proposed as an extension of the parameter-classified methods to identify the quasi-ARX radial basis function network (RBFN) model. Firstly, a clustering method is utilized to provide statistical properties of the dataset for determining the parameters nonlinear to the model, which are interpreted meaningfully in the sense of interpolation parameters of a local linear model. Secondly, support vector regression is used to estimate the parameters linear to the model; meanwhile, an explicit kernel mapping is given in terms of the nonlinear parameter identification procedure, in which the model is transformed from the nonlinear-in-nature to the linear-in-parameter. Numerical and real cases are carried out finally to demonstrate the effectiveness and generalization ability of the proposed method.
N‐Butanol and Aqueous Fractions of Red Maca Methanolic Extract Exerts Opposite Effects on Androgen and Oestrogens Receptors (Alpha and Beta) in Rats with Testosterone‐Induced Benign Prostatic Hyperplasia
Authors: Fano Diego , Vásquez-Velásquez Cinthya , Gonzales-Castañeda Cynthia , Guajardo-Correa Emanuel , Orihuela Pedro A. , Gonzales Gustavo F.
Published: December 2017

Benign Prostatic Hyperplasia (BPH) affects, worldwide, 50% of 60‐year‐old men. The Peruvian plant red maca (Lepidium meyenii) inhibits BPH in rodents. This study aimed to determine the effects of methanolic red maca extract and its n‐butanol and aqueous fractions on expression of androgen and oestrogen receptors in rats with testosterone enanthate‐induced BPH. Thirty‐six rats in six groups were studied. Control group received 2 mL of vehicle orally and 0.1 mL of propylene glycol intramuscularly. The second group received vehicle orally and testosterone enanthate (TE) (25 mg/0.1 mL) intramuscularly in days 1 and 7. The other four groups were BPH‐induced with TE and received, during 21 days, 3.78 mg/mL of finasteride, 18.3 mg/mL methanol extract of red maca, 2 mg/mL of n‐butanol fraction, or 16.3 mg/mL of aqueous fraction from red maca. Treatments with red maca extract and its n‐butanol but not aqueous fraction reduced prostate weight similar to finasteride. All maca treated groups restored the expression of ERβ, but only the aqueous fraction increased androgen receptors and ERα. In conclusion, butanol fraction of red maca reduced prostate size in BPH by restoring expression of ERβ without affecting androgen receptors and ERα. This effect was not observed with aqueous fraction of methanolic extract of red maca.
On the Sums of Powers of Chebyshev Polynomials and Their Divisible Properties
Authors: Zhang Lan , Zhang Wenpeng
Published: December 2017

The main purpose of this paper is using mathematical induction and the Girard and Waring formula to study a problem involving the sums of powers of the Chebyshev polynomials and prove some divisible properties. We obtained two interesting congruence results involving Fibonacci numbers and Lucas numbers as some applications of our theorem.
Nkx2-2as Suppression Contributes to the Pathogenesis of Sonic Hedgehog Medulloblastoma
Authors: Zhang Yimeng , Wang Ting , Wang Shan , Xiong Yanlu , Zhang Rui , Zhang Xiang , Zhao Jing , Yang An-Gang , Wang Lei , Jia Lintao
Published: December 2017

Aberrant Hedgehog signaling and excessive activation of the Gli family of transcriptional activators are key drivers of medulloblastoma (MB), the most common human pediatric brain malignancy. MB originates mainly from cerebellar granule neuron progenitors (CGNP), but the mechanisms underlying CGNP transformation remain largely obscure. In this study, we found that suppression of the noncoding RNA Nkx2-2as promoted Sonic Hedgehog (Shh)-potentiated MB development. Nkx2-2as functioned as a competing endogenous RNA against miR-103 and miR-107, sequestering them and thereby derepressing their tumor suppressive targets BTG2 and LATS1 and impeding cell division and migration. We also found that Nkx2-2as tethered miR-548m and abrogated its LATS2 targeting activity. Shh signaling impaired Nkx2-2as expression by upregulating the transcriptional repressor FoxD1. In clinical specimens of Shh-subgroup MB, we validated coordinated expression of the aforementioned proteins. Notably, exogenous expression of Nkx2-2as suppressed tumorigenesis and prolonged animal survival in MB mouse models. Our findings illuminate the role of noncoding RNAs in Hedgehog signaling and MB occurrence, with implications for identifying candidate therapeutic targets for MB treatment.

Significance: These findings illuminate the role of noncoding RNAs in Hedgehog signaling and an interplay between the Hedgehog and Hippo pathways in medulloblastoma pathogenesis. Cancer Res; 78(4); 962–73. ©2017 AACR.
Transcription Factor Activities Enhance Markers of Drug Sensitivity in Cancer
Authors: Garcia-Alonso Luz , Iorio Francesco , Matchan Angela , Fonseca Nuno , Jaaks Patricia , Peat Gareth , Pignatelli Miguel , Falcone Fiammetta , Benes Cyril H. , Dunham Ian , Bignell Graham , McDade Simon S. , Garnett Mathew J. , Saez-Rodriguez Julio
Published: December 2017

Transcriptional dysregulation induced by aberrant transcription factors (TF) is a key feature of cancer, but its global influence on drug sensitivity has not been examined. Here, we infer the transcriptional activity of 127 TFs through analysis of RNA-seq gene expression data newly generated for 448 cancer cell lines, combined with publicly available datasets to survey a total of 1,056 cancer cell lines and 9,250 primary tumors. Predicted TF activities are supported by their agreement with independent shRNA essentiality profiles and homozygous gene deletions, and recapitulate mutant-specific mechanisms of transcriptional dysregulation in cancer. By analyzing cell line responses to 265 compounds, we uncovered numerous TFs whose activity interacts with anticancer drugs. Importantly, combining existing pharmacogenomic markers with TF activities often improves the stratification of cell lines in response to drug treatment. Our results, which can be queried freely at dorothea.opentargets.io, offer a broad foundation for discovering opportunities to refine personalized cancer therapies.

Significance: Systematic analysis of transcriptional dysregulation in cancer cell lines and patient tumor specimens offers a publicly searchable foundation to discover new opportunities to refine personalized cancer therapies. Cancer Res; 78(3); 769–80. ©2017 AACR.