bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissimilar Metal Analysis and Issues
Authors: Ainsworth Robert A.
Published: December 2016

Detailed analysis of dissimilar metal welds (DMWs) is difficult and the accuracy of the results is often limited by the availability of materials data and knowledge of operating conditions. There are few design or assessment procedures that explicitly take account of the presence of DMWs under high temperature creep and fatigue conditions. One that does is the UK R5 procedure, which provides a simplified assessment approach based on laboratory testing and stress analysis supported by service experience. This paper briefly summarises the R5 approach. Then, more recent work on performance of DMWs operating at high temperature and issues for development of analysis methods is discussed.
Spatially separating language masker from target results in spatial and linguistic masking release
Authors: Viswanathan Navin , Kokkinakis Kostas , Williams Brittany T.
Published: December 2016

Several studies demonstrate that in complex auditory scenes, speech recognition is improved when the competing background and target speech differ linguistically. However, such studies typically utilize spatially co-located speech sources which may not fully capture typical listening conditions. Furthermore, co-located presentation may overestimate the observed benefit of linguistic dissimilarity. The current study examines the effect of spatial separation on linguistic release from masking. Results demonstrate that linguistic release from masking does extend to spatially separated sources. The overall magnitude of the observed effect, however, appears to be diminished relative to the co-located presentation conditions.
Dam-building threatens Mekong fisheries
Authors: Stone Richard
Published: December 2016

With scores of dams planned, scientists debate measures to soften the impact.
Quest for qubits
Authors: Popkin Gabriel
Published: December 2016

How small startups are vying with corporate behemoths for quantum supremacy.
Quantized Faraday and Kerr rotation and axion electrodynamics of a 3D topological insulator
Authors: Wu Liang , Salehi M. , Koirala N. , Moon J. , Oh S. , Armitage N. P.
Published: December 2016

Time-domain terahertz polarimetry is used to measure the fine-structure constant in the solid state.
Intracellular innate immune surveillance devices in plants and animals
Authors: Jones Jonathan D. G. , Vance Russell E. , Dangl Jeffery L.
Published: December 2016

Shared logic in diverse immune systems

The innate immune systems of both plants and animals depend on the ability to recognize pathogen-derived molecules and stimulate a defense response. Jones
et al.
review how that common function is achieved in such diverse kingdoms by similar molecules. The recognition system is built for hair-trigger sensitivity and constructed in a modular manner. Understanding such features could be useful in building new pathways through synthetic biology, whether for broadening disease defenses or constructing new signal-response circuits.

Science
, this issue p.
10.1126/science.aaf6395
Spectroscopic snapshots of the proton-transfer mechanism in water
Authors: Wolke Conrad T. , Fournier Joseph A. , Dzugan Laura C. , Fagiani Matias R. , Odbadrakh Tuguldur T. , Knorke Harald , Jordan Kenneth D. , McCoy Anne B. , Asmis Knut R. , Johnson Mark A.
Published: December 2016

A view of acidic proton transport emerges in vibrational spectra of deuterated water clusters bound to a succession of bases.
Crystal structures of a group II intron lariat primed for reverse splicing
Authors: Costa Maria , Walbott Hélène , Monachello Dario , Westhof Eric , Michel François
Published: December 2016

Tie me up, cut me down

Group II in trons are mobile genetic elements found in all domains of life. They are large ribozymes that can excise themselves from host RNA. Costa
et al.
determined the structure of an excised group II intron in its branched conformation. This conformation is comparable to the branched “lariat” seen during the splicing of nuclear RNA transcripts. The lariat conformation helps assemble the group II active site for the reverse splicing reaction. The lariat in spliceosomal splicing may also have a similar role in the second step of messenger RNA intron removal.

Science
, this issue p.
10.1126/science.aaf9258
Selective modulation of cortical state during spatial attention
Authors: Engel Tatiana A. , Steinmetz Nicholas A. , Gieselmann Marc A. , Thiele Alexander , Moore Tirin , Boahen Kwabena
Published: December 2016

Brain state is controlled locally according to cognitive demands.
Galaxy formation through cosmic recycling
Authors: Hatch Nina
Published: December 2016

Direct observations reveal how massive galaxies formed in the early universe
When stop makes sense
Authors: Zinshteyn Boris , Green Rachel
Published: December 2016

RNA sequence context matters in the termination of protein translation
As the bat flies
Authors: Hayman David T. S.
Published: December 2016

Can virus transmission from bats to humans be predicted?
Spying on the neighbors' pool
Authors: Xantheas Sotiris S.
Published: December 2016

Spectral signatures are obtained for the movement of protons in cold water clusters
Trial and error
Authors: Eshel Neir
Published: December 2016

Optogenetic techniques offer insight into the dopamine circuit underlying learning
Passing the point of no return
Authors: Seekell David
Published: December 2016

Early warning signals indicate impending ecosystem regime changes
Yeast HMO1: Linker Histone Reinvented
Authors: Panday Arvind , Grove Anne
Published: December 2016

Eukaryotic genomes are packaged in chromatin. The higher-order organization of nucleosome core particles is controlled by the association of the intervening linker DNA with either the linker histone H1 or high mobility group box (HMGB) proteins. While H1 is thought to stabilize the nucleosome by preventing DNA unwrapping, the DNA bending imposed by HMGB may propagate to the nucleosome to destabilize chromatin. For metazoan H1, chromatin compaction requires its lysine-rich C-terminal domain, a domain that is buried between globular domains in the previously characterized yeast
Saccharomyces cerevisiae
linker histone Hho1p. Here, we discuss the functions of
S. cerevisiae
HMO1, an HMGB family protein unique in containing a terminal lysine-rich domain and in stabilizing genomic DNA. On ribosomal DNA (rDNA) and genes encoding ribosomal proteins, HMO1 appears to exert its role primarily by stabilizing nucleosome-free regions or “fragile” nucleosomes. During replication, HMO1 likewise appears to ensure low nucleosome density at DNA junctions associated with the DNA damage response or the need for topoisomerases to resolve catenanes. Notably, HMO1 shares with the mammalian linker histone H1 the ability to stabilize chromatin, as evidenced by the absence of HMO1 creating a more dynamic chromatin environment that is more sensitive to nuclease digestion and in which chromatin-remodeling events associated with DNA double-strand break repair occur faster; such chromatin stabilization requires the lysine-rich extension of HMO1. Thus, HMO1 appears to have evolved a unique linker histone-like function involving the ability to stabilize both conventional nucleosome arrays as well as DNA regions characterized by low nucleosome density or the presence of noncanonical nucleosomes.
Global burden of all-cause and cause-specific mortality due to smokeless tobacco use: systematic review and meta-analysis
Authors: Sinha Dhirendra N , Suliankatchi Rizwan A , Gupta Prakash C , Thamarangsi Thaksaphon , Agarwal Naveen , Parascandola Mark , Mehrotra Ravi
Published: December 2016

Objectives

To systematically review and meta-analyse the studies investigating the association between smokeless tobacco (SLT) use and all-cause mortality and cause-specific mortality outcomes among adult users of SLT and estimate the number of attributable deaths worldwide.

Methods

Random-effects meta-analysis was used to estimate the pooled risk of death due to SLT use. Population attributable fractions were derived and used to calculate the number of attributable deaths. Observational studies published upto 2015 were identified through MEDLINE, IndMED, Google Scholar and other databases. Data on the prevalence of SLT use was obtained from latest reports or national surveys. Data on the disease burden were obtained from the Global Burden of Disease Study. Hospital-based or community-based case–control and cohort studies that adjusted for the smoking status were included.

Results

16 studies that provided estimates for mortality due to all cause, all cancer, upper aerodigestive tract (UADT) cancer, stomach cancer, cervical cancer, ischaemic heart disease (IHD) and stroke were included. A significant association was found for mortality due to all cause (1.22; 1.11–1.34), all cancer (1.31; 1.16–1.47), UADT cancer (2.17; 1.47–3.22), stomach cancer (1.33; 1.12–1.59), cervical cancer (2.07; 1.64–2.61), IHD (1.10; 1.04–1.17) and stroke (1.37; 1.24–1.51). Subgroup analysis showed major regional differences. Globally, the number of attributable deaths from all-cause mortality was 652 494 (234 008–1 081 437), of which 88% was borne by the South-East Asian region.

Conclusions

SLT is responsible for a large number of deaths worldwide with the South-East Asian region bearing a substantial share of the burden.
SU(3) Polyakov linear-sigma model: Conductivity and viscous properties of QCD matter in thermal medium
Authors: Tawfik Abdel Nasser , Diab Abdel Magied , Hussein M. T.
Published: December 2016

In mean field approximation, the grand canonical potential of SU(3) Polyakov linear-[Formula: see text] model (PLSM) is analyzed for chiral phase transition, [Formula: see text] and [Formula: see text] and for deconfinement order-parameters, [Formula: see text] and [Formula: see text] of light- and strange-quarks, respectively. Various PLSM parameters are determined from the assumption of global minimization of the real part of the potential. Then, we have calculated the subtracted condensates [Formula: see text]. All these results are compared with recent lattice QCD simulations. Accordingly, essential PLSM parameters are determined. The modeling of the relaxation time is utilized in estimating the conductivity properties of the QCD matter in thermal medium, namely electric [Formula: see text] and heat [Formula: see text] conductivities. We found that the PLSM results on the electric conductivity and on the specific heat agree well with the available lattice QCD calculations. Also, we have calculated bulk and shear viscosities normalized to the thermal entropy, [Formula: see text] and [Formula: see text], respectively, and compared them with recent lattice QCD. Predictions for [Formula: see text] and [Formula: see text] are introduced. We conclude that our results on various transport properties show some essential ingredients, that these properties likely come up with, in studying QCD matter in thermal and dense medium.
Electronic and optical properties of pentagonal-B2C monolayer: A first-principles calculation
Authors: Naseri Mosayeb , Jalilian Jafar , Reshak A. H.
Published: December 2016

The electronic and optical properties of pentagonal B2C (penta-B2C) monolayer are investigated by means of the first-principles calculations in the framework of the density functional theory. The cohesive energy consideration confirms the good stability of the B2C nanostructure in this phase. The electronic band structure reveals that the valence band maximum (VBM) is located at [Formula: see text]-point of the first Brillouin zone (BZ) whereas the conduction band minimum (CBM) is situated at the center of the BZ, resulting in an indirect energy bandgap of about 1.5 eV. Furthermore, a calculated low absorption and low reflection of the material in low energy ranges denote the transparency of the B2C monolayer in the investigated range for normal light incidence. The obtained results may find application in fabrication of future opto-electronic devices.
A New Aggregating Operator for Linguistic Information Based on D Numbers
Authors: Mo Hongming , Deng Yong
Published: December 2016

How to efficiently make decision under uncertain is a hot research topic. In this paper, a new aggregating operator for linguistic decision making based on D numbers is proposed. D numbers is a new mathematic tool to model uncertainty, since it ignores the condition that elements on the frame must be mutually exclusive. Compared with these existing aggregating operators, the new method is clear, concise and less computational complexity. A numerical example is used to demonstrate the effectiveness of the proposed method.
Deep Learning
Authors: Hao Xing , Zhang Guigang , Ma Shang
Published: December 2016

Deep learning is a branch of machine learning that tries to model high-level abstractions of data using multiple layers of neurons consisting of complex structures or non-liner transformations. With the increase of the amount of data and the power of computation, neural networks with more complex structures have attracted widespread attention and been applied to various fields. This paper provides an overview of deep learning in neural networks including popular architecture models and training algorithms.
The origin and occurrence of subaqueous sedimentary cracks
Authors: McMahon Sean , van Smeerdijk Hood Ashleigh , McIlroy Duncan
Published: December 2016

The rock record attests that sediments have cracked at or below the sediment–water interface in strictly subaqueous settings throughout Earth history. In recent decades, a number of hypotheses have been advanced to explain this phenomenon, but these are widely regarded as being mutually exclusive and there is little consensus about which model is correct. In this paper, we first review the geometries, lithologies and range of facies in which subaqueous sedimentary cracks occur in the geological record, with particular attention to cracks in carbonates. We then evaluate current models for subaqueous cracking, emphasizing that different models may be correct with respect to different sets of cracks, but that cracking is generally a two-step process involving sediment stabilization prior to disruption. We also present the results of some simple new experiments designed to test the dominant models of crack formation. These results demonstrate for the first time that microbial mats can produce thin, shallow cracks at the sediment–water interface. We conclude that the presence of cracks in marine, brackish and lacustrine rocks should not be used uncritically to infer fluctuations in salinity in the depositional environment.

Supplementary material:
A video showing a micro-CT scan of a hand-sample from the Monteville Formation, South Africa is available at
https://doi.org/10.6084/m9.figshare.c.3580673
Anticipating policy and social implications of named data networking
Authors: Shilton Katie , Burke Jeffrey A. , Claffy KC , Zhang Lixia
Published: December 2016

Considering the social impact of a proposed future Internet architecture.
A Fault-Tolerant Ripple-Carry Adder with Controllable-Polarity Transistors
Authors: Mohammadi Hassan Ghasemzadeh , Gaillardon Pierre-Emmanuel , Zhang Jian , Micheli Giovanni De , Sanchez Ernesto , Reorda Matteo Sonza
Published: December 2016

This article first explores the effects of faults on circuits implemented with controllable-polarity transistors. We propose a new fault model that suits the characteristics of these devices, and we report the results of a SPICE-based analysis of the effects of faults on the behavior of some basic gates implemented with them. Hence, we show that the considered devices are able to intrinsically tolerate a rather high number of faults. We finally exploit this property to build a robust and scalable adder whose area, performance, and leakage power characteristics are improved by 15%, 18%, and 12%;, respectively, when compared to an equivalent FinFET solution at 22nm technology node.
Src-independent ERK signaling through the rat α3 isoform of Na/K-ATPase
Authors: Madan Namrata , Xu Yunhui , Duan Qiming , Banerjee Moumita , Larre Isabel , Pierre Sandrine V. , Xie Zijian
Published: December 2016

The Na/K-ATPase α1 polypeptide supports both ion-pumping and signaling functions. The Na/K-ATPase α3 polypeptide differs from α1 in both its primary structure and its tissue distribution. The expression of α3 seems particularly important in neurons, and recent clinical evidence supports a unique role of this isoform in normal brain function. The nature of this specific role of α3 has remained elusive, because the ubiquitous presence of α1 has hindered efforts to characterize α3-specific functions in mammalian cell systems. Using Na/K-ATPase α1 knockdown pig kidney cells (PY-17), we generated the first stable mammalian cell line expressing a ouabain-resistant form of rat Na/K-ATPase α3 in the absence of endogenous pig α1 detectable by Western blotting. In these cells, Na/K-ATPase α3 formed a functional ion-pumping enzyme and rescued the expression of Na/K-ATPase β1 and caveolin-1 to levels comparable with those observed in PY-17 cells rescued with a rat Na/K-ATPase α1 (AAC-19). The α3-containing enzymes had lower Na+ affinity and lower ouabain-sensitive transport activity than their α1-containing counterparts under basal conditions, but showed a greater capacity to be activated when intracellular Na+ was increased. In contrast to Na/K-ATPase α1, α3 could not regulate Src. Upon exposure to ouabain, Src activation did not occur, yet ERK was activated through Src-independent pathways involving PI3K and PKC. Hence, α3 expression confers signaling and pumping properties that are clearly distinct from that of cells expressing Na/K-ATPase α1.
Autophagy in chronic liver diseases: the two faces of Janus
Authors: Gual Philippe , Gilgenkrantz Hélène , Lotersztajn Sophie
Published: December 2016

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are the leading causes of cirrhosis and increase the risk of hepatocellular carcinoma and liver-related death. ALD and NAFLD share common pathogenic features extending from isolated steatosis to steatohepatitis and steatofibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of NAFLD and ALD are complex and still unclear. Important links between the regulation of autophagy (macroautophagy and chaperone-mediated autophagy) and chronic liver diseases have been reported. Autophagy may protect against steatosis and progression to steatohepatitis by limiting hepatocyte injury and reducing M1 polarization, as well as promoting liver regeneration. Its role in fibrosis and hepatocarcinogenesis is more complex. It has pro- and antifibrogenic properties depending on the hepatic cell type concerned, and beneficial and deleterious effects on hepatocarcinogenesis at initiating and late phases, respectively. This review summarizes the latest advances on the role of autophagy in different stages of fatty liver disease progression and describes its divergent and cell-specific effects during chronic liver injury.
Changes in mitochondrial morphology and organization can enhance energy supply from mitochondrial oxidative phosphorylation in diabetic cardiomyopathy
Authors: Jarosz Jan , Ghosh Shouryadipta , Delbridge Lea M. D. , Petzer Amorita , Hickey Anthony J. R. , Crampin Edmund J. , Hanssen Eric , Rajagopal Vijay
Published: December 2016

Diabetic cardiomyopathy is accompanied by metabolic and ultrastructural alterations, but the impact of the structural changes on metabolism itself is yet to be determined. Morphometric analysis of mitochondrial shape and spatial organization within transverse sections of cardiomyocytes from control and streptozotocin-induced type I diabetic Sprague-Dawley rats revealed that mitochondria are 20% smaller in size while their spatial density increases by 53% in diabetic cells relative to control myocytes. Diabetic cells formed larger clusters of mitochondria (60% more mitochondria per cluster) and the effective surface-to-volume ratio of these clusters increased by 22.5%. Using a biophysical computational model we found that this increase can have a moderate compensatory effect by increasing the availability of ATP in the cytosol when ATP synthesis within the mitochondrial matrix is compromised.
Maximum heart rate in brown trout (Salmo trutta fario) is not limited by firing rate of pacemaker cells
Authors: Haverinen Jaakko , Abramochkin Denis V. , Kamkin Andre , Vornanen Matti
Published: December 2016

Temperature-induced changes in cardiac output (Q̇) in fish are largely dependent on thermal modulation of heart rate ( fH), and at high temperatures Q̇ collapses due to heat-dependent depression of fH. This study tests the hypothesis that firing rate of sinoatrial pacemaker cells sets the upper thermal limit of fHin vivo. To this end, temperature dependence of action potential (AP) frequency of enzymatically isolated pacemaker cells (pacemaker rate, fPM), spontaneous beating rate of isolated sinoatrial preparations ( fSA), and in vivo fHof the cold-acclimated (4°C) brown trout ( Salmo trutta fario) were compared under acute thermal challenges. With rising temperature, fPMsteadily increased because of the acceleration of diastolic depolarization and shortening of AP duration up to the break point temperature (TBP) of 24.0 ± 0.37°C, at which point the electrical activity abruptly ceased. The maximum fPMat TBPwas much higher [193 ± 21.0 beats per minute (bpm)] than the peak fSA(94.3 ± 6.0 bpm at 24.1°C) or peak fH(76.7 ± 2.4 at 15.7 ± 0.82°C) ( P < 0.05). These findings strongly suggest that the frequency generator of the sinoatrial pacemaker cells does not limit fHat high temperatures in the brown trout in vivo.
Passive heat acclimation improves skeletal muscle contractility in humans
Authors: Racinais S. , Wilson M. G. , Périard J. D.
Published: December 2016

The aim of this study was to investigate the effect of repeated passive heat exposure (i.e., acclimation) on muscle contractility in humans. Fourteen nonheat-acclimated males completed two trials including electrically evoked twitches and voluntary contractions in thermoneutral conditions [Cool: 24°C, 40% relative humidity (RH)] and hot ambient conditions in the hyperthermic state (Hot: 44–50°C, 50% RH) on consecutive days in a counterbalanced order. Rectal temperature was ~36.5°C in Cool and was maintained at ~39°C throughout Hot. Both trials were repeated after 11 days of passive heat acclimation (1 h per day, 48–50°C, 50% RH). Heat acclimation decreased core temperature in Cool (−0.2°C, P < 0.05), increased the time required to reach 39°C in Hot (+9 min, P < 0.05) and increased sweat rate in Hot (+0.7 liter/h, P < 0.05). Moreover, passive heat acclimation improved skeletal muscle contractility as evidenced by an increase in evoked peak twitch amplitude both in Cool (20.5 ± 3.6 vs. 22.0 ± 4.0 N·m) and Hot (20.5 ± 4.7 vs. 22.0 ± 4.0 N·m) (+9%, P < 0.05). Maximal voluntary torque production was also increased both in Cool (145 ± 42 vs. 161 ± 36 N·m) and Hot (125 ± 36 vs. 145 ± 30 N·m) (+17%, P < 0.05), despite voluntary activation remaining unchanged. Furthermore, the slope of the relative torque/electromyographic linear relationship was improved postacclimation ( P < 0.05). These adjustments demonstrate that passive heat acclimation improves skeletal muscle contractile function during electrically evoked and voluntary muscle contractions of different intensities both in Cool and Hot. These results suggest that repeated heat exposure may have important implications to passively maintain or even improve muscle function in a variety of performance and clinical settings.
Spinal Epidural Abscess: A Review with Special Emphasis on Earlier Diagnosis
Authors: Bond Allison , Manian Farrin A.
Published: December 2016

Spinal epidural abscess (SEA) is an uncommon but serious condition with significant morbidity and mortality. The prognosis of SEA is highly dependent on the timeliness of its diagnosis before neurological deficits develop. Unfortunately, often due to its nonspecific presentation, such as back pain, the diagnosis of SEA may be delayed in up to 75% of cases. Although many risk factors for SEA can be found in the published literature, their utility is limited by their frequent lack of objective evidence, numerousness, and absence in a significant proportion of cases. In this review, we call for a more discriminate evidence-based use of the term “risk factor” when discussing SEA and explore several approaches to its earlier diagnosis, including a simple algorithm based on its pathophysiology and serum C-reactive protein or erythrocyte sedimentation rate.
Modeling Radiotherapy Induced Normal Tissue Complications: An Overview beyond Phenomenological Models
Authors: D’Andrea Marco , Benassi Marcello , Strigari Lidia
Published: December 2016

An overview of radiotherapy (RT) induced normal tissue complication probability (NTCP) models is presented. NTCP models based on empirical and mechanistic approaches that describe a specific radiation induced late effect proposed over time for conventional RT are reviewed with particular emphasis on their basic assumptions and related mathematical translation and their weak and strong points.
A Model for Spheroid versus Monolayer Response of SK-N-SH Neuroblastoma Cells to Treatment with 15-Deoxy-PGJ2
Authors: Wallace Dorothy I. , Dunham Ann , Chen Paula X. , Chen Michelle , Huynh Milan , Rheingold Evan , Prosper Olivia
Published: December 2016

Researchers have observed that response of tumor cells to treatment varies depending on whether the cells are grown in monolayer, asin vitrospheroids orin vivo. This study uses data from the literature on monolayer treatment of SK-N-SH neuroblastoma cells with 15-deoxy-PGJ2and couples it with data on growth rates for untreated SK-N-SH neuroblastoma cells grown as multicellular spheroids. A linear model is constructed for untreated and treated monolayer data sets, which is tuned to growth, death, and cell cycle data for the monolayer case for both control and treatment with 15-deoxy-PGJ2. The monolayer model is extended to a five-dimensional nonlinear model ofin vitrotumor spheroid growth and treatment that includes compartments of the cell cycle (G1,S,G2/M) as well as quiescent (Q) and necrotic (N) cells. Monolayer treatment data for 15-deoxy-PGJ2is used to derive a prediction of spheroid response under similar treatments. For short periods of treatment, spheroid response is less pronounced than monolayer response. The simulations suggest that the difference in response to treatment of monolayer versus spheroid cultures observed in laboratory studies is a natural consequence of tumor spheroid physiology rather than any special resistance to treatment.
Quantitative Characterization of the Toxicities of Cd-Ni and Cd-Cr Binary Mixtures Using Combination Index Method
Authors: Mo Lingyun , Zheng Minyi , Qin Meng , Zhang Xin , Liu Jie , Qin Litang , Zeng Honghu , Liang Yanpeng
Published: December 2016

Direct equipartition ray design was used to construct Cd-Ni and Cd-Cr binary mixtures. Microplate toxicity analysis was used to evaluate the toxicity of individual substance and the Cd-Ni and Cd-Cr mixtures on Chlorella pyrenoidosa and Selenastrum capricornutum. The interacting toxicity of the mixture was analyzed with concentration addition (CA) model. In addition, combination index method (CI) was proposed and used to quantitatively characterize the toxicity of the binary mixtures of Cd-Ni and Cd-Cr observed in experiment and find the degree of deviation from the predicted outcome of the CA model, that is, the intensity of interacting toxicity. Results indicate that most of the 20 binary mixtures exhibit enhancing and synergistic effect, and only Cd-Cr-R4 and Cd-Cr-R5 mixtures have relatively high antagonistic effects against C. pyrenoidosa. Based on confidence interval, CI can compare the intensities of interaction of the mixtures under varying levels of effect. The characterization methods are applicable for analyzing binary mixture with complex interaction.
Novel Biomarker MicroRNAs for Subtyping of Acute Coronary Syndrome: A Bioinformatics Approach
Authors: Zhu Yujie , Lin Yuxin , Yan Wenying , Sun Zhandong , Jiang Zhi , Shen Bairong , Jiang Xiaoqian , Shi Jingjing
Published: December 2016

Acute coronary syndrome (ACS) is a life-threatening disease that affects more than half a million people in United States. We currently lack molecular biomarkers to distinguish the unstable angina (UA) and acute myocardial infarction (AMI), which are the two subtypes of ACS. MicroRNAs play significant roles in biological processes and serve as good candidates for biomarkers. In this work, we collected microRNA datasets from the Gene Expression Omnibus database and identified specific microRNAs in different subtypes and universal microRNAs in all subtypes based on our novel network-based bioinformatics approach. These microRNAs were studied for ACS association by pathway enrichment analysis of their target genes. AMI and UA were associated with 27 and 26 microRNAs, respectively, nine of them were detected for both AMI and UA, and five from each subtype had been reported previously. The remaining 22 and 21 microRNAs are novel microRNA biomarkers for AMI and UA, respectively. The findings are then supported by pathway enrichment analysis of the targets of these microRNAs. These novel microRNAs deserve further validation and will be helpful for personalized ACS diagnosis.
The 3D Tele Motion Tracking for the Orthodontic Facial Analysis
Authors: Mummolo Stefano , Nota Alessandro , Marchetti Enrico , Padricelli Giuseppe , Marzo Giuseppe
Published: December 2016

Aim. This study aimed to evaluate the reliability of 3D-TMT, previously used only for dynamic testing, in a static cephalometric evaluation. Material and Method. A group of 40 patients (20 males and 20 females; mean age 14.2±1.2 years; 12–18 years old) was included in the study. The measurements obtained by the 3D-TMT cephalometric analysis with a conventional frontal cephalometric analysis were compared for each subject. Nine passive markers reflectors were positioned on the face skin for the detection of the profile of the patient. Through the acquisition of these points, corresponding plans for three-dimensional posterior-anterior cephalometric analysis were found. Results. The cephalometric results carried out with 3D-TMT and with traditional posterior-anterior cephalometric analysis showed the 3D-TMT system values are slightly higher than the values measured on radiographs but statistically significant; nevertheless their correlation is very high. Conclusion. The recorded values obtained using the 3D-TMT analysis were correlated to cephalometric analysis, with small but statistically significant differences. The Dahlberg errors resulted to be always lower than the mean difference between the 2D and 3D measurements. A clinician should use, during the clinical monitoring of a patient, always the same method, to avoid comparing different millimeter magnitudes.
Ultrasound for Appendicitis: Performance and Integration with Clinical Parameters
Authors: Löfvenberg Fanny , Salö Martin
Published: December 2016

Objective. To evaluate the performance of ultrasound in pediatric appendicitis and the integration of US with the pediatric appendicitis score (PAS) and C-reactive protein (CRP).Method. An institution-based, retrospective study of children who underwent abdominal US for suspected appendicitis between 2012 and 2015 at a tertiary pediatric surgery center. US results were dichotomized, with a nonvisualized appendix considered as a negative examination.Results. In total, 438 children were included (mean 8.5 years, 54% boys), with an appendicitis rate of 29%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for US were 82%, 97%, 92%, and 93%, respectively, without significant age or gender differences. Pediatric radiologists had significantly higher sensitivity compared to general radiologists, 88% and 71%, respectively (p<0.01), but no differences were seen for specificity, PPV, and NPV. The sensitivity, NPV, and negative likelihood ratio for the combination of negative US, PAS < 5, and CRP < 5 mg/L were 98%, 98%, and 0.05 (95% CI 0.03–0.15).Conclusion. US may be a useful tool for evaluating children with suspected appendicitis, regardless of age or gender, and should be the first choice of imaging modalities. Combining US with PAS and CRP may reduce several unnecessary admissions for in-hospital observation.
Filling the Tank: Keeping Antitumor T Cells Metabolically Fit for the Long Haul
Authors: Delgoffe Greg M.
Published: December 2016

Discoveries in tumor immunology and subsequent clinical advances in cancer immunotherapy have revealed that the immune system is not oblivious to tumor progression but heavily interacts with developing neoplasia and malignancy. A major factor preventing immune destruction is the establishment of a highly immunosuppressive tumor microenvironment (TME), which provides architecture to the tumor, supports indirect means of immunosuppression such as the recruitment of tolerogenic cells like regulatory T cells and myeloid-derived suppressor cells (MDSC), and represents a zone of metabolically dearth conditions. T-cell activation and consequent effector function are cellular states characterized by extreme metabolic demands, and activation in the context of insufficient metabolic substrates results in anergy or regulatory differentiation. Thus, T cells must endure both immunosuppression (co-inhibitory molecule ligation, regulatory T cells, and suppressive cytokines) but also a sort of metabolic suppression in the TME. Here I will review the general features of the TME, identify the metabolic demands of activated effector T cells, discuss the known metabolic checkpoints associated with intratumoral T cells, and propose strategies for generating superior antitumor T cells, whether in vitro for adoptive cell therapy or through in vivo reinvigoration of the existing immune response. Cancer Immunol Res; 4(12); 1001–6. ©2016 AACR.
Late-Onset Multiple Self-Healing Squamous Epithelioma Ferguson-Smith Recurrence Induced by Radiotherapy
Authors: Feldmeyer Laurence , Szeverényi Ildiko , Mandallaz Michèle , Lane E. Birgit , Hohl Daniel
Published: December 2016

We report the case of a woman in her 60s with confirmed multiple self-healing squamous epitheliomas (MSSE) Ferguson-Smith. After recurrences following surgery and radiotherapy, the patient was successfully treated with minimal surgical intervention combined with intralesional injections of triamcinolone acetate. The histological comparison between mature and regressed keratoacanthomas (KA) revealed an increased inflammatory infiltrate with numerous plasmacytoid dendritic cells in the regressed KA in comparison to the mature one, speaking in favor of an inflammation-mediated regression process. Corticosteroids injection in MSSE may have paradoxical effects with action on the proliferation phase rather than the inflammatory regression phase of the KA. Our case confirms previous reports showing that radiotherapy may exacerbate MSSE and should be avoided. Intralesional triamcinolone acetate injection is a safe and easy to use method also effective for multiple lesions. Our case underlines the difference between squamous cell carcinoma and KA, responding differently to therapies like imiquimod or radiotherapy.
Late Onset of Acute Urticaria after Bee Stings
Authors: Asai Yuko , Uhara Hisashi , Miyazaki Atsushi , Saiki Minoru , Okuyama Ryuhei
Published: December 2016

Here we report the cases of five patients with a late onset of acute urticaria after a bee sting. The ages of the five Japanese patients ranged from 33 to 86 years (median: 61). All patients had no history of an allergic reaction to bee stings. The onset of urticaria was 6–14 days (median: 10) after a bee sting. Although four of the patients did not describe experiencing a bee sting at their presentation, the subsequent examination detected anti-bee-specific IgE antibodies. So, we think a history of a bee sting should thus be part of the medical interview sheet for patients with acute urticaria, and an examination of IgE for bees may help prevent a severe bee-related anaphylactic reaction in the future.
Distinct Contributory Factors Determine Basophil-Allergen Sensitivity in Grass Pollen Rhinitis and in Anaphylactic Wasp Venom Allergy
Authors: Korošec Peter , Šilar Mira , Kopač Peter , Eržen Renato , Zidarn Mihaela , Košnik Mitja
Published: December 2016

Background: We sought to determine whether basophil-allergen sensitivity could be transferred to donor basophils by passive IgE sensitisation in allergic rhinitis and anaphylactic Hymenoptera venom hypersensitivity. Methods: We studied 15 wasp venom-, 19 grass pollen- and 2 house dust mite-allergic patients, 2 healthy donors, and 8 wasp venom-allergic donors. In all subjects, we first evaluated the initial basophil response to wasp venom, grass pollen, or house dust mite allergen. Donor basophils were then stripped, sensitised with the different patients' serum IgE, and challenged with the corresponding allergen. The CD63 response of donor basophils was then compared with initial basophil responses. Results: In wasp venom-allergic subjects, the IgE transfer did not reflect the initial basophil-allergen sensitivity, because the venom IgE of subjects with high or low basophil sensitivity induced comparable responsiveness in healthy donor basophils. Furthermore, vice versa, when we sensitised the donor basophils of wasp venom-allergic individuals with different wasp venom or house dust mite IgE, we demonstrated that their response was predictable by their initial basophil allergen sensitivity. In the rhinitis allergy model, the IgE transfer correlated with the patients' initial basophil responsiveness because the grass pollen IgE of the subjects with high basophil allergen sensitivity induced significantly higher responsiveness of donor basophils than the IgE of subjects with initially low basophil allergen sensitivity. Conclusions: Our results suggest that basophil allergen sensitivity evaluated by flow-cytometric CD63 analysis depends on two distinct contribution factors. In anaphylactic Hymenoptera allergy, the major factor was intrinsic cellular sensitivity, whereas in pollen allergy, the major factor was allergen-specific IgE on the cell surface.
Effect of ticagrelor on endothelial calcium signalling and barrier function
Authors: Gündüz Dursun , Tanislav Christian , Schluter Klaus-Dieter , Schulz Rainer , Hamm Christian , Aslam Muhammad
Published: December 2016

The P2Y12 receptor is a Gi-coupled receptor whose activation inhibits adenylyl cyclase and thereby reduces the concentration of intracellular cAMP. Here the hypothesis was tested whether AR-C 66096 or ticagrelor, two direct-acting and reversibly binding P2Y12 receptor antagonists, protect endothelial cell (EC) barrier function by raising intracellular cAMP in ECs. The study was carried out on primary human umbilical vein ECs (HUVECs) and human pulmonary microvascular ECs (hPMECs). AR-C66096 (10 µM) induced a 50 % increase in cAMP in ECs whereas ticagrelor (2–10 µM) had no effect. Likewise, AR-C666096 antagonised thrombin-induced hyperpermeability in both HUVECs and hPMECs, but ticagrelor had no effect on basal EC monolayer permeability. Ticagrelor, however, sensitised ECs for thrombin-induced hyperpermeability and potentiated the thrombin effect. Ticagrelor but not AR-C66096 caused an increase in cytosolic calcium ([Ca2+]i). This increase in [Ca2+]i was abrogated by LaCl3 (Ca2+ influx inhibitor) but not by xestospongin C (IP3 receptor antagonist) or by depletion of intracellular stores with thapsigargin, suggesting a Ca2+ influx from the extracellular space. Accordingly, ticagrelor caused an increase in myosin light chain (MLC) phosphorylation, an important regulator of EC contractile machinery and thus permeability, which was abrogated by LaCl3. The ability of ticagrelor to potentiate EC permeability was abrogated by a MLC kinase inhibitor (ML-7; 10 µM). Our data demonstrate that the P2Y12 receptor antagonist AR-C66096 exerts a protective effect on ECs in vitro, possibly by raising intracellular cAMP, whereas ticagrelor sensitises EC barrier function by inducing Ca2+ influx and activating downstream EC contractile machinery.

Supplementary Material to this article is available online at www.thrombosis-online.com.
A novel hirudin derivative inhibiting thrombin without bleeding for subcutaneous injection
Authors: Zhao Bing , Zhang Yanling , Huang Yinong , Yu Jinchao , Li Yaran , Wang Qi , Ma Yixin , Song Hou-Yan , Yu Min , Mo Wei
Published: December 2016

Currently, anticoagulants would be used to prevent thrombosis. Thrombin is an effector enzyme for haemostasis and thrombosis. We designed a direct thrombin inhibitor peptide (DTIP) using molecular simulation and homology modelling and demonstrated that the C-terminus of DTIP interacts with exosite I, and N-terminus with the activity site of thrombin, respectively. DTIP interfered with thrombin-mediated coagulation in human, rat and mouse plasma (n=10 per group) and blocked clotting in human whole blood in vitro. When administered subcutaneously, DTIP showed potent and dose-dependent extension of aPTT, PT, TT and CT in rats (n=10 per group). The antithrombotic dose of DTIP induced significantly less bleeding than bivalirudin determined by transecting distal tail assay in rats. Furthermore, DTIP reached peak blood concentration in 0.5–1 hour and did not cause increased bleeding after five days of dosing compared to dabigatran etexilate. The antithrombotic effect of DTIP was evaluated in mice using lethal pulmonary thromboembolism model and FeCl3-induced mesenteric arteriole thrombus model. DTIP (1.0 mg/kg, sc) prevented deep venous thrombosis and increased the survival rate associated with pulmonary thromboembolism from 30 % to 80 %. Intravital microscopy showed that DTIP (1.0 mg/kg, sc) decelerated mesenteric arteriole thrombosis caused by FeCl3 injury. These data establish that DTIP is a novel antithrombotic agent that could be used to prevent thrombosis without conferring an increased bleeding risk.

Supplementary Material to this article is available at www.thrombosis-online.com.
Effects of Transendocardial Delivery of Bone Marrow–Derived CD133
+
Cells on Left Ventricle Perfusion and Function in Patients With Refractory Angina
Authors: Wojakowski Wojciech , Jadczyk Tomasz , Michalewska-Włudarczyk Aleksandra , Parma Zofia , Markiewicz Mirosław , Rychlik Wojciech , Kostkiewicz Magdalena , Gruszczyńska Katarzyna , Błach Anna , Dzier˙zak-Mietła Monika , Wańha Wojciech , Ciosek Joanna , Ochała Beata , Rzeszutko Łukasz , Cybulski Wiesław , Partyka Łukasz , Zasada Wojciech , Włudarczyk Witold , Dworowy Sebastian , Kuczmik Wacław , Smolka Grzegorz , Pawłowski Tomasz , Ochała Andrzej , Tendera Michał
Published: December 2016

Rationale
:

New therapies for refractory angina are needed.

Objective
:

Assessment of transendocardial delivery of bone marrow CD133
+
cells in patients with refractory angina.

Methods and Results
:

Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II–IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6],
P
=0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3],
P
=0.32; absolute changes of summed difference score: −1.38 [5.2] versus −0.73 [1.9],
P
=0.65; and total perfusion deficit: −1.33 [3.3] versus −2.19 [6.6],
P
=0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: −4.3 [11.3] versus 7.4 [11.8],
P
=0.02; end-diastolic volume: −9.1 [14.9] versus 7.4 [15.8],
P
=0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%;
P
=0.68), 4 (50% versus 33.3%;
P
=0.63), 6 (70% versus 50.0%;
P
=0.42), and 12 months (55.6% versus 81.8%;
P
=0.33) and use of nitrates after 12 months.

Conclusion
:

Transendocardial CD133
+
cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo.

Clinical Trial Registration
:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01660581.
Aggressive defence of food by precocial chicks varies with its concentration in space
Authors: Hernández-Reyes Reyna , Rodríguez Cristina , Drummond Hugh
Published: December 2016

In juvenile and adult animals, including mammals, birds, fishes and a crustacean, competition for food becomes increasingly aggressive as its spatial concentration increases. This ecological relationship has not been investigated in infant animals, although it is thought that broods of precocial chicks of some avian species compete aggressively for food or status in a brood hierarchy. When pairs of common quail broodmates were offered the same amount of ground corn in four spatial concentrations between ages 15 and 59 days, aggression increased progressively with concentration, culminating in an overall 16-fold increase when corn was in a single clump. These results suggest that aggressive defence may increase with spatial concentration of food in precocial chicks generally, and raise the possibility that a similar pattern could occur in some altricial chicks during the transition to independence and in infants of other animal species.
The Forgotten Genocide in Colonial America: Reexamining the 1622 Jamestown Massacre within the Framework of the un Genocide Convention
Authors: Bennett John T.
Published: December 2016

In 1622, in Jamestown, Virginia, Powhatan warriors launched a surprise attack against English settlements. In terms of the percentage of a group or tribe killed in a single massacre, the 1622 attack was the deadliest attack committed by either side – Native Americans or English settlers – in early American history. The Powhatan attempted to wipe out every English person, combatant or non-combatant. They killed at least one-quarter of the English in the Jamestown region. Historians label this event a ‘massacre’ or ‘uprising’, which are inaccurate analytical labels. Scholars have not analysed the 1622 attack within the appropriate framework of genocide. To remedy that omission, this article reexamines the attack within the un Genocide Convention framework. The Convention provides methodological, empirical, and normative benefits for understanding past conflict. In planning and executing the attack, the Powhatan had the intent to destroy, in whole or in part, the English colonists as such.
The Uzun Hasan Mosque in Tabriz: New Perspectives on a Tabrizi Ceramic Tile Workshop
Authors: Aube Sandra
Published: December 2016

The recent rediscovery of the mosque erected around 1477–84 (882–89) in Tabriz by the Aq Qoyunlu ruler Uzun Hasan (r. 1457–78]) provides new perspectives on ceramic tile production in the former Turkmen capital. The Blue Mosque and its exceptional tile decoration have long been considered to be the last vestiges of the innovative features of the Qara Qoyunlu workshops in Tabriz. The recovery of the Uzun Hasan Mosque sheds new light on this prestigious artistic center: besides confirming the innovative traits of Tabrizi production, its architectural decoration highlights the strong artistic continuity from Qara Qoyunlu to Aq Qoyunlu workshops. These unusual ceramic tiles also constitute a previously unknown stage in the history of Iranian ceramic tiles.