bluuebunny/crossref_metadata_2025 huggingface dataset:
Airway anomalies in patients with craniosynostosis
Authors: Mathews Fasil , Shaffer Amber D. , Georg Matthew W. , Ford Matthew D. , Goldstein Jesse A. , Jabbour Noel , Simons Jeffrey P.
Published: November 2018

Objectives

1) Characterize the spectrum of airway anomalies in patients with craniosynostosis, and 2) identify clinical characteristics of these patients that may be associated with the development of airway anomalies.

Methods

This study is a retrospective case series assessing the type and frequency of airway anomalies in all patients with craniosynostosis seen at a tertiary‐care children's hospital between 2000 and 2016. Cohort analyses were then performed to identify differences in airway anomalies dependent on syndromic associations, multisutural fusion, and location of suture fusion. Clinical characteristics examined included demographics and additional neurologic and craniofacial abnormalities.

Results

Four hundred and ninety‐six patients with craniosynostosis (83.5% white, 64.5% male; 33.9% sagittal, 28.8% metopic, 11.5% coronal, 1.2% lambdoid, and 24.6% multisutural) were included. Notable airway anomalies included the following: 13.3% adenotonsillar hypertrophy, 8.9% laryngomalacia, 7.3% tracheomalacia, 7.1% subglottic stenosis, 4.0% bronchomalacia, 3.8% laryngeal cleft, and 1.2% vocal fold paresis. Multisutural craniosynostosis patients (n = 122) were more likely to have obstructive sleep apnea (P = 0.005), adenotonsillar hypertrophy (P = 0.014), tracheomalacia (P = 0.011), subglottic stenosis (P < 0.001), and epiglottic/base of tongue collapse (P = 0.003) and require tracheostomy (P = 0.001) and mechanical ventilation (P = 0.017) compared with single suture craniosynostosis. Syndromic craniosynostosis patients (n = 33) were more likely to have obstructive sleep apnea (P < 0.001), laryngomalacia (P = 0.047), and subglottic stenosis (P = 0.009) compared with nonsyndromic patients.

Conclusion

Airway anomalies are prevalent in patients with craniosynostosis; patients with multisutural or syndromic types have an increased risk of developing certain abnormalities. There should be a lower threshold for referral for airway evaluation in these populations.

Level of Evidence

4. Laryngoscope, 129:2594–2602, 2019
A remark on pseudo proof systems and hard instances of the satisfiability problem
Authors: Maly Jan , Müller Moritz
Published: November 2018

We link two concepts from the literature, namely hard sequences for the satisfiability problem sat and so‐called pseudo proof systems proposed for study by Krajíček. Pseudo proof systems are elements of a particular nonstandard model constructed by forcing with random variables. We show that the existence of mad
pseudo proof systems is equivalent to the existence of a randomized polynomial time procedure with a highly restrictive use of randomness which produces satisfiable formulas whose satisfying assignments are probably hard to find.
Automated Synthesis Protocol of Sequence‐Defined Oligo‐Urethane‐Amides Using Thiolactone Chemistry
Authors: Holloway Joshua O. , Mertens Chiel , Du Prez Filip E. , Badi Nezha
Published: November 2018

An automated, iterative protocol for the synthesis of multifunctional, sequence‐defined oligo‐urethane‐amides using thiolactone chemistry is reported. Here, sequenced functionalization of the backbone is easily introduced using commercially available primary amines. The chemistry is carried out on solid phase using different supports for better optimization of the synthetic protocol and in order to demonstrate the versatility of the approach. This technique is very effective for iterative synthesis and solid‐phase chemistry and enables the exploration of full automation of this approach using a robotic peptide synthesizer. As a result, this automated protocol allows for the synthesis of a sequence‐defined nonamer of high purity.
A two‐scale FE‐FFT approach to nonlinear magneto‐elasticity
Authors: Rambausek Matthias , Göküzüm Felix Selim , Nguyen Lu Trong Khiem , Keip Marc‐André
Published: November 2018

Fourier‐based approaches are a well‐established class of methods for the theoretical and computational characterization of microheterogeneous materials. Driven by the advent of computational homogenization techniques, Fourier schemes gained additional momentum over the past decade. In recent contributions, the interpretation of Green operators central to Fourier solvers as projections opened up a new perspective. Based on such a viewpoint, the present work addresses a multiscale framework for magneto‐mechanically coupled materials at finite strains. The key ingredient for the solution of magneto‐mechanic boundary value problems at the microscale is the construction of suitable operators in Fourier space that project vector fields onto either curl‐free or divergence‐free subspaces. The resulting linear system of equations is solved by a conjugate gradient method. In addition to that, we describe the computation of the consistent macroscopic tangent operator based on the same linear operators as the microscopic equilibrium with appropriately defined right‐hand sides. We employ the framework for the simulation of representative two‐scale boundary value problems and compare the results with pure finite element schemes.
Preserving the reactivity of coatings plasma deposited from oxazoline precursors − An in depth study
Authors: MacGregor Melanie , Sinha Ujala , Visalakshan Rahul M. , Cavallaro Alex , Vasilev Krasimir
Published: November 2018

Plasma coatings deposited from oxazoline precursors have recently emerged as a valuable utility in many biotechnology application, however, their wider utilization by researchers and industry rely on their long term performance, and more specifically on the retention of their reactivity. Yet, plasma polymers are known to be susceptible to post‐fabrication oxidation processes and intrinsic restructuration. Here, the aging of coatings deposited from oxazoline precursors was studied over 12 months via XPS, ToF‐SIMS, and sessile drop contact angle analysis for samples stored under various conditions. The extent of the damages caused by light and oxygen are identified and explained. Storage away from ambient light and under vacuum proved to retain high reactivity toward COOH‐bearing ligand and biomolecules even 12 months post deposition.
Optimal tuning of H∞ fixed‐structure robust controller against multiple high‐level requirements using evolutionary computation
Authors: Feyel P. , Duc G. , Sandou G.
Published: November 2018

This work deals with the optimal controller synthesis against high‐level multiple requirements using evolutionary computation. Indeed, such stochastic algorithms are interesting to solve problems based on complex industrial specifications and so seem to be particularly well suited to optimal robust controller synthesis. Using the H∞ loop‐shaping framework, the optimal weights/controller tuning without any structural assumption (in terms of poles/zeros/damping) on the searched filters (except of course their order) is investigated. The absence of such any structural assumption is important to avoid affecting the quality of the solution toward a complex specification and allows reducing the synthesis problem to a simple one with static scalings in place of frequency weights. Using a version of differential evolution algorithm well adapted for high dimensional control problems, computing directly a fixed‐structure controller for complex industrial specifications toward a generic nonconstraint fitness with quite reasonable computing time is achieved. The illustrating example deals with the line‐of‐sight stabilization problem.
Noble‐Metal‐Free Electrocatalysts for Oxygen Evolution
Authors: Lyu Fenglei , Wang Qingfa , Choi Sung Mook , Yin Yadong
Published: November 2018

Oxygen evolution reaction (OER) plays a vital role in many energy conversion and storage processes including electrochemical water splitting for the production of hydrogen and carbon dioxide reduction to value‐added chemicals. IrO2 and RuO2, known as the state‐of‐the‐art OER electrocatalysts, are severely limited by the high cost and low earth abundance of these noble metals. Developing noble‐metal‐free OER electrocatalysts with high performance has been in great demand. In this review, recent advances in the design and synthesis of noble‐metal‐free OER electrocatalysts including Ni, Co, Fe, Mn‐based hydroxides/oxyhydroxides, oxides, chalcogenides, nitrides, phosphides, and metal‐free compounds in alkaline, neutral as well as acidic electrolytes are summarized. Perspectives are also provided on the fabrication, evaluation of OER electrocatalysts and correlations between the structures of the electrocatalysts and their OER activities.
Trophic Ecology of Sheepshead and Stone Crabs at Oil and Gas Platforms in the Northern Gulf of Mexico's Hypoxic Zone
Authors: Reeves David B. , Chesney Edward J. , Munnelly Ryan T. , Baltz Donald M. , Maiti Kanchan
Published: November 2018

Oil and gas platforms (platforms) may provide important habitat for reef‐associated organisms in the Gulf of Mexico's hypoxic zone. While summer hypoxia typically affects the bottom 3.0 m of the water column, platforms span from the bottom to above the surface and provide hard substrate in oxygenated waters overlaying hypoxia. However, little is known about the effects of hypoxia on organisms living at these platforms. We compared diets of Sheepshead Archosargus probatocephalus and Gulf stone crabs Menippe adina during early and late summer at platforms with mild (shoal platforms) and intense hypoxia (seaward platforms) using a combination of stable isotopes (δ13C and δ15N) and gut contents analyses. We hypothesized that diets at seaward platforms would shift from bottom to platform‐dwelling prey during late summer when hypoxia had fully developed and decimated benthic communities, but no such effect was found. Barnacles (Balanidae) were the most common prey found in Sheepshead guts for all samples collected (64.1% of gut contents). Sheepshead gut contents showed high predation of mantis shrimp (Squillidae; 35.2% of gut contents) soon after the formation of hypoxia at seaward platforms, likely reflecting Sheepshead exploiting benthic prey that were vulnerable because of hypoxia. These findings indicate that hypoxia affected the behavior of mantis shrimp in a way that altered their availability for Sheepshead associated with platforms. Comparisons of Sheepshead and stone crab isotope values (δ13C and δ15N) to those of their potential prey and basal sources suggested a high dependence on barnacles (proxy for water column particulate organic matter) and filamentous algae throughout the summer. However, comparisons of isotope values in early and late summer indicated no apparent effect of hypoxia. High contributions of barnacles to Sheepshead diet showed that platform‐dwelling prey were an important resource for Sheepshead.
Microwave Flow: A Perspective on Reactor and Microwave Configurations and the Emergence of Tunable Single‐Mode Heating Toward Large‐Scale Applications
Authors: Barham Joshua P. , Koyama Emiko , Norikane Yasuo , Ohneda Noriyuki , Yoshimura Takeo
Published: November 2018

Microwave heating in chemical reactions was first reported in 1986. There have since been many reports employing microwave heating in organic chemistry, where microwave heating has afforded higher yields of products in shorter time periods. However, such reactions are challenging to scale in batch due to the limited penetration depth of microwaves as well as the wave propagation dependence on cavity size. Continuous flow has addressed both these issues, enabling scalability of microwave processes. As such, a host of reports employing microwave flow chemistry have emerged, employing various microwave heating and reactor configurations in the context of either custom‐built or commercial apparatus. The focus of this review is to present the benefits of microwave heating in the context of continuous flow and to characterize the different types of microwave flow apparatus by their design (oscillator, cavity type and reactor vessel). We advocate the adoption of tunable, solid‐state oscillator single‐mode microwave flow reactors which are more versatile heaters, impart better process control and energy efficiency toward laboratory and larger‐scale synthetic chemistry applications.
On the statistical significance of protein complex
Authors: Su Youfu , Zhao Can , Chen Zheng , Tian Bo , He Zengyou
Published: November 2018

Background

Statistical validation of predicted complexes is a fundamental issue in proteomics and bioinformatics. The target is to measure the statistical significance of each predicted complex in terms of p‐values. Surprisingly, this issue has not received much attention in the literature. To our knowledge, only a few research efforts have been made towards this direction.

Methods

In this article, we propose a novel method for calculating the p‐value of a predicted complex. The null hypothesis is that there is no difference between the number of edges in target protein complex and that in the random null model. In addition, we assume that a true protein complex must be a connected subgraph. Based on this null hypothesis, we present an algorithm to compute the p‐value of a given predicted complex.

Results

We test our method on five benchmark data sets to evaluate its effectiveness.

Conclusions

The experimental results show that our method is superior to the state‐of‐the‐art algorithms on assessing the statistical significance of candidate protein complexes.
Analysis of protein features and machine learning algorithms for prediction of druggable proteins
Authors: Sun Tanlin , Lai Luhua , Pei Jianfeng
Published: November 2018

Background

Computational tools have been widely used in drug discovery process since they reduce the time and cost. Prediction of whether a protein is druggable is fundamental and crucial for drug research pipeline. Sequence based protein function prediction plays vital roles in many research areas. Training data, protein features selection and machine learning algorithms are three indispensable elements that drive the successfulness of the models.

Methods

In this study, we tested the performance of different combinations of protein features and machine learning algorithms, based on FDA‐approved small molecules’ targets, in druggable proteins prediction. We also enlarged the dataset to include the targets of small molecules that were in experiment or clinical investigation.

Results

We found that although the 146‐d vector used by Li et al. with neuron network achieved the best training accuracy of 91.10%, overlapped 3‐gram word2vec with logistic regression achieved best prediction accuracy on independent test set (89.55%) and on newly approved‐targets. Enlarged dataset with targets of small molecules in experiment and clinical investigation were trained. Unfortunately, the best training accuracy was only 75.48%. In addition, we applied our models to predict potential targets for references in future study.

Conclusions

Our study indicates the potential ability of word2vec in the prediction of druggable protein. And the training dataset of druggable protein should not be extended to targets that are lack of verification. The target prediction package could be found on https://github.com/pkumdl/target_prediction.
Private Financing or Not, That is the Question: Lessons from the Light Rail Systems in Spain
Authors: Calvo-Poyo Francisco , Ferri-García Ramón , Hermoso Alberto , de Oña Juan
Published: November 2018

The objective of this paper is to analyze if there is any difference between the light rail systems in Spain according to whether they have been carried out through public financing or private financing (totally or partially). The importance of this study lies in the fact that, for decades, the public–private partnership has been proposed as an alternative to public financing of public transport projects in order to obtain additional financial resources, reduce the public deficit, and increase efficiency. However, there are hardly any detailed studies describing how these initiatives have turned out. Therefore, the present study analyzes if there is any difference in the main variables explaining the performance of light rail projects in Spain depending on their source of funding can be found. For this, the relationship between variables related to design, operation and costs of the projects, and the percentage of private financing were statistically analyzed. As the most relevant conclusion, we underline the fact that the investment per passenger increases when financing is completely private. This would indicate that the most cost-effective lines, from a social standpoint, were financed totally or partially by the public administrations, whereas the least beneficial ones for society were assigned to private enterprises. This finding provides an advance in the knowledge of the consequences of private participation in the financing of public transport projects, indicating, moreover, that the biggest beneficiaries of this type of projects might be the construction companies and the politicians involved.
Role of hypothalamic tanycytes in nutrient sensing and energy balance
Authors: Travaglio Marco , Ebling Francis J. P.
Published: November 2018

Animal models are valuable for the study of complex behaviours and physiology such as the control of appetite because genetic, pharmacological and surgical approaches allow the investigation of underlying mechanisms. However, the majority of such studies are carried out in just two species, laboratory mice and rats. These conventional laboratory species have been intensely selected for high growth rate and fecundity, and have a high metabolic rate and short lifespan. These aspects limit their translational relevance for human appetite control. This review will consider the value of studies carried out in a seasonal species, the Siberian hamster, which shows natural photoperiod-regulated annual cycles in appetite, growth and fattening. Such studies reveal that this long-term control is not simply an adjustment of the known hypothalamic neuronal systems that control hunger and satiety in the short term. Long-term cyclicity is probably driven by hypothalamic tanycytes, glial cells that line the ventricular walls of the hypothalamus. These unique cells sense nutrients and metabolic hormones, integrate seasonal signals and effect plasticity of surrounding neural circuits through their function as a stem cell niche in the adult. Studies of glial cell function in the hypothalamus offer new potential for identifying central targets for appetite and body weight control amenable to dietary or pharmacological manipulation.
Profiles of visuospatial memory dysfunction in opioid-exposed and dependent populations
Authors: Baldacchino A. , Tolomeo S. , Balfour D.J. , Matthews K
Published: November 2018

Background

Chronic opioid exposure is common world-wide, but behavioural performance remains under-investigated. This study aimed to investigate visuospatial memory performance in opioid-exposed and dependent clinical populations and its associations with measures of intelligence and cognitive impulsivity.

Methods

We recruited 109 participants: (i) patients with a history of opioid dependence due to chronic heroin use (n = 24), (ii) heroin users stabilised on methadone maintenance treatment (n = 29), (iii) participants with a history of chronic pain and prescribed tramadol and codeine (n = 28) and (iv) healthy controls (n = 28). The neuropsychological tasks from the Cambridge Neuropsychological Test Automated Battery included the Delayed Matching to Sample (DMS), Pattern Recognition Memory, Spatial Recognition Memory, Paired Associate Learning, Spatial Span Task, Spatial Working Memory and Cambridge Gambling Task. Pre-morbid general intelligence was assessed using the National Adult Reading Test.

Results

As hypothesised, this study identified the differential effects of chronic heroin and methadone exposures on neuropsychological measures of visuospatial memory (p < 0.01) that were independent of injecting behaviour and dependence status. The study also identified an improvement in DMS performance (specifically at longer delays) when the methadone group was compared with the heroin group and also when the heroin group was stabilised onto methadone. Results identified differential effects of chronic heroin and methadone exposures on various neuropsychological measures of visuospatial memory independently from addiction severity measures, such as injecting behaviour and dependence status.
Misrecognition and the Indian state: the desire for sovereign agency
Authors: Kinnvall Catarina , Svensson Ted
Published: November 2018

A focus on misrecognition allows us to move between levels of analysis in a holistic fashion. If misrecognition works through the conscious and the unconscious we can account for the many overlapping insecurities and securities believed to exist at the individual, group, or state level – and thus felt. These insecurities also present themselves through the categories used to describe them and the policies through which they become materialised, technologised, and depoliticised, often by closing down discursive boundaries. Lacan’s concepts of desire, real and lack are here important for understanding the impossibility of recognising something that cannot be recognised. Hence, a perspective that takes misrecognition not as an end result or as failed attempts to reformulate the exceptional as the normal, has the potential to rethink the political subject. In empirical terms, the article discusses how this process of misrecognition has been shaped in the Indian context of postcolonial state formation and articulations of sovereignty. We show how the Indian state is being rethought, restructured, and reimagined through Hindu nationalism and how the concept of misrecognition accounts for desires for sovereign agency and group cohesiveness, but also for resistance to various reimaginations of the Indian state.
Prävention von stoffgebundenen Suchtstörungen
Authors: Arnaud Nicolas , Thomasius Rainer
Published: November 2018

Zusammenfassung. Einleitung: Substanzbezogene Suchtstörungen stellen ein erhebliches Entwicklungsrisiko für junge Menschen dar und sind in dieser Altersgruppe sehr verbreitet. Der Verlauf mit der Hauptinzidenzphase im Kindes- und Jugendalter indiziert frühzeitig ansetzende Prävention. Ergebnissen zur Wirksamkeit von Präventionsmaßnahmen kommt eine hohe Bedeutung zu. In diesem Beitrag fassen wir die Evidenz zu verhaltensbezogenen Präventionsmaßnahmen in unterschiedlichen Handlungsfeldern, in denen sie implementiert werden, zusammen. Ergebnisse: Insbesondere für die Handlungsfelder Schule, Familie und zunehmend auch das Internet liegen aktuelle Evidenzsynthesen vor. Die Studienlage für methodologisch zufriedenstellend untersuchte Programme ist für die verschiedenen Handlungsfelder, Zielgruppen und Substanzen ungleich verteilt. Dominierend sind US-amerikanische Studien zur universellen schulbasierten Prävention des Alkohol- und Tabakkonsum bei jüngeren Schülern. Es liegen vergleichsweise wenige Wirksamkeitsstudien aus Deutschland vor. Insgesamt liegen die berichteten Effekte überwiegend im statistisch signifikanten, aber kleinen bis mittleren Bereich. Ergebnisse zur differenziellen Wirksamkeit im schulischen Kontext legen nahe, dass die Effekte indizierter Ansätze mit steigendem Alter höher ausfallen, während bei jüngeren Schülern eher universelle, entwicklungsorientierte Programme effektiv sind, insbesondere dann, wenn sie erwachsene Bezugspersonen einbeziehen. Schlussfolgerung: In den wesentlichen Handlungsfeldern stehen eine Reihe von effektiven Maßnahmen zur substanzbezogenen Suchtprävention zur Verfügung. Zur Verbesserung bedarf es differenzierter Forschung zu effektiven Komponenten und der koordinierten Umsetzung in den Präventionsaktivitäten auf kommunaler Ebene.
From Point to Area: Worldwide Assessment of the Representativeness of Monthly Surface Solar Radiation Records
Authors: Schwarz M. , Folini D. , Hakuba M. Z. , Wild M.
Published: November 2018

The representativeness of surface solar radiation (SSR) point observations is an important issue when using them in combination with gridded data. We conduct a comprehensive near‐global (50°S to 55°N) analysis on the representativeness of SSR point observations on the monthly mean time scale. Thereto, we apply the existing concepts of decorrelation lengths (δ), spatial sampling biases (β), and spatial sampling errors (ε) to three high‐resolution gridded monthly mean SSR data sets (CLARA, SARAH‐P, and SARAH‐E) provided by the Satellite Application Facility on Climate Monitoring. While δ quantifies the area for which a point observation is representative, β and ε are uncertainty estimates with respect to the 1‐degree reference grid (G). For this grid we find a near‐global average δG=3.4°, βG=1.4 W/m2, and εG=7.6 W/m2 with substantial regional differences. Disregarding tropical, mountainous, and some coastal regions, monthly SSR point observations can largely be considered representative of a 1‐degree grid. Since ε is an uncorrectable error the total uncertainty when combining point with 1‐degree gridded data is roughly 40% higher than the uncertainty of station‐based SSR measurements alone if a rigorous bias correction is applied. Cloud cover and terrain data can at maximum explain 50% of the patterns of the representativeness metrics. We apply our methodology to the stations of the Baseline Surface Radiation Network. Overall, this study shows that representativeness is strongly dependent on local conditions and that all three metrics (δ, β, and ε) must be considered for a comprehensive assessment of representativeness.
Broadband Measurements of the Complex Permittivity of Carbonaceous Asteroid Regolith Analog Materials
Authors: Boivin A. L. , Hickson D. , Tsai C. , Cunje A. , Ghent R. R. , Daly M. G.
Published: November 2018

We develop a full methodology to measure the complex relative permittivity of planetary regolith analog materials in vacuum and up to 120 °C over a broad range of frequencies (400 MHz to 8.5 GHz or wavelengths 18.8–3.5 cm). We demonstrate our method with measurements of analog regolith materials appropriate for asteroid (101955) Bennu, the target of National Aeronautics and Space Administration's OSIRIS‐REx mission: individual and mixed components of UCF/DSI‐CI‐2, a new carbonaceous asteroid regolith simulant produced by Deep Space Industries based on CI chondrite meteorite mineralogy. We measure, for the first time, the effect of carbonaceous material on the complex relative permittivity of asteroid regolith analogs by measuring the powdered serpentine component of the simulant mixed with varying amounts of carbonaceous material in vacuum at 25 and 40 °C. We find that at a bulk density of 1.60 g/cm3 and wavelength of 12.6 cm, serpentine with 5 wt% carbonaceous material has
 = 3.30 ± 0.01 and
 = 0.016 ± 0.003 and that carbonaceous material increases the attenuation of electromagnetic energy in our samples. Ground‐based radar (at 12.6‐ and 3.5‐cm wavelengths) has previously been used to investigate carbonaceous asteroid (101955) Bennu. Our measurements provide new constraints on the attenuation of radar energy in granular carbonaceous materials.
Production and Transformation of Dissolved and Particulate Organic Matter as Indicated by Amino Acids in the Pearl River Estuary, China
Authors: Li Xiaolin , Liu Zhanfei , Chen Wei , Wang Lei , He Biyan , Wu Kai , Gu Shuai , Jiang Peng , Huang Bangqin , Dai Minhan
Published: November 2018

Production and transformation of dissolved and particulate organic matter (DOM, POM) in estuaries regulate the carbon export from land to ocean, yet tracing their source and diagenetic status is challenging in these dynamic environments. Here we study the production, transport, and diagenetic status of DOM in the Pearl River Estuary (PRE), China, based on total dissolved amino acids, their enantiomers (D/L ratios), and other ancillary biogeochemical parameters with a complete coverage of upper, middle, and lower estuary. Inferred from amino acid composition and D/L ratios, DOM in the upper PRE was highly altered by bacteria, while the carbon yields of total dissolved amino acids were relatively high showing a conflicting pattern likely contributed by multiple sources including planktonic production, soil leachates, and sewage discharge. Conservative mixing between freshwater and seawater predominantly controlled DOM dynamics in the middle PRE. In contrast, the lower PRE was characterized by high planktonic production, leading to the accumulation of labile DOC in the surface water. The compositional pattern of amino acids differed significantly between dissolved and particulate phases, yet the diagenetic indices of POM and DOM were both relatively lower in the upper and middle PRE compared to the lower PRE, suggesting that primary production is a major driving factor in the lower PRE. Overall, our study emphasizes the highly dynamic and spatially heterogeneous nature of the PRE, and the results from molecular level characterization provide new insights into the complex sources, diagenesis, and transformation processes of DOM in different regions of the estuary, as well as its connection with POM.
Annexin A1-suppressed autophagy promotes nasopharyngeal carcinoma cell invasion and metastasis by PI3K/AKT signaling activation
Authors: Zhu Jin-Feng , Huang Wei , Yi Hong-Mei , Xiao Ta , Li Jiao-Yang , Feng Juan , Yi Hong , Lu Shan-Shan , Li Xin-Hui , Lu Rou-Huang , He Qiu-Yan , Xiao Zhi-Qiang
Published: November 2018

Annexin A1 (ANXA1) is dysregulated in the various tumors. However, the role and mechanism of ANXA1 in the cancers are poorly understood. In this study, we first showed a clinically positive correlation between ANXA1 and autophagy-associated protein SQSTM1 expression in nasopharyngeal carcinoma (NPC) and ANXA1-regulating SQSTM1 expression through autophagy, and further demonstrated that ANXA1 inhibited BECN1 and ATG5-dependent autophagy in the NPC cells. Using phospho-kinase antibody array to identify signaling through which ANXA1 regulated NPC cell autophagy, we found that ANXA1-suppressed autophagy was associated with PI3K/AKT signaling activation. We also showed that ANXA1 expression was significantly increased in the NPCs with metastasis relative to NPCs without metastasis and positively correlated with lymphonode and distant metastasis; high ANXA1 expression in the NPC cells promoted in vitro tumor cell migration and invasion and in vivo metastasis. Lastly, we showed that inhibition of autophagy restored the ability of tumor cell migration and invasion, epithelial–mesenchymal transition (EMT)-like alterations and in vivo metastasis in the ANXA1 knockdown NPC cells with autophagy activation; ANXA1-suppresed autophagy induced EMT-like alterations possibly by inhibiting autophagy-mediated degradation of Snail. Our data suggest that ANXA1-suppressed autophagy promotes NPC cell migration, invasion and metastasis by activating PI3K/AKT signaling pathway, highlighting that the activation of autophagy may inhibit metastasis of NPC with high ANXA1 expression.
The Virtual-Environment-Foraging Task enables rapid training and single-trial metrics of attention in head-fixed mice
Authors: Havenith Martha N. , Zijderveld Peter M. , van Heukelum Sabrina , Abghari Shaghayegh , Glennon Jeffrey C. , Tiesinga Paul
Published: November 2018

Attention – the flexible allocation of processing resources based on behavioural demands – is essential to survival. Mouse research offers unique tools to dissect the underlying pathways, but is hampered by the difficulty of accurately measuring attention in mice. Current attention tasks for mice face several limitations: Binary (hit/miss), temporally imprecise metrics, behavioural confounds and overtraining. Thus, despite the increasing scope of neuronal population measurements, insights are limited without equally precise behavioural measures. Here we present a virtual-environment task for head-fixed mice based on ‘foraging-like’ navigation. The task requires animals to discriminate gratings at orientation differences from 90° to 5°, and can be learned in only 3–5 sessions (<550 trials). It yields single-trial, non-binary metrics of response speed and accuracy, which generate secondary metrics of choice certainty, visual acuity, and most importantly, of sustained and cued attention – two attentional components studied extensively in humans. This allows us to examine single-trial dynamics of attention in mice, independently of confounds like rule learning. With this approach, we show that C57/BL6 mice have better visual acuity than previously measured, that they rhythmically alternate between states of high and low alertness, and that they can be prompted to adopt different performance strategies using minute changes in reward contingencies.
miR-146a regulates the crosstalk between intestinal epithelial cells, microbial components and inflammatory stimuli
Authors: Anzola Andrea , González Raquel , Gámez-Belmonte Reyes , Ocón Borja , Aranda Carlos J. , Martínez-Moya Patricia , López-Posadas Rocío , Hernández-Chirlaque Cristina , Sánchez de Medina Fermín , Martínez-Augustin Olga
Published: November 2018

Regulation of miR-146a abundance and its role in intestinal inflammation and particularly in intestinal epithelial cells (IECs) has been poorly studied. Here we study the relationship between bacterial antigens and inflammatory stimuli, and miR-146a expression using IEC lines and models of colitis (trinitrobenzenesulfonic acid (TNBS), dextran sulfate sodium (DSS) and the CD4 + CD62L + T cell transfer model). Specific bacterial antigens and cytokines (LPS, flagelin and IL-1β/TNF) stimulate miR-146a expression, while peptidoglycan, muramyldipeptide and CpG DNA have no effect. Overexpression of miR-146a by LPS depends on the activation of the TLR4/MyD88/NF-kB and Akt pathways. Accordingly, the induction of miR-146a is lower in TLR4, but not in TLR2 knock out mice in both basal and colitic conditions. miR-146a overexpression in IECs induces immune tolerance, inhibiting cytokine production (MCP-1 and GROα/IL-8) in response to LPS (IEC18) or IL-1β (Caco-2). Intestinal inflammation induced by chemical damage to the epithelium (DSS and TNBS models) induces miR-146a, but no effect is observed in the lymphocyte transfer model. Finally, we found that miR-146a expression is upregulated in purified IECs from villi vs. crypts. Our results indicate that miR-146a is a key molecule in the interaction among IECs, inflammatory stimuli and the microbiota.
A novel fluorescein-bisphosphonate based diagnostic tool for the detection of hydroxyapatite in both cell and tissue models
Authors: Sim Alisia M. , Rashdan Nabil A. , Cui Lin , Moss Alastair J. , Nudelman Fabio , Dweck Marc R. , MacRae Vicky E. , Hulme Alison N.
Published: November 2018

A rapid and efficient method for the detection of hydroxyapatite (HAP) has been developed which shows superiority to existing well-established methods. This fluorescein-bisphosphonate probe is highly selective for HAP over other calcium minerals and is capable of detecting lower levels of calcification in cellular models than either hydrochloric acid-based calcium leaching assays or the Alizarin S stain. The probe has been shown to be effective in both in vitro vascular calcification models and in vitro bone calcification models. Moreover we have demonstrated binding of this probe to vascular calcification in rat aorta and to areas of microcalcification, in human vascular tissue, beyond the resolution of computed tomography in human atherosclerotic plaques. Fluorescein-BP is therefore a highly sensitive and specific imaging probe for the detection of vascular calcification, with the potential to improve not only ex vivo assessments of HAP deposition but also the detection of vascular microcalcification in humans.
Author Correction: Directional sound beam emission from a configurable compact multi-source system
Authors: Zhao Jiajun , Jahdali Rasha Al , Zhang Likun , Wu Ying
Published: November 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Coordinated Regulation of Axonal Microtubule Organization and Transport by Drosophila Neurexin and BMP Pathway
Authors: Banerjee Swati , Riordan Maeveen
Published: November 2018

Neurexins are well known trans-synaptic cell adhesion molecules that are required for proper synaptic development and function across species. Beyond synapse organization and function, little is known about other roles Neurexins might have in the nervous system. Here we report novel phenotypic consequences of mutations in Drosophila neurexin (dnrx), which alters axonal microtubule organization and transport. We show that dnrx mutants display phenotypic similarities with the BMP receptor wishful thinking (wit) and one of the downstream effectors, futsch, which is a known regulator of microtubule organization and stability. dnrx has genetic interactions with wit and futsch. Loss of Dnrx also results in reduced levels of other downstream effectors of BMP signaling, phosphorylated-Mad and Trio. Interestingly, postsynaptic overexpression of the BMP ligand, Glass bottom boat, in dnrx mutants partially rescues the axonal transport defects but not the synapse undergrowth at the neuromuscular junctions. These data suggest that Dnrx and BMP signaling are involved in many diverse functions and that regulation of axonal MT organization and transport might be distinct from regulation of synaptic growth in dnrx mutants. Together, our work uncovers a novel function of Drosophila Neurexin and may provide insights into functions of Neurexins in vertebrates.
Effects of oil and global environmental drivers on two keystone marine invertebrates
Authors: Arnberg Maj , Calosi Piero , Spicer John I. , Taban Ingrid C. , Bamber Shaw D. , Westerlund Stig , Vingen Sjur , Baussant Thierry , Bechmann Renée K. , Dupont Sam
Published: November 2018

Ocean warming (OW) and acidification (OA) are key features of global change and are predicted to have negative consequences for marine species and ecosystems. At a smaller scale increasing oil and gas activities at northern high latitudes could lead to greater risk of petroleum pollution, potentially exacerbating the effects of such global stressors. However, knowledge of combined effects is limited. This study employed a scenario-based, collapsed design to investigate the impact of one local acute stressor (North Sea crude oil) and two chronic global drivers (pH for OA and temperature for OW), alone or in combination on aspects of the biology of larval stages of two key invertebrates: the northern shrimp (Pandalus borealis) and the green sea urchin (Strongylocentrotus droebachiensis). Both local and global drivers had negative effects on survival, development and growth of the larval stages. These effects were species- and stage-dependent. No statistical interactions were observed between local and global drivers and the combined effects of the two drivers were approximately equal to the sum of their separate effects. This study highlights the importance of adjusting regulation associated with oil spill prevention to maximize the resilience of marine organisms to predicted future global conditions.
Comparison between kinetic and kinetic-kinematic driven knee joint finite element models
Authors: Bolcos Paul O. , Mononen Mika E. , Mohammadi Ali , Ebrahimi Mohammadhossein , Tanaka Matthew S. , Samaan Michael A. , Souza Richard B. , Li Xiaojuan , Suomalainen Juha-Sampo , Jurvelin Jukka S. , Töyräs Juha , Korhonen Rami K.
Published: November 2018

Use of knee joint finite element models for diagnostic purposes is challenging due to their complexity. Therefore, simpler models are needed for studies where a high number of patients need to be analyzed, without compromising the results of the model. In this study, more complex, kinetic (forces and moments) and simpler, kinetic-kinematic (forces and angles) driven finite element models were compared during the stance phase of gait. Patella and tendons were included in the most complex model, while they were absent in the simplest model. The greatest difference between the most complex and simplest models was observed in the internal-external rotation and axial joint reaction force, while all other rotations, translations and joint reaction forces were similar to one another. In terms of cartilage stresses and strains, the simpler models behaved similarly with the more complex models in the lateral joint compartment, while minor differences were observed in the medial compartment at the beginning of the stance phase. We suggest that it is feasible to use kinetic-kinematic driven knee joint models with a simpler geometry in studies with a large cohort size, particularly when analyzing cartilage responses and failures related to potential overloads.
Understanding flow dynamics, viability and metastatic potency of cervical cancer (HeLa) cells through constricted microchannel
Authors: Nath Binita , Raza Asif , Sethi Vishal , Dalal Amaresh , Ghosh Siddhartha Sankar , Biswas Gautam
Published: November 2018

To understand the burgeoning challenges of metastasis, a microchannel of 35 μm diameter, constricted to 7 μm for a distance of 200 μm in a total length of 3 mm, was designed and fabricated using a mask aligner made of polydimethylsiloxane (PDMS) to mimic in vivo capillaries. A thin glass cover-slide was mounted on top to monitor the motion of single or aggregated malignant HeLa cells (size 17–30 μm) microscopically through the constricted microchannel at a constant flow rate of 30 μl/h. Quantitative deconvolution of high-speed videographs of a single cell of 30 μm revealed cellular deformation while passing through constriction, having elongation index, average transit velocity and entry time of 2.67, 18 mm/s and 5.1 ms, respectively. Morphological analysis of live and apoptotic cells by dual staining with Acridine Orange/Ethidium Bromide demonstrated retention of a significant viable cell population after exit through the constriction and a viability index of 50% was quantified by dye exclusion assay. The cumulative data for microfluidic parameters, morphology and relevant metastatic MMP2 gene expression efficiency measured by real-time polymerase chain reaction revealed retention of virulence potency that could possibly cause metastasis, would be beneficial in developing futuristic MEMS device for cancer theranostics.
Exploring the Magnetoelectric Coupling at the Composite Interfaces of FE/FM/FE Heterostructures
Authors: Pradhan Dhiren K. , Kumari Shalini , Vasudevan Rama K. , Strelcov Evgheni , Puli Venkata S. , Pradhan Dillip K. , Kumar Ashok , Gregg J. Marty , Pradhan A. K. , Kalinin Sergei V. , Katiyar Ram S.
Published: November 2018

Multiferroic materials have attracted considerable attention as possible candidates for a wide variety of future microelectronic and memory devices, although robust magnetoelectric (ME) coupling between electric and magnetic orders at room temperature still remains difficult to achieve. In order to obtain robust ME coupling at room temperature, we studied the Pb(Fe0.5Nb0.5)O3/Ni0.65Zn0.35Fe2O4/Pb(Fe0.5Nb0.5)O3 (PFN/NZFO/PFN) trilayer structure as a representative FE/FM/FE system. We report the ferroelectric, magnetic and ME properties of PFN/NZFO/PFN trilayer nanoscale heterostructure having dimensions 70/20/70 nm, at room temperature. The presence of only (00l) reflection of PFN and NZFO in the X-ray diffraction (XRD) patterns and electron diffraction patterns in Transmission Electron Microscopy (TEM) confirm the epitaxial growth of multilayer heterostructure. The distribution of the ferroelectric loop area in a wide area has been studied, suggesting that spatial variability of ferroelectric switching behavior is low, and film growth is of high quality. The ferroelectric and magnetic phase transitions of these heterostructures have been found at ~575 K and ~650 K, respectively which are well above room temperature. These nanostructures exhibit low loss tangent, large saturation polarization (Ps ~ 38 µC/cm2) and magnetization (Ms ~ 48 emu/cm3) with strong ME coupling at room temperature revealing them as potential candidates for nanoscale multifunctional and spintronics device applications.
Using Frameshift Peptide Arrays for Cancer Neo-Antigens Screening
Authors: Zhang Jian , Shen Luhui , Johnston Stephen Albert
Published: November 2018

It has been demonstrated that DNA mutations generating neo-antigens are important for an effective immune response to tumors as evident from recent clinical studies of immune checkpoint inhibitors (ICIs). Further, it was shown that frameshift peptides (FSP) generated in tumors from insertions and deletions (INDELs) of microsatellites (MS) in coding region are a very good correlate of positive response to PD1 treatment. However, these types of DNA-sourced FSPs are infrequent in cancer. We hypothesize that tumors may also generate FSPs in transcription errors through INDELs in MS or by exon mis-splicing. Since there are a finite number of predictable sequences of such possible FSPs in the genome, we propose that peptide arrays with all possible FSPs could be used to analyze antibody reactivity to FSPs in patient sera as a FS neo-antigen screen. If this were the case it would facilitate finding common tumor neoantigens for cancer vaccines. Here we test this proposal using an array of 377 predicted FS antigens. The results of screening 9 types of dog cancer sera indicate that cancer samples had significantly higher antibody responses against FSPs than non-cancer samples. Both common reactive FSPs and cancer-type specific immune responses were detected. In addition, the protection of a common reactive FSP was tested in mouse tumor models, comparing to the non-reactive FSPs. The mouse homologs non-reactive FSPs did not offer protection in either the mouse melanoma or breast cancer models while the reactive FSP did in both models. The tumor protection was positively correlated to antibody response to the FSP. These data suggest that FSP arrays could be used for cancer neo-antigen screening.
High glycolytic activity of tumor cells leads to underestimation of electron transport system capacity when mitochondrial ATP synthase is inhibited
Authors: Ruas Juliana S. , Siqueira-Santos Edilene S. , Rodrigues-Silva Erika , Castilho Roger F.
Published: November 2018

This study sought to elucidate how oligomycin, an ATP synthase blocker, leads to underestimation of maximal oxygen consumption rate (maxOCR) and spare respiratory capacity (SRC) in tumor cells. T98G and U-87MG glioma cells were titrated with the protonophore CCCP to induce maxOCR. The presence of oligomycin (0.3–3.0 µg/mL) led to underestimation of maxOCR and a consequent decrease in SRC values of between 25% and 40% in medium containing 5.5 or 11 mM glucose. The inhibitory effect of oligomycin on CCCP-induced maxOCR did not occur when glutamine was the metabolic substrate or when the glycolytic inhibitor 2-deoxyglucose was present. ATP levels were reduced and ADP/ATP ratios increased in cells treated with CCCP, but these changes were minimized when oligomycin was used to inhibit reverse activity of ATP synthase. Exposing digitonin-permeabilized cells to exogenous ATP, but not ADP, resulted in partial inhibition of CCCP-induced maxOCR. We conclude that underestimation of maxOCR and SRC in tumor cells when ATP synthase is inhibited is associated with high glycolytic activity and that the glycolytic ATP yield may have an inhibitory effect on the metabolism of respiratory substrates and cytochrome c oxidase activity. Under CCCP-induced maxOCR, oligomycin preserves intracellular ATP by inhibiting ATP synthase reverse activity.