bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi‐electron Reduction Capacity and Multiple Binding Pockets in Metal–Organic Redox Assembly at Surfaces
Authors: Morris Tobias W. , Huerfano I. J. , Wang Miao , Wisman David L. , Cabelof Alyssa C. , Din Naseem U. , Tempas Christopher D. , Le Duy , Polezhaev Alexander V. , Rahman Talat S. , Caulton Kenneth G. , Tait Steven L.
Published: February 2019

Metal–ligand complexation at surfaces utilizing redox‐active ligands has been demonstrated to produce uniform single‐site metals centers in regular coordination networks. Two key design considerations are the electron storage capacity of the ligand and the metal‐coordinating pockets on the ligand. In an effort to move toward greater complexity in the systems, particularly dinuclear metal centers, we designed and synthesized tetraethyltetra‐aza‐anthraquinone, TAAQ, which has superior electron storage capabilities and four ligating pockets in a diverging geometry. Cyclic voltammetry studies of the free ligand demonstrate its ability to undergo up to a four‐electron reduction. Solution‐based studies with an analogous ligand, diethyldi‐aza‐anthraquinone, demonstrate these redox capabilities in a molecular environment. Surface studies conducted on the Au(111) surface demonstrate TAAQ′s ability to complex with Fe. This complexation can be observed at different stoichiometric ratios of Fe:TAAQ as Fe 2p core level shifts in X‐ray photoelectron spectroscopy. Scanning tunneling microscopy experiments confirmed the formation of metal–organic coordination structures. The striking feature of these structures is their irregularity, which indicates the presence of multiple local binding motifs. Density functional theory calculations confirm several energetically accessible Fe:TAAQ isomers, which accounts for the non‐uniformity of the chains.
Fully Collapsed Imploded Cryptophanes in Solution and in the Solid State
Authors: Thorp‐Greenwood Flora L. , Howard Mark J. , Kuhn Lars T. , Hardie Michaele J.
Published: February 2019

Cryptophanes with flexible linkers derived from (±)‐tris‐(4‐formyl‐phenyl)‐cyclotriguaiacylene with either bisoxydi(ethylamine) or bis(aminopropyl)ether were isolated as single crystals, the crystal structures of which showed the proposed, but previously uncharacterised, out‐in conformation, in which both cyclotriguaiacylene fragments adopt a crown conformation with one crown sitting inside the other. The usual cage‐like out‐out conformation of the cryptophanes was observed when crystals were dissolved upon heating, and the molecules collapsed back to the out‐in isomers over time. In contrast, a cryptophane also derived from (±)‐tris‐(4‐formyl‐phenyl)‐cyclotriguaiacylene but with rigid dibenzalhydrazine linkers was isolated as the more usual out‐out isomer.
Catalytic Asymmetric Hydrogenation of Dehydroamino Acid Esters with Biscarbamate Protection and Its Application to the Synthesis of xCT Inhibitors
Authors: Yasuno Yoko , Mizutani Iho , Sueuchi Yuki , Wakabayashi Yuuka , Yasuo Nozomi , Shimamoto Keiko , Shinada Tetsuro
Published: February 2019

Catalytic asymmetric hydrogenation of dehydroamino acid esters with biscarbamate protection was examined for the first time to prepare optically active amino acids. The new method was successfully applied to the synthesis of new cystine–glutamate exchanger inhibitors.
Ground State of the Conformal Flow on 𝕊3
Authors: Bizoń Piotr , Hunik‐Kostyra Dominika , Pelinovsky Dmitry E.
Published: February 2019

We consider the conformal flow model derived in Bizoń et al. (2017) as a normal form for the conformally invariant cubic wave equation on 𝕊3. We prove that the energy attains a global constrained maximum at a family of particular stationary solutions that we call the ground state family. Using this fact and spectral properties of the linearized flow (which are interesting in their own right due to a supersymmetric structure), we prove nonlinear orbital stability of the ground state family. The main difficulty in the proof is due to the degeneracy of the ground state family as a constrained maximizer of the energy. © 2019 Wiley Periodicals, Inc.
Utilizing iVariantGuide for Variant Assessment of Next‐Generation Sequencing
Authors: Chaudhry Sophia R. , Tainsky Michael A.
Published: February 2019

Molecular genetic testing provides the capability for personalized prediction, diagnosis, and pharmacological treatments of disease and disorders. Variant assessment of next‐generation sequencing (NGS) is a crucial component of genetic testing for clinicians to counsel patients on risk and management. The iVariantGuide application is a dynamic Web‐based application made for the tertiary analysis of NGS. Along with variant assessment, iVariantGuide provides a unique interactive pathway impact analysis of genetic variants, as well as a unique Gene Ontology (GO) analysis. Here we provide a step‐by‐step guide on how to utilize iVariantGuide, employing a publicly available NGS dataset consisting of a cohort of germline DNAs from high‐risk serous ovarian cancer (OVCA) patients. The application will be used to exhibit the ease in filtering down to a set of compelling novel variants and their impact on biological pathways and GO terms. © 2019 by John Wiley & Sons, Inc.
A study on popular auto‐parallelization frameworks
Authors: Prema S. , Nasre Rupesh , Jehadeesan R. , Panigrahi B.K.
Published: February 2019

We study five popular auto‐parallelization frameworks (Cetus, Par4all, Rose, ICC, and Pluto) and compare them qualitatively as well as quantitatively. All the frameworks primarily deal with loop parallelization but differ in the techniques used to identify parallelization opportunities. Due to this variance, various aspects, such as certain loop transformations, are supported only in a few frameworks. The frameworks exhibit varying abilities in handling loop‐carried dependence and, therefore, achieve different amounts of speedup on widely used PolyBench and NAS parallel benchmarks. In particular, Intel C Compiler (ICC) fares as an overall good parallelizer. Our study also highlights the need for more sophisticated analyses, user‐driven parallelization, and meta‐auto‐parallelizer that provides combined benefits of various frameworks.
Affinity Isolation of Defined Genomic Fragments Cleaved by Nuclease S1‐based Artificial Restriction DNA Cutter
Authors: Rajendran Arivazhagan , Shigi Narumi , Sumaoka Jun , Komiyama Makoto
Published: February 2019

The human genome is highly susceptible to various modifications, lesions, and damage. To analyze lesions and proteins bound to a defined region of the human genome, the genome should be fragmented at desired sites and the region of interest should be isolated. The few available methods for isolating a desired region of the human genome have serious drawbacks and can only be applied to specific sequences or require tedious experimental procedures. We have recently developed a novel method to isolate a desired fragment of the genome released by site‐specific scission of DNA using a pair of pseudo‐complementary peptide nucleic acids (pcPNAs) and S1 nuclease. When conjugated to biotin, one of the pcPNAs can be used to affinity purify the cleavage product. Here we report a detailed protocol to isolate defined kilobase‐length DNA fragments that can be applied to plasmid or genomic DNA and is not limited by sequence. © 2019 by John Wiley & Sons, Inc.
Living the life you want following a diagnosis of bipolar disorder: A grounded theory approach
Authors: Warwick Helen , Tai Sara , Mansell Warren
Published: February 2019

Bipolar disorder (BD) is considered a severe and lifelong mental health diagnosis. However, there is growing evidence of people defying the odds and recovering. Processes underlying recovery remain poorly understood. This study aimed to explore these recovery processes and extend on the length of recovery defined within previous research. Twelve people previously diagnosed with BD, who had not experienced an episode of depression and/or mania for four or more years, were interviewed. Standardised diagnostic interviews (Structured Clinical Interview for Diagnostic and Statistical Manual‐V, Research version) confirmed past diagnosis and recovery time. Qualitative methodology via grounded theory was used to analyse these personal accounts. The analysis revealed 10 overarching categories of what participants reported to be important in their recovery: support, recognition of the problem, believing that things can change and not giving up, instinctive curiosity, medication, psychological therapy, becoming the director of your own life, changing how I think, accepting who I am and how I feel, and looking after me. A model was developed to represent how categories were related. The study was limited by recruitment not leading to the inclusion of people who had distanced themselves from the label of BD. Potential transdiagnostic recovery processes also require further direct exploration. Critically, the study highlights that following a diagnosis of BD, people do experience long‐term recovery achieved through self‐determined pathways and that being able to live the life you want is therefore achievable. This challenges current diagnostic perspectives and societal messages of lifelong conditions.
Partial fraction expansion–based realizations of fractional‐order differentiators and integrators using active filters
Authors: Bertsias Panagiotis , Psychalinos Costas , Maundy Brent J. , Elwakil Ahmed S. , Radwan Ahmed G.
Published: February 2019

Approximations of the fractional‐order differentiator and integrator operators s±r are proposed in this work. These approximations target the realization of these operators using standard active filter transfer functions. Hence, circuit implementations in integrated circuit form or in discrete component form are significantly facilitated. Complementary metal‐oxide‐semiconductor (CMOS) realizations of the proposed approximations are given and validated via simulations using the AMS 0.35 μm CMOS technology, while experimental results using operational amplifier circuits are tested and confirm the proposed theory.
Performances of machine learning algorithms for mapping fractional cover of an invasive plant species in a dryland ecosystem
Authors: Shiferaw Hailu , Bewket Woldeamlak , Eckert Sandra
Published: February 2019

In recent years, an increasing number of distribution maps of invasive alien plant species (IAPS) have been published using different machine learning algorithms (MLAs). However, for designing spatially explicit management strategies, distribution maps should include information on the local cover/abundance of the IAPS. This study compares the performances of five MLAs: gradient boosting machine in two different implementations, random forest, support vector machine and deep learning neural network, one ensemble model and a generalized linear model; thereby identifying the best‐performing ones in mapping the fractional cover/abundance and distribution of IPAS, in this case calledProsopis juliflora (SW. DC.). Field levelProsopiscover and spatial datasets of seventeen biophysical and anthropogenic variables were collected, processed, and used to train and validate the algorithms so as to generate fractional cover maps ofProsopisin the dryland ecosystem of the Afar Region, Ethiopia. Out of the seven tested algorithms, random forest performed the best with an accuracy of 92% and sensitivity and specificity >0.89. The next best‐performing algorithms were the ensemble model and gradient boosting machine with an accuracy of 89% and 88%, respectively. The other tested algorithms achieved comparably low performances. The strong explanatory variables forProsopisdistributions in all models were NDVI, elevation, distance to villages and distance to rivers; rainfall, temperature, near‐infrared and red reflectance, whereas topographic variables, except for elevation, did not contribute much to the current distribution ofProsopis. According to the random forest model, a total of 1.173 million ha (12.33% of the study region) was found to be invaded byProsopisto varying degrees of cover. Our findings demonstrate that MLAs can be successfully used to develop fractional cover maps of plant species, particularly IAPS so as to design targeted and spatially explicit management strategies.
Biases in studies of spatial patterns in insect herbivory
Authors: Zvereva Elena L. , Kozlov Mikhail V.
Published: February 2019

The properties of the human mind are responsible for a number of biases that affect the quality of scientific research. However, scientists working in the fields of ecology and environmental science rarely take these biases into account. We conducted a meta‐analysis of data extracted from 125 publications comparing woody plant damage by defoliating insects in different environments in order to understand the extent to which our knowledge on spatial patterns in herbivory is affected by various biases. We asked which research methods are most prone to biases and whether these biases lead to overestimation of the effects under study. The effect sizes (ESs) decreased with increases in the numbers of plant species involved in the study, with 61% lower ESs for herbivory estimated on all plants growing in study plots compared to herbivory on selected species. ESs also depended on the leaf sampling procedure: when all leaves from a tree or branch were sampled for measurements of herbivory or when random or systematic selection protocols were applied, ESs were 74% smaller than in cases of more subjective haphazard selection. In addition, ESs were 97% and 135% greater when the person conducting sampling and measuring was aware of the research hypothesis or sample origin, when compared with situations when the observer was blinded to these factors. The impacts of cognitive biases on the study outcomes significantly decreased with the increase in publication year; however, this pattern emerged mostly due to high‐ranked journals and was non‐significant for other journals. Using the studies of spatial patterns in herbivory as an example, we showed that our ecological and environmental knowledge is considerably biased due to an unconscious tendency of researchers to find support for their hypotheses and expectations, which generally leads to overestimation of the effects under study. Cognitive biases can be avoided by using different methods, such as applying randomization procedures in sampling and blinding of research hypotheses and sample origins. These measures should be seen as obligatory; otherwise, accumulation of the biased results in primary studies may ultimately lead to false general conclusions in subsequent research synthesis.
How big is enough? Vegetation structure impacts effective fuel treatment width and forest resiliency
Authors: Kennedy Maureen C. , Johnson Morris C. , Fallon Kendra , Mayer Deborah
Published: February 2019

Fuel treatments are designed with multiple management goals, including improving suppression capacity and restoring the historical structure of dry forests. Fuelbreaks are a class of fuel treatment that remove fuels within a wide strip of land, with an overarching objective to reduce fire behavior and provide safe access for suppression. In an empirical analysis of shaded fuelbreaks that burned during the 2014 Bald Fire (15,950 ha on the Lassen National Forest, California,USA), we found that overall fire severity was reduced in the treated areas relative to untreated. A non‐linear mixed effects model estimates that the reduction was detected more than 400 m into the treated area, greater than the standard width of the prescribed fuelbreak. Both pre‐ and post‐fire species composition differed between treated and untreated forest, with few living stems remaining in the measured untreated areas. In the post‐fire treated area, we documented a mixed conifer forest dominated by larger diameterPinus, implying that the fuelbreak did result in a more resilient post‐fire structure and composition. These results indicate that fuelbreak design may need to be wider than generally prescribed and that even during extreme fire conditions fuel treatments can result in resilient forest structures.
Predator recovery, shifting baselines, and the adaptive management challenges they create
Authors: Cammen Kristina M. , Rasher Douglas B. , Steneck Robert S.
Published: February 2019

Recent species recoveries following historical depletion have been widely celebrated as conservation success stories. However, the recovery of highly interactive species, particularly predators, generates new management challenges that arise from their potential for wide‐ranging effects on local ecosystems and their poorly understood ecology. In marine systems, many pinniped species share parallel histories of depletion, recovery, and human conflict. Recovering from post‐exploitation populations of small size, these pinnipeds have returned to their present abundance from a largely absent, or severely reduced, recent role in many coastal ecosystems. To address the challenges arising today from real or perceived overabundance of protected pinniped species, we evaluate the prehistorical, historical, and contemporary abundances of six pinniped species that breed in the contiguous United States. This review highlights gaps in current knowledge that limit the implementation of ecologically grounded approaches to adaptive management of protected species in a time of shifting, or lifting, baselines. To address these gaps will require a diverse cadre of natural and social scientists as well as stakeholders to tackle the questions of how we define recovery at a species or ecosystem level, and when we have reached this point, how we move forward in a way that does not repeat a history of depletion, conservation, and recovery. Doing so will require an understanding of what role highly interactive species play in their ecosystems and how this role shifts with changes in ecological context, as well as the sociological and economic impacts of species restoration to humans. This knowledge is integral to the ongoing transition from a focus on preventing species extinction to new, and often unanticipated, challenges arising from the functional implications of species recovery.
Strength and range of movement deficits are associated with symptom severity in people scheduled for hip arthroscopy
Authors: Freke Matthew , Kemp Joanne , Crossley Kay , Sims Kevin , Russell Trevor , Semciw Adam
Published: February 2019

Background

Identifying the physical impairments associated with worse symptoms and greater functional limitations in people with hip pain could enable targeted rehabilitation programmes designed to improve quality of life. The objective of this study was to compare physical characteristics between subgroups of symptoms and functional limitation severity in individuals with hip pain scheduled for arthroscopic surgery.

Methods

Hip range of motion (ROM) and muscle strength were measured in 114 individuals (48 women; aged 32 ± 8 years) with hip pain scheduled for hip arthroscopy. Pain and disability were measured with the International Hip Outcome Tool (iHOT33) subscale of Symptoms and Functional Limitation, and a cluster analysis was used to identify mild, moderate and severe subgroups. Between‐group differences were then evaluated using multivariate analysis of covariance, including sex as a covariate, followed by post hoc testing. Significance was set at 0.05.

Results

Lesser hip muscle strength in all directions was reported in the severe symptoms and functional limitation group compared to the mild group. Hip flexion ROM differed when comparing the moderate to both the mild and severe subgroups. Hip internal rotation did not differ between subgroups of severity.

Conclusions

Individuals with hip pain and severe scores in the iHOT33 subscale of symptoms and functional limitations present with significantly lesser hip muscle strength and hip flexion ROM than individuals with moderate or mild scores. Targeted programmes to improve hip strength and flexion ROM in more severe patients may help reduce symptoms and improve function.

Significance

Individuals with severe hip pain and functional limitation possess significantly lesser muscle strength and flexion ROM than individuals with moderate or mild scores.
“Freedom of speech requires actions”: Exploring the discourse of politicians convicted of hate‐speech against Muslims
Authors: Pettersson Katarina
Published: February 2019

This study explores how politicians convicted of hate‐speech against Muslims account for their actions in statements on their Facebook‐pages as well as in reported interviews. Taking a critical discursive psychological perspective, the study examines the strategies through which the politicians discursively claim and resist various subject positions, thus managing to construct their hate‐speech as everything from trivial mishaps to acts of virtue. The study examines the multifaceted dynamics of these constructions, and shows how elements from the Five Step Social Identity Model of the Development of Collective Hate are flexibly deployed in the discourse to serve distinct social and political purposes. By allowing the Social Identity and (critical) discursive approaches to challenge and develop each other, the study advances social psychological research on political communication and persuasion, and contributes to the debate on the boundaries between hate‐speech and freedom of speech.
Phenolic Composition and Total Antioxidant Capacity by Electrochemical, Spectrophotometric and HPLC‐EC Evaluation in Portuguese Red and White Wines
Authors: de Araújo Rodrigues Isaíde , Gomes Sara M. C. , Fernandes Isabel Patrícia Garrido , Oliveira‐Brett Ana Maria
Published: February 2019

Phenolic composition and in vitro total antioxidant capacity have been evaluated, in red and white Portuguese wines, by electrochemical methods, spectrophotometric methods, and reverse‐phase high performance liquid chromatography with electrochemical detection (HPLC‐EC). The different phenolic compounds present in seventeen red and white wines, with different grape varieties, and from different geographical locations, were successfully identified and detected. The wines in vitro total antioxidant capacity, using the method of capture of diphenilpicrilhydrazil (DPPH.) free radical “efficient concentration” (EC50), and the electrochemical quantitative index (EI), was determined. The wine with the highest total antioxidant capacity exhibited the lowest antioxidant power, and the EI and EC50 assays had a very good correlation.
A Smart Dental Floss for Biosensing of Glucose
Authors: Sha Pengju , Luo Xiaojin , Shi Weihua , Liu Yiqun , Cui Yue
Published: February 2019

The development of a simple directly wearable approach for the rapid, specific and sensitive determination of biomarkers is of great importance to a variety of biomedical applications. Dental floss can provide a unique device platform for sensing of oral biomarkers. We show here for the first time the development of a smart dental floss for biosensing of glucose. The sensor was made by painting carbon graphite ink and Ag/AgCl ink on dental floss. Via the immobilization of glucose oxidase, we show the detection of glucose with a detection range of 0.048 mM to 19.5 mM and a response time of about 2 min. It is expected that our results could provide new exciting opportunities for the development of various flexible smart sensing devices in oral health applications.
A new pattern of underground space‐time tridimensional gas drainage: A case study in Yuwu coal mine, China
Authors: Li Yankui , Wu Shiyue , Nie Baisheng , Ma Yankun
Published: February 2019

With the increase of mining depth, the high gassy coal mine confronts with a variety of gas problems, such as gas concentration exceeding the limit in the working face, gas outburst and gas explosion. According to the situation of gas drainage in Qinshui Basin (South of Shanxi Province, China) and enlightened by horizontal directional drillings (HDD) and multi‐branched horizontal wells, a new gas drainage pattern that invertedπ‐shape km borehole layout was proposed. Verified in Yuwu Coal Mine, the gas drainage data were standardized via the unified theory of standardization. It could dropped the coal seam gas content to 7.71 m3/t, and increased the gas drainage rate to 34.2%, which conformed to the Chinese regulation (<8 m3/t, >30%, respectively). This pattern has a significant effect on coal mines with a single seam, where protective seam mining technology was unsuitable to prevent gas outburst and gas explosion.
Fire performance of closed‐cell charring insulation materials in plasterboard‐insulation assemblies
Authors: Hidalgo Juan P. , Torero José L. , Welch Stephen
Published: February 2019

This paper presents an experimental study on the fire performance of two types of plastic charring insulation materials when covered by a plasterboard lining. The specific insulation materials correspond to rigid closed‐cell plastic foams, a type of polyisocyanurate (foam A) and a type of phenolic foam (foam B), whose thermal decomposition and flammability were characterised in previous studies. The assemblies were instrumented with thermocouples. The plasterboard facing was subjected to constant levels of irradiation of 15, 25, and 65 kW m−2 using the heat‐transfer rate inducing system. These experiments serve as (1) an assessment of the fire behaviour of these materials studied at the assembly scale and (2) an identification of the fire hazards that these systems pose in building construction. The manifestation of the hazards occurred via initial pyrolysis reactions and release of volatiles followed by various complex behaviours including char oxidation (smouldering), cracking, and expansion of the foam. Gas‐phase conditions may support ignition of the volatiles, sustained burning, and ultimately spread of the flame through the unexposed insulation face. The results presented herein are used to validate the insulation “critical temperature” concept used for a performance‐based methodology focused on the selection of suitable thermal barriers for flammable insulation.
Discontinuous Galerkin finite element method applied to the coupled unsteady Stokes/Cahn‐Hilliard equations
Authors: Pigeonneau F. , Hachem E. , Saramito P.
Published: February 2019

Two‐phase flows driven by the interfacial dynamics are studied by tracking implicitly interfaces in the framework of the Cahn‐Hilliard theory. The fluid dynamics is described by the Stokes equations with an additional source term in the momentum equation taking into account the capillary forces. A discontinuous Galerkin finite element method is used to solve the coupled Stokes/Cahn‐Hilliard equations. The Cahn‐Hilliard equation is treated as a system of two coupled equations corresponding to the advection‐diffusion equation for the phase field and a nonlinear elliptic equation for the chemical potential. First, the variational formulation of the Cahn‐Hilliard equation is presented. A numerical test is achieved showing the optimal order in error bounds. Second, the variational formulation in discontinuous Galerkin finite element approach of the Stokes equations is recalled, in which the same space of approximation is used for the velocity and the pressure with an adequate stabilization technique. The rates of convergence in space and time are evaluated leading to an optimal order in error bounds in space and a second order in time with a backward differentiation formula at the second order. Numerical tests devoted to two‐phase flows are provided on ellipsoidal droplet retraction, on the capillary rising of a liquid in a tube, and on the wetting drop over a horizontal solid wall.
The impacts of public news announcements on intraday implied volatility dynamics
Authors: Lee Jieun , Ryu Doojin
Published: February 2019

We examine the responses of intraday option‐implied volatilities to scheduled announcements of macroeconomic indicators. The increase in implied volatility around macroeconomic news announcements is more pronounced for puts than for calls and is stronger for announcements made during trading hours than for those made during nontrading hours. These effects are also more pronounced in the crisis and postcrisis periods than in the precrisis period. Monetary policy announcements have a more substantial impact on volatility than other announcements have, even after controlling for news surprise components. The impact appears to be greater for policy rate hikes than for policy rate cuts.
Effect on California of Winding Down Natural Gas
Authors: Elder Catherine
Published: February 2019

We offer a beginning list of issues to consider in winding down the natural gas business in California.
Cooling Water Intake Regulated Through Clean Water Act Section 316(b): A Critical Issue
Authors: Lester Gary T.
Published: February 2019

Section 316(b) protects the aquatic ecology of the nation's waters. In May 2014, the Environmental Protection Agency (EPA) issued the final rule under Section 316(b) of the Clean Water Act. It outlined the regulations and standards for the design and operation of cooling water intake structures.
HPV as a marker for molecular characterization in head and neck oncology: Looking for a standardization of clinical use and of detection method(s) in clinical practice
Authors: Bussu Francesco , Ragin Camille , Boscolo‐Rizzo Paolo , Rizzo Davide , Gallus Roberto , Delogu Giovanni , Morbini Patrizia , Tommasino Massimo
Published: February 2019

Background

A consensus about the most appropriate diagnostic method(s) for head and neck human papillomavirus (HPV)‐induced carcinogenesis is still lacking because most of the commercially available assays have been designed for the cervix.

Methods

This article summarizes current data and trends concerning HPV diagnostic strategies in oropharyngeal squamous cell carcinoma (OPSCC). Six main approaches are described.

Results

The diagnostic gold standard for HPV‐related OPSCC, focusing on E6/E7 mRNA detection, requires fresh samples. Because most frequently available samples are formalin‐fixed paraffin‐embedded (FFPE), the pros and cons of the different approaches were analyzed.

Conclusions

In the FFPE samples, the immunohistochemistry of p16, which is considered appropriate to assess HPV‐driven carcinogenesis in OPSCC according to the 8th American Joint Committee on Cancer TNM classification, may not be specific enough to become the diagnostic standard in the perspective of treatment deintensification. p16 may play a safer role in combination with another highly sensible assay. Other promising approaches are based on DNA detection through real‐time polymerase chain reaction and RNAscope.
Hepatic Interferon Regulatory Factor 6 Alleviates Liver Steatosis and Metabolic Disorder by Transcriptionally Suppressing Peroxisome Proliferator‐Activated Receptor γ in Mice
Authors: Tong Jingjing , Han Cui‐Juan , Zhang Jia‐Zhen , He Wen‐Zhi , Zhao Guo‐Jun , Cheng Xu , Zhang Lei , Deng Ke‐Qiong , Liu Ye , Fan Hui‐Fen , Tian Song , Cai Jingjing , Huang Zan , She Zhi‐Gang , Zhang Peng , Li Hongliang
Published: February 2019

Nonalcoholic fatty liver disease (NAFLD) has become a worldwide epidemic. A large and growing unmet therapeutic need has inspired numerous studies in the field. Integrating the published genomic data available in the Gene Expression Omnibus (GEO) with NAFLD samples from rodents, we discovered that interferon regulatory factor 6 (IRF6) is significantly downregulated in high‐fat diet (HFD)‐induced fatty liver. In the current study, we identified IRF6 in hepatocytes as a protective factor in liver steatosis (LS). During HFD challenge, hepatic Irf6 was suppressed by promoter hypermethylation. Severity of HFD‐induced LS was exacerbated in hepatocyte‐specific Irf6 knockout mice, whereas hepatocyte‐specific transgenic mice overexpressing Irf6 (IRF6‐HTG) exhibited alleviated steatosis and metabolic disorder in response to HFD feeding. Mechanistic studies in vitro demonstrated that hepatocyte IRF6 directly binds to the promoter of the peroxisome proliferator‐activated receptor γ (PPARγ) gene and subsequently halts the transcription of Pparγ and its target genes (e.g., genes that regulate lipogenesis and lipid acid uptake) under physiological conditions. Conclusion: Irf6 is downregulated by promoter hypermethylation upon metabolic stimulus exposure, which fail to inhibit Pparγ and its targets, driving abnormalities of lipid metabolism.
Using a portfolio‐based process to develop agility among employees
Authors: Doeze Jager‐van Vliet Sandra B. , Born Marise Ph. , van der Molen Henk T.
Published: February 2019

The fast‐paced and changeable nature of contemporary society results in organizations that increasingly need to train their employees to become more energetic, flexible, and adaptable: the so called “agile” employees. This study used personal development portfolios including frequent feedback interviews (with mentors and peers) over 2.5 years to assist 32 employees working in an organization undergoing change to become more agile. A portfolio implies setting agility goals, recording and assessing progress in one's agility. Data were collected on employees' agility, and were related to their portfolio. Results showed that the portfolio use significantly increased employees' agility and significantly enhanced the agreement between self‐rated and other‐rated agility. Findings favor the use of development portfolios by organizations in improving agility among their employees. Therefore, this study gives tools for the practice of Human Resources Development (HRD).
Role of Akirin1 in the regulation of skeletal muscle fiber‐type switch
Authors: Rao Vanitha Venkoba , Sangiah Umamaheswari , Mary Kavitha Arockia , Akira Shizuo , Mohanty Abhishek
Published: February 2019

Akirin1 is a highly conserved ubiquitously expressed nuclear protein. Owing to its strong nuclear localization signal and protein‐protein interaction properties, Akirin1 has been speculated to regulate transcription of target genes as a cofactor. Previous studies have reported Akirin1 as a downstream target of myostatin, a potent negative regulator of myogenesis. Mice lacking myostatin displayed enhanced Akirin1 gene expression. Further, in vitro evidence has shown Akirin1 overexpression leads to hypertrophy in C2C
12 myotubes. In this study, we used Akirin1 knockout mice as a model system to further elucidate the function of Akirin1 in fully differentiated skeletal muscle. Akirin1 knockout mice did not show any obvious phenotypic difference when compared with wild type. However, promoter‐reporter assay suggested that Akirin1 regulated the transcription of muscle‐specific RING finger 1 (MuRF‐1), an important E3 ubiquitin ligase in skeletal muscle. Furthermore, ablation of Akirin1 resulted in increased type IIa and decreased type I muscle fibers, which was further supported by an increase in Myh2 and decrease in Myh7 gene expression. Also, histochemical studies for succinate dehydrogenase activity revealed a less oxidative muscle in the absence of Akirin1. Together, our study suggests a novel role of Akirin1 in maintaining the muscle fiber type and regulation of the metabolic activity of the skeletal muscle.
Identifying novel biomarkers in hepatocellular carcinoma by weighted gene co‐expression network analysis
Authors: Li Boxuan , Pu Ke , Wu Xinan
Published: February 2019

Hepatocellular carcinoma (HCC) is a highly malignant tumor found in the bile duct epithelial cells, and the second most common tumor of the liver. However, the pivotal roles of most molecules of tumorigenesis in HCC are still unclear. Hence, it is essential to detect the tumorigenic mechanism and develop novel prognostic biomarkers for clinical application. The data of HCC mRNA‐seq and clinical information from The Cancer Genome Atlas (TCGA) database were analyzed by weighted gene co‐expression network analysis (WGCNA). Co‐expression modules and clinical traits were constructed by the Pearson correlation analysis, interesting modules were selected and gene ontology and pathway enrichment analysis were performed. Intramodule analysis and protein–protein interaction construction of selected modules were conducted to screen hub genes. In addition, upstream transcription factors and microRNAs of hub genes were predicted by miRecords and NetworkAnalyst database. Afterward, a high connectivity degree of hub genes from two networks was picked out to perform the differential expression validation in the Gene Expression Profiling Interactive Analysis database and Human Protein Atlas database and survival analysis in Kaplan–Meier plotter online tool. By utilizing WGCNA, several hub genes that regulate the mechanism of tumorigenesis in HCC were identified, which was associated with clinical traits including the pathological stage, histological grade, and liver function. Surprisingly, ZWINT, CENPA, RACGAP1, PLK1, NCAPG, OIP5, CDCA8, PRC1, and CDK1 were identified statistically as hub genes in the blue module, which were closely implicated in pathological T stage and histologic grade of HCC. Moreover, these genes also were strongly associated with the HCC cell growth and division. Network and survival analyses found that nine hub genes may be considered theoretically as indicators to predict the prognosis of patients with HCC or clinical treatment target, it will be necessary for basic experiments and large‐scale cohort studies to validate further.
Molecular docking, dynamics, and pharmacology studies on bexarotene as an agonist of ligand‐activated transcription factors, retinoid X receptors
Authors: Chitranshi Nitin , Dheer Yogita , Kumar Sanjay , Graham Stuart L. , Gupta Vivek
Published: February 2019

Retinoid X receptors (RXRs) belong to the nuclear receptor superfamily, and upon ligand activation, these receptors control gene transcription via either homodimerization with themselves or heterodimerization with the partner‐nuclear receptor. The protective effects of RXRs and RXR agonists have been reported in several neurodegenerative diseases, including in the retina. This study was aimed to prioritize compounds from natural and synthetic origin retinoids as potential RXR agonists by molecular docking and molecular dynamic simulation strategies. The docking studies indicated bexarotene as a lead compound that can activate various RXR receptor isoforms (α, β, and γ) and has a strong binding affinity to the receptor protein than retinoic acid, which is known as a natural endogenous RXR agonist. Dynamic simulation studies confirmed that the hydrogen bonding and hydrophobic interactions were highly stable in all the three isoforms of the RXR‐bexarotene complex. To further validate the significance of the RXR receptor in neurons, in vitro pharmacological treatment of neuronal SH‐SY5Y cells with bexarotene was performed. In vitro data from SH‐SY5Y cells confirmed that bexarotene activated RXR‐simulated neurite outgrowth significantly. We conclude that bexarotene could be potentially used as an exogenous activator of RXRs and emerge as a good drug target for several neurodegenerative disorders.
Effect of cell source and osteoblast differentiation on gene expression profiles of mesenchymal stem cells derived from bone marrow or adipose tissue
Authors: Fideles Simone Ortiz Moura , Ortiz Adriana Cassia , Assis Amanda Freire , Duarte Max Jordan , Oliveira Fabiola Singaretti , Passos Geraldo Aleixo , Beloti Márcio Mateus , Rosa Adalberto Luiz
Published: February 2019

Mesenchymal stem cells (MSCs) have been used in therapies for bone tissue healing. The aim of this study was to investigate the effect of cell source and osteoblast differentiation on gene expression profiles of MSCs from bone marrow (BM‐MSCs) or adipose tissue (AT‐MSCs) to contribute for selecting a suitable cell population to be used in cell‐based strategies for bone regeneration. BM‐MSCs and AT‐MSCs were cultured in growth medium to keep MSCs characteristics or in osteogenic medium to induce osteoblast differentiation (BM‐OBs and AT‐OBs). The transcriptomic analysis was performed by microarray covering the entire rat functional genome. It was observed that cells from bone marrow presented higher expression of genes related to osteogenesis, whereas cells from adipose tissue showed a higher expression of genes related to angiogenesis and adipocyte differentiation, irrespective of cell differentiation. By comparing cells from the same source, MSCs from both sources exhibited higher expression of genes involved in angiogenesis, osteoblast differentiation, and bone morphogenesis than osteoblasts. The clustering analysis showed that AT‐OBs exhibited a gene expression profile closer to MSCs from both sources than BM‐OBs, suggesting that BM‐OBs were in a more advanced stage of differentiation. In conclusion, our results suggest that in cell‐based therapies for bone regeneration AT‐MSCs could be considered for angiogenic purposes, whereas BM‐MSCs and osteoblasts differentiated from either source could be better for osteogenic approaches.
Thioredoxin‐interacting protein deficiency alleviates phenotypic alterations of podocytes via inhibition of mTOR activation in diabetic nephropathy
Authors: Song Shan , Qiu Duojun , Shi Yonghong , Wang Shuai , Zhou Xinbo , Chen Nan , Wei Jinying , Wu Ming , Wu Haijiang , Duan Huijun
Published: February 2019

Thioredoxin‐interacting protein (TXNIP) is induced by high glucose (HG), whereupon it acts to inhibit thioredoxin, thereby promoting oxidative stress. We have found that TXNIP knockdown in human renal tubular cells helped prevent the epithelial‐to‐mesenchymal transition (EMT). Here, we studied the potential effect of TXNIP on podocyte phenotypic alterations in diabetic nephropathy (DN) in vivo and in vitro. In conditionally immortalized mouse podocytes under HG conditions, knocking down TXNIP disrupted EMT, reactive oxygen species (ROS) production, and mammalian target of rapamycin (mTOR) pathway activation. Further, Raptor short hairpin RNA (shRNA), Rictor shRNA, and mTOR specific inhibitor KU‐0063794 were used to assess if the mTOR signal pathway is involved in HG‐induced EMT in podocytes. We found that Raptor shRNA, Rictor shRNA, and KU‐0063794 could all restrain HG‐induced EMT and ROS production in podocytes. In addition, antioxidant Tempol or N‐acetylcysteine presented a prohibitive effect on HG‐induced EMT in podocytes. Streptozotocin was utilized to render equally diabetic in wild‐type (WT) control and TXNIP
−/− (TKO) mice. Diabetes did not increase levels of 24‐hr urinary protein, serum creatinine, blood urea nitrogen, and triglyceride in TXNIP
−/− mice. Podocyte phenotypic alterations and podocyte loss were detected in WT but not in TKO diabetic mice. Oxidative stress was also suppressed in diabetic TKO mice relative to WT controls. Also, TXNIP deficiency suppresses the activation of mTOR in glomeruli of streptozotocin‐induced diabetic mice. Moreover, TXNIP expression, mTOR activation, Nox1, and Nox4 could be detected in renal biopsy tissues of patients with DN. This suggests that decreased TXNIP could ameliorate phenotypic alterations of podocytes via inhibition of mTOR in DN, highlighting TXNIP as a promising therapeutic target.
Allogeneic hematopoietic stem cell transplantation with myeloablative conditioning for adult cerebral X‐linked adrenoleukodystrophy
Authors: Waldhüter Nils , Köhler Wolfgang , Hemmati Philipp G. , Jehn Christian , Peceny Rudolf , Vuong Giang L. , Arnold Renate , Kühl Jörn‐Sven
Published: February 2019

The adult cerebral form of X‐linked adrenoleukodystrophy (ACALD), an acute inflammatory demyelinating disease, results in a rapidly progressive neurodegeneration, typically leading to severe disability or death within a few years after onset. We have treated 15 men who had developed ACALD with allogeneic hematopoietic stem cell transplantation (HSCT) from matched donors after myeloablative conditioning with busulfan and cyclophosphamide. All patients engrafted and 11 survived (estimated survival 73 ± 11%), 8 with stable cognition and 7 of them with stable motor function (estimated event‐free survival 36 ± 17%). Death after transplantation occurred within the first year after HSCT and was caused either primarily by infection (N = 3) or due to disease progression triggered by infection (N = 1). Patients with minor myelopathic symptoms (N = 4) or with no or mild cerebral symptoms pre‐transplant (N = 7) had an excellent outcome. In contrast, no patient with major neurological symptoms associated with an extensive involvement of pyramidal tract fibres in the internal capsule (N = 5) survived without cognitive deterioration. Notably, early leukocyte recovery was associated with dismal outcome for yet unknown reasons. All 10 tested survivors showed a reduction of plasma hexacosanoic acid (C26:0) in the absence of Lorenzo's oil. Over time, the event‐free survival could be improved from 2 out of 8 patients (25%) before 2013 to 5 out of 7 patients (71%) thereafter. Therefore, allogeneic HSCT appears to be a suitable treatment option for carefully selected ACALD patients when transplanted from matched donors after myeloablative, busulfan‐based conditioning.
IFN-γ-dependent nitric oxide suppresses Brucella-induced arthritis by inhibition of inflammasome activation
Authors: Lacey Carolyn A , Chambers Catherine A , Mitchell William J , Skyberg Jerod A
Published: February 2019

Brucellosis, caused by the intracellular bacterial pathogen Brucella, is a globally important zoonotic disease for which arthritis is the most common focal complication in humans. Wild-type mice infected systemically with Brucella typically do not exhibit arthritis, but mice lacking IFN-γ develop arthritis regardless of the route of Brucella infection. Here, we investigated mechanisms by which IFN-γ suppresses Brucella-induced arthritis. Several cell types, including innate lymphoid cells, contributed to IFN-γ production and suppression of joint swelling. IFN-γ deficiency resulted in elevated joint IL-1β levels, and severe joint inflammation that was entirely inflammasome dependent, and in particular, reliant on the NLRP3 inflammasome. IFN-γ was vital for induction of the nitric oxide producing enzyme, iNOS, in infected joints, and nitric oxide directly inhibited IL-1β production and inflammasome activation in Brucella-infected macrophages in vitro. During in vivo infection, iNOS deficiency resulted in an increase in IL-1β and inflammation in Brucella-infected joints. Collectively, this data indicate that IFN-γ prevents arthritis both by limiting Brucella infection, and by inhibiting excessive inflammasome activation through the induction of nitric oxide.
Characterization of a novel xylanase from Aspergillus flavus with the unique properties in production of xylooligosaccharides
Authors: Chen Zhou , Liu Yangliu , Zaky Ahmed A. , Liu Lu , Chen Yaoyao , Li Siting , Jia Yingmin
Published: February 2019

A novel xylanase from the filamentous fungus Aspergillus flavus was purified and characterized as the β‐1, 4‐endoxylanase (designed as AfXynB) with a molecular mass (32.2 kDa), which is different from all of the previously reported xylanases from the same strain. AfXynB was optimally active at pH 7.5 and 55 °C, respectively. It was stable up to 50 °C within range of pH 4.0–9.5, and displayed an excellent tolerance to various cations, reagents, and proteases. AfXynB showed specific activity toward beechwood xylan but no detected activity toward CMC and pNP‐β‐D‐xylopyranoside. The xylanase is a typical endo‐xylanase; it could hydrolyze beechwood xylan to only yield xylobiose (X2) and xylopentaose (X5). Actually, this may be the first report for the endo‐xylanases that displayed such a unique hydrolytic property. These findings in the present study have great implications for its future applications of the novel xylanase.