bluuebunny/crossref_metadata_2025 huggingface dataset:
Orthography and Modality Influence Speech Production in Adults and Children
Authors: Saletta Meredith , Goffman Lisa , Hogan Tiffany P.
Published: December 2016

Purpose

The acquisition of literacy skills influences the perception and production of spoken language. We examined if orthography influences implicit processing in speech production in child readers and in adult readers with low and high reading proficiency.

Method

Children (n= 17), adults with typical reading skills (n= 17), and adults demonstrating low reading proficiency (n= 18) repeated or read aloud nonwords varying in orthographic transparency. Analyses of implicit linguistic processing (segmental accuracy and speech movement stability) were conducted. The accuracy and articulatory stability of productions of the nonwords were assessed before and after repetition or reading.

Results

Segmental accuracy results indicate that all 3 groups demonstrated greater learning when they were able to read, rather than just hear, the nonwords. Speech movement results indicate that, for adults with poor reading skills, exposure to the nonwords in a transparent spelling reduces the articulatory variability of speech production. Reading skill was correlated with speech movement stability in the groups of adults.

Conclusions

In children and adults, orthography interacts with speech production; all participants integrate orthography into their lexical representations. Adults with poor reading skills do not use the same reading or speaking strategies as children with typical reading skills.
Reduction of photodiode non‐linearity by adaptive bias control
Authors: Frigo N.J. , Hutchinson M.N. , Williams C.R.S.
Published: December 2016

It is shown that data from frequency sweeps of photodiode (PD) second‐order intermodulation distortion products, parameterised on the applied bias voltage and average photocurrent, enables optimisation of the in situ PD's non‐linear performance by adaptively changing the bias voltage in response to system changes in optical input power and required system bandwidth.
Hyperspectral face recognition via feature extraction and CRC‐based classifier
Authors: Chen Guangyi , Li Changjun , Sun Wei
Published: December 2016

Hyperspectral face recognition provides improved classification rates due to its abundant information in the face cubes of every subject in hyperspectral face databases. However, it is less popular in face recognition due to its difficulty in data acquisition, low signal‐to‐noise ratio, and high dimensionality. The authors compare five existing descriptors that are frequently used in 2D face recognition, and use collaborative representation classifier (CRC) with two voting techniques for hyperspectral face recognition. Experimental results demonstrate that, for PolyU‐HSFD database, Gabor filter bank‐based features are very robust to both Gaussian white noise and shot noise, and it achieves very competitive classification results. For CMU‐HSFD database, when the noise level is low, histogram of oriented gradients (HOG) yields good classification results. In addition, when the noise level is high, raw facial images without feature extraction perform very well in term of correct classification rate. The local binary pattern and HOG descriptor are very sensitive to noise even though they achieve rather good classification rates if the facial images contain no noise. The best recognition result for the PolyU‐HSFD is 96.4% ± 2.3 and for the CMU‐HSFD is 98.0% ± 0.7.
Ag‐decorated SnO2 nanorods: microwave‐assisted green synthesis and enhanced ethanol gas sensing properties
Authors: Zhang Jie , Li Chensha , Wang Binsong
Published: December 2016

The green synthesis of gas‐sensing materials, which monitor volatile organic compounds, avoid synthesis‐induced pollution, and thus is a major challenge faced by scientific researchers. Herein, we report a microwave‐assisted green synthesis of Ag‐decorated SnO2 nanorods with water being used as solvent and comparatively non‐toxic chemicals being used as reactant. The as‐prepared product was characterised by X‐ray diffraction, scanning electron microscopy and transmission electron microscopy. The results showed one‐dimensional Ag‐decorated SnO2 nanorods constituted of tetragonal rutile phase of SnO2 and cubic phase of Ag were successfully prepared. Ethanol was used as a model system for measuring gas‐sensing properties and an enhanced gas‐sensing property was found due to Ag decoration. Moreover, a linear dependence of the sensitivity on the ethanol concentration was observed.
What’s really new about New Atheism?
Authors: Kettell Steven
Published: December 2016

The rise of new atheism has attracted significant attention but its novelty is often assumed rather than explained. By exploring the origins of new atheism and drawing comparisons to earlier atheist forms, this article argues that new atheism contains aspects that are genuinely new. The most notable of these features are its expansive political activities and its hybrid combination of Enlightenment-based rationality with postmodern themes and concerns.
Transcriptome profiling of rice seedlings under cold stress
Authors: da Maia Luciano C. , Cadore Pablo R. B. , Benitez Leticia C. , Danielowski Rodrigo , Braga Eugenia J. B. , Fagundes Paulo R. R. , Magalhães Ariano M. , Costa de Oliveira Antonio
Published: December 2016

Rice (Oryza sativa L.) is one of the most important species for food production worldwide, besides being an excellent genetic model among the grasses. Cold is one of the major abiotic factors reducing rice yield, primarily affecting germination and reproduction phases. Currently, the RNAseq technique allows the identification of differential expressed genes in response to a given treatment, such as cold stress. In the present work, a transcriptome (RNAseq) analysis was performed in the V3 phase for contrasting genotypes Oro (tolerant) and Tio Taka (sensitive), in response to cold (13°C). A total of 241 and 244 M readings were obtained, resulting in the alignment of 25.703 and 26.963 genes in genotypes Oro and Tio Taka respectively. The analyses revealed 259 and 5579 differential expressed genes in response to cold in the genotypes Oro and Tio Taka respectively. Ontology classes with larger changes were metabolic process ~27%, cellular process ~21%, binding ~30% and catalytic activity ~22%. In the genotype Oro, 141 unique genes were identified, 118 were common between Oro and Tio Taka and 5461 were unique to Tio Taka. Genes involved in metabolic routes of signal transduction, phytohormones, antioxidant system and biotic stress were identified. These results provide an understanding that breeding for a quantitative trait, such as cold tolerance at germination, several gene loci must be simultaneously selected. In general, few genes were identified, but it was not possible to associate only one gene function as responsible for the cultivar tolerance; since different genes from different metabolic routes were identified. The genes described in the present work will be useful for future investigations and for the detailed validation in marker assisted selection projects for cold tolerance in the germination of rice.
Towards improved quality of soil morphology and analytical data in Australia: starting the discussion
Authors: Biggs Andrew J. W. , Searle Ross
Published: December 2016

The development and implementation of a national data schema for soil data in Australia over the last two decades, coupled with advances in information technology, has led to the realisation of more comprehensive state and national soil databases. This has facilitated increased access to soil data for many purposes, including the creation of many digital soil-mapping products, such as the Soil and Landscape Grid of Australia. Consequently, users of soil data have a growing need for clarity concerning the quality of the data; many new users have little understanding of the varying quality of the data. To date, statements about the quality of primary soil data have typically been qualitative and/or judgemental rather than explicit. The consequences of poor-quality primary data and of the lack of a coding system for data quality are growing with increased usage and with demand for soil data at the regional to national scale. Pillar 4 of the Global Soil Partnership and the National Soil Research, Development and Extension Strategy both identify the need to improve the quality of soil data. Various international standards do exist with respect to the quality of soil data but these tend to focus on general principles and quality-assurance frameworks rather than the detail of describing data quality. The aim of this paper is to stimulate a discussion in the Australian soil science community on how to quantify and describe the quality of primary soil data. We provide examples of the data quality issues and propose a framework for structured data-quality checking procedures and quality coding of soil morphological and analytical data in Australia.
Loss of
O
-GlcNAc glycosylation in forebrain excitatory neurons induces neurodegeneration
Authors: Wang Andrew C. , Jensen Elizabeth H. , Rexach Jessica E. , Vinters Harry V. , Hsieh-Wilson Linda C.
Published: December 2016

Significance

O
-GlcNAcylation is an abundant posttranslational modification suggested to have both neuroprotective and neurodegenerative functions. Although previous studies on
O
-GlcNAc have illustrated its potential to modulate preexisting phenotypes in neurodegenerative animal models, the importance of
O
-GlcNAcylation in both the induction of neuropathology and the functioning of healthy adult neurons remained unclear. We generated a forebrain-specific
O
-GlcNAc transferase conditional knockout mouse and found that diminution of
O
-GlcNAc signaling induced progressive neurodegeneration in vivo, including pathogenic processing of tau and amyloid precursor protein, widespread neuronal death, gliosis, and memory loss. These results indicate that
O
-GlcNAcylation regulates pathways critical for neuronal health and survival and that modulating
O
-GlcNAc signaling may represent a neuroprotective strategy for neurodegenerative diseases.
Experimental and theoretical evidence for bilayer-by-bilayer surface melting of crystalline ice
Authors: Sánchez M. Alejandra , Kling Tanja , Ishiyama Tatsuya , van Zadel Marc-Jan , Bisson Patrick J. , Mezger Markus , Jochum Mara N. , Cyran Jenée D. , Smit Wilbert J. , Bakker Huib J. , Shultz Mary Jane , Morita Akihiro , Donadio Davide , Nagata Yuki , Bonn Mischa , Backus Ellen H. G.
Published: December 2016

Significance

Over 150 years ago, Faraday discovered the presence of a water layer on ice below the bulk melting temperature. This layer is important for surface chemistry and glacier sliding close to subfreezing conditions. The nature and thickness of this quasi-liquid layer has remained controversial. By combining experimental and simulated surface-specific vibrational spectroscopy, the thickness of this quasi-liquid layer is shown to change in a noncontinuous, stepwise fashion around 257 K. Below this temperature, the first bilayer is already molten; the second bilayer melts at this transition temperature. The blue shift in the vibrational response of the outermost water molecules accompanying the transition reveals a weakening of the hydrogen bond network upon an increase of the water layer thickness.
Stratospheric solar geoengineering without ozone loss
Authors: Keith David W. , Weisenstein Debra K. , Dykema John A. , Keutsch Frank N.
Published: December 2016

Significance

The combination of emissions cuts and solar geoengineering could reduce climate risks in ways that cannot be achieved by emissions cuts alone: It could keep Earth under the 1.5-degree mark agreed at Paris, and it might stop sea level rise this century. However, this promise comes with many risks. Injection of sulfuric acid into the stratosphere, for example, would damage the ozone layer. Injection of calcite (or limestone) particles rather than sulfuric acid could counter ozone loss by neutralizing acids resulting from anthropogenic emissions, acids that contribute to the chemical cycles that destroy stratospheric ozone. Calcite aerosol geoengineering may cool the planet while simultaneously repairing the ozone layer.
GppFst: genomic posterior predictive simulations of FST and dXY for identifying outlier loci from population genomic data
Authors: Adams Richard H , Schield Drew R , Card Daren C , Blackmon Heath , Castoe Todd A
Published: December 2016

We introduce GppFst, an open source R package that generates posterior predictive distributions of FST and dx under a neutral coalescent model to identify putative targets of selection from genomic data.

Availability and Implementation

GppFst is available at (https://github.com/radamsRHA/GppFst).

Supplementary information

Supplementary data are available at Bioinformatics online.
Wright–Fisher exact solver (WFES): scalable analysis of population genetic models without simulation or diffusion theory
Authors: Krukov Ivan , de Sanctis Bianca , de Koning A P Jason
Published: December 2016

Motivation

The simplifying assumptions that are used widely in theoretical population genetics may not always be appropriate for empirical population genetics. General computational approaches that do not require the assumptions of classical theory are therefore quite desirable. One such general approach is provided by the theory of absorbing Markov chains, which can be used to obtain exact results by directly analyzing population genetic Markov models, such as the classic bi-allelic Wright–Fisher model. Although these approaches are sometimes used, they are usually forgone in favor of simulation methods, due to the perception that they are too computationally burdensome. Here we show that, surprisingly, direct analysis of virtually any Markov chain model in population genetics can be made quite efficient by exploiting transition matrix sparsity and by solving restricted systems of linear equations, allowing a wide variety of exact calculations (within machine precision) to be easily and rapidly made on modern workstation computers.

Results

We introduce Wright–Fisher Exact Solver (WFES), a fast and scalable method for direct analysis of Markov chain models in population genetics. WFES can rapidly solve for both long-term and transient behaviours including fixation and extinction probabilities, expected times to fixation or extinction, sojourn times, expected allele age and variance, and others. Our implementation requires only seconds to minutes of runtime on modern workstations and scales to biological population sizes ranging from humans to model organisms.

Availability and Implementation

The code is available at https://github.com/dekoning-lab/wfes

Supplementary information

Supplementary data are available at Bioinformatics online.
The contribution of autoantibodies to post-translationally modified proteins to inflammatory arthritis
Authors: van der Woude Diane , Toes René E.M.
Published: December 2016

Purpose of review

This article provides an overview of the recent findings present in the field of antimodified protein antibodies and their relevance for rheumatic disease, with a focus on rheumatoid arthritis.

Recent findings

Next to anticitrullinated protein antibodies, also other antimodified protein antibodies such as anticarbamylated protein antibodies or antiacetylated protein antibodies are emerging. Likewise, their possible pathological contributions are getting detailed attention. Their possible relation to disease, both from a clinical as well as biological perspective will be summarized.

Current evidence is pointing to the notion that especially a combination of antimodified protein antibodies associates best with clinical phenotype and outcome.
The Interface of Clinical Decision-Making With Study Protocols for Knowledge Translation From a Walking Recovery Trial
Authors: Hershberg Julie A. , Rose Dorian K. , Tilson Julie K. , Brutsch Bettina , Correa Anita , Gallichio Joann , McLeod Molly , Moore Craig , Wu Sam , Duncan Pamela W. , Behrman Andrea L.
Published: December 2016

Background and Purpose:

Despite efforts to translate knowledge into clinical practice, barriers often arise in adapting the strict protocols of a randomized, controlled trial (RCT) to the individual patient. The Locomotor Experience Applied Post-Stroke (LEAPS) RCT demonstrated equal effectiveness of 2 intervention protocols for walking recovery poststroke; both protocols were more effective than usual care physical therapy. The purpose of this article was to provide knowledge-translation tools to facilitate implementation of the LEAPS RCT protocols into clinical practice.

Methods:

Participants from 2 of the trial's intervention arms: (1) early Locomotor Training Program (LTP) and (2) Home Exercise Program (HEP) were chosen for case presentation. The two cases illustrate how the protocols are used in synergy with individual patient presentations and clinical expertise. Decision algorithms and guidelines for progression represent the interface between implementation of an RCT standardized intervention protocol and clinical decision-making.

Outcomes:

In each case, the participant presents with a distinct clinical challenge that the therapist addresses by integrating the participant's unique presentation with the therapist's expertise while maintaining fidelity to the LEAPS protocol. Both participants progressed through an increasingly challenging intervention despite their own unique presentation.

Decision algorithms and exercise progression for the LTP and HEP protocols facilitate translation of the RCT protocol to the real world of clinical practice. The two case examples to facilitate translation of the LEAPS RCT into clinical practice by enhancing understanding of the protocols, their progression, and their application to individual participants.

Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A147).
BioMake: a GNU Make-compatible utility for declarative workflow management
Authors: Holmes Ian H. , Mungall Christopher J.
Published: December 2016

The Unix “make” program is widely used in bioinformatics pipelines, but suffers from problems that limit its application to large analysis datasets. These include reliance on file modification times to determine whether a target is stale, lack of support for parallel execution on clusters, and restricted flexibility to extend the underlying logic program. We present BioMake, a make-like utility that is compatible with most features of GNU Make and adds support for popular cluster-based job-queue engines, MD5 signatures as an alternative to timestamps, and logic programming extensions in Prolog. BioMake is available fromhttps://github.com/evoldoers/biomakeunder the Creative Commons Attribution 3.0 US license. The only dependency is SWI-Prolog, available fromhttp://www.swi-prolog.org/. Contact: Ian Holmesihholmes+biomake@gmail.comor Chris Mungallcmungall+biomake@gmail.com.
VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation
Authors: Artemov Artem V. , Zhigalova Nadezhda , Zhenilo Svetlana , Mazur Alexander M. , Prokhortchouk Egor B.
Published: December 2016

VHL inactivation is a key oncogenic event for renal carcinomas. In normoxia, VHL suppresses HIF1a-mediated response to hypoxia. It has previously been shown that hypoxic conditions inhibit TET-dependent hydroxymethylation of cytosines and cause DNA hypermethylation at gene promoters. In this work, we performed VHL inactivation by CRISPR/Cas9 and studied its effects on gene expression and DNA methylation. We showed that even without hypoxia, VHL inactivation leads to hypermethylation of the genome which mainly occurred in AP-1 and TRIM28 binding sites. We also observed promoter hypermethylation of several transcription regulators associated with decreased gene expression.
From food defence to food supply chain integrity
Authors: Davidson Rebecca K. , Antunes Wilson , Madslien Elisabeth H. , Belenguer José , Gerevini Marco , Torroba Perez Tomas , Prugger Raffaello
Published: December 2016

Purpose

Consumer confidence in the European food industry has been shaken by a number of recent scandals due to food fraud and accidental contamination, reminding the authors that deliberate incidents can occur. Food defence methods aim to prevent or mitigate deliberate attacks on the food supply chain but are not a legal requirement. The purpose of this paper is to discuss how proactive and reactive food defence practices can help prevent or mitigate malicious attacks on the food chain and also food fraud, food crime and food safety. The authors look at how food defence differs from food safety and how it contributes to food supply chain integrity.

Design/methodology/approach

Food defence has been the focus of two different EU FP7 security projects, EDEN and SNIFFER. Food industry stakeholders participated in workshops and demonstrations on food defence and relevant technology was tested in different food production scenarios.

Findings

Food industry end-users reported a lack of knowledge regarding food defence practices. They wished for further guidelines and training on risk assessment as well as access to validated test methods. Novel detection tools and methods showed promise with authentication, identification, measurement, assessment and control at multiple levels of the food supply chain prior to distribution and retail.

Practical implications

The prevention of a contamination incident, prior to retail, costs less than dealing with a large foodborne disease outbreak. Food defence should therefore be integral to food supply chain integrity and not just an afterthought in the wake of an incident.

Originality/value

It is argued that food defence practices have a vital role to play across the board in unintentional and intentional food contamination incidents. The application of these methods can help ensure food supply chain integrity.
Documenting entrepreneurial opportunism in action
Authors: Smith Robert
Published: December 2016

Purpose

The contemporary rustler is a shrewd businessman, or rogue farmer exploiting food supply chain anomalies. Indeed, the first conviction in the UK for 20 years was a farmer stealing from neighbouring farmers. The theft of sheep in the UK is an expanding criminal enterprise which remains under researched. The purpose of this paper is to examine what is known of the illegal trade and its links to food fraud from a supply chain perspective with an emphasis on food integrity issues.

Design/methodology/approach

There is a dearth of current viable literature on livestock theft in a western context making it necessary to turn to socio-historical research and to official documents such as those published by the NFU and other insurance companies to build up a picture of this illegal practice. This is supplemented by documentary research of articles published in the UK press.

Findings

From this raw data a typology of rustlers is developed. The findings point to insider “supply chain” knowledge being a key facet in the theft of livestock. Other examples in the typology relate to urban thieves wrestling live sheep into a car and to industry insiders associated with the abattoir sector.

Research limitations/implications

The obvious limitations is that as yet there are few detected cases of rustling in the UK so the developing typology of rustlers is sketchy. Another limitation is that much of the evidence upon which the typology is developed is anecdotal.

Originality/value

The typology should prove helpful to academics, insurance companies, investigators, industry insiders and farmers to help them understand this contemporary crime and how to prevent its spread. It also sheds light on food integrity in relation to the purchase and consumption of the end product in that customers expect to be purchasing legally and ethically reared animal products.
A supply chain integrity framework for halal food
Authors: Ali Mohd Helmi , Tan Kim Hua , Ismail Md Daud
Published: December 2016

Purpose

The purpose of this paper is to propose a food supply chain (SC) integrity framework in the context of halal food.

Design/methodology/approach

This paper provides a discussion on the development of food SC integrity framework using triangulation of interviews’ insights with literature.

Findings

Current industry practices such as standards have not been sufficient in embracing the concept of food SC integrity. As the food SC is complex, food SC integrity framework is proposed as a solution. This paper proposes food SC integrity framework for halal food. It consists of four dimensions, namely: raw material, production, service, and information integrity. In addition, key elements for each dimension are derived from the interviews’ insights.

Research limitations/implications

The framework provides the evidence that the safeguarding of halal food integrity does not rely solely on certification; but it requires an extensive effort beyond certification.

Practical implications

Safeguarding of food integrity should involve all stages and actors of the SC. Religious standards should incorporate SC integrity profiling through a controlling mechanism to promote higher food product integrity.

Originality/value

Food SC integrity framework is important to religious food as it plays a significant role to the population. This study contributes to a newly developed SC integrity framework in the context of halal food.
Open accelerators for start-ups success: a case study
Authors: Battistella Cinzia , De Toni Alberto F. , Pessot Elena
Published: December 2016

Purpose

The purpose of this paper is to investigate how the context of open innovation offered by accelerators can affect the successful growth of start-ups. The authors explore accelerators practices and tools in sustaining start-ups and increasing survival probability in their innovation process, with the aim of addressing the following research question: how can start-ups benefit from participation in an accelerator programme from an open innovation perspective?

Design/methodology/approach

A review of the literature on start-up successes and failures and on major practices in the open innovation paradigm was carried out, delineating them in the context of accelerators. Given the absence of literature on accelerator practices for supporting start-ups, and aiming at a comprehensive understanding of how the open environment within the accelerator influences a start-up’s survival (or even success) by mitigating the probability of failure, the authors conducted an exploratory case study in an English accelerator.

Findings

The open innovation practices mediated by an accelerator and the ones that are not covered, but that can benefit a start-up’s survival, are shown. On the one hand, main effective practices, such as dyadic co-creation with accelerator network partners and crowdsourcing, are revealed to address mostly the lack of, or wrong direction in, product, marketing and relative managerial abilities, which are not usually owned by a start-up due to its “newness”. On the other hand, some causes of failures, such as the intrinsic characteristics of founder teams, do not seem to be addressed by an open approach and neither does participation in an accelerator programme.

Originality/value

This paper is the first to study and link the literature on accelerators, start-ups and open innovation.
“Welcome to The Shop”
Authors: Hall H. Bernard
Published: December 2016

Purpose

The purpose of this paper is to describe the ways in which hip-hop pedagogies and literacies encouraged middle school students to explore performance poetry as a tool to “(w)right” the truth(s) about learning and living in their local and global communities.

Design/methodology/approach

Collaborative self-study research methodologies were used by the author, a black male teacher educator and hip-hop cultural insider, along with two white, female reading specialists and hip-hop cultural outsiders, to collect and analyze the practices and behaviors used in The Shop – an after-school hip-hop-based spoken word poetry club for middle school students in a small, urban public school district in Northeastern USA.

Findings

Three primary findings emerge: teachers with limited cultural and content knowledge of hip-hop may struggle to negotiate real and perceived curricular constraints associated with using pedagogies with hip-hop texts and aesthetics in traditional school contexts, the intersections of teachers’ racial, cultural and gender identities informed the respective practices and behaviors in a number of interesting ways, and using hip-hop pedagogies for social justice in public schools requires a delicate balance of both transparency and discretion on the part of teachers.

Originality/value

Study findings are salient for in- and pre-service English teachers and English educators, as they offer insights and reflections on the instructional and relational challenges cultural outsiders may face when using hip-hop culture to create spaces and opportunities for young people to talk back and speak truth to power.
Simultaneous Identification of Four “Legal High” Plant Species in a Multiplex PCR High‐Resolution Melt Assay,
Authors: Elkins Kelly M. , Perez Anjelica C. U. , Quinn Alicia A.
Published: December 2016

The international prevalence of “legal high” drugs necessitates the development of a method for their detection and identification. Herein, we describe the development and validation of a tetraplex multiplex real‐time polymerase chain reaction (PCR) assay used to simultaneously identify morning glory, jimson weed, Hawaiian woodrose, and marijuana detected by high‐resolution melt using LCGreen Plus®. The PCR assay was evaluated based on the following: (i) specificity and selectivity—primers were tested on DNA extracted from 30 species and simulated forensic samples, (ii) sensitivity—serial dilutions of the target DNA were prepared, and (iii) reproducibility and reliability—sample replicates were tested and remelted on different days. The assay is ideal for cases in which inexpensive assays are needed to quickly detect and identify trace biological material present on drug paraphernalia that is too compromised for botanical microscopic identification and for which analysts are unfamiliar with the morphology of the emerging “legal high” species.
Inter‐Method Variability of Ferritin and Transferrin Saturation Measurement Methods in Patients on Hemodialysis
Authors: Kamei Daigo , Tsuchiya Ken , Miura Hitomi , Nitta Kosaku , Akiba Takashi
Published: December 2016

Serum ferritin level and transferrin saturation (TSAT) are widely used to evaluate iron status in patients with chronic kidney disease, and are also important variables for performing statistical analyses. Many guidelines have set control targets or upper limits for these markers. Inter‐method variability is an important consideration in iron control and statistical analysis. We used 10 ferritin assay kits and five iron/unsaturated iron‐binding capacity/total iron‐binding capacity assay kits to determine ferritin levels and TSAT in 114 patients on maintenance dialysis, and evaluated measurement bias using Passing‐Bablok regression analyses. The variance of distributions categorized by differences in assay kits was examined using Fisher's exact test. Slopes ranged from 1.00 to 1.63 (1.00 to 0.61) for ferritin and 1.00 to 1.10 (1.00 to 0.91) for TSAT. The distribution according to the 2015 JSDT Guideline for Renal Anemia in Chronic Kidney Disease significantly changed (P = 0.01). TSAT thus provides more precise control than ferritin in multi‐center comparisons where no particular assay is specified. Developers must reduce variability in serum ferritin assay kits. Researchers must analyze measured values by taking into account the propagation of errors, and clinicians must evaluate laboratory data carefully.
Optimal pharmacological treatment and adherence to medication in secondary prevention of cardiovascular events in Spain: Results from the CAPS study
Authors: Cordero Alberto , Rodriguez Padial Luis , Batalla Alberto , López Barreiro Luis , Torres Calvo Francisco , Castellano Jose M. , Ruiz Emilio , Bertomeu‐Martínez Vicente ,   the CAPS study investigators
Published: December 2016

Introduction

Despite the large amount of evidence supporting the use of antiplatelet agents, beta‐blockers, angiotensin antagonists, and lipid‐lowering statins in patients with stable coronary artery disease, several studies have documented underprescription of optimal medical treatment (OMT) in Spain.

Aims

The present study aimed to describe the current trend of pharmacological prescription in secondary prevention treatment for cardiovascular diseases (CVDs) in a Spanish cohort.

Methods

This study was a multicenter, observational, cross‐sectional study (CAPS study, FER‐CAR‐2014‐01) in the context of only one visit. Adherence levels to the prescribed medication, the reasons for not prescription of each medication, the existence of possible associations between sociodemographic features, different CVDs, and different drugs with treatment compliance were also analyzed in patients who have suffered cardiovascular effects.

Results

Six hundred and twelve patients (68.5±10.7 years old; 78% males) were included. OMT was prescribed in 40.8% of the patients. The main reason for not prescribing was due to the physician's discretion. Adherence to medication, measured by the Morisky‐Green questionnaire, was 45.8%, and it was positively related to the presence of coronary events (OR 1.80; 95% CI: 1.05‐3.21) but not with any drug type. Moreover, a higher educational background implied a higher percentage of adherence to medication. Finally, nonadherent patients were prescribed more daily medicine intakes.

Conclusions

Low adherence to guideline‐oriented treatment as well as low adherence to medication was found by a self‐reported questionnaire. Enhancing adherence to guideline‐recommended therapy and reducing treatment complexity seem to be reasonable strategies to improve adherence to secondary prevention medications.
d‐Cycloserine enhanced extinction of cocaine‐induced conditioned place preference is attenuated in serotonin transporter knockout rats
Authors: Karel Peter , Calabrese Francesca , Riva Marco , Brivio Paola , Van der Veen Bas , Reneman Liesbeth , Verheij Michel , Homberg Judith
Published: December 2016

d‐Cycloserine (DCS), a partial NMDA receptor agonist, has been proposed as a cognitive enhancer to facilitate the extinction of drug‐related memories. However, it is unknown whether there are individual differences in the efficacy of DCS. Here, we set out to investigate the influence of serotonin transporter (5‐HTT) genotype on DCS treatment outcome and the underlying neural mechanism. To that end, we first determined the mRNA levels of several NMDA receptor subunits and observed a reduction in NR1/NR2C receptors in the ventromedial prefrontal cortex and nucleus accumbens of 5‐HTT−/− compared with 5‐HTT+/+ rats. Based on this finding, we hypothesized a lower sensitivity to DCS in the 5‐HTT−/− rats. To test this, rats were trained in a cocaine‐induced conditioned place preference (CPP) paradigm. A significant extinction of CPP was observed in 5‐HTT+/+ rats receiving 1 mg/kg i.v. DCS, while a similar effect was found in the 5‐HTT−/− rats only after 5 mg/kg. Following CPP, we tested if DCS were able to reduce FosB/∆FosB protein expression, a molecular switch for cocaine‐seeking behaviour. We observed an overall lower number of FosB/∆FosB positive cells in 5‐HTT−/− ventromedial prefrontal cortex and amygdala and an overall effect of DCS treatment on the number of positive cells in the nucleus accumbens. In conclusion, in this study, we show that the dosing of DCS to facilitate the extinction of cocaine‐seeking behaviour is, at least partially, determined by 5‐HTT genotype.
The impact of olodaterol on the risk of mortality and serious adverse events: a systematic review and meta‐analysis
Authors: Lee Hyun Woo , Kim Hyung‐Jun , Lee Chang‐Hoon
Published: December 2016

Aims

Olodaterol is a novel inhaled long‐acting β2‐agonist (LABA) that showed efficacy as a bronchodilator for patients with chronic obstructive pulmonary disease (COPD) and asthma. However, it is unclear whether olodaterol reduces mortality; the safety issues of olodaterol have not been fully evaluated.

Methods

Randomized controlled trials comparing olodaterol with placebo for patients with COPD or asthma, which evaluated mortality or serious adverse events, were included. Eighteen trials reporting mortality and 26 trials reporting nonfatal serious adverse events were included.

Results

Inhaled olodaterol did not reduce the risk of mortality (Peto fixed OR 1.31; 95% CI 0.90–1.89) and had no significant impacts on nonfatal serious adverse events (Peto fixed OR 1.03; 95% CI 0.91–1.15).

Conclusions

Inhaled olodaterol has no impact on mortality risk in clinical trials conducted on patients with COPD and asthma. However, the interpretation is limited by a high OR (1.31) and a wide CI that includes the hazardous effect. We could not find any relationship between inhaled olodaterol use and nonfatal serious adverse events.
Leukemogenic kinase FIP1L1‐PDGFRA and a small ubiquitin‐like modifier E3 ligase, PIAS1, form a positive cross‐talk through their enzymatic activities
Authors: Ibata Makoto , Iwasaki Junko , Fujioka Yoichiro , Nakagawa Koji , Darmanin Stephanie , Onozawa Masahiro , Hashimoto Daigo , Ohba Yusuke , Hatakeyama Shigetsugu , Teshima Takanori , Kondo Takeshi
Published: December 2016

Fusion tyrosine kinases play a crucial role in the development of hematological malignancies. FIP1L1‐PDGFRA is a leukemogenic fusion kinase that causes chronic eosinophilic leukemia. As a constitutively active kinase, FIP1L1‐PDGFRA stimulates downstream signaling molecules, leading to cellular proliferation and the generation of an anti‐apoptotic state. Contribution of the N‐terminal FIP1L1 portion is necessary for FIP1L1‐PDGFRA to exert its full transforming activity, but the underlying mechanisms have not been fully characterized. We identified PIAS1 as a FIP1L1‐PDGFRA association molecule by yeast two‐hybrid screening. Our analyses indicate that the FIP1L1 portion of FIP1L1‐PDGFRA is required for efficient association with PIAS1. As a consequence of the association, FIP1L1‐PDGFRA phosphorylates PIAS1. Moreover, the kinase activity of FIP1L1‐PDGFRA stabilizes PIAS1. Therefore, PIAS1 is one of the downstream targets of FIP1L1‐PDGFRA. Moreover, we found that PIAS1, as a SUMO E3 ligase, sumoylates and stabilizes FIP1L1‐PDGFRA. In addition, suppression of PIAS1 activity by a knockdown experiment resulted in destabilization of FIP1L1‐PDGFRA. Therefore, FIP1L1‐PDGFRA and PIAS1 form a positive cross‐talk through their enzymatic activities. Suppression of sumoylation by ginkgolic acid, a small molecule compound inhibiting a SUMO E1‐activating enzyme, also destabilizes FIP1L1‐PDGFRA, and while the tyrosine kinase inhibitor imatinib suppresses FIP1L1‐PDGFRA‐dependent cell growth, ginkgolic acid or siRNA of PIAS1 has a synergistic effect with imatinib. In conclusion, our results suggest that sumoylation by PIAS1 is a potential target in the treatment of FIP1L1‐PDGFRA‐positive chronic eosinophilic leukemia.
Prediction and prioritization of neoantigens: integration of RNA sequencing data with whole‐exome sequencing
Authors: Karasaki Takahiro , Nagayama Kazuhiro , Kuwano Hideki , Nitadori Jun‐ichi , Sato Masaaki , Anraku Masaki , Hosoi Akihiro , Matsushita Hirokazu , Takazawa Masaki , Ohara Osamu , Nakajima Jun , Kakimi Kazuhiro
Published: December 2016

The importance of neoantigens for cancer immunity is now well‐acknowledged. However, there are diverse strategies for predicting and prioritizing candidate neoantigens, and thus reported neoantigen loads vary a great deal. To clarify this issue, we compared the numbers of neoantigen candidates predicted by four currently utilized strategies. Whole‐exome sequencing and RNA sequencing (RNA‐Seq) of four non‐small‐cell lung cancer patients was carried out. We identified 361 somatic missense mutations from which 224 candidate neoantigens were predicted using MHC class I binding affinity prediction software (strategy I). Of these, 207 exceeded the set threshold of gene expression (fragments per kilobase of transcript per million fragments mapped ≥1), resulting in 124 candidate neoantigens (strategy II). To verify mutant mRNA expression, sequencing of amplicons from tumor cDNA including each mutation was undertaken; 204 of the 207 mutations were successfully sequenced, yielding 121 mutant mRNA sequences, resulting in 75 candidate neoantigens (strategy III). Sequence information was extracted from RNA‐Seq to confirm the presence of mutated mRNA. Variant allele frequencies ≥0.04 in RNA‐Seq were found for 117 of the 207 mutations and regarded as expressed in the tumor, and finally, 72 candidate neoantigens were predicted (strategy IV). Without additional amplicon sequencing of cDNA, strategy IV was comparable to strategy III. We therefore propose strategy IV as a practical and appropriate strategy to predict candidate neoantigens fully utilizing currently available information. It is of note that different neoantigen loads were deduced from the same tumors depending on the strategies applied.
Intravital Förster resonance energy transfer imaging reveals osteopontin‐mediated polymorphonuclear leukocyte activation by tumor cell emboli
Authors: Kamioka Yuji , Takakura Kanako , Sumiyama Kenta , Matsuda Michiyuki
Published: December 2016

Myeloid‐derived suppressor cells (MDSCs) cause paraneoplastic leukemoid reactions and facilitate tumor cell metastasis. However, the interaction of MDSCs with tumor cells in live tissue has not been adequately visualized. To accomplish this task, we developed an intravital imaging protocol to observe metastasized tumor cells in mouse lungs. For visualization of the activation of MDSCs, bone marrow cells derived from transgenic mice expressing a Förster resonance energy transfer biosensor for ERK were implanted into host mice. Under a two‐photon excitation microscope, numerous polymorphonuclear cells (PMNs) were found to infiltrate the lungs of tumor‐bearing mice in which 4T1 mammary tumor cells were implanted into the footpads. By Förster resonance energy transfer imaging, we found ERK activation in PMNs around the 4T1 tumor emboli in the lungs. Because antibody array analysis implied the involvement of osteopontin (OPN) in the metastasis of 4T1 cells, we further analyzed the effect of OPN knockdown. The OPN knockdown in 4T1 cells did not affect the cell growth, but markedly suppressed lung metastasis of 4T1 cells and ERK activation in PMNs in the lung. Intravenous injection of recombinant OPN restored the lung metastasis of OPN‐deficient 4T1 cells, suggesting that OPN functioned in a paracrine manner. It has been reported that ERK activation of neutrophils causes NETosis and that PMNs promote metastasis of tumor cells by NETosis. In agreement with previous reports, the NETosis inhibitor DNase I inhibited lung metastasis of 4T1 cells. These observations suggest that OPN promotes metastasis of 4T1 cells by activating PMNs and inducing NETosis.
Emerin self‐assembly mechanism: role of the LEM domain
Authors: Samson Camille , Celli Florian , Hendriks Kitty , Zinke Maximilian , Essawy Nada , Herrada Isaline , Arteni Ana‐Andreea , Theillet François‐Xavier , Alpha‐Bazin Béatrice , Armengaud Jean , Coirault Catherine , Lange Adam , Zinn‐Justin Sophie
Published: December 2016

At the nuclear envelope, the inner nuclear membrane protein emerin contributes to the interface between the nucleoskeleton and the chromatin. Emerin is an essential actor of the nuclear response to a mechanical signal. Genetic defects in emerin cause Emery–Dreifuss muscular dystrophy. It was proposed that emerin oligomerization regulates nucleoskeleton binding, and impaired oligomerization contributes to the loss of function of emerin disease‐causing mutants. We here report the first structural characterization of emerin oligomers. We identified an N‐terminal emerin region from amino acid 1 to amino acid 132 that is necessary and sufficient for formation of long curvilinear filaments. In emerin monomer, this region contains a globular LEM domain and a fragment that is intrinsically disordered. Solid‐state nuclear magnetic resonance analysis identifies the LEM β‐fragment as part of the oligomeric structural core. However, the LEM domain alone does not self‐assemble into filaments. Additional residues forming a β‐structure are observed within the filaments that could correspond to the unstructured region in emerin monomer. We show that the delK37 mutation causing muscular dystrophy triggers LEM domain unfolding and increases emerin self‐assembly rate. Similarly, inserting a disulfide bridge that stabilizes the LEM folded state impairs emerin N‐terminal region self‐assembly, whereas reducing this disulfide bridge triggers self‐assembly. We conclude that the LEM domain, responsible for binding to the chromatin protein BAF, undergoes a conformational change during self‐assembly of emerin N‐terminal region. The consequences of these structural rearrangement and self‐assembly events on emerin binding properties are discussed.
Macrophage polarization: a key event in the secondary phase of acute spinal cord injury
Authors: Kong Xiangyi , Gao Jun
Published: December 2016

Acute spinal cord injury (SCI) has become epidemic in modern society. Despite advances made in the understanding of the pathogenesis and improvements in early recognition and treatment, it remains a devastating event, often producing severe and permanent disability.SCIhas two phases: acute and secondary. Although the acute phase is marked by severe local and systemic events such as tissue contusion, ischaemia, haemorrhage and vascular damage, the outcome ofSCIare mainly influenced by the secondary phase.SCIcauses inflammatory responses through the activation of innate immune responses that contribute to secondary injury, in which polarization‐based macrophage activation is a hallmarker. Macrophages accumulated within the epicentre and the haematoma of the injured spinal cord play a significant role in this inflammation. Depending on their phenotype and activation status, macrophages may initiate secondary injury mechanisms and/or promoteCNSregeneration and repair. When it comes to therapies forSCI, very few can be performed in the acute phase. However, as macrophage activation and polarization switch are exquisitely sensitive to changes in microenvironment, some trials have been conducted to modulate macrophage polarization towards benefiting the recovery ofSCI. Given this, it is important to understand how macrophages andSCIinterrelate and interact on a molecular pathophysiological level. This review provides a comprehensive overview of the immuno‐pathophysiological features of acuteSCImainly from the following perspectives:(i)the overview of the pathophysiology of acuteSCI,(ii)the roles of macrophage, especially its polarization switch in acuteSCI, and(iii)newly developed neuroprotective therapies modulating macrophage polarization in acuteSCI.