bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma folate and its association with folic acid supplementation, socio-demographic and lifestyle factors among New Zealand pregnant women
Authors: Bulloch Rhodi E. , McCowan Lesley M. E. , Thompson John M. D. , Houghton Lisa A. , Wall Clare R.
Published: July 2019

Folic acid (FA) supplementation is recommended in the periconceptional period, for the prevention of neural tube defects. Limited data are available on the folate status of New Zealand (NZ) pregnant women and its association with FA supplementation intake. Objectives were to examine the relationship between plasma folate (PF) and reported FA supplement use at 15 weeks’ gestation and to explore socio-demographic and lifestyle factors associated with PF. We used data and blood samples from NZ participants of the Screening for Pregnancy Endpoints cohort study. Healthy nulliparous women with singleton pregnancy (n 1921) were interviewed and blood samples collected. PF was analysed via microbiological assay. Of the participants, 73 % reported taking an FA supplement at 15 weeks’ gestation – of these, 79 % were taking FA as part of/alongside a multivitamin supplement. Of FA supplement users, 56 % reported consuming a daily dose of ≥800 μg; 39 % reported taking less than 400 µg/d. Mean PF was significantly higher in women reporting FA supplementation (54·6 (se 1·5) nmol/l) v. no FA supplementation (35·1 (se 1·6) nmol/l) (P<0·0001). Reported daily FA supplement dose and PF were significantly positively correlated (r 0·41; P<0·05). Younger maternal age, Pacific and Maori ethnicity and obesity were negatively associated with PF levels; vegetarianism was positively associated with PF. Reported FA supplement dose was significantly associated with PF after adjustment for socio-demographic, lifestyle confounders and multivitamin intake. The relationship observed between FA supplementation and PF demonstrates that self-reported intake is a reliable proxy for FA supplement use in this study population.
Predicting bilingual preschoolers’ patterns of language development: Degree of non-native input matters
Authors: Unsworth Sharon , Brouwer Susanne , de Bree Elise , Verhagen Josje
Published: July 2019

While numerous studies have recently shown that variation in input quantity predicts children’s rate of acquisition across a range of language skills, comparatively little is known about the impact of variation in inputqualityon (bilingual) children’s language development. This study investigated the relation between specific quality-oriented properties of bilingual children’s input and measures of children’s language development across a number of skills while at the same time taking family constellation into account. Participants were bilingual preschoolers (n= 50) acquiring Dutch alongside another language. Preschoolers’ receptive and productive vocabulary and morphosyntax in Dutch were assessed. Parental questionnaires were used to derive estimates of input quality. Family constellation was first operationalized as presence of a native-speaker parent and subsequently in terms of patterns of parental language use. Results showed that proportion of native input and having a native-speaker parent were never significant predictors of children’s language skills, whereas the degree of non-nativeness in the input, family constellation in terms of parental language use, and language richness were. This study shows that what matters is not how much exposure bilingual children have to native rather than non-native speakers, but how proficient any non-native speakers are.
Hybrid Methodology for Path Planning and Computational Vision Applied to Autonomous Mission: A New Approach
Authors: Coelho Fabrício O. , Pinto Milena F. , Souza João Pedro C. , Marcato André L. M.
Published: July 2019

In recent years, mobile robots have become increasingly frequent in daily life applications, such as cleaning, surveillance, support for the elderly and people with disabilities, as well as hazardous activities. However, a big challenge arises when the robotic system must perform a fully autonomous mission. The main problems of autonomous missions include path planning, localisation, and mapping. Thus, this research proposes a hybrid methodology for mobile robots on an autonomous mission involving an offline approach that uses the Direct-DRRT* algorithm and the artificial potential fields algorithm as the online planner. The experimental design covers three scenarios with an increasing degree of accuracy in respect of the real world. Additionally, an extensive evaluation of the proposed methodology is reported.
Predicting potential to benefit from an iron intervention: a randomized controlled trial of double-fortified salt in female Indian tea pluckers
Authors: Nevins Julie EH , Venkatramanan Sudha , Mehta Saurabh , Haas Jere D
Published: July 2019

Objective:

The present study examines characteristics of those who benefited from a dietary Fe intervention comprised of salt double-fortified with iodine and Fe (DFS).

Design:

Data from a randomized controlled trial were analysed to identify predictors of improved Fe status and resolution of Fe deficiency (serum ferritin (sFt) < 12 μg/l) and low body Fe (body Fe (BI) < 0·0 mg/kg) using non-parametric estimations and binomial regression models.

Setting:

A tea estate in West Bengal, India.

Participants:

Female tea pluckers, aged 18–55 years.

Results:

Consuming DFS significantly (P= 0·01) predicted resolution of Fe deficiency (relative risk (RR) = 2·31) and of low BI (RR = 2·78) compared with consuming iodized salt. Baseline sFt (β= –0·32 (se0·03),P< 0·001) and treatment group (β= 0·13 (se0·03),P< 0·001) significantly predicted change in sFt. The interaction of baseline BI with treatment group (β= –0·11 (se0·06),P= 0·08) predicted the change in BI. DFS did not significantly predict change in Hb and marginally predicted resolution of anaemia (Hb < 120 g/l).

Conclusions:

Baseline Fe status, as assessed by sFt and BI, and consumption of DFS predict change in Fe status and resolution of Fe deficiency and low BI. Anaemia prevalence and Hb level, although simple and inexpensive to measure, may not be adequate to predict resolution of Fe deficiency in response to an intervention of DFS in similar populations with high prevalence of Fe deficiency and multiple nutritional causes of anaemia. These findings will guide appropriate targeting of future interventions.
A cross-sectional study of the nutritional quality of student canteen purchases from New South Wales primary-school canteens
Authors: Delaney Tessa , Sutherland Rachel , Wyse Rebecca , Wolfenden Luke , Lecathelinais Christophe , Janssen Lisa , Reilly Kathryn , Wiggers John , Lin Yoong Sze
Published: July 2019

Objective:

To assess the nutritional quality of student canteen purchases at recess and lunch, including: (i) the mean energy (kilojoules), saturated fat (grams), total sugar (grams) and Na (milligrams) and percentage of energy from saturated fat and total sugar; and (ii) the proportion and types of foods purchased that are healthier (green) and less healthy (amber/red) according to a state school canteen policy.

Design:

A cross-sectional study of student canteen food and beverage recess and lunch purchases.

Setting:

Twenty-six randomly selected government primary schools that were non-compliant with a state school canteen policy from a region of New South Wales, Australia, were approached to participate.

Participants:

Students (aged 5–12 years) of participating schools.

Results:

Eighteen schools (69 %) consented to participate. On average students’ recess purchases contained 571·2 kJ energy, 1·6 g saturated fat, 11·6 g total sugar and 132·4 mg Na with 10·0 % of energy from saturated fat and 37·8 % of energy from total sugar. Students’ lunch purchases contained 685·4 kJ energy, 1·8 g saturated fat, 12·7 g total sugar and 151·4 mg Na with 9·5 % of energy from saturated fat and 31·8 % of energy from total sugar. Less healthy items represented 72 and 76 % of all items purchased at recess and lunch, respectively, with ‘savoury snacks’ and ‘sugar-sweetened ice blocks and slushies’ being the most common recess and lunch purchases, respectively.

Conclusions:

There is considerable scope to improve the nutritional quality of student purchases from primary-school canteens, with a high percentage of energy from total sugar. Future research is required to identify effective strategies to enhance compliance with canteen policies and support the purchase of healthier foods from school canteens.
A COMBINATORIAL SOLUTION TO MŒGLIN’S PARAMETRIZATION OF ARTHUR PACKETS FOR -ADIC QUASISPLIT AND
Authors: Xu Bin
Published: July 2019

We develop a general procedure to study the combinatorial structure of Arthur packets for $p$-adic quasisplit $\mathit{Sp}(N)$ and $O(N)$ following the works of Mœglin. This will allow us to answer many delicate questions concerning the Arthur packets of these groups, for example the size of the packets.
“An indelible mark” the response to participation in euthanasia and physician-assisted suicide among doctors: A review of research findings
Authors: Kelly Brian , Handley Tonelle , Kissane David , Vamos Marina , Attia John
Published: July 2019

Introduction

The debate regarding euthanasia and physician-assisted suicide (E/PAS) raises key issues about the role of the doctor, and the professional, ethical, and clinical dimensions of the doctor-patient relationship. This review aimed to examine the published evidence regarding the response of doctors who have participated in E/PAS.

Methods

Original research papers were identified reporting either qualitative or qualitative data published in peer-reviewed literature between 1980 and March 2018, with a specific focus on the impact on, or response from, physicians to their participation in E/PAS. PRISMA and CASP guidelines were followed.

Results

Nine relevant papers met selection criteria. Given the limited published data, a descriptive synthesis of quantitative and qualitative findings was performed. Quantitative surveys were limited in scope but identified a mixed set of responses. Where studies measured psychological impact, 30–50% of doctors described emotional burden or discomfort about participation, while findings also identified a comfort or satisfaction in believing the request of the patient was met. Significant, ongoing adverse personal impact was reported between 15% to 20%. A minority of doctors sought personal support, generally from family or friends, rather than colleagues. The themes identified from the qualitative studies were summarized as: 1) coping with a request; 2) understanding the patient; 3) the doctor's role and agency in the death of a patient; 4) the personal impact on the doctor; and 5) professional guidance and support.

Significance of results

Participation in E/PAS can have a significant emotional impact on participating clinicians. For some doctors, participation can contrast with perception of professional roles, responsibilities, and personal expectations. Despite the importance of this issue to medical practice, this is a largely neglected area of empirical research. The limited studies to date highlight the need to address the responses and impact on clinicians, and the support for clinicians as they navigate this challenging area.
Using classical reception to develop students’ engagement with classical literature in translation
Authors: Forde Shane
Published: July 2019

While observing A-level students at my PP2 school, I noticed that their responses to classical texts largely consisted of the identification of stylistic tropes. The students could identify a text's stylistic features but they struggled to articulate and develop their own personal reactions to the text. They had been well-trained in this sort of ‘feature-spotting’ and therefore their reading experience was narrowly mechanical rather than genuinely exploratory. Every passage they encountered was put through the same analytical process with the unsurprising result that every classical author ended up sounding much the same. This seemed to me to be fundamentally passive way of engaging with literature. I was struck by Muir's contention that ‘the pupil should not be a passive recipient in the study of literature’ (!974, p.515). Hence, I wanted to devise a teaching strategy that would enable my students to be more active in the formulation of a personal response to the text.
Comprehensible Input FAQs
Authors: Rogers Keith
Published: July 2019

Many teachers in the UK are aware of the issues surrounding a grammar-translation approach to teaching the classical languages but do not see any alternatives. One of the purposes of this edition of the Journal of Classics Teaching is to offer a series of articles which provides an overview of an approach called Comprehensible Input. This brief article has been written to provide an introduction to some of the basic questions and point the reader towards the relevant articles.
Untextbooking for the CI Latin class: why and how to begin
Authors: Ash Rachel
Published: July 2019

When I first dreamed about leaving my textbook behind in any serious manner, the thought was spurred by a post authored by Audrey Watters in her blog Hack Education, ‘Hacking the Textbook (Open).’ In her post, Watters describes an event in which teachers are trained to create, cultivate, and collectively share their own curriculum content. I had already spent years modifying my textbook to make it work with the way I teach, and while I still believe that it is the best textbook for a Comprehensible Input-based class, I found myself struggling more and more against the book the further students progressed just to maintain a semblance of comprehensibility. Whether or not the text was compelling—another pillar of Comprehensible Input—was not even a concern at that point.
legere discitur legendo: extensive reading in the Latin classroom
Authors: Olimpi Andrew
Published: July 2019

As a Latin teacher, I think a lot about reading. Without texts I would not have a subject to teach, and the goal of many Latin programs (including my own) is teaching students to read Latin texts. I began my Latin teaching career while teaching the language to myself as well. The goal (both for myself and my students) was to read Latin confidently and fluidly, from left to right, processing the meaning of the words as my eye scanned the pages. Yet my good intentions were soon frustrated, and I was baffled by a problem which I soon realised was not unique to my situation: despite years of training, neither I nor my students could read Latin in a natural, fluid way. Furthermore, textbooks and colleagues seemed resigned to the view that such a goal was unrealistic or unobtainable. Best to treat language as a puzzle to be solved, or linguistic knot to be untangled, rather than a language expressing a message. Only the most intellectually gifted students continued in my ‘puzzle-solving’ course; consequently, my enrolment dropped off steeply after the second year. Looking for more help, I even implemented various ‘rules for reading’ and ‘reading strategies’ advocated by others, yet rather than improve student reading ability, I felt my curriculum begin to feel increasingly cluttered with activities and processes that stole away from my students the valuable time needed to interact with the language itself. It was not until I began investigating the field of Second Language Acquisition (hereafter SLA) that I discovered some simple, yet fundamental principles about language that helped explain my students’ struggles and helped me rethink language teaching in general.
Categorising and comparing ancient religions to modern groups: teaching with taxonomy worksheets
Authors: Robertson Paul
Published: July 2019

This article introduces an approach to teaching ancient Mediterranean religions by using types of classification to compare ancient to modern groups. A brief narrative introduces pedagogy challenges around understanding the multi-various intersections of ancient group affiliations with other aspects of society. Different modes of classification and comparison are presented as a way to enable such understanding. Finally, worksheets meant for copy and classroom use are presented, explained, and detailed for their potential in Classics pedagogy at both the secondary and tertiary levels.
TwinLIFE: The Twin Longitudinal Investigation of FEtal Discordance
Authors: Groene Sophie G. , Todtenhaupt Pia , van Zwet Erik W. , van Pel Melissa , Berkhout Romy J. M. , Haak Monique C. , Roest Arno A. W. , Lopriore Enrico , van Klink Jeanine M. M. , Heijmans Bastiaan T.
Published: July 2019

Lifelong health is thought to be partially set during intrauterine life by persistent epigenetic changes induced by the prenatal environment. To evaluate this hypothesis, we initiated a prospective longitudinal study in monochorionic (MC) twins: the TwinLIFE study. MC twins are monozygotic, thus in origin genetically identical, and share a single placenta. Although MC twins have many environmental factors in common, in one-third of the MC twin pairs, one fetus has significantly less access to nutrients and resources during pregnancy than its co-twin often resulting in a significant discordance in prenatal growth. Hence, MC twins constitute a unique natural experiment to study the influence of the prenatal environment on health. In TwinLIFE, we will chart intrapair differences in DNA methylation focusing on mesenchymal stromal cells isolated from cord as an advanced proxy of epigenetic dysregulation relevant for long-term health consequences. Next, we will follow up the MC twins for growth, cardiovascular and neurodevelopmental outcomes during childhood and evaluate the impact of an epigenetic signature at birth on future health. The current target is to include 100 MC twin pairs, but we aim to continue enrollment after procuring additional funding. TwinLIFE will not only address an unmet clinical need in the high-risk group of MC twins, but may also advance early-life strategies to prevent adverse growth, cardiovascular and neurodevelopmental outcomes in the general population.
Are We Getting Better in Using Nitrogen?: Variations in Nitrogen Use Efficiency of Two Cereal Crops Across the United States
Authors: Lu Chaoqun , Zhang Jien , Cao Peiyu , Hatfield Jerry L.
Published: July 2019

Spatial variation and temporal trajectory of crop nitrogen use efficiency (NUE) have important implications for nitrogen management and environmental conservation. Previous studies have examined cross‐nation divergences in crop NUE but often overlooked its spatial heterogeneity and cross‐crop differences at subnational scales. We examined the relationship between state‐level NUE and nitrogen fertilizer use for two major fertilizer‐consuming crops, corn and winter wheat, which account for over half of national N fertilizer use in the United States. Since 1970, as N fertilizer use rates have changed, the responses of crop yield and NUE have exhibited large temporal and spatial variations. It is evident that NUE of corn begins to decline when N fertilizer application rate exceeds ~150 kg N ha−1 yr−1, and that yield response of winter wheat slows down with annual N fertilizer input above ~50 kg N ha−1 yr−1. State‐level NUE in both crops has risen in recent decades, which could potentially reduce N loss from agricultural production. Across the United States, some major corn‐producing states demonstrate a shift from an increasing trend of NUE during the period 1970 to 1999 to a decreasing trend after 2000, whereas winter wheat‐producing states present an opposite pattern. Furthermore, this study indicates that annual dynamics of N surplus in corn is closely tied with grain yields, while that in winter wheat significantly correlates with N fertilizer input. A larger proportion of N loss would be anticipated if no further increase in corn yield was obtained or fertilizer use kept rising in winter wheat.
The Ups and Downs of Rainfall in Chad Since 1950
Authors: Shultz David
Published: July 2019

A new study finds that rainfall rates are recovering in some cities since a 1966–1990 dry spell, but precipitation is still down overall since 1950.
Correction: The ALK inhibitor AZD3463 effectively inhibits growth of sorafenib-resistant acute myeloid leukemia
Authors: Moharram Sausan A. , Shah Kinjal , Khanum Fatima , Rönnstrand Lars , Kazi Julhash U.
Published: July 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Covalently-assembled single-chain protein nanostructures with ultra-high stability
Authors: Bai Wenqin , Sargent Cameron J. , Choi Jeong-Mo , Pappu Rohit V. , Zhang Fuzhong
Published: July 2019

Protein nanostructures with precisely defined geometries have many potential applications in catalysis, sensing, signal processing, and drug delivery. While many de novo protein nanostructures have been assembled via non-covalent intramolecular and intermolecular interactions, a largely unexplored strategy is to construct nanostructures by covalently linking multiple individually folded proteins through site-specific ligations. Here, we report the synthesis of single-chain protein nanostructures with triangular and square shapes made using multiple copies of a three-helix bundle protein and split intein chemistry. Coarse-grained simulations confirm the experimentally observed flexibility of these nanostructures, which is optimized to produce triangular structures with high regularity. These single-chain nanostructures also display ultra-high thermostability, resist denaturation by chaotropes and organic solvents, and have applicability as scaffolds for assembling materials with nanometer resolution. Our results show that site-specific covalent ligation can be used to assemble individually folded proteins into single-chain nanostructures with bespoke architectures and high stabilities.
FDA-ARGOS is a database with public quality-controlled reference genomes for diagnostic use and regulatory science
Authors: Sichtig Heike , Minogue Timothy , Yan Yi , Stefan Christopher , Hall Adrienne , Tallon Luke , Sadzewicz Lisa , Nadendla Suvarna , Klimke William , Hatcher Eneida , Shumway Martin , Aldea Dayanara Lebron , Allen Jonathan , Koehler Jeffrey , Slezak Tom , Lovell Stephen , Schoepp Randal , Scherf Uwe
Published: July 2019

FDA proactively invests in tools to support innovation of emerging technologies, such as infectious disease next generation sequencing (ID-NGS). Here, we introduce FDA-ARGOS quality-controlled reference genomes as a public database for diagnostic purposes and demonstrate its utility on the example of two use cases. We provide quality control metrics for the FDA-ARGOS genomic database resource and outline the need for genome quality gap filling in the public domain. In the first use case, we show more accurate microbial identification of Enterococcus avium from metagenomic samples with FDA-ARGOS reference genomes compared to non-curated GenBank genomes. In the second use case, we demonstrate the utility of FDA-ARGOS reference genomes for Ebola virus target sequence comparison as part of a composite validation strategy for ID-NGS diagnostic tests. The use of FDA-ARGOS as an in silico target sequence comparator tool combined with representative clinical testing could reduce the burden for completing ID-NGS clinical trials.
Single-crosslink microscopy in a biopolymer network dissects local elasticity from molecular fluctuations
Authors: Jiang Lingxiang , Xie Qingqiao , Tsang Boyce , Granick Steve
Published: July 2019

Polymer networks are fundamental from cellular biology to plastics technology but their intrinsic inhomogeneity is masked by the usual ensemble-averaged measurements. Here, we construct direct maps of crosslinks—symbolic depiction of spatially-distributed elements highlighting their physical features and the relationships between them—in an actin network. We selectively label crosslinks with fluorescent markers, track their thermal fluctuations, and characterize the local elasticity and cross-correlations between crosslinks. Such maps display massive heterogeneity, reveal abundant anticorrelations, and may contribute to address how local responses scale up to produce macroscopic elasticity. Single-crosslink microscopy offers a general, microscopic framework to better understand crosslinked molecular networks in undeformed or strained states.
Author Correction: A practical guide for mutational signature analysis in hematological malignancies
Authors: Maura Francesco , Degasperi Andrea , Nadeu Ferran , Leongamornlert Daniel , Davies Helen , Moore Luiza , Royo Romina , Ziccheddu Bachisio , Puente Xose S. , Avet-Loiseau Herve , Campbell Peter J. , Nik-Zainal Serena , Campo Elias , Munshi Nikhil , Bolli Niccolò
Published: July 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper
Universal optimal geometry of minimal phoretic pumps
Authors: Michelin Sébastien , Lauga Eric
Published: July 2019

Unlike pressure-driven flows, surface-mediated phoretic flows provide efficient means to drive fluid motion on very small scales. Colloidal particles covered with chemically-active patches with nonzero phoretic mobility (e.g. Janus particles) swim using self-generated gradients, and similar physics can be exploited to create phoretic pumps. Here we analyse in detail the design principles of phoretic pumps and show that for a minimal phoretic pump, consisting of 3 distinct chemical patches, the optimal arrangement of the patches maximizing the flow rate is universal and independent of chemistry.
Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis
Authors: Nishida Keigo , Hasegawa Aiko , Yamasaki Satoru , Uchida Ryota , Ohashi Wakana , Kurashima Yosuke , Kunisawa Jun , Kimura Shunsuke , Iwanaga Toshihiko , Watarai Hiroshi , Hase Koji , Ogura Hideki , Nakayama Manabu , Kashiwakura Jun-ichi , Okayama Yoshimichi , Kubo Masato , Ohara Osamu , Kiyono Hiroshi , Koseki Haruhiko , Murakami Masaaki , Hirano Toshio
Published: July 2019

Zinc (Zn) is an essential nutrient and its deficiency causes immunodeficiency and skin disorders. Various cells including mast cells release Zn-containing granules when activated; however, the biological role of the released Zn is currently unclear. Here we report our findings that Zn transporter ZnT2 is required for the release of Zn from mast cells. In addition, we found that Zn and mast cells induce IL-6 production from inflammatory cells such as skin fibroblasts and promote wound healing, a process that involves inflammation. Zn induces the production of a variety of pro-inflammatory cytokines including IL-6 through signaling pathways mediated by the Zn receptor GPR39. Consistent with these findings, wound healing was impaired in mice lacking IL-6 or GPR39. Thus, our results show that Zn and mast cells play a critical role in wound healing through activation of the GPR39/IL-6 signaling axis.
Natural killer cells impede the engraftment of cardiomyocytes derived from induced pluripotent stem cells in syngeneic mouse model
Authors: Nakamura Yuki , Miyagawa Shigeru , Yoshida Shohei , Sasawatari Shigemi , Toyofuku Toshihiko , Toda Koichi , Sawa Yoshiki
Published: July 2019

Transplantation of cardiomyocytes derived from induced pluripotent stem cell (iPSC-CMs) is a promising approach for increasing functional CMs during end-stage heart failure. Although major histocompatibility complex (MHC) class I matching between donor cells and recipient could reduce acquired immune rejection, innate immune responses may have negative effects on transplanted iPSC-CMs. Here, we demonstrated that natural killer cells (NKCs) infiltrated in iPSC-CM transplants even in a syngeneic mouse model. The depletion of NKCs using an anti-NKC antibody rescued transplanted iPSC-CMs, suggesting that iPSC-CMs activated NKC-mediated innate immunity. Surprisingly, iPSC-CMs lost inhibitory MHCs but not activating ligands for NKCs. Re-expression of MHC class I induced by IFN-γ as well as suppression of activating ligands by an antibody rescued the transplanted iPSC-CMs. Thus, NKCs impede the engraftment of transplanted iPSC-CMs because of lost MHC class I, and our results provide a basis for an approach to improve iPSC-CM engraftment.
Phylogeographic and genetic characterization of porcine circovirus type 2 in Taiwan from 2001–2017
Authors: Tsai Guang-Ting , Lin Yung-Cheng , Lin Wei-Hao , Lin Jih-Hui , Chiou Ming-Tang , Liu Hsin-Fu , Lin Chao-Nan
Published: July 2019

Porcine circovirus type 2 (PCV2) is an important pathogen that causes significant economic losses in the swine industry worldwide. Five major PCV2 genotypes have been identified, including PCV2a, PCV2b, PCV2c, PCV2d, and PCV2e. To investigate the prevalence and phylodynamics of the different PCV2 genotypes in Taiwan, 214 PCV2 ORF2 sequences from Taiwan and other countries were analyzed. Genotypic differences were observed among PCV2a, 2b, and 2d at amino acid position 89 in ORF2, with isoleucine (I), arginine (R), and leucine (L), respectively. Similar to other countries, a genotypic shift was also observed in Taiwan, where the predominant genotype shifted from PCV2b to 2d after 2010. The estimated nucleotide substitution rate of Taiwanese strains in the ORF2 region was 8.467 × 10−4 substitutions per site per year. This rapid evolution rate of PCV2 may lead to the genotypic shift observed in Taiwan. The times to the most recent common ancestor (TMRCA) for PCV2a, -2b, and -2d-2 was dated to 1970, 1992 and 2004, respectively. Thus, the PCV2a, -2b, and -2d genotypes were already present in Taiwan before the introduction of the PCV2 vaccine.
Differential binding affinity of tau repeat region R2 with neuronal-specific β-tubulin isotypes
Authors: Bhandare Vishwambhar Vishnu , Kumbhar Bajarang Vasant , Kunwar Ambarish
Published: July 2019

Tau is a microtubule-associated protein whose C-terminal domain consisting of four repeat regions R1, R2, R3 and R4 binds to microtubules to stabilize them. In several neurodegenerative diseases, tau detaches from microtubules to form insoluble aggregates leading to tauopathy. Microtubules are made up of αβ tubulin subunits. Seven α-tubulin and nine β-tubulin isotypes have been reported to be present in humans till date. These tubulin isotypes show residue composition variations mainly at C-terminal region and bind to motor proteins and anti-mitotic drugs differently. These tubulin isotypes show tissue specific expression as their relative proportion varies significantly in different type of cells. It is also known that tau binds differently to different cell lines and can either promote or demote microtubule polymerization. However, the relative binding affinity of tau to the different β-tubulin isotypes present in different cell lines is completely unknown. Here, we study relative binding affinity of Tau repeat region R2 to neuronal specific tubulin isotypes βI, βIIb, and βIII using molecular modelling approach. The order of binding energy of tau with tubulin is βIII > βIIb > βI. Our strategy can be potentially adapted to understand differential binding affinity of tau towards β-tubulin isotypes present in other cell lines.
Parylene Based Memristive Devices with Multilevel Resistive Switching for Neuromorphic Applications
Authors: Minnekhanov Anton A. , Emelyanov Andrey V. , Lapkin Dmitry A. , Nikiruy Kristina E. , Shvetsov Boris S. , Nesmelov Alexander A. , Rylkov Vladimir V. , Demin Vyacheslav A. , Erokhin Victor V.
Published: July 2019

In this paper, the resistive switching and neuromorphic behaviour of memristive devices based on parylene, a polymer both low-cost and safe for the human body, is comprehensively studied. The Metal/Parylene/ITO sandwich structures were prepared by means of the standard gas phase surface polymerization method with different top active metal electrodes (Ag, Al, Cu or Ti of ~500 nm thickness). These organic memristive devices exhibit excellent performance: low switching voltage (down to 1 V), large OFF/ON resistance ratio (up to 104), retention (≥104 s) and high multilevel resistance switching (at least 16 stable resistive states in the case of Cu electrodes). We have experimentally shown that parylene-based memristive elements can be trained by a biologically inspired spike-timing-dependent plasticity (STDP) mechanism. The obtained results have been used to implement a simple neuromorphic network model of classical conditioning. The described advantages allow considering parylene-based organic memristors as prospective devices for hardware realization of spiking artificial neuron networks capable of supervised and unsupervised learning and suitable for biomedical applications.
A suite of kinetically superior AEP ligases can cyclise an intrinsically disordered protein
Authors: Harris Karen S. , Guarino Rosemary F. , Dissanayake Ravindu S. , Quimbar Pedro , McCorkelle Owen C. , Poon Simon , Kaas Quentin , Durek Thomas , Gilding Edward K. , Jackson Mark A. , Craik David J. , van der Weerden Nicole L. , Anders Robin F. , Anderson Marilyn A.
Published: July 2019

Asparaginyl endopeptidases (AEPs) are a class of enzymes commonly associated with proteolysis in the maturation of seed storage proteins. However, a subset of AEPs work preferentially as peptide ligases, coupling release of a leaving group to formation of a new peptide bond. These “ligase-type” AEPs require only short recognition motifs to ligate a range of targets, making them useful tools in peptide and protein engineering for cyclisation of peptides or ligation of separate peptides into larger products. Here we report the recombinant expression, ligase activity and cyclisation kinetics of three new AEPs from the cyclotide producing plant Oldenlandia affinis with superior kinetics to the prototypical recombinant AEP ligase OaAEP1b. These AEPs work preferentially as ligases at both acidic and neutral pH and we term them “canonical AEP ligases” to distinguish them from other AEPs where activity preferences shift according to pH. We show that these ligases intrinsically favour ligation over hydrolysis, are highly efficient at cyclising two unrelated peptides and are compatible with organic co-solvents. Finally, we demonstrate the broad scope of recombinant AEPs in biotechnology by the backbone cyclisation of an intrinsically disordered protein, the 25 kDa malarial vaccine candidate Plasmodium falciparum merozoite surface protein 2 (MSP2).
Transferrin-decorated thymoquinone-loaded PEG-PLGA nanoparticles exhibit anticarcinogenic effect in non-small cell lung carcinoma via the modulation of miR-34a and miR-16
Authors: Upadhyay Priyanka , Sarker Sushmita , Ghosh Avijit , Gupta Payal , Das Shaswati , Ahir Manisha , Bhattacharya Saurav , Chattopadhyay Sreya , Ghosh Swatilekha , Adhikary Arghya
Published: July 2019

The detailed molecular mechanism of transferrin-tagged thymoquinone nanoparticle mediated apoptotic induction in non-small cell lung carcinoma showing the involvement of p53 dependent synergistic activation of miR-34a and miR-16 in the pathway.
In situ chemical redox and functionalization of graphene oxide: toward new cathodic photoelectrochemical bioanalysis
Authors: Gu Tiantian , Gu Mengmeng , Liu Yi-Li , Dong Yuming , Zhu Li-Bang , Li Zaijun , Wang Guang-Li , Zhao Wei-Wei
Published: July 2019

The in situ chemical redox and functionalization reaction between graphene oxide and catechols greatly stimulates the photocurrent of GO, offering an innovative sensing strategy applicable to versatile and high-throughput cathodic PEC bioanalysis.
Scandium catalysed stereoselective thio-allylation of allenyl-imidates
Authors: Parodi Adriano , Battaglioli Simone , Liu Yang , Monari Magda , Marín-Luna Marta , Silva-López Carlos , Bandini Marco
Published: July 2019

The site-selective thio-allylation of electron-deficient 1,2-dienes is documented under scandium catalysis.
Dialing in on pharmacological features for a therapeutic antioxidant small molecule
Authors: Green Kayla N. , Pota Kristof , Tircsó Gyula , Gogolák Réka Anna , Kinsinger Olivia , Davda Collin , Blain Kimberly , Brewer Samantha M. , Gonzalez Paulina , Johnston Hannah M. , Akkaraju Giridhar
Published: July 2019

Incorporation of pyridol into 12-membered pyridinophanes results in exceptional metabolic stability, low-toxicity, and controlled metal binding suggesting good pharmacological potential.
Intrinsically strained noble metal-free oxynitrides for solar photoreduction of CO2
Authors: Maiti Debtanu , Meier Anne J. , Cairns Johnnie , Ramani Swetha , Martinet Karen , Kuhn John N. , Bhethanabotla Venkat R.
Published: July 2019

Metal oxynitrides show promising activity for photocatalytic solar water splitting and CO2 reduction under solar irradiance even in the absence of noble metals.
A family of planar hexanuclear CoIII4LnIII2 clusters with lucanidae-like arrangement and single-molecule magnet behavior
Authors: Li Qipeng , Peng Yan , Qian Jinjie , Yan Tong , Du Lin , Zhao Qihua
Published: July 2019

A family of planar hexanuclear CoIII4LnIII2 clusters with lucanidae-like arrangement have been synthesized and structurally characterized. In addition, the single-molecule magnet (SMM) behavior is observed in 1.
New linker installation in metal–organic frameworks
Authors: Pang Qingqing , Tu Binbin , Li Qiaowei
Published: July 2019

Installation of new organic components (including multitopic anionic and neutral linkers) in MOFs and MOPs for multicomponent materials.
Electronic and optical properties of a novel fluoroaluminate red phosphor Cs2NaAl3F12:Mn4+ with high color purity for white light-emitting diodes
Authors: Liang Zibo , Yang Zhaofeng , Xie Xiaoling , Pu Haiqi , Shi Dongxin , Zhou Qiang , Wang Zhengliang , Guo Junming , Wu Mingmei
Published: July 2019

The red Cs2NaAl3F12:Mn4+ phosphor with intense ZPL emission was obtained via the occupation of Mn4+ for Al3+, indicating its high colour purity and potential use in WLEDs.
Investigations into the effects of linker length elongation on the behaviour of calcium-responsive MRI probes
Authors: Connah Liam , Truffault Vincent , Platas-Iglesias Carlos , Angelovski Goran
Published: July 2019

The effects of subtle structural changes on the coordination behaviour and subsequent relaxometric properties of two novel calcium-responsive magnetic resonance imaging probes have been assessedviaa range of physicochemical techniques.
New binding modes for CSe: coinage metal coordination to a tungsten selenocarbonyl complex
Authors: Frogley Benjamin J. , Hill Anthony F. , Watson Lachlan J.
Published: July 2019

The reaction of the new tungsten selenocarbonylate [Et4N][W(CSe)(CO)2(Tp*)] (Tp* = hydrotris(dimethyl-pyrazolyl)borate) with coinage metal based electrophiles provides access to a range of new bridging modes for the selenocarbonyl ligand.
Robust monolithic polymer(resorcinol-formaldehyde) reinforced alumina aerogel composites with mutually interpenetrating networks
Authors: Zhong Ya , Shao Gaofeng , Wu Xiaodong , Kong Yong , Wang Xue , Cui Sheng , Shen Xiaodong
Published: July 2019

Monolithic polymer(resorcinol-formaldehyde) reinforced alumina (RF/Al2O3) aerogel composites were prepared using a sol–gel method and supercritical fluid CO2 drying.
Synthesis and antibacterial and antiviral activities of myricetin derivatives containing a 1,2,4-triazole Schiff base
Authors: Chen Ying , Li Pu , Su Shijun , Chen Mei , He Jun , Liu Liwei , He Ming , Wang Hua , Xue Wei
Published: July 2019

The myricetin derivatives containing a 1,2,4-triazole Schiff base were designed and synthesized. Antibacterial mechanism was investigated through SEM.
Design rules for high mobility xanthene-based hole transport materials
Authors: Tabor Daniel P. , Chiykowski Valerie A. , Friederich Pascal , Cao Yang , Dvorak David J. , Berlinguette Curtis P. , Aspuru-Guzik Alán
Published: July 2019

A set of design principles for high mobility xanthene-based organic hole transport materials are elucidated by combining multiple scales of theoretical chemistry (from virtual screening to bulk simulation) with experimental synthesis and characterization.
Formation of compound I in heme bound Aβ-peptides relevant to Alzheimer's disease
Authors: Pal Ishita , Nath Arnab Kumar , Roy Madhuparna , Seal Manas , Ghosh Chandradeep , Dey Abhishek , Dey Somdatta Ghosh
Published: July 2019

Compound I is an active oxidant responsible for the peroxidase activity of heme–Aβ and can cause oxidative degradation of neurotransmitters like serotonin, a marker of Alzheimer's disease.
An open-space microfluidic chip with fluid walls for online detection of VEGF via rolling circle amplification
Authors: Feng Shuo , Mao Sifeng , Dou Jinxin , Li Weiwei , Li Haifang , Lin Jin-Ming
Published: July 2019

We report an open-space microfluidic chip with fluid walls, integrating functions of cell culture and online detection of secreted proteins controlled by the interfacial tension value.
Phase change material with anisotropically high thermal conductivity and excellent shape stability due to its robust cellulose/BNNSs skeleton
Authors: Lei Chuxin , Wu Kai , Wu Lingyu , Liu Wenjie , Du Rongni , Chen Feng , Fu Qiang
Published: July 2019

An anisotropic and robust 3D interconnected cellulose/BNNSs skeleton was designed within PEG composites for thermal management and as a solar light-to-thermal energy storage material.
Ultrafast preparation of saccharide-derived carbon microspheres with excellent dispersibility via ammonium persulfate-assisted hydrothermal carbonization
Authors: Liu Pei , Cai Weiquan , Wei Jiahao , Cai Zhijun , Zhu Mengyuan , Han Bowen , Yang Zhichao , Chen Junwu , Jaroniec Mietek
Published: July 2019

An ammonium persulfate-assisted hydrothermal strategy was successfully used to prepare carbon microspheres with excellent dispersibility from sucrose rapidly. The method can also be extended to glucose, starch and sunflower seed shells.
Structural engineering of pyrrolo[3,4-f]benzotriazole-5,7(2H,6H)-dione-based polymers for non-fullerene organic solar cells with an efficiency over 12%
Authors: Abdulahi Birhan A. , Li Xiaoming , Mone Mariza , Kiros Bisrat , Genene Zewdneh , Qiao Shanlin , Yang Renqiang , Wang Ergang , Mammo Wendimagegn
Published: July 2019

Two wide band gap donor polymers based on benzo[1,2-b:4,5-b′]dithiophene (BDT) and pyrrolo[3,4-f]benzotriazole-5,7(2H,6H)-dione (TzBI), namely, PBDT-TzBI and PBDT-F-TzBI were synthesized and studied in solar cells with ITIC as an acceptor.
In situbiosynthesized gold nanoclusters inhibiting cancer developmentviathe PI3K–AKT signaling pathway
Authors: Wang Maonan , Yu Zeqian , Feng Huan , Wang Jianling , Wang Lishan , Zhang Yu , Yin Lihong , Du Ying , Jiang Hui , Wang Xuemei , Zhou Jiahua
Published: July 2019

Nanomaterials have made great breakthroughs in drug delivery.
Generation of TD50 values for carcinogenicity study data
Authors: Thresher Andrew , Gosling John Paul , Williams Richard
Published: July 2019

Carcinogenic potency is a key factor in the understanding of chemical risk assessment. Measures of carcinogenic potency, for example TD50, are instrumental in the determination of metrics such as the threshold of toxicological concern (TTC), acceptable intake (AI) and permitted daily exposure (PDE), which in turn impact on human exposure. The Carcinogenic Potency Data Base (CPDB) has provided a source of study information, complete with calculated TD50 values. However, this is no longer actively updated. An understanding of carcinogenic potency, which can be derived from dose–response data, can be used as part of human risk assessments to generate safety thresholds under which cancer risk is judged to be minimal. The aim of this paper is to produce a transparent methodology for calculating TD50 values from experimental data in a manner consistent with the CPDB. This was then applied across the same data as used in the CPDB and analysis done on the correlation with the CPDB TD50 values. While the two sets of values showed a high level of correlation overall, there were some significant discrepancies. These were predominantly due to a lack of clarity in the CPDB methodology and inappropriate use of a linear model in TD50 calculation where the data was not suitable for such an approach.
Protective effects of delphinidin against H2O2–induced oxidative injuries in human retinal pigment epithelial cells
Authors: Ni Timin , Yang Wanju , Xing Yiqiao
Published: July 2019

Age-related macular degeneration (AMD) is now one of the leading causes of blindness in the elderly population and oxidative stress-induced damage to retinal pigment epithelial (RPE) cells occurs as part of the pathogenesis of AMD. In the present study, we evaluated the protective effect of delphinidin (2-(3,4,5-trihydroxyphenyl) chromenylium-3,5,7-triol) against hydrogen peroxide (H2O2)-induced toxicity in human ARPE-19 cells and its molecular mechanism. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry demonstrated that pretreatment of ARPE-19 cells with delphinidin (25, 50, and 100 μg/ml) significantly increased cell viability and reduced the apoptosis from H2O2 (0.5 mM)-induced oxidative stress in a concentration-dependent manner, which was achieved by the inhibition of Bax, cytochrome c, and caspase-3 protein expression and enhancement of Bcl-2 protein. The same tendency was observed in ARPE-19 cells pre-treated with 15 mM of N-acetylcysteine (NAC) before the addition of H2O2. Furthermore, pre-incubation of ARPE-19 cells with delphinidin markedly inhibited the intracellular reactive oxygen species (ROS) generation and Nox1 protein expression induced by H2O2. Moreover, the decreased antioxidant enzymes activities of superoxide dismutase (SOD), catalase (CAT), and glutathione-peroxidase (GSH-PX) and elevated (MDA) level in H2O2-treated cells were reversed to the normal standard by the addition of delphinidin, which was regulated by increasing nuclear Nrf2 protein expression in ARPE-19 cells. Our results suggest that delphinidin effectively protects human ARPE-19 cells from H2O2-induced oxidative damage via anti-apoptotic and antioxidant effects.
New therapeutic targets for the prevention of infectious acute exacerbations of COPD: role of epithelial adhesion molecules and inflammatory pathways
Authors: Atto Brianna , Eapen Mathew Suji , Sharma Pawan , Frey Urs , Ammit Alaina J. , Markos James , Chia Collin , Larby Josie , Haug Greg , Weber Heinrich C. , Mabeza George , Tristram Stephen , Myers Stephen , Geraghty Dominic P. , Flanagan Katie L. , Hansbro Philip M. , Sohal Sukhwinder Singh
Published: July 2019

Chronic respiratory diseases are among the leading causes of mortality worldwide, with the major contributor, chronic obstructive pulmonary disease (COPD) accounting for approximately 3 million deaths annually. Frequent acute exacerbations (AEs) of COPD (AECOPD) drive clinical and functional decline in COPD and are associated with accelerated loss of lung function, increased mortality, decreased health-related quality of life and significant economic costs. Infections with a small subgroup of pathogens precipitate the majority of AEs and consequently constitute a significant comorbidity in COPD. However, current pharmacological interventions are ineffective in preventing infectious exacerbations and their treatment is compromised by the rapid development of antibiotic resistance. Thus, alternative preventative therapies need to be considered. Pathogen adherence to the pulmonary epithelium through host receptors is the prerequisite step for invasion and subsequent infection of surrounding structures. Thus, disruption of bacterial–host cell interactions with receptor antagonists or modulation of the ensuing inflammatory profile present attractive avenues for therapeutic development. This review explores key mediators of pathogen–host interactions that may offer new therapeutic targets with the potential to prevent viral/bacterial-mediated AECOPD. There are several conceptual and methodological hurdles hampering the development of new therapies that require further research and resolution.