bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation, characterization and flocculation performance of the inorganic–organic composite coagulant polyferric chloride and polydimethyldiallylammonium chloride
Authors: Wang Bing , Shui Yiyu , Liu Puzhen , He Min
Published: August 2016

BACKGROUND

A novel composite coagulant was prepared from polyferric chloride (PFC) and polydimethyldiallylammonium chloride (PDM) using two different methods: co‐polymerization and composite polymerization. In this investigation, effects of preparation parameters such as PDM/Fe weight ratio (P) and PDM molecular weight on zeta potential and Fe (III) species distribution were also studied. In addition, the effects of those parameters on coagulation efficiency of prepared coagulants in treating drilling wastewater was evaluated and the synthetic coagulants were characterized in terms of typical properties and morphological analysis.

RESULTS

The improvements in preparation parameters were better charge neutralization capacity and the highest content of active Fe (III) coagulating species due to the presence of cationic polymer. The optimal coagulation efficiency was obtained at a PDM/PFC weight ratio of 0.3 and PDM molecular weight of 200–350 kDa. PFC‐PDM turned out to be a physical mixture according to Fourier transform infrared (FTIR) analysis, although the coagulation behavior was changed after the PFC/PDM composite was formed. Morphology analysis displayed an irregular surface and multi‐branched structure for PFC‐PDM.

CONCLUSION

The novel composite coagulant PFC‐PDM exhibited a superior flocculation performance and obtained favorable coagulation behavior with more compact flocs and a much better sludge compressibility compared with PFC alone. © 2016 Society of Chemical Industry
Effects of TGF‐β1 on mineralization mediated by rat calvaria‐derived osteogenic cells
Authors: Donato Tatiani A. G. , Martinez Elizabeth F. , Arana‐Chavez Victor E.
Published: August 2016

In this study, we have analyzed the viability and cell growth, as well as, the mineralization of extracellular matrix (ECM) by alizarin red and von Kossa staining of calvaria‐derived osteogenic cultures, treated with TGF‐β1 alone or associated with Dex comparing with acid ascorbic (AA) + β‐glicerophosphate (βGP) (positive mineralization control). The expression of the noncollagenous proteins bone sialoprotein (BSP), osteopontin (OPN) and fibronectin (FN) were evaluated by indirect immunofluorescence. In addition, the main ultrastructural morphological findings were assessed by transmission electron microscopy. Osteogenic cells were isolated of calvaria bone from newborn (2‐day‐old) Wistar rats were treated with TGF‐β1 alone or with dexamethasone for 7, 10, and 14 days. As positive mineralization control, the cells were supplemented only with AA+ βGP. As negative control, the cells were cultured with basal medium (α‐MEM + 10%FBS + 1%gentamicin). The treatment with TGF‐β1, even when combined with Dex, decreased the viability and cell growth when compared with the positive control. Osteoblastic cell cultures were positive to alizarin red and von Kossa stainings after AA + βGP and Dex alone treatments. Positive immunoreaction was found for BSP, OPN and FN in all studied treatments. Otherwise, when the cell cultures were supplemented with TGF‐β1 and TGF‐β1 + Dex, no mineralization was observed in any of the studied periods. These present findings suggest that TGF‐β1, in the studied in vitro doses, inhibits the proliferation and differentiation of osteoblastic cells by impairment of nodule formation.
How human IgGs against DNA recognize oligonucleotides and DNA
Authors: Andreev Sergey L. , Buneva Valentina N. , Nevinsky Georgy A.
Published: August 2016

In the literature, there are no available data on how anti‐DNA antibodies recognize DNA. In the present work, to study the molecular mechanism of DNA recognition by antibodies, we have used anti‐DNA IgGs from blood sera of patients with multiple sclerosis. A stepwise increase in ligand complexity approach was used to estimate the relative contributions of virtually every nucleotide unit of different single‐ (ss) and double‐stranded (ds) oligonucleotides to their affinity for IgG fraction having high affinity to DNA‐cellulose. DNA‐binding site disposed on the heavy chain demonstrates higher affinity to different dNMPs (Kd = 0.63μM‐3.8μM) than the site located on the light chain (28μM‐170μM). The heavy and light chains interact independently forming relatively strong contacts with 2 to 4 nucleotides of short homo‐ and hetero‐d(pN)2‐9. Then the increase in the affinity of different d(pN)n became minimal, and at n ≥ 8 to 9, all dependencies reached plateaus: approximately 3.2nM to 20nM and approximately 200nM to 460nM for the heavy and light chains, respectively. A similar situation was observed for different ribooligonucleotides, in which their affinity is 6‐fold to 100‐fold lower than that for d(pN)n. Transition from ss to ds d(pN)n leads to a moderate increase in affinity of ligands to DNA‐binding site of heavy chains, while light chains demonstrate the same affinity for ss and ds d(pN)n. Long supercoiled DNA interacts with both heavy and light chains with affinity of approximately 10‐fold higher than that for short oligonucleotides. The thermodynamic models were constructed to describe the interactions of IgGs light and heavy chains with DNA.
Myelin repair by transplantation of myelin‐forming cells in globoid cell leukodystrophy
Authors: Kondo Yoichi , Duncan Ian D.
Published: August 2016

Globoid cell leukodystrophy (GLD), or Krabbe disease, is a devastating demyelinating disease that affects both the central and peripheral nervous systems. It is caused by genetic deficiency in the activity of a lysosomal enzyme, galactocerebrosidase (GALC), which is necessary for the maintenance of myelin. Hematopoietic stem cell transplantation (HSCT) including umbilical cord stem cell transplantation is the only effective therapy available to date. HSCT significantly prolongs the life span of patients with GLD when performed before disease onset, although it is not curative. In HSCT, infiltrating donor‐derived macrophages are thought to indirectly supply the enzyme (called “cross‐correction”) to the host's myelinating cells. Given the limitation in treating GLD, it is hypothesized that remyelinating demyelinated axons with GALC‐competent myelinating cells by transplantation will result in more stable myelination than endogenous myelin repair supported by GALC cross‐correction. Transplantation of myelin‐forming cells in a variety of animal models of dysmyelinating and demyelinating disorders suggests that this approach is promising in restoring saltatory conduction and protecting neurons by providing new healthy myelin. However, GLD is one of the most challenging diseases in terms of the aggressiveness of the disease and widespread pathology. Experimental transplantation of myelin‐forming cells in the brain of a mouse model of GLD has been only modestly effective to date. Thus, a practical strategy for myelin repair in GLD would be to combine the rapid and widespread cross‐correction of GALC by HSCT with the robust, stable myelination provided by transplanted GALC‐producing myelin‐forming cells. This short review will discuss such possibilities. © 2016 Wiley Periodicals, Inc.
Assessing reference evapotranspiration estimation from reanalysis weather products. An application to the Iberian Peninsula
Authors: Martins Diogo S. , Paredes Paula , Raziei Tayeb , Pires Carlos , Cadima Jorge , Pereira Luis S.
Published: August 2016

ABSTRACT

Computing crop reference evapotranspiration (ETo) with the FAO Penman–Monteith method (PM‐ETo) requires maximum and minimum air temperature, shortwave radiation, relative air humidity and wind speed. These data are often not available, thus requiring alternative computation procedures. Although some proposed approximations may provide ETo values with small estimation errors, the physics of the ET processes may then not be well described. The use of reanalysis data, which is common in climate studies, represents an alternative to observation data for the weather variables referred above, when these are not available. This study focuses on the use of the National Center for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) blended reanalysis products with gridded data sets for the computation of PM‐ETo in the Iberian Peninsula. A monthly time step was adopted. The PM‐ETo time series computed with the blended reanalysis data sets were compared with those obtained using observations for 130 weather stations in the Iberian Peninsula. Results show that the PM‐ETo computed with blended reanalysis compares well with the series computed from observation data (average root mean square error, RMSE = 0.49 mm day−1). The weather variables derived from reanalysis were also compared with observation data. Results supported the quality of ETo computations because, overall, there was a good match between solar radiation (average RMSE = 1.76 MJm−2 day−1) and maximum temperature (average RMSE = 1.48 °C) derived from reanalysis and in situ observations. By contrast, the wind speed from reanalysis highly overestimated observations and this is likely a reason for the slight overestimation of ETo computed from reanalysis (percentage bias, PBIAS>20% in 89% of cases). In addition, the reanalysis products are apparently influenced by modelled warming, which contributes to overestimation of the minimum temperature and, to a lesser extent, of the relative humidity. The spatial pattern of accuracy indicators reveals that poorer results correspond to the southern and south‐eastern coastal areas of Iberia, where climate is semi‐arid. The compatibility of the PM‐ETo computed with monthly inputs and of the daily ETo cumulated to the month using the PM‐ETo equation was confirmed, thus allowing to extend conclusions of this study to daily computations. Alternative reanalysis products were also assessed. Tests for ERA‐Interim reanalysis products revealed overestimation of ETo and those for NCEP/NCAR Reanalysis II have shown large underestimation. Results suggest that the blended reanalysis products are suitable for the estimation of ETo in Iberia since they integrate an appropriate correction of radiation and temperature, which proved essential for the good estimation results obtained.
Discrimination of botanical origins for Chinese honey according to free amino acids content by high‐performance liquid chromatography with fluorescence detection with chemometric approaches
Authors: Chen Hui , Jin Linghe , Chang Qiaoying , Peng Tao , Hu Xueyan , Fan Chunlin , Pang Guofang , Lu Meiling , Wang Wenwen
Published: August 2016

BACKGROUND

The contents of 18 free amino acids in 87 Chinese honey samples from four botanical origins (linden, acacia, vitex and rape) were determined by developing a high‐performance liquid chromatography with fluorescence detector (HPLC‐FLD) method with an in‐loop automated pre‐column derivatization. The free amino acid profiles of these samples were used to construct a statistical model to distinguish honeys from various floral origins.

RESULTS

The average contents of all free amino acids in linden honey were lower than in the other three types of honey. Phenylalanine was particularly useful in the present study because its average content in vitex honey was far higher than in any other honey samples. There is no doubt that both phenylalanine and tyrosine can be considered as the marker free amino acid in Chinese vitex honey. Principal component analysis (PCA) was conducted based on 15 free amino acids and showed significant differences among the honey samples. The cumulative variance for the first two components was 80.62%, and the four principal components can explain 94.18% of the total variance. In the two first component scores, the honey samples can be separated according to their botanical origins. Cluster analysis of amino acid data also revealed that the botanical origins of honey samples correlated with their amino acid content. Back‐propagation artificial neural network (BP‐ANN) and naïve Bayes methods were employed to construct the classification models. The results revealed an excellent separation among honey samples according to their botanical origin with 100% accuracy in model training for both BP‐ANN and naïve Bayes.

CONCLUSION

It indicated that the free amino acid profile determined by HPLC‐FLD can provide sufficient information to discriminate honey samples according to their botanical origins. © 2016 Society of Chemical Industry
Origin of Chemical Composition of Ethylene/Propylene Copolymer Produced with Ziegler–Natta Catalyst
Authors: Takahashi Shougo , Wada Toru , Chammingkwan Patchanee , Taniike Toshiaki , Terano Minoru
Published: August 2016

The origin of the chemical composition of ethylene/propylene copolymer produced with Ziegler–Natta catalysts is investigated in terms of the active site nature and transient monomer concentration during polymerization. Using various catalysts including TiCl3/MgCl2 model catalysts with controlled Ti dispersion and TiCl4/internal donor/MgCl2 traditional catalysts, normal‐pressure and pressurized slurry copolymerization is conducted at various ethylene/propylene feed ratios. This study finds that the copolymer composition strongly depends on the copolymerization yield rather than the active site nature for both of the normal‐pressure and pressurized copolymerization. The ethylene concentration becomes smaller than its equilibrium concentration during copolymerization primarily due to the great activity enhancement in the copolymerization and secondarily due to the high reactivity and low solubility of ethylene. It is shown that the decrease in the ethylene concentration during copolymerization causes the variation of the copolymer composition in a way dependent on the kinetic profile of employed catalysts, thus broadening the chemical composition distribution.

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Optimal anthropometric measures and thresholds to identify undiagnosed type 2 diabetes in three major Asian ethnic groups
Authors: Alperet Derrick Johnston , Lim Wei‐Yen , Mok‐Kwee Heng Derrick , Ma Stefan , van Dam Rob M.
Published: August 2016

Objective

To identify optimal anthropometric measures and cutoffs to identify undiagnosed diabetes mellitus (UDM) in three major Asian ethnic groups (Chinese, Malays, and Asian‐Indians).

Methods

Cross‐sectional data were analyzed from 14,815 ethnic Chinese, Malay, and Asian‐Indian participants of the Singapore National Health Surveys, which included anthropometric measures and an oral glucose tolerance test. Receiver operating characteristic curve analyses were used with calculation of the area under the curve (AUC) to evaluate the performance of body mass index (BMI), waist circumference (WC), waist‐to‐hip ratio (WHR), and waist‐to‐height ratio (WHTR) for the identification of UDM.

Results

BMI performed significantly worse (AUCMEN = 0.70; AUCWOMEN = 0.75) than abdominal measures, whereas WHTR (AUCMEN = 0.76; AUCWOMEN = 0.79) was among the best performing measures in both sexes and all ethnic groups. Anthropometric measures performed better in Chinese than in Asian‐Indian participants for the identification of UDM. A WHTR cutoff of 0.52 appeared optimal with a sensitivity of 76% in men and 73% in women and a specificity of 63% in men and 70% in women.

Conclusions

Although ethnic differences were observed in the performance of anthropometric measures for the identification of UDM, abdominal adiposity measures generally performed better than BMI, and WHTR performed best in all Asian ethnic groups.
Household‐level correlates of children's physical activity levels in and across 12 countries
Authors: Harrington Deirdre M. , Gillison Fiona , Broyles Stephanie T. , Chaput Jean‐Philippe , Fogelholm Mikael , Hu Gang , Kuriyan Rebecca , Kurpad Anura , LeBlanc Allana G. , Maher Carol , Maia Jose , Matsudo Victor , Olds Timothy , Onywera Vincent , Sarmiento Olga L. , Standage Martyn , Tremblay Mark S. , Tudor‐Locke Catrine , Zhao Pei , Katzmarzyk Peter T. ,   for the ISCOLE Research Group
Published: August 2016

Objective

Household factors (electronic media equipment, play equipment, physical activity in the home, and social support) have been associated with childhood moderate‐ to vigorous‐intensity physical activity (MVPA), but little is known about how these factors differ across diverse countries. The objective was to explore household correlates of objective MVPA in children from 12 countries.

Methods

Overall, 5,859 nine‐ to eleven‐year‐old children from 12 countries representing a range of human and socioeconomic development indicators wore an accelerometer for 7 days and parents reported on household factors. Multilevel general linear models explored associations among household factors and MVPA variables controlling for age, sex, and parental education.

Results

Across sites, children with at least one piece of bedroom electronic media had lower MVPA (∼4 min/day; P < 0.001) than those who did not. More frequent physical activity in the home and yard, ownership of more frequently used play equipment, and higher social support for physical activity were associated with more MVPA (all P < 0.001). The association between play equipment ownership and MVPA was inconsistent across countries (interaction P < 0.01).

Conclusions

With the exception of play equipment ownership, modifiable household factors showed largely consistent and important associations with MVPA across high‐, mid‐, and low‐income countries.
Serum protein profiling in diffuse large B‐cell lymphoma
Authors: Riby Jacques , Mobley James , Zhang Jianqing , Bracci Paige M. , Skibola Christine F.
Published: August 2016

Purpose

The aim of this pilot study was to conduct a nontargeted exploratory proteomics profiling analysis on sera obtained from patients diagnosed with diffuse large B‐cell lymphoma (DLBCL) with the goal of identifying disease‐specific biomarkers.

Experimental design

Sera from 87 participants (57 chemotherapy‐naïve diffuse DLBCL patients, 30 controls frequency‐matched by age group and World Health Organization (WHO) BMI categories) that were part of a large San Francisco Bay Area case‐control study of non‐Hodgkin lymphoma were analyzed by liquid chromatography combined with tandem mass spectrometry.

Results

Thirty‐five proteins (p‐adjusted <0.05) were identified as differentially abundant between the DLBCL patients at various disease stages as compared to the controls. Of these, five proteins were randomly selected for further confirmation by ELISA: adiponectin (AdipoQ), cluster of differentiation 14 (CD14), heparin sulfate proteoglycan core protein (HSPG2), extracellular matrix 1 (ECM1), and alpha‐1‐antichymotrypsin (ACT). These proteins were statistically significantly elevated by 68.8, 37.0, 61.6, 68.0, and 32.0%, respectively, in DLBCL patient sera as compared to controls.

Conclusion and clinical relevance

These preliminary data when combined with other cancer‐related data regarding these proteins warrant continued research in clinical and large prospective studies to clarify the role for these biomarkers in DLBCL pathogenesis and/or prognosis.
Efficient and provably secure random oracle‐free adaptive identity‐based encryption with short‐signature scheme
Authors: Karati Arijit , Biswas G. P.
Published: August 2016

Identity‐based encryption (IBE) is one of the important public key encryption techniques where not only the identity of the receiver is used for secure and efficient encryption, but it also has several merits over other traditional public‐key ones. However, two main disadvantages of many such IBE‐based systems are the requirement of a large number of public parameters and different random oracle operations, where it is known that a random oracle due to improper implementation is vulnerable under chosen ciphertext attack. This paper designs an efficient IBE scheme (ROFIBE) with recipient anonymity, reduction in public parameters and random oracle‐free operation. The scheme is developed based on a proposed hard problem, named as decisional extended bilinear Diffie‐Hellman assumption (DEBDH) and on analysis it is found to be secured under standard security model. In addition, a new short‐signature scheme based on the proposed IBE is developed under the difficulty of solving proposed q−extended bilinear strong Diffie–Hellman assumption (q‐EBSDH). As performance analysis, we compare both the proposed schemes with other existing related ones and find that our schemes are computationally and communicationally efficient and effectively usable in real life applications. Copyright © 2016 John Wiley & Sons, Ltd.
Implicit learning with certificate warning messages on SSL web pages: what are they teaching?
Authors: Bostan Atila
Published: August 2016

SSL‐based web services are the most common technology in secure transactions on the Internet today. The security level of these services is inevitably related with that of digital certificates and user awareness. With the high number of nonconforming digital certificate usage, which eventually invokes warning messages on the Internet, users are implicitly forced to develop unsecure usage habits. In this study, we have studied the implicit learning effect of certificate warning messages on the SSL web pages. We have conducted two different experimental studies on university students and on instructors in IT departments. The results point to acquired indifference towards these warnings in users. Copyright © 2016 John Wiley & Sons, Ltd.
Macrophages as Active Nanocarriers for Targeted Early and Adjuvant Cancer Chemotherapy
Authors: Si Jingxing , Shao Shiqun , Shen Youqing , Wang Kai
Published: August 2016

Taking advantage of the highly permeable vasculature and lack of lymphatic drainage in solid tumors (EPR effect), nanosized drug delivery systems or nanomedicines have been extensively explored for tumor‐targeted drug delivery. However, in most clinical cases tumors such as the early stage tumors and post‐surgery microscopic residual tumors have not yet developed such pathological EPR features, i.e., EPR‐deficient. Therefore, nanomedicines may not be applicable for such these tumors. Macrophages by nature can actively home and extravasate through the tight vascular wall into tumors and migrate to their hypoxic regions, and possess perfect stealth ability for long blood circulation and impressive phagocytosis for drug loadings. Thus, nanomedicines loaded in macrophages would harness both merits and gain the active tumor homing capability independent of the EPR effect for treatments of the EPR‐deficient tumors. Herein, the critical considerations, current progress, challenges and future prospects of macrophages as carriers for nanomedicines are summarized, aiming at rational design of EPR‐independent tumor‐targeting active nanomedicines for targeted early and adjuvant cancer chemotherapy.
Impact of holoprosencephaly, exomphalos, megacystis and increased nuchal translucency on first‐trimester screening for chromosomal abnormalities
Authors: Syngelaki A. , Guerra L. , Ceccacci I. , Efeturk T. , Nicolaides K. H.
Published: August 2016

Objectives

To examine the prevalence of alobar holoprosencephaly, exomphalos, megacystis and nuchal translucency thickness (NT) ≥ 3.5 mm, the incidence and types of chromosomal abnormalities associated with these conditions and their overall impact on the rate of invasive testing and performance of screening at 11–14 weeks.

Methods

This was a prospective screening study for trisomies 21, 18 and 13 by the first‐trimester combined test at three maternity units in England.

Results

In the study population of 108 982 singleton pregnancies, 870 (0.8%) had abnormal karyotype, including 654 (75.2%) with trisomies 21, 18 or 13 and 216 (24.8%) with other chromosomal abnormalities. The prevalence of alobar holoprosencephaly, exomphalos, megacystis and NT ≥ 3.5 mm was 1 in 2945, 1 in 419, 1 in 1345 and 1 in 119, respectively. Chromosomal abnormalities were observed in 78.4% of cases of holoprosencephaly, 40.8% of exomphalos, 18.5% of megacystis and 48.5% of those with NT ≥ 3.5 mm. The most common chromosomal abnormality associated with holoprosencephaly was trisomy 13, with exomphalos and megacystis was trisomy 18 and with increased NT was trisomy 21. Fetal karyotyping of cases with major fetal defects or increased NT would potentially detect 57% of all chromosomal abnormalities at an invasive testing rate of 1.1%.

Conclusion

Major fetal defects and increased NT at 11–13 weeks' gestation are associated with a high risk of chromosomal abnormalities and merit invasive fetal testing. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Research on Primary Biodegradation of Alkyl Ethoxy Glucoside
Authors: Dong Qingbin , Zhao Yonghong , Zhang Guangliang , Ren Yingjie
Published: August 2016

This investigation was performed to determine the anaerobic biodegradation of alkyl ethoxy glucoside (AEG) nonionic surfactants using the OECD 311 method. The influence of different initial concentrations of AEG on the primary biodegradation rate was investigated using the anthrone analysis method. The results show that different initial concentrations have similar good biodegradability and the biodegradation rate can reach more than 90 % even at the highest initial concentration of 100 mg/l. Alkyl polyglucoside (APG) surfactants have previously been confirmed as readily biodegradable. The profile of concentration changes over the incubation time of AEG and APG had similar trends. Therefore, AEG are also considered as readily biodegradable. The gas chromatograph‐mass spectrometer analytical method was used to identify the metabolites. The content of alcohol ethoxylate (AEO) increased with decrease in the number of AEG at the initial stage of degradation. It was found that AEO with longer EO chains disappeared first. Accordingly, a degradation pathway that accounts for the experiment results was proposed.
An Automated Approach for Localizing Retinal Blood Vessels in Confocal Scanning Laser Ophthalmoscopy Fundus Images
Authors: Kromer Robert , Shafin Rahman , Boelefahr Sebastian , Klemm Maren
Published: August 2016

In this work, we present a rules-based method for localizing retinal blood vessels in confocal scanning laser ophthalmoscopy (cSLO) images and evaluate its feasibility. A total of 31 healthy participants (17 female; mean age: 64.0 ± 8.2 years) were studied using manual and automatic segmentation. High-resolution peripapillary scan acquisition cSLO images were acquired. The automated segmentation method consisted of image pre-processing for gray-level homogenization and blood vessel enhancement (morphological opening operation, Gaussian filter, morphological Top-Hat transformation), binary thresholding (entropy-based thresholding operation), and removal of falsely detected isolated vessel pixels. The proposed algorithm was first tested on the publically available dataset DRIVE, which contains color fundus photographs, and compared to performance results from the literature. Good results were obtained. Monochromatic cSLO images segmented using the proposed method were compared to those manually segmented by two independent observers. For the algorithm, a sensitivity of 0.7542, specificity of 0.8607, and accuracy of 0.8508 were obtained. For the two independent observers, a sensitivity of 0.6579, specificity of 0.9699, and accuracy of 0.9401 were obtained. The results demonstrate that it is possible to localize vessels in monochromatic cSLO images of the retina using a rules-based approach. The performance results are inferior to those obtained using fundus photography, which could be due to the nature of the technology.
Rationale and design of ASSAF‐K (A study of the safety and efficacy of anticoagulant therapy in the treatment of atrial fibrillation in Kanagawa)
Authors: Hatori Yutaka , Sakai Hiroyuki , Kunishima Tomoyuki , Hatori Nobuo , Chen Lin , Ishigami Tomoaki , Satoh Naoki ,   ASSAF‐K Investigators
Published: August 2016

Background

Atrial fibrillation (AF) is one of the most prevalent cardiac arrhythmias associated with substantially increased risks of ischemic stroke and thromboembolism. Oral anticoagulants (OACs) are the cornerstone of AF management and effectively prevent AF‐related stroke. As new non‐vitamin K antagonist OACs (NOACs) have become available, the landscape of stroke prevention in AF has changed. However, there are considerable gaps between daily clinical practice and current guideline‐based recommendations for anticoagulant therapy in Japan. Consequently, little is known about the real‐world setting and the current use of NOACs, especially by practitioners in Japan.

Methods

We conducted a prospective, observational study in 3847 patients with AF who were enrolled in clinics and hospitals located in Kanagawa Prefecture from September 2013 through March 2015. The participating centers included practitioners (small clinics), medium‐sized hospitals, and university hospitals. The primary endpoints were epidemiologic characteristics, status of treatment with anticoagulants and antiplatelet agents, outcomes, and adverse events, including cerebrovascular disease, bleeding, and death.

Results

The mean CHADS2 score was 1.81±1.27, the mean CHADS2‐Vasc score was 3.02±1.58, and the mean HAS‐BLED score was 2.23±1.06, respectively. The usage rate of warfarin was 44.2% overall, and the usage rate of NOACs was 33.5%.

Conclusions

The results of the study are expected to serve as the basis for providing clinical practice guidance to healthcare institutions in Japan, with the ultimate goals of better characterizing the appropriate use of OACs and providing clinical decision support to physicians to facilitate the design of appropriate therapeutic strategies and the selection of anticoagulants for the management of AF.
Neutrons in a nanosecond low-pressure discharge in deuterium
Authors: Tarasenko Victor F. , Lomaev Mikhail I. , Sorokin Dmitry A. , Nechaev Boris A. , Padalko Vladimir N. , Dudkin Gennady N.
Published: August 2016

Stable neutron generation with a yield of ∼1.2 × 104 neutrons per pulse was obtained during d(d,n)3He reaction initiated by the high-voltage nanosecond discharge in a gap with a potential tungsten cylinder (anode) and a grounded deuterated zirconium plate (cathode) filled with deuterium at a pressure of ∼102 Pa. Estimated duration of the neutron pulse was ∼1.5 ns. Less intensive neutron emission was registered without deuterated plate. Splashing of material of the tungsten electrode was observed during the high-voltage nanosecond discharge in the deuterium, hydrogen, helium and argon at pressures of 102–104 Pa.
Alzheimer's drug‐development pipeline: 2016
Authors: Cummings Jeffrey , Morstorf Travis , Lee Garam
Published: August 2016

Background

Alzheimer's disease (AD) is growing in frequency and new therapies are urgently needed.

Methods

We assessed clinicaltrials.gov (accessed 1‐4‐2016) to determine the number and characteristics of trials in phase I, phase II, and phase III for treatment of AD.

Results

There are currently 24 agents in 36 trials in phase III of AD drug development. Seven of these 24 agents are symptomatic cognitive‐enhancing compounds, and 17 are disease‐modifying treatments (DMTs). Most DMTs address amyloid‐related targets (76%). There are 45 agents in phase II being assessed in 52 clinical trials. Phase II trials include 30 DMTs, with 26 small molecules and 4 immunotherapies. There are 24 agents in the first phase of AD drug development.

Discussion

Amyloid is the principal target of late‐stage development programs. There are relatively few agents in clinical trials for AD suggesting a need to amplify the drug discovery ecosystem.
Nahrungsmittelallergie: Sinn und Unsinn von diagnostischen Abklärungen
Authors: Ballmer-Weber Barbara K.
Published: August 2016

Zusammenfassung. Jeder vierte Erwachsene in der Schweiz ist gegen mindestens ein Lebensmittel sensibilisiert. Da nur 25–50 % der Sensibilisierten eine Nahrungsmittelallergie entwickeln, ist das ungezielte Einsetzen von Hauttests oder auf IgE-Antikörper-Nachweis basierten In-vitro-Tests im Sinne eines Nahrungsmittelallergie-Screenings unsinnig. Diese Testverfahren sollen erst bei Vorliegen einer suggestiven Anamnese einer Nahrungsmittelallergie veranlasst werden. Häufig kann die definitive Klärung der Relevanz einer Sensibilisierung gegen Lebensmittel erst durch die orale Provokationstestung erbracht werden. Die sogenannte Komponenten-spezifische Diagnostik, bei der nach IgE-Antikörpern gegen Einzelallergene gesucht wird, hilft bei gewissen Nahrungsmitteln, eine Risikobewertung der Sensibilisierung vorzunehmen. Die Verwendung von wissenschaftlich nicht validierten Testmethoden zur Diagnose einer Nahrungsmittelunverträglichkeit oder Allergie ist strikt abzulehnen, denn sie führt häufig zu nicht-indizierten und damit unsinnigen Diäten.
Emergent nanoscale superparamagnetism at oxide interfaces
Authors: Anahory Y. , Embon L. , Li C. J. , Banerjee S. , Meltzer A. , Naren H. R. , Yakovenko A. , Cuppens J. , Myasoedov Y. , Rappaport M. L. , Huber M. E. , Michaeli K. , Venkatesan T. , Ariando  , Zeldov E.
Published: August 2016

Atomically sharp oxide heterostructures exhibit a range of novel physical phenomena that are absent in the parent compounds. A prominent example is the appearance of highly conducting and superconducting states at the interface between LaAlO3 and SrTiO3. Here we report an emergent phenomenon at the LaMnO3/SrTiO3 interface where an antiferromagnetic Mott insulator abruptly transforms into a nanoscale inhomogeneous magnetic state. Upon increasing the thickness of LaMnO3, our scanning nanoSQUID-on-tip microscopy shows spontaneous formation of isolated magnetic nanoislands, which display thermally activated moment reversals in response to an in-plane magnetic field. The observed superparamagnetic state manifests the emergence of thermodynamic electronic phase separation in which metallic ferromagnetic islands nucleate in an insulating antiferromagnetic matrix. We derive a model that captures the sharp onset and the thickness dependence of the magnetization. Our model suggests that a nearby superparamagnetic–ferromagnetic transition can be gate tuned, holding potential for applications in magnetic storage and spintronics.
Intermediate magnetization state and competing orders in Dy2Ti2O7 and Ho2Ti2O7
Authors: Borzi R. A. , Gómez Albarracín F. A. , Rosales H. D. , Rossini G. L. , Steppke A. , Prabhakaran D. , Mackenzie A. P. , Cabra D. C. , Grigera S. A.
Published: August 2016

Among the frustrated magnetic materials, spin-ice stands out as a particularly interesting system. Residual entropy, freezing and glassiness, Kasteleyn transitions and fractionalization of excitations in three dimensions all stem from a simple classical Hamiltonian. But is the usual spin-ice Hamiltonian a correct description of the experimental systems? Here we address this issue by measuring magnetic susceptibility in the two most studied spin-ice compounds, Dy2Ti2O7 and Ho2Ti2O7, using a vector magnet. Using these results, and guided by a theoretical analysis of possible distortions to the pyrochlore lattice, we construct an effective Hamiltonian and explore it using Monte Carlo simulations. We show how this Hamiltonian reproduces the experimental results, including the formation of a phase of intermediate polarization, and gives important information about the possible ground state of real spin-ice systems. Our work suggests an unusual situation in which distortions might contribute to the preservation rather than relief of the effects of frustration.
RNF168 and USP10 regulate topoisomerase IIα function via opposing effects on its ubiquitylation
Authors: Guturi Kiran Kumar Naidu , Bohgaki Miyuki , Bohgaki Toshiyuki , Srikumar Tharan , Ng Deborah , Kumareswaran Ramya , El Ghamrasni Samah , Jeon Justin , Patel Parasvi , Eldin Mohamed Saad , Bristow Rob , Cheung Peter , Stewart Grant S. , Raught Brian , Hakem Anne , Hakem Razqallah
Published: August 2016

Topoisomerase IIα (TOP2α) is essential for chromosomal condensation and segregation, as well as genomic integrity. Here we report that RNF168, an E3 ligase mutated in the human RIDDLE syndrome, interacts with TOP2α and mediates its ubiquitylation. RNF168 deficiency impairs decatenation activity of TOP2α and promotes mitotic abnormalities and defective chromosomal segregation. Our data also indicate that RNF168 deficiency, including in human breast cancer cell lines, confers resistance to the anti-cancer drug and TOP2 inhibitor etoposide. We also identify USP10 as a deubiquitylase that negatively regulates TOP2α ubiquitylation and restrains its chromatin association. These findings provide a mechanistic link between the RNF168/USP10 axis and TOP2α ubiquitylation and function, and suggest a role for RNF168 in the response to anti-cancer chemotherapeutics that target TOP2.
Erratum: Percolation-based precursors of transitions in extended systems
Authors: Rodríguez-Méndez Víctor , Eguíluz Víctor M. , Hernández-García Emilio , Ramasco José J.
Published: August 2016

Scientific Reports 6: Article number: 29552; published online: 14 July 2016; updated: 25 August 2016 The original HTML version of this Article contained a typographical error in the spelling of the author Víctor M. Eguíluz which was incorrectly given as Víctor M. Eguíluz M. This has now been corrected.
Erratum: Determining Chemically and Spatially Resolved Atomic Profile of Low Contrast Interface Structure with High Resolution
Authors: Nayak Maheswar , Pradhan P. C. , Lodha G. S. , Sokolov A. , Schäfers F.
Published: August 2016

Scientific Reports 5: Article number: 8618; published online: 02 March 2015; updated: 25 August 2016 In this Article, A. Sokolov & F. Schäfers are incorrectly listed as being affiliated with ‘Indus Synchrotrons Utilization Division, Raja Ramanna Centre for Advanced Technology, Indore-452013 (M P), India’.
Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery
Authors: Kumar Niyanta N. , Gautam Mohan , Lochhead Jeffrey J. , Wolak Daniel J. , Ithapu Vamsi , Singh Vikas , Thorne Robert G.
Published: August 2016

Intranasal administration provides a non-invasive drug delivery route that has been proposed to target macromolecules either to the brain via direct extracellular cranial nerve-associated pathways or to the periphery via absorption into the systemic circulation. Delivering drugs to nasal regions that have lower vascular density and/or permeability may allow more drug to access the extracellular cranial nerve-associated pathways and therefore favor delivery to the brain. However, relative vascular permeabilities of the different nasal mucosal sites have not yet been reported. Here, we determined that the relative capillary permeability to hydrophilic macromolecule tracers is significantly greater in nasal respiratory regions than in olfactory regions. Mean capillary density in the nasal mucosa was also approximately 5-fold higher in nasal respiratory regions than in olfactory regions. Applying capillary pore theory and normalization to our permeability data yielded mean pore diameter estimates ranging from 13–17 nm for the nasal respiratory vasculature compared to <10 nm for the vasculature in olfactory regions. The results suggest lymphatic drainage for CNS immune responses may be favored in olfactory regions due to relatively lower clearance to the bloodstream. Lower blood clearance may also provide a reason to target the olfactory area for drug delivery to the brain.
Multiscale dispersion-state characterization of nanocomposites using optical coherence tomography
Authors: Schneider Simon , Eppler Florian , Weber Marco , Olowojoba Ganiu , Weiss Patrick , Hübner Christof , Mikonsaari Irma , Freude Wolfgang , Koos Christian
Published: August 2016

Nanocomposite materials represent a success story of nanotechnology. However, development of nanomaterial fabrication still suffers from the lack of adequate analysis tools. In particular, achieving and maintaining well-dispersed particle distributions is a key challenge, both in material development and industrial production. Conventional methods like optical or electron microscopy need laborious, costly sample preparation and do not permit fast extraction of nanoscale structural information from statistically relevant sample volumes. Here we show that optical coherence tomography (OCT) represents a versatile tool for nanomaterial characterization, both in a laboratory and in a production environment. The technique does not require sample preparation and is applicable to a wide range of solid and liquid material systems. Large particle agglomerates can be directly found by OCT imaging, whereas dispersed nanoparticles are detected by model-based analysis of depth-dependent backscattering. Using a model system of polystyrene nanoparticles, we demonstrate nanoparticle sizing with high accuracy. We further prove the viability of the approach by characterizing highly relevant material systems based on nanoclays or carbon nanotubes. The technique is perfectly suited for in-line metrology in a production environment, which is demonstrated using a state-of-the-art compounding extruder. These experiments represent the first demonstration of multiscale nanomaterial characterization using OCT.
RNA sequencing from neural ensembles activated during fear conditioning in the mouse temporal association cortex
Authors: Cho Jin-Hyung , Huang Ben S. , Gray Jesse M.
Published: August 2016

The stable formation of remote fear memories is thought to require neuronal gene induction in cortical ensembles that are activated during learning. However, the set of genes expressed specifically in these activated ensembles is not known; knowledge of such transcriptional profiles may offer insights into the molecular program underlying stable memory formation. Here we use RNA-Seq to identify genes whose expression is enriched in activated cortical ensembles labeled during associative fear learning. We first establish that mouse temporal association cortex (TeA) is required for remote recall of auditory fear memories. We then perform RNA-Seq in TeA neurons that are labeled by the activity reporter Arc-dVenus during learning. We identify 944 genes with enriched expression in Arc-dVenus+ neurons. These genes include markers of L2/3, L5b, and L6 excitatory neurons but not glial or inhibitory markers, confirming Arc-dVenus to be an excitatory neuron-specific but non-layer-specific activity reporter. Cross comparisons to other transcriptional profiles show that 125 of the enriched genes are also activity-regulated in vitro or induced by visual stimulus in the visual cortex, suggesting that they may be induced generally in the cortex in an experience-dependent fashion. Prominent among the enriched genes are those encoding potassium channels that down-regulate neuronal activity, suggesting the possibility that part of the molecular program induced by fear conditioning may initiate homeostatic plasticity.
Assessing bleeding risk in 4824 Asian patients with atrial fibrillation: The Beijing PLA Hospital Atrial Fibrillation Project
Authors: Guo Yu-tao , Zhang Ye , Shi Xiang-min , Shan Zhao-liang , Wang Chun-jiang , Wang Yu-tang , Chen Yun-dai , Lip Gregory Y. H.
Published: August 2016

The risks of major bleeding and intracranial hemorrhage (ICH) are higher in Asian patients with atrial fibrillation (AF) compared to non-Asians. We aimed to investigate risk factors for bleeding and validate the predictive value of available bleeding risk scores (mOBRI, HEMORR2HAGES, Shireman, HAS-BLED, ATRIA and ORBIT) in a large cohort of Chinese inpatients with AF. Using hospital electronic medical databases, we identified 4824 AF patients (mean age 67 years; 34.9% female) from January 1, 1995 to May 30, 2015, with median (interquartile) in-hospital days of 10 (7–16) days. On multivariate analysis, prior bleeds, vascular disease, anemia, prior stroke and liver dysfunction were independent risk factors of major bleeding (all p < 0.05). C-statistics (95%CI) of the HAS-BLED score were 0.72 (0.65–0.79) for major bleeding events and 0.83 (0.75–0.91) for ICH (all p < 0.001). Compared to other risk scores, the HAS-BLED score was significantly better in predicting major bleeding events (Delong test, all P < 0.05, apart from mOBRI, HEMORR2HAGES) and ICH (all p < 0.05) and additionally, resulted in a net reclassification improvement (NRI) of 17.1–65.5% in predicting major bleeding events and 29.5–67.3% in predicting ICH (all p < 0.05). We conclude that the HAS-BLED score had the best predictive and discriminatory ability for major bleeding and ICH in an Asian/Chinese AF population.
Recent evolution of the salivary mucin MUC7
Authors: Xu Duo , Pavlidis Pavlos , Thamadilok Supaporn , Redwood Emilie , Fox Sara , Blekhman Ran , Ruhl Stefan , Gokcumen Omer
Published: August 2016

Genomic structural variants constitute the majority of variable base pairs in primate genomes and affect gene function in multiple ways. While whole gene duplications and deletions are relatively well-studied, the biology of subexonic (i.e., within coding exon sequences), copy number variation remains elusive. The salivary MUC7 gene provides an opportunity for studying such variation, as it harbors copy number variable subexonic repeat sequences that encode for densely O-glycosylated domains (PTS-repeats) with microbe-binding properties. To understand the evolution of this gene, we analyzed mammalian and primate genomes within a comparative framework. Our analyses revealed that (i) MUC7 has emerged in the placental mammal ancestor and rapidly gained multiple sites for O-glycosylation; (ii) MUC7 has retained its extracellular activity in saliva in placental mammals; (iii) the anti-fungal domain of the protein was remodified under positive selection in the primate lineage; and (iv) MUC7 PTS-repeats have evolved recurrently and under adaptive constraints. Our results establish MUC7 as a major player in salivary adaptation, likely as a response to diverse pathogenic exposure in primates. On a broader scale, our study highlights variable subexonic repeats as a primary source for modular evolutionary innovation that lead to rapid functional adaptation.
Idiopathic Choroidal Neovascularization: Intraocular Inflammatory Cytokines and the Effect of Intravitreal Ranibizumab Treatment
Authors: Yin Houfa , Fang Xiaoyun , Ma Jian , Chen Min , Yang Yabo , Guo Shenchao , Chen Zhiqing , Su Zhaoan , Feng Lei , Ye Panpan , Wu Fang , Yin Jinfu
Published: August 2016

Idiopathic choroidal neovascularization (ICNV) is a disorder that primarily affecting patients younger than 50 years and can cause severe loss of vision. Choroidal abnormalities, especially choroidal inflammation, have been thought to be involved in the pathophysiology of ICNV. However, the exact pathogenesis of ICNV remains unclear. The aim of our study was investigate the levels of 27 inflammatory cytokines in the aqueous humor of eyes with ICNV and to determine the effect of intravitreal injection of ranibizumab (IVR) on cytokine levels. Significantly higher levels of IL-2, IL-10, IL-15, IL-17, basic FGF and GM-CSF were observed in patients with ICNV compared with controls. However, only IL-17 levels were significantly higher in patients with ICNV compared with controls after adjusting for axial length. Furthermore, there were significant correlations between the levels of IL-10, IL-17, GM-CSF and VEGF and the lesion area. Significant changes in visual acuity and central retinal thickness were observed after IVR. Besides VEGF, IVR also significantly reduced the levels of IL-2, IL-10, basic FGF and IL-12, however, the IL-6 levels were significantly increased. Our results suggest that there may be an involvement of IL-17-related inflammatory processes in the etiology of ICNV.