bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Genetics of Fibrodysplasia Ossificans Progressiva
Authors: Hüning Irina , Gillessen‐Kaesbach Gabriele
Published: November 2016

Fibrodysplasia ossificans progressiva (FOP, MIM 135100) is an autosomal‐dominant genetic disorder, caused by heterozygous mutations in the
ACVR1
gene. Its defining clinical feature is heterotopic (extraskeletal) ossifications (HO). Almost all patients show also fibular deviation and shortness of the great toes from birth. However, the phenotypes of FOP patients vary and there seem to be a genotype–phenotype correlation even if the number of patients is still small to definitely establish it. Recent literature data support that all of the identified
ACVR1
germ line missense mutations influence the postnatal induction of cartilage and bone cell differentiation. Moreover, it has been recently shown that the most common
ACVR1
mutation p.R206H leads to a protein which causes FOP by gaining responsiveness to the normally antagonistic ligand activin A, important discovery for new therapeutic approaches.

Key Concepts

FOP is caused by heterozygous missense activating mutations of the
ACVR1
gene.

A clear genotype–phenotype correlation in FOP is highly presumable, even though the number of patients is small.

Analysis of the mutations, different from the common R206H mutation supply FOP research with valuable knowledge of the mechanisms of disease and possible therapeutic approaches.

Understanding of molecular mechanisms causing FOP is a major key step for developing therapy concepts.

Understanding FOP and the pathomechanisms of this extremely rare disease may be very helpful for the understanding of other more common forms of heterotopic ossifications, such as Posttraumatic Heterotopic Ossification and Neurogenic Heterotopic Ossification.
Statistical Signal Processing
Authors: Kannan Nandini , Kundu Debasis
Published: November 2016

Statistical signal processing is an important area of research with extensive applications in the fields of communication theory, array processing, seismology, and medical diagnosis. The goal of signal processing is to recover characteristics of the underlying process from observed data. The random nature of the signals underscores the need for statistical techniques in model formulation, estimation, and data analysis. A brief discussion of the different models that have been widely studied in the statistical signal‐processing literature is provided. In addition, different methods of estimation are presented, and some unique characteristics of these models are highlighted.
Gibbs Sampling
Authors: Christen José Andrés
Published: November 2016

Gibbs sampling is a Monte Carlo simulation tool for obtaining marginal distributions from a nonnormalized joint density (“nonnormalized” means that it has not yet been scaled to integrate to one) and is a particular case of Markov chain Monte Carlo (MCMC) methods. The Gibbs sampling was the first MCMC method of general use by statisticians and since its introduction into the mainstream statistical literature by the Gelfand and Smith 1990 paper, it has become a widely employed computational tool in Bayesian statistics as well as in other non‐Bayesian applications.

This landmark paper set the foundations for a massive increase in the use of Bayesian methods and changed the statistical practice ever since. With the wide availability of high‐speed computing, the Gibbs sampler and, in fact, general sampling‐based approaches have become basic tools in current modern statistics.
Assessment of Probabilities
Authors: O'Hagan Anthony
Published: November 2016

This article addresses the situation where you are uncertain about the truth of a propositionAand wish to quantify your uncertainty in the form of a probability Pr() that is true, based on your current state of knowledge . A variety of approaches are considered for assessing such a probability value, including classical assessment, frequency assessment, direct assessment, scoring rules, elaborative assessment, and elicitation.
Asset Liability Management for Life Insurers
Authors: Sherris Michael
Published: November 2016

This article outlines approaches used to quantify risk using ALM for life insurers.
Data Management and Coordination
Authors: McFadden Eleanor T.
Published: November 2016

Accurate and timely management of data is key to the success of any clinical trial. Data that is relevant to the objectives of the study must be defined and then collected in a way that minimizes the work at the participating sites and ensures the collection of accurate and meaningful data. This article describes general principles for data management and provides guidance on the steps that must be taken to ensure that the data collected can be used to answer the trial objectives.
Statistical Methods for Hospital Monitoring
Authors: Morton Anthony , Whitby Michael , Tierney Nicholas , Sibanda Nokuthaba , Mengersen Kerrie
Published: November 2016

Hospitals are complex adaptive systems that can display emergent behavior as the result of the interaction of many agents. This can be an unintended consequence of policy or staff action or can seem to appear spontaneously, so that its nature and consequences may be difficult or impossible to predict.

Appropriate statistical approaches are required that accommodate important features of the data, such as rare adverse events following a power law distribution. Moreover, approaches are needed to seek to understand the combined effect of the numerous interacting agents in the system.
Reduced Major Axis Regression
Authors: Harper William V.
Published: November 2016

The theoretical underpinnings of standard least‐squares (LS) regression analysis are based on the assumption that the independent variable (often thought of asx) is measured without error as a design variable. The dependent variable (often labeledy) is modeled as having uncertainty or error. Both independent and dependent measurements may have multiple sources of error. Thus, the underlying least‐squares regression assumptions can be violated. Reduced major axis (RMA) regression is specifically formulated to handle errors in both thexandyvariables. It is an alternative to least squares and demonstrates the importance of understanding the assumptions underlying statistical procedures.
Porous Pt Nanoparticles with High Near‐Infrared Photothermal Conversion Efficiencies for Photothermal Therapy
Authors: Zhu Xiao‐Ming , Wan Hong‐Ye , Jia Henglei , Liu Liang , Wang Jianfang
Published: November 2016

Plasmonic nanostructures are of potential in acting as a type of optical agents for cancer photothermal therapy. To effectively function as photothermal therapy agents, plasmonic nanostructures are strongly desired to have good biocompatibility and high photothermal conversion efficiencies. In this study, poly(diallyldimethylammonium chloride)‐coated porous Pt nanoparticles are synthesized for photothermal therapy. The Pt nanoparticles possess broadband near‐infrared light absorption in the range from 650 to 1200 nm, therefore allowing for selecting different laser wavelengths for photothermal therapy. The as‐prepared Pt nanoparticles exhibit remarkable photothermal conversion efficiencies under 809 and 980 nm laser irradiation. In vitro studies indicate that the Pt nanoparticles display good biocompatibility and high cellular uptake efficiencies through an endocytosis pathway. Photothermal heating using 808 nm laser irradiation (>7.0 W cm−2, 3 min) leads to notable cytotoxic effect, and more than 70% of cells are photothermally ablated after 3 min irradiation at 8.4 W cm−2. Furthermore, simultaneous application of photothermal therapy synergistically enhances the cytotoxicity of an anti‐cancer drug doxorubicin. Therefore, the porous Pt nanoparticles have great potential as an attractive photothermal agent for cancer therapy.
Advanced Electron Holography Applied to Electromagnetic Field Study in Materials Science
Authors: Shindo Daisuke , Tanigaki Toshiaki , Park Hyun Soon
Published: November 2016

Advances and applications of electron holography to the study of electromagnetic fields in various functional materials are presented. In particular, the development of split‐illumination electron holography, which introduces a biprism in the illumination system of a holography electron microscope, enables highly accurate observations of electromagnetic fields and the expansion of the observable area. First, the charge distributions on insulating materials were studied by using split‐illumination electron holography and including a mask in the illumination system. Second, the three‐dimensional spin configurations of skyrmion lattices in a helimagnet were visualized by using a high‐voltage holography electron microscope. Third, the pinning of the magnetic flux lines in a high‐temperature superconductor YBa2Cu3O7−y was analyzed by combining electron holography and scanning ion microscopy. Finally, the dynamic accumulation and collective motions of electrons around insulating biomaterial surfaces were observed by utilizing the amplitude reconstruction processes of electron holography.
Amorphous MoS3 Infiltrated with Carbon Nanotubes as an Advanced Anode Material of Sodium‐Ion Batteries with Large Gravimetric, Areal, and Volumetric Capacities
Authors: Ye Hualin , Wang Lu , Deng Shuo , Zeng Xiaoqiao , Nie Kaiqi , Duchesne Paul N. , Wang Bo , Liu Simon , Zhou Junhua , Zhao Feipeng , Han Na , Zhang Peng , Zhong Jun , Sun Xuhui , Li Youyong , Li Yanguang , Lu Jun
Published: November 2016

The search for earth‐abundant and high‐performance electrode materials for sodium‐ion batteries represents an important challenge to current battery research. 2D transition metal dichalcogenides, particularly MoS2, have attracted increasing attention recently, but few of them so far have been able to meet expectations. In this study, it is demonstrated that another phase of molybdenum sulfide—amorphous chain‐like MoS3—can be a better choice as the anode material of sodium‐ion batteries. Highly compact MoS3 particles infiltrated with carbon nanotubes are prepared via the facile acid precipitation method in ethylene glycol. Compared to crystalline MoS2, the resultant amorphous MoS3 not only exhibits impressive gravimetric performance—featuring excellent specific capacity (≈615 mA h g−1), rate capability (235 mA h g−1 at 20 A g−1), and cycling stability but also shows exceptional volumetric capacity of ≈1000 mA h cm−3 and an areal capacity of >6.0 mA h cm−2 at very high areal loadings of active materials (up to 12 mg cm−2). The experimental results are supported by density functional theory simulations showing that the 1D chains of MoS3 can facilitate the adsorption and diffusion of Na+ ions. At last, it is demonstrated that the MoS3 anode can be paired with an Na3V2(PO4)3 cathode to afford full cells with great capacity and cycling performance.
Single‐Particle Performances and Properties of LiFePO4 Nanocrystals for Li‐Ion Batteries
Authors: Hu Jiangtao , Li Wen , Duan Yandong , Cui Suihan , Song Xiaohe , Liu Yidong , Zheng Jiaxin , Lin Yuan , Pan Feng
Published: November 2016

It has been recently reported that the solution diffusion, efficiency porosity, and electrode thickness can dominate the high rate performance in the 3D‐printed and traditional LiMn0.21Fe0.79PO4 electrodes for Li‐ions batteries. Here, the intrinsic properties and performances of the single‐particle (SP) of LiFePO4 are investigated by developing the SP electrode and creating the SP‐model, which will share deep insight on how to further improve the performance of the electrode and related materials. The SP electrode is generated by fully scattering and distributing LiFePO4 nanoparticles to contact with the conductive network of carbon nanotube or conductive carbon to demonstrate the sharpest cyclic voltammetry peak and related SP‐model is developed, by which it is found that the interfacial rate constant in aqueous electrolyte is one order of magnitude higher, accounting for the excellent rate performance in aqueous electrolyte for LiFePO4. For the first time it has been proposed that the insight of pre‐exponential factor of interface kinetic Arrhenius equation is related to desolvation/solvation process. Thus, this much higher interfacial rate constant in aqueous electrolyte shall be attributed to the much larger pre‐exponential factor of interface kinetic Arrhenius equation, because the desolvation process is much easier for Li‐ions jumping from aqueous electrolyte to the Janus solid–liquid interface of LiFePO4.
Artifact Interpretation of Spectral Response Measurements on Two‐Terminal Multijunction Solar Cells
Authors: Si Fai Tong , Isabella Olindo , Zeman Miro
Published: November 2016

Multijunction solar cells promise higher power‐conversion efficiency than the single‐junction. With respect to two‐terminal devices, an accurate measurement of the spectral response requires a delicate adjustment of the light‐ and voltage‐biasing; otherwise it can result in artifacts in the data and thus misinterpretation of the cell properties. In this paper, the formation of measurement artifacts is analyzed by modeling the measurement process, that is, how the current–voltage characteristics of the component subcells evolve with the photoresponse to the incident spectrum. This enables the examination on the operation conditions of the subcells, offering additional information for the study of artifacts. In particular, the influence of shunt resistance, bias‐light intensity, and bias voltage on the measurement is examined. Having observed the dynamics and vulnerability of the measurement, the proper ways to configure and interpret a measurement are discussed in depth. As a practical example, simulations of the measurements on a quadruple‐junction thin‐film silicon solar cell demonstrate that the modeling can be used to interpret eventual irregularities in the measured spectral response. The application of such tool is especially meaningful taking account of the diverse and rapid development of novel hybrid multijunction solar cells, in which the role of reliable characterizations is essential.
Copper and zinc isotope ratios in human bone and enamel
Authors: Jaouen Klervia , Herrscher Estelle , Balter Vincent
Published: November 2016

Objectives

Here, we report Cu and Zn isotope ratios of bones and teeth of French people from various historical periods with the aim to understand how Cu and Zn isotope ratios of bone, a tissue that is continuously remodeled throughout life but that is prone to post‐mortem diagenesis, compare with that of tooth enamel, a tissue that forms once during childhood but that is more resistant to diagenesis. Specifically, we examine (1) the potential existence of sex‐related differences in the Cu isotope ratios (represented as δ65Cu) in the tooth enamel of identified men and women, and (2) a decrease of Zn isotope delta ratios (represented as δ66Zn) related to the increase of meat and fish consumption during the 20th century.

Methods

Four series of material were studied: the archeological population of Saint‐Laurent de Grenoble (17th–18th centuries AD), an anatomical collection of skulls (19th century AD), a contemporary anatomical collection of bones never buried, and contemporary teeth samples. The metals were purified by liquid chromatography and their isotopic ratios measured by means of multicollector inductively coupled plasma mass spectrometry.

Results

We describe a clear offset between bone and tooth enamel for Zn isotope ratios, as previously observed in animals. There is a similar offset for Cu isotope ratios. We did not observe any difference between the δ65Cu values of men and women when looking at dental enamel. For the contemporary samples, the δ66Zn values of bioapatite decreased, which might be explained by the increase of animal product consumption among the French people during this period, notably when the access to seafood became widespread.

Conclusions

Our study demonstrates that the Cu and Zn isotope compositions of dental enamel are promising tools for childhood diet reconstruction. Meanwhile, the Cu isotope ratio of tooth enamel is unlikely to be useful for the identification of biological sex, even in the case of populations with early menarche. Further works are needed to understand the relationships between trophic level and Zn isotope ratios of human remains.
Accidental falls related to clearing heavy snow on rooftops in a rural heavy snow area in Japan
Authors: Yamaguchi Seigo , Endoh Hiroshi , Nitta Masakazu
Published: November 2016

Aim

The purpose of this study is to describe our experience with patients who fell from rooftops while clearing snow. The falls occurred in rural areas that receive heavy snowfall and are undergoing depopulation and an increasing proportion of elderly residents.

Methods

A retrospective observational chart review was carried out at the sole hospital providing emergency services in a rural heavy snow area in Japan.

Results

A total of 70 patients were enrolled during four winter seasons between December 2009 and March 2013. Their mean age was 61 years, and 90% were male. The mean vertical height of falls was 4.1 m. A total of 174 injuries was observed, averaging 2.5 injuries per patient. Fractures accounted for 78% of all injuries, and main fractures included vertebra with lower extremities or rib fractures; 86% of patients sustained a maximum abbreviated injury scale score of 2–3.

Conclusions

In a rural heavy snow area in Japan, the incidence of accidental falls related to clearing snow was high, and the victims were elderly. Fractures accounted for 78% of all injuries, and most patients suffered from moderate to serious injuries.
Decarboxylative Peptide Macrocyclization through Photoredox Catalysis
Authors: McCarver Stefan J. , Qiao Jennifer X. , Carpenter Joseph , Borzilleri Robert M. , Poss Michael A. , Eastgate Martin D. , Miller Michael M. , MacMillan David W. C.
Published: November 2016

A method for the decarboxylative macrocyclization of peptides bearing N‐terminal Michael acceptors has been developed. This synthetic method enables the efficient synthesis of cyclic peptides containing γ‐amino acids and is tolerant of functionalities present in both natural and non‐proteinogenic amino acids. Linear precursors ranging from 3 to 15 amino acids cyclize effectively under this photoredox method. To demonstrate the preparative utility of this method in the context of bioactive molecules, we synthesized COR‐005, a somatostatin analogue that is currently in clinical trials.
Supramolecular Diblock Copolymers Featuring Well‐defined Telechelic Building Blocks
Authors: Elacqua Elizabeth , Croom Anna , Manning Kylie B. , Pomarico Scott K. , Lye Diane , Young Lauren , Weck Marcus
Published: November 2016

We report supramolecular AB diblock copolymers comprised of well‐defined telechelic building blocks. Helical motifs, formed via reversible addition‐fragmentation chain‐transfer (RAFT) or anionic polymerization, are assembled with coil‐forming and sheet‐featuring blocks obtained via atom‐transfer radical polymerization (ATRP) or ring‐opening metathesis polymerization (ROMP). Interpolymer hydrogen bonding or metal‐coordination achieves dynamic diblock architectures featuring hybrid topologies of coils, helices, and/or π‐stacked sheets that, on a basic level, mimic protein structural motifs in fully synthetic systems. The intrinsic properties of each block (e.g., circular dichroism and fluorescence) remain unaffected in the wake of self‐assembly. This strategy to develop complex synthetic polymer scaffolds from functional building blocks is significant in a field striving to produce architectures reminiscent of biosynthesis, yet fully synthetic in nature. This is the first plug‐and‐play approach to fabricate hybrid π‐sheet/helix, π‐sheet/coil, and helix/coil architectures via directional self‐assembly.
Light‐Controlled Ion Transport through Biomimetic DNA‐Based Channels
Authors: Li Pei , Xie Ganhua , Kong Xiang‐Yu , Zhang Zhen , Xiao Kai , Wen Liping , Jiang Lei
Published: November 2016

Light‐controlled nanochannels are fabricated through self‐assembling azobenzene‐incorporated DNA (Azo‐DNA) strands to regulate ion transport. By switching between collapsed and relaxed states using visible and ultraviolet light alternately, the Azo‐DNA channels can be opened and closed because the conformation of Azo‐DNA changes, that is, Azo‐DNA is used as switchable controlling unit. In addition to sharing short response time and reversibility with other photoresponsive apparatuses, the Azo‐DNA‐based nanochannel system has advantages in good biocompatibility and versatile design, which could potentially be applied in light‐controlled drug release, optical information storage, and logic networks.
Engineered Substrate‐Specific Delta PKC Antagonists to Enhance Cardiac Therapeutics
Authors: Qvit Nir , Kornfeld Opher S. , Mochly‐Rosen Daria
Published: November 2016

Most protein kinases phosphorylate multiple substrates, each of which induces different and sometimes opposing functions. Determining the role of phosphorylation of each substrate following a specific stimulus is challenging but is essential to elucidate the role of that substrate in the signaling event. Here we describe a rational approach to identify inhibitors of delta protein kinase C (δPKC), each inhibiting the phosphorylation of only one of δPKC′s substrates. δPKC regulates many signaling events and we hypothesized that a docking inhibitor of a given substrate to δPKC should selectively abrogate the phosphorylation of only that substrate, without affecting the phosphorylation of the other δPKC substrates. Here we report the development of selective inhibitors of three δPKC substrates (in vitro Kd≈3 nm); two greatly reduced ischemia‐induced cardiac injury with an IC50 of ≈200 nm and the third had no effect, indicating that its respective substrate phosphorylation by δPKC has no role in the response to cardiac ischemia and reperfusion. The three inhibitors are highly specific; even at 1 μm, the phosphorylation of other δPKC protein substrates was unaffected. The rationale we describe is likely applicable for the development of other substrate‐specific inhibitors as well.
PhSO2SCF2H: A Shelf‐Stable, Easily Scalable Reagent for Radical Difluoromethylthiolation
Authors: Zhu Dianhu , Shao Xinxin , Hong Xin , Lu Long , Shen Qilong
Published: November 2016

A new shelf‐stable and easily scalable difluoromethylthiolating reagent S‐(difluoromethyl) benzenesulfonothioate (PhSO2SCF2H) was developed. PhSO2SCF2H is a powerful reagent for radical difluoromethylthiolation of aryl and alkyl boronic acids, decarboxylative difluoromethylthiolation of aliphatic acids, and a phenylsulfonyl‐difluoromethylthio difunctionalization of alkenes under mild reaction conditions.
Carboxymethyl cellulose reinforced poly(vinyl alcohol) with trimethylol melamine as a chemical crosslinker
Authors: Gao Zijian , Yu Zhe , Huang Chang , Duan Lijie , Gao Guang Hui
Published: November 2016

In this investigation, carboxymethyl cellulose (CMC)‐reinforced poly(vinyl alcohol) (PVA) were prepared with trimethylol melamine as a chemical crosslinker. The structure and property of hydrogels were measured by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), texture analysis, and rheometry. The FTIR spectra demonstrated that the etherification reaction successfully occurred in the PVA–CMC hydrogels, and the SEM figures exhibited the homogeneous porous structure of the CMC–PVA hydrogels. The compression strength of the PVA–CMC hydrogels was 15 times higher than that of the PVA hydrogels. Moreover, the PVA–CMC hydrogels exhibited a higher storage modulus than that of the PVA hydrogels; this illustrated better elasticity for the PVA–CMC hydrogels. As a result, CMC‐modified PVA hydrogels with high mechanical behavior will broaden the potential applications of hydrogels, such as in wound dressings, facial masks, and skin‐protection layers. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44590.
Electrochemical studies on composite gel polymer electrolytes for lithium sulfur‐batteries
Authors: Natarajan Angulakshmi , Stephan Arul Manuel , Chan Chin Han , Kalarikkal Nandakumar , Thomas Sabu
Published: November 2016

Poly(ethylene oxide)‐based composite gel polymer electrolytes (CGPE's) were prepared for various concentrations of magnesium aluminate (MgAl2O4) and LiTFSI as salt with a combination of 1,3‐dioxolane (DOL) and tetraethylene glycol dimethyl ether (TEGDME) as plasticizer by a simple solution casting technique. The addition of plasticizers has significantly improved the ionic conductivity of the gel electrolytes. The prepared CGPEs were subjected to scanning electron microscopy, thermal, and FT‐IR analysis. The electrochemical properties such as ionic conductivity, compatibility, and charge–discharge behavior have also been studied. Preliminary studies revealed that the prepared CGPE can be employed as a potential electrolyte for lithium–sulfur (Li–S) batteries. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44594.
Self‐assembly properties of ultra‐long‐chain gemini surfactant with high performance in a fracturing fluid application
Authors: Yang Chunpeng , Hu Zhiyuan , Song Zhaozheng , Bai Jianyong , Zhang Yuan , Luo JiaQing , Du Yongxin , Jiang Qingzhe
Published: November 2016

A new cationic gemini surfactant (C25‐6‐C25), which had a special structure consisting of ultra‐long hydrophobic chains and amide groups, was synthesized using a main feedstock source obtained from rapeseed for thickening purposes. The 12 mmol L−1 C25‐6‐C25 fluid containing 0.19 mol L−1 potassium chloride (KCl) exhibited highly elastic properties at the angular frequency of 0.04–10 rad s−1. Its viscosity could be maintained at 55 mPa s for 1.5 h under a shear rate of 170 s−1 at 110 °C and it also showed a good proppant‐suspending property. C25‐6‐C25/KCl fluid exhibited high viscoelasticity and good performance, which were attributed to intermolecular forces, hydrogen bonding, and the shielding effect of electrostatic repulsion by KCl. Thus, C25‐6‐C25 is a very promising candidate for fracturing. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44602.
Sarilumab and Nonbiologic Disease‐Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis and Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors
Authors: Fleischmann Roy , van Adelsberg Janet , Lin Yong , Castelar‐Pinheiro Geraldo da Rocha , Brzezicki Jan , Hrycaj Pawel , Graham Neil M. H. , van Hoogstraten Hubert , Bauer Deborah , Burmester Gerd R.
Published: November 2016

Objective

To evaluate the efficacy and safety of sarilumab plus conventional synthetic disease‐modifying antirheumatic drugs (DMARDs) in patients with active moderate‐to‐severe rheumatoid arthritis (RA) who had an inadequate response or intolerance to anti–tumor necrosis factor (anti‐TNF) therapy.

Methods

Patients were randomly allocated to receive sarilumab 150 mg, sarilumab 200 mg, or placebo every 2 weeks for 24 weeks with background conventional synthetic DMARDs. The co‐primary end points were the proportion of patients achieving a response according to the American College of Rheumatology 20% criteria for improvement (ACR20) at week 24, and change from baseline in the Health Assessment Questionnaire disability index (HAQ DI) at week 12. Each sarilumab dose was evaluated against placebo; differences between the 2 sarilumab doses were not assessed.

Results

The baseline characteristics of the treatment groups were similar. The ACR20 response rate at week 24 was significantly higher with sarilumab 150 mg and sarilumab 200 mg every 2 weeks compared with placebo (55.8%, 60.9%, and 33.7%, respectively; P < 0.0001). The mean change from baseline in the HAQ DI score at week 12 was significantly greater for sarilumab (least squares mean change: for 150 mg, −0.46 [P = 0.0007]; for 200 mg, −0.47 [P = 0.0004]) versus placebo (−0.26). Infections were the most frequently reported treatment‐emergent adverse events. Serious infections occurred in 1.1%, 0.6%, and 1.1% of patients receiving placebo, sarilumab 150 mg, and sarilumab 200 mg, respectively. Laboratory abnormalities included decreased absolute neutrophil count and increased transaminase levels in both sarilumab groups compared with placebo. In this study, reductions in the absolute neutrophil count were not associated with an increased incidence of infections or serious infections.

Conclusion

Sarilumab 150 mg and sarilumab 200 mg every 2 weeks plus conventional synthetic DMARDs improved the signs and symptoms of RA and physical function in patients with an inadequate response or intolerance to anti‐TNF agents. Safety data were consistent with interleukin‐6 receptor blockade and the known safety profile of sarilumab.
Targeting the D Series Resolvin Receptor System for the Treatment of Osteoarthritis Pain
Authors: Huang Junting , Burston James J. , Li Li , Ashraf Sadaf , Mapp Paul I. , Bennett Andrew J. , Ravipati Srinivasarao , Pousinis Petros , Barrett David A. , Scammell Brigitte E. , Chapman Victoria
Published: November 2016

Objective

Pain is a major symptom of osteoarthritis (OA); currently available analgesics either do not provide adequate pain relief or are associated with serious side effects. The aim of this study was to investigate the therapeutic potential of targeting the resolvin receptor system to modify OA pain and pathology.

Methods

Gene expression of 2 resolvin receptors (ALX and ChemR23) was quantified in synovium and medial tibial plateau specimens obtained from patients with OA at the time of joint replacement surgery. Two models of OA joint pain were used for the mechanistic studies. Gene expression in the joint and central nervous system was quantified. The effects of exogenous administration of the D series resolvin precursor 17(R)‐hydroxy‐docosahexaenoic acid (17[R]‐HDoHE) on pain behavior, joint pathology, spinal microglia, and astroglyosis were quantified. Plasma levels of relevant lipids, resolvin D2, 17(R)‐HDoHE, and arachidonic acid, were determined in rats, using liquid chromatography tandem mass spectrometry.

Results

There was a positive correlation between resolvin receptor and interleukin‐6 (IL‐6) expression in human OA synovial and medial tibial plateau tissue. In rats, synovial expression of ALX was positively correlated with expression of IL‐1β, tumor necrosis factor, and cyclooxygenase 2. Treatment with 17(R)‐HDoHE reversed established pain behavior (but not joint pathology) in 2 models of OA pain. This was associated with a significant elevation in the plasma levels of resolvin D2 and a significant reduction in astrogliosis in the spinal cord in the monosodium iodoacetate–induced OA rat model.

Conclusion

Our preclinical data demonstrate the robust analgesic effects of activation of the D series resolvin pathways in 2 different animal models of OA. Our data support a predominant central mechanism of action in clinically relevant models of OA pain.
Consensus Problem with a Reference State for Fractional‐Order Multi‐Agent Systems
Authors: Bai Jing , Wen Guoguang , Rahmani Ahmed , Yu Yongguang
Published: November 2016

In this paper, the consensus problem of fractional‐order multi‐agent systems with a reference state is studied under fixed directed communication graph. At the beginning, the convergence speeds of fractional‐order multi‐agent systems are investigated based on the Mittag‐Leffler function. Then, a common consensus control law and a consensus control law based on error predictor are proposed, and it is shown that the consensus tracking can be achieved using the above control laws when a communication graph has a directed spanning tree. Finally, the convergence speeds of fractional‐order systems are compared, and it is discovered that the convergence of systems is faster using the control law based on error predictor than using the common one.
Growth characteristics of maize seeds exposed to magnetic field
Authors: Vashisth Ananta , Joshi Devendra Kumar
Published: November 2016

Standardization of magnetic field was done for maximum enhancement in germination characteristics of maize seeds. Seeds of maize were exposed to static magnetic fields of strength 50, 100, 150, 200, and 250 for 1, 2, 3, and 4 h for all field strengths. Results indicate that magnetic field application enhanced seed performance in terms of percentage germination, speed of germination, seedling length, and seedling dry weight significantly compared to unexposed control. Among the various combinations of field strength and duration, 200 mT for 1 h exposure gave best results. Exposure of seeds to magnetic fields improved seed coat membrane integrity as it reduced cellular leakage and, consequently, electrical conductivity. Experiments conducted at a research farm as well as farmer's field showed that plants raised from seeds exposed to 200 mT for 1 h had higher values of leaf area index, shoot length, number of leaves, chlorophyll content, shoot/root dry weight, and root characteristics as compared to corresponding values in untreated control. From the studies, it may be concluded that exposure of dry seeds to static magnetic field of 200 mT for 1 h improved shoot and root growth. Improved root system and biomass led to increased seed yield. Improved functional root parameters suggested that magnetically treated maize seeds could be used under moisture stress conditions. Bioelectromagnetics. 38:151–157, 2017. © 2016 Wiley Periodicals, Inc.
Systematic review of educational interventions for looked‐after children and young people: Recommendations for intervention development and evaluation
Authors: Evans Rhiannon , Brown Rachel , Rees Gwyther , Smith Philip
Published: November 2016

Looked‐after children and young people (LACYP) are educationally disadvantaged compared to the general population. A systematic review was conducted of randomised controlled trials evaluating interventions aimed at LACYP aged ≤18 years. Restrictions were not placed on delivery setting or delivery agent. Intervention outcomes were: academic skills; academic achievement and grade completion; special education status; homework completion; school attendance, suspension, and drop‐out; number of school placements; teacher‐student relationships; school behaviour; and academic attitudes. Fifteen studies reporting on 12 interventions met the inclusion criteria. Nine interventions demonstrated tentative impacts. However, evidence of effectiveness could not be ascertained due to variable methodological quality, as appraised by the Cochrane risk of bias tool. Theoretical and methodological recommendations are provided to enhance the development and evaluation of educational interventions.
Chemiluminescence of off‐line and on‐line gold nanoparticle‐catalyzed luminol system in the presence of flavonoid
Authors: Wu Dong , Zhang Xiaoyue , Liu Yong , Ma Yan , Wang Xiaowu , Wang Xiaojuan , Xu Liuxin
Published: November 2016

It was found that flavonoids could remarkably inhibit the chemiluminescence (CL) intensity of an off‐line gold nanoparticle (AuNP)‐catalyzed luminol–H2O2 CL system. By contrast, flavonoids enhanced the CL intensity of an on‐line AuNP‐catalyzed luminol–H2O2 CL system. In the off‐line system, the AuNPs were prepared beforehand, whereas in the on‐line system, AuNPs were produced by on‐line mixing of luminol prepared in a buffer solution of NaHCO3 − Na2CO3 and HAuCl4 with no need for the preliminary preparation of AuNPs. The on‐line system had prominent advantages over the off‐line system, namely a lowering of the background noise and improvements in the stability of the CL system. The results show that differences in the signal suppression effect of flavonoids on the off‐line AuNP‐catalyzed CL system are influenced by the combined action of a free radical scavenging effect and occupy‐sites function; the latter was proved to be predominant using controlled experiments. Enhancement of the on‐line system was ascribed to the presence of flavonoids promoting the on‐line formation of AuNPs, which better catalyzed the luminol–H2O2 CL reaction, and the enhancement activity of the six flavonoids increased with the increase in reducibility. This work broadens the scope of practical applications of an AuNP‐catalyzed CL system.
Predictive glycoengineering of biosimilars using a Markov chain glycosylation model
Authors: Spahn Philipp N. , Hansen Anders H. , Kol Stefan , Voldborg Bjørn G. , Lewis Nathan E.
Published: November 2016

Biosimilar drugs must closely resemble the pharmacological attributes of innovator products to ensure safety and efficacy to obtain regulatory approval. Glycosylation is one critical quality attribute that must be matched, but it is inherently difficult to control due to the complexity of its biogenesis. This usually implies that costly and time‐consuming experimentation is required for clone identification and optimization of biosimilar glycosylation. Here, a computational method that utilizes a Markov model of glycosylation to predict optimal glycoengineering strategies to obtain a specific glycosylation profile with desired properties is described. The approach uses a genetic algorithm to find the required quantities to perturb glycosylation reaction rates that lead to the best possible match with a given glycosylation profile. Furthermore, the approach can be used to identify cell lines and clones that will require minimal intervention while achieving a glycoprofile that is most similar to the desired profile. Thus, this approach can facilitate biosimilar design by providing computational glycoengineering guidelines that can be generated with a minimal time and cost.
Gram (−) microorganisms DNA polymerase inhibition, antibacterial and chemical properties of fruit and leaf extracts of Sorbus acuparia and Sorbus caucasica var. yaltirikii
Authors: Turumtay Halbay , Midilli Ahmet , Turumtay Emine Akyuz , Demir Adem , Selvi Emine Kılıçkaya , Budak Emine Esra , Er Havva , Kocaimamoglu Fatih , Baykal Hüseyin , Belduz Ali Osman , Atamov Vagif , Sandallı Cemal
Published: November 2016

Investigation of novel plant‐based agents might provide alternative antibiotics and thus fight antibiotic resistance. Here, we measured the ability of fruit and leaf extracts of Sorbus aucuparia (Sauc) and endemic Sorbus caucasica var. yaltirikii (Scau) to inhibit nonreplicative (Klenow Fragment‐KF and Bacillus Large Fragment‐BLF) and replicative (DnaE and PolC) bacterial DNA polymerases along with their antimicrobial, DPPH free radical scavenging activity (RSA), and chemical contents by total phenolic content and HPLC‐DAD analysis. We found that leaf extracts had nearly 10‐fold higher RSA and 5‐fold greater TPC than the corresponding fruit extracts. All extracts had large amounts of chlorogenic acid (CGA) and rutin, while fruit extracts had large amounts of quercetin. Hydrolysis of fruit extracts revealed mainly caffeic acid from CGA (caffeoylquinic acid) and quercetin from rutin (quercetin‐3‐O‐rutinoside), as well as CGA and derivatives of CGA and p‐coumaric acid. Plant extracts of Sorbus species showed antimicrobial activity against Gram‐negative microorganisms. Scau leaf extracts exhibited strong inhibition of KF activity. Sauc and Scau leaf extracts also strongly inhibited two replicative DNA polymerases. Thus, these species can be considered a potential source of novel antimicrobial agents specific for Gram‐negative bacteria.
Biomass‐water interactions correlate to recalcitrance and are intensified by pretreatment: An investigation of water constraint and retention in pretreated spruce using low field NMR and water retention value techniques
Authors: Weiss Noah D. , Thygesen Lisbeth Garbrecht , Felby Claus , Roslander Christian , Gourlay Keith
Published: November 2016

The underlying mechanisms of the recalcitrance of biomass to enzymatic deconstruction are still not fully understood, and this hampers the development of biomass based fuels and chemicals. With water being necessary for most biological processes, it is suggested that interactions between water and biomass may be key to understanding and controlling biomass recalcitrance. This study investigates the correlation between biomass recalcitrance and the constraint and retention of water by the biomass, using SO2 pretreated spruce, a common feedstock for lignocellulosic biofuel production, as a substrate to evaluate this relationship. The water retention value (WRV) of the pretreated materials was measured, and water constraint was assessed using time domain Low Field Nuclear Magnetic Resonance (LFNMR) relaxometry. WRV increased with pretreatment severity, correlating to reduced recalcitrance, as measured by hydrolysis of cellulose using commercial enzyme preparations. Water constraint increased with pretreatment severity, suggesting that a higher level of biomass‐water interaction is indicative of reduced recalcitrance in pretreated materials. Both WRV and water constraint increased significantly with reductions in particle size when pretreated materials were further milled, suggesting that particle size plays an important role in biomass water interactions. It is suggested that WRV may be a simple and effective method for measuring and comparing biomass recalcitrance. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:146–153, 2017
ZAKβ antagonizes and ameliorates the cardiac hypertrophic and apoptotic effects induced by ZAKα
Authors: Fu Chien‐Yao , Kuo Wei‐Wen , Ho Tsung‐Jung , Wen Su‐Ying , Lin Ling‐Chun , Tseng Yan‐Shen , Hung Hui‐Chuan , Viswanadha Vijaya Padma , Yang Jaw‐Ji , Huang Chih‐Yang
Published: November 2016

ZAK (sterile alpha motif and leucine zipper containing kinase AZK), a serine/threonine kinase with multiple biochemical functions, has been associated with various cell processes, including cell proliferation, cell differentiation, and cardiac hypertrophy. In our previous reports, we found that the activation of ZAKα signaling was critical for cardiac hypertrophy. In this study, we show that the expression of ZAKα activated apoptosis through both a FAS‐dependent pathway and a mitochondria‐dependent pathway by subsequently inducing caspase‐3. ZAKβ, an isoform of ZAKα, is dramatically expressed during cardiac hypertrophy and apoptosis. The interaction between ZAKα and ZAKβ was demonstrated here using immunoprecipitation. The results show that ZAKβ has the ability to diminish the expression level of ZAKα. These findings reveal an inherent regulatory role of ZAKβ to antagonize ZAKα and to subsequently downregulate the cardiac hypertrophy and apoptosis induced by ZAKα.
Carotid artery stenting: Avoiding the perfect storm
Authors: Safian Robert D.
Published: November 2016

Key Points

Carotid artery stenting (CAS) and carotid artery endarterectomy (CEA) have achieved equipoise for most patients with carotid artery stenosis.

Studies of outcomes after CAS and CEA must consider important patient and anatomic characteristics.

A perfect storm for CAS is observed in a clinical scenario characterized by acute stroke, high likelihood for unstable plaque and thrombus, early revascularization, operator inexperience, and failure to use closed‐cell stents and embolic protection. Adverse outcomes in these situations are not shortcomings of CAS, but are due to poor clinical decision‐making and judgment.
STEMI with multivessel disease: An ongoing battle for the optimal treatment strategy
Authors: Farhan Serdar , Mehran Roxana
Published: November 2016

Key Points

Multivessel compared to single vessel PCI in patients with STEMI is associated with younger age and less comorbid conditions

Multivessel PCI for patients with STEMI and multivessel disease appears to be safe without increased mortality compared to infarct‐related artery only PCI.

Results from ongoing large‐scale randomized trials are under way to provide robust evidence of the ideal interventional therapy of patients with STEMI and multivessel disease.
The newly occluded ectatic vessel: Not an ecstatic time
Authors: Butman Samuel M.
Published: November 2016

Key Points

No or slow reflow is more common in patients with coronary ectasia in the setting of a STEMI

Smoking and hypertension appears to be risk factors for coronary ectasia

The why and how of coronary ectasia in atherosclerosis still eludes us
Left atrial appendage closure: Initial experience with the ultraseal device
Authors: Regueiro Ander , Bernier Mathieu , O'Hara Gilles , O'Connor Kim , Paradis Jean‐Michel , Beaudoin Jonathan , Rodriguez‐Gabella Tania , Champagne Jean , Rodés‐Cabau Josep
Published: November 2016

Objectives

We report the initial experience of percutaneous left atrial appendage (LAA) closure with the Ultraseal device.

Background

LAA closure is an alternative to oral anticoagulation for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) and high risk of bleeding. The Ultraseal device is a new LAA closure prosthesis that consists of a distal soft bulb and a proximal sail attached by an articulating joint that allows a high degree of device conformability to the different variations of the LAA anatomy.

Methods

We included 12 consecutive patients with NVAF who underwent LAA closure with the Ultraseal device between January and December 2015 in our center. Patients had clinical and transesophageal echocardiography (TEE) examinations at baseline and at 45 days following LAA closure.

Results

The device was successfully implanted in all patients, with no periprocedural complications. There were no episodes of bleeding, stroke, pericardial effusion, or device embolization at 45‐day follow‐up. No cases with residual leaks >5 mm were observed at TEE. One patient presented a device related thrombus without clinical consequences.

Conclusions

This initial experience with the Ultraseal LAA closure device demonstrates preliminary safety and feasibility. Further larger studies with longer follow‐up are warranted. © 2016 Wiley Periodicals, Inc.
Genetic and prenatal findings in two Japanese patients with Schinzel–Giedion syndrome
Authors: Hishimura Nozomi , Watari Michiko , Ohata Hiroki , Fuseya Naho , Wakiguchi Sadae , Tokutomi Tomoharu , Okuhara Kouji , Takahashi Nobuhiro , Iizuka Susumu , Yamamoto Hiroshi , Mishima Takashi , Fujieda Satoko , Kobayashi Ryoji , Cho Kazutoshi , Kuroda Yukiko , Kurosawa Kenji , Tonoki Hidefumi
Published: November 2016

Key Clinical Message

We report two Japanese patients with Schinzel–Giedion syndrome. When polyhydramnios is observed, additional fetal findings such as overlapping fingers, hydrocephalus, hydronephrosis, and very characteristic facial appearance comprising high, prominent forehead, hypertelorism, and depressed nasal root may suggest Schinzel–Giedion syndrome.
Excited‐State Intramolecular Proton‐Transfer Properties of Three Tris(N‐Salicylideneaniline)‐Based Chromophores with Extended Conjugation
Authors: Jagadesan Pradeepkumar , Whittemore Tyler , Beirl Toni , Turro Claudia , McGrier Psaras L.
Published: November 2016

The synthesis and photophysical properties of three tris(N‐salicylideneaniline) (TSA) compounds containing 1,3,5‐triarylbenzene, ‐tristyrylbenzene, and ‐tris(arylethynyl)benzene core units are reported. The TSA compounds underwent efficient excited‐state intramolecular proton transfer (ESIPT) in solution and in solid state due to the preformed C=N⋅⋅⋅H−O hydrogen‐bonded motifs of the structures. Steady‐state fluorescence emission spectra of the TSA molecules revealed dual bands only in DMSO, and large Stokes shifts in other polar aprotic and protic solvents. Femtosecond transient absorption spectroscopic measurements in THF revealed lifetime values in the range of 14–16 ps for the excited‐state keto‐tautomer. The TSA compounds are also responsive to metal ions (Cu2+ and Zn2+) in DMSO, exhibit enhanced aggregate‐induced emission (AIE) properties in DMSO/water mixtures, and are highly luminescent in the solid state.