bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognition and Clustering of Dirichlet Mixtures
Authors: Fan Wentao , Bouguila Nizar
Published: March 2015

Finite mixture models of Dirichlet distributions arise in a natural way in several applications involving proportional data. The basic model assumes that the unknown density can be written as a weighted finite sum of Dirichlet distributions, with different mixing weights and different parameters. In this article, on the one hand, we aim to present the finite Dirichlet mixture. On the other hand, we discuss two learning approaches to estimate the parameters of this mixture when dealing with the case of an unknown number of components. We also show the potential of the Dirichlet mixture through a series of experiments involving artificial data and real data that concern the challenging problem of images categorization.
Permanent‐Magnet Machines
Authors: Chau K. T.
Published: March 2015

Being fueled by continual development of permanent‐magnet (PM) materials and machine structures, PM machines are becoming attractive for a wide range of applications. In this article, the magnet‐materials that have been used for PM machines are first introduced. Then, the classification of various PM machines is discussed. Consequently, major PM machines are described, with emphasis on their machine structures and operating principles. Also, the corresponding variants due to morphological changes are discussed. Finally, a quantitative evaluation of those viable PM machines is given to identify their prospects and potential applications.
Classifier Ensemble Methods
Authors: Nanni Loris , Brahnam Sheryl , Lumini Alessandra
Published: March 2015

Multiclassifier systems, the focus of this article, provide scientists and data professionals with powerful techniques for tackling complex datasets. The basic idea behind the multiclassifier approach is to average the decisions or hypotheses of a diverse group of classifiers in order to produce a better decision or hypothesis.

As an introduction to our subject, we begin with a detailed examination of the canonic single‐classifier system, as this provides the mathematical foundation needed in our presentation of multiclassifier systems. We then describe some important methods for constructing multiclassifier systems at all the levels mentioned above: the classifier level, the combination level, the data level, and the feature level.

We thus end our overview of multiclassifier systems with a section that provides guidance for experimentally constructing general‐purpose (GP) multiclassifier systems.
Nafion
Authors: Tang Haolin , Pan Mu
Published: March 2015

Nafion is a perfluorinated sulfonic acid resin (PFSA), which was developed by the E. I. DuPont Company. Owing to its stability, superior mechanical properties, high chemical inertness, and proton conductivity, Nafion is currently used in commercial membranes and catalyst layers of fuel cells. This article overviews the structure, morphology, and mechanical and electrochemical properties of Nafion. In addition, important research as well as practical industrial applications, such as brine electrolysis, chlor‐alkali cells, salt splitting, clean power generation by Nafion polymer electrolyte fuel cells, batteries, gas separation, gas sensors, and electrodialysis, is also presented.
Heat Resistant Polymers
Authors: Mehdipour‐Ataei Shahram , Tabatabaei‐Yazdi Zahra
Published: March 2015

Over time human needs have been changing. Science and technology are responsible for providing these needs. One of these needs, especially in high‐tech technology is a polymer that can tolerate high temperatures. Progress in this field is due to meet the requirements of the aerospace industry, where heat‐resistant polymers with low weights and suitable formability and processability are needed to substitute many high weight metals.

In this article, a brief introduction covers some basic information about heat‐resistant characteristics, factors influencing it, and some well‐established analytical methods for estimating heat‐resistant features of polymeric materials. In the following sections, a number of most important commonly used heat‐resistant polymers are selected and their overall properties are reviewed particularly focusing on their heat resistance. These polymers include polyimides and their copolymers, polyamides and related copolymers, polyesters, aromatic polyethers and their derivatives, benzimidazoles, and ladder polymers. It should be noted that a number of other heat‐resistant synthetically developed or commercially successful polymers (less important) are not included in this category, which are fully described in other books and review papers.
America's water risk: Current demand and climate variability
Authors: Devineni Naresh , Lall Upmanu , Etienne Elius , Shi Daniel , Xi Chen
Published: March 2015

A new indicator of drought‐induced water stress is introduced and applied at the county level in the USA. Unlike most existing drought metrics, we directly consider current daily water demands and renewable daily water supply to estimate the potential stress. Water stress indices developed include the Normalized Deficit Cumulated to represent multiyear droughts by computing the maximum cumulative deficit between demand and supply over the study period (1949–2009) and the Normalized Deficit Index representing drought associated with maximum cumulative deficit each year. These water stress indices map directly to storage requirements needed to buffer multiyear and within‐year climate variability and can reveal the dependence on exogenous water transferred by rivers/canals to the area. Future climate change and variability can be also incorporated into this framework to inform climate‐driven drought for additional storage development and potential applications of water trading across counties.
The development of a bursty precipitation front with intense localized parallel electric fields driven by whistler waves
Authors: Drake J. F. , Agapitov O. V. , Mozer F. S.
Published: March 2015

The dynamics and structure of whistler turbulence relevant to electron acceleration in the Earth's outer radiation belt are explored with simulations and comparisons with observations. An initial state with an electron temperature anisotropy in a spatially localized domain drives whistlers which scatter electrons. An outward propagating front of whistlers and hot electrons nonlinearly evolves to form regions of intense parallel electric field with structure similar to observations. The precipitating hot electrons propagate away from the source region in intense bunches rather than as a smooth flux.
A unified approach for process‐based hydrologic modeling: 1. Modeling concept
Authors: Clark Martyn P. , Nijssen Bart , Lundquist Jessica D. , Kavetski Dmitri , Rupp David E. , Woods Ross A. , Freer Jim E. , Gutmann Ethan D. , Wood Andrew W. , Brekke Levi D. , Arnold Jeffrey R. , Gochis David J. , Rasmussen Roy M.
Published: March 2015

This work advances a unified approach to process‐based hydrologic modeling to enable controlled and systematic evaluation of multiple model representations (hypotheses) of hydrologic processes and scaling behavior. Our approach, which we term the Structure for Unifying Multiple Modeling Alternatives (SUMMA), formulates a general set of conservation equations, providing the flexibility to experiment with different spatial representations, different flux parameterizations, different model parameter values, and different time stepping schemes. In this paper, we introduce the general approach used in SUMMA, detailing the spatial organization and model simplifications, and how different representations of multiple physical processes can be combined within a single modeling framework. We discuss how SUMMA can be used to systematically pursue the method of multiple working hypotheses in hydrology. In particular, we discuss how SUMMA can help tackle major hydrologic modeling challenges, including defining the appropriate complexity of a model, selecting among competing flux parameterizations, representing spatial variability across a hierarchy of scales, identifying potential improvements in computational efficiency and numerical accuracy as part of the numerical solver, and improving understanding of the various sources of model uncertainty.
Transfer
RNA
Synthetase Editing of Errors in Amino Acid Selection
Authors: Jakubowski Hieronim
Published: March 2015

Aminoacyl‐tRNA synthetases (AARSs) define genetic code by pairing amino acids with their cognate tRNAs and maintain ‘quality control’ in the flow of information from gene to protein. Binding energies of amino acids to AARSs are often inadequate to assure the required accuracy of translation. This has necessitated the evolution of a second determinant of specificity, proofreading or editing mechanisms that remove amino acid selection errors, thereby maintaining accuracy and preventing access to the genetic code of non‐protein amino acids, including homocysteine, ornithine, homoserine and norvaline. Editing is part of the tRNA aminoacylation process in living organisms from bacteria to humans. Impaired amino acid editing reduces cell proliferation under stress conditions and can lead to disease. Despite a strong selective pressure to minimise mistranslation, some organisms possess error‐prone AARSs that cause mistranslation, which can be beneficial for pathogens by increasing their phenotypic variation essential for the evasion of host defences.

Key Concepts

Aminoacyl‐tRNA synthetases match tRNAs with corresponding amino acids, thereby translating genetic information from the nucleic acid to the protein language.

Faithful translation of the genetic information depends on editing of amino acid misactivation errors.

Editing occurs at the synthetic active site by hydrolysis of aminoacyl‐adenylates (
pre‐transfer
editing) and/or at a separate editing site by deacylation of aminoacyl‐tRNA (
post‐transfer
editing).

Access of the non‐protein amino acids, such as homocysteine, ornithine or norvaline to the genetic code is prevented by editing.

Preventing mistranslation by editing of misactivated amino acids is crucial to cellular homeostasis.

Impaired editing increases sensitivity of cells to oxidative stress and nutritional imbalance.

Some pathogenic organisms possess editing‐defective, error‐prone AARSs that cause mistranslation, which is essential for the evasion of host defences.

Synthetic biology targets AARSs to engineer new proteins containing non‐canonical amino acids (alloproteins).
F
lemming,
W
alther
Authors: Dröscher Ariane
Published: March 2015

Walther Flemming (1843–1906) – German histologist who made numerous important cytological discoveries. In particular, in the 1870s, he clarified the stages of karyokinesis, observed the regular distribution of the individual chromosomes and their longitudinal split during this process, coined the terms ‘chromatin’, ‘equatorial plate’ and ‘mitosis’, and pronounced the aphorism ‘
omnis nucleus e nucleo
’ (all nuclei derive from predecessor nuclei). In 1887, he was one of the first to describe meiosis, and in 1885, he detailed the breaking down of the nucleus during the process of cell death. Flemming was an excellent microscopist who, among other technical devices, developed a mixture of chromic anhydride, osmium tetroxide and acetic acid, still known as Flemming's fluid.
Ketone Bodies
Authors: Morio Beatrice , Wolfe Robert R
Published: March 2015

Ketone bodies are water‐soluble equivalents of fatty acids. They can substitute for glucose in peripheral tissues, especially in the brain, when glucose becomes limited in physiological and pathological states. Recent findings demonstrate that they also act as signalling metabolites, thus participating in the organism adaptation to the environment, such as during fasting, calorie restriction or prolonged exercise. Diabetes is the most common pathological cause of elevated blood ketone bodies. Ketone bodies are produced in excess in response to low insulin levels and high levels of counterregulatory hormones, the result being the development of metabolic acidosis that is associated with serious health complications. Yet, ketogenic diets have been used for decades to increase ketone body synthesis for their neuroprotective properties as central signalling metabolites and as main energy‐providing substrate for the brain, in epilepsy and neurodegenerative diseases.

Key Concepts

Ketone bodies are key energy substrates and signalling molecules

Ketone bodies participate in energy homeostasis

Diabetic ketoacidosis is the most common pathological cause of elevated blood ketone bodies and is associated with serious health complications

Ketone bodies are neuroprotective

Ketone bodies offer promising perspectives in clinical therapy for certain metabolic diseases, neurodegenerative diseases and cancers
Telomere
Authors: Raffa Grazia D , Cenci Giovanni
Published: March 2015

Telomeres are specialised structures that protect chromosome ends from degradation and fusion events. In most eukaryotes, including yeast and mammals, telomeric DNA consists of short, repetitive G‐rich sequences, which end with 3′ G‐rich overhangs and are elongated by the specialised reverse transcriptase telomerase. Telomeric repeats are bound by several DNA‐binding proteins, which regulate telomerase activity and protect (cap) chromosome ends from degradation and inappropriate DNA repair. If uncapped, telomeres are sensed as DNA breaks and undergo unwanted DNA repair, which can eventually lead to the activation of cell cycle checkpoints and/or to end‐to‐end fusion. The dicentric chromosomes generated by telomeric fusion can cause non‐disjunction and chromosome breakage during anaphase. These events result in loss of genetic material and chromosome rearrangements that in mammals might lead to several diseases including cancer. Thus, it has become evident that telomeres play critical roles in the maintenance of genome stability.

Key Concepts

Telomeres are required for chromosome end maintenance and genome stability.

Telomeres are special chromatin architectures found at the end of linear chromosomes

Telomeres protects chromosome ends from degradation and fusion events

Telomeric DNA consists of tandem repeats that are bound by several DNA-binding proteins

Critically short telomeres become dysfunctional and eventually lead to chromosome fusions and cell death
DNA
Demethylation
Authors: Wade Paul A
Published: March 2015

Steady‐state levels of deoxyribonucleic acid (DNA) methylation result from a balance of two opposing biological forces: deposition of methyl groups by DNA methyltransferases and their removal by DNA demethylases. The removal of methyl groups from cytosine residues in DNA is an essential biological process that occurs at multiple points during development, differentiation and adult life in both plants and mammals. Demethylation can occur through passive dilution or through active enzymatic processes. Much progress has been made in recent years in the identification of enzymes responsible for active demethylation events. Higher plants have 5‐methylcytosine glycosylases that excise methylated cytosine. Mammals appear to rely on modification of 5‐methylcytosine through deamination or oxidation reactions that predispose the resulting base to repair pathways that result in replacement of 5‐methylcytosine with cytosine. The candidate demethylase enzymes in mammals are subject to translocation and inhibition in cancer, underscoring the biological importance of this process.

Key Concepts

Cytosine methylation is essential for mammalian life; demethylation of 5‐methylcytosine is likely to also be essential.

Demethylation of 5‐methylcytosine could occur through either a passive mechanism involving dilution through rounds of DNA replication or through an active, enzyme‐catalysed process.

Deamination of 5‐methylcytosine by APOBEC family enzymes in the context of DNA results in creation of thymine and a G:T mismatch, a substrate for conventional DNA repair machinery.

TET family enzymes progressively oxidise cytosine residues in DNA to forms that are recognised and excised by well‐characterised DNA glycosylases.

Enzymes identified as candidates in DNA demethylation are frequently mutated or translocated in cancer, suggesting that their precise spatial and temporal regulation is critical to mammalian cells.
Molecular Genetics of Gallbladder Cancer
Authors: Espinoza Jaime A , García Patricia , Bizama Carolina , Roa Juan C
Published: March 2015

Gallbladder cancer (GBC) is a deadly biliary neoplasia with marked ethnic and geographical distribution. The prognosis of GBC is often dismal due to late diagnosis and lack of effective therapeutic options. The main risk factor for GBC is gallstone carriage over long periods of time, which leads to persistent damage and chronic inflammation. This condition promotes genetic/epigenetic alterations and the progressive impairment of the epithelial architecture, mainly through a metaplasia–dysplasia–carcinoma sequence. New molecular alterations have been identified that may help improve the clinical management of patients through the application of more specific therapies. The application of new DNA sequencing technologies is making it possible to catalogue the spectrum of genetic alterations that characterise GBC and is aiding in the understanding of the biology behind gallbladder carcinogenesis. Here, a stepwise model of morphogenetic progression from inflammatory to neoplastic tissues is proposed based on currently available evidence.

Key Concepts

Gallbladder cancer is essentially an inflammatory disease, primarily caused by chronic exposure of the epithelium to gallstones.

Morphological alterations of the epithelium arise mainly through a metaplasia–dysplasia–carcinoma sequence.

Inactivation of tumour suppressor pathway is an early and important carcinogenic event for gallbladder cancer.

Genome‐level alterations such as loss of heterozygosity, microsatellite instability and epigenetic alterations arise early during gallbladder carcinogenesis and increase progressively to advanced stages.

Prevention of chronic inflammation may reduce the onset of early genetic alterations and therefore contribute to reducing gallbladder cancer mortality.

A future challenge is to elucidate molecular subtypes of GBC and identify new potential therapeutic targets in order to improve patient survival.
A Review of Tools, Practices, and Approaches for Sustainable Supply Chain Management
Authors: Reefke Hendrik , Lo Jason
Published: March 2015

Purpose—Sustainable supply chain management has become a continuing stream of research with increased interest especially from the year 2005 onwards. The purpose of this article is to conduct a literature review of academic publications on relevant tools, methods, and practices that can be instrumental in the creation of sustainable supply chains.

Design/Methodology—A systematic and reproducible literature review was conducted in order to identify, evaluate, and interpret the existing body of knowledge on sustainable supply chain management. The review process comprised material collection, descriptive analysis, categorisation, and interpretation.

Findings/Implications—A content analysis of approaches for sustainable supply chain management is presented. The review is structured along categories that relate directly to well‐established key issues in supply chain management. This process provides tangibility to the review insights as they are enfolded against familiar aspects of supply chains. The findings can guide scholars in the field and their understanding thereof.

Originality/Value—With the rapid expansion of theoretical contributions and practical developments with regard to sustainable supply chain management, this article offers a needed reference point. It informs researchers of the state of knowledge, guides potential avenues for future research, and may influence practitioners in their selection of approaches that are applicable to their specific requirements.
Radiographic Progression of Patients With Psoriatic Arthritis Who Achieve Minimal Disease Activity in Response to Golimumab Therapy: Results Through 5 Years of a Randomized, Placebo‐Controlled Study
Authors: Kavanaugh Arthur , van der Heijde Désirée , Beutler Anna , Gladman Dafna , Mease Philip , Krueger Gerald G. , McInnes Iain B. , Helliwell Philip , Coates Laura C. , Xu Stephen
Published: March 2015

Objective

To evaluate long‐term outcomes in psoriatic arthritis (PsA) patients who achieved or did not achieve minimal disease activity (MDA) through 5 years of golimumab treatment in the GO‐REVEAL trial.

Methods

The GO‐REVEAL trial was a phase III, randomized, double‐blind trial with placebo‐control through week 24 followed by an open‐label extension of golimumab 50/100 mg treatment up to 5 years. In these post‐hoc analyses, MDA was defined by the presence of ≥5 of 7 PsA outcome measures (≤1 swollen joint, ≤1 tender joint, Psoriasis Area and Severity Index [PASI] ≤1, patient pain score ≤15, patient global disease activity score ≤20 [range 0–100], Health Assessment Questionnaire disability index [HAQ DI] ≤0.5, and ≤1 tender enthesis point).

Results

Treatment with golimumab yielded significantly higher MDA response rates versus patients randomized to placebo at week 14 (23.5% versus 1.0%; P < 0.0001), week 24 (28.1% versus 7.7%; P < 0.0001), and week 52 (42.4% versus 30.2%; P = 0.037). MDA was achieved at least once by ∼50% of golimumab‐treated patients overall. Irrespective of treatment randomization, achievement of MDA at ≥3 and ≥4 consecutive visits was associated with significantly less radiographic progression and more improvement in MDA components allowing specific assessment of physical function (HAQ DI) and overall disease activity (patient global assessment of disease activity) at week 256 versus patients not achieving MDA. Logistic regression analyses indicated that a 1‐unit higher baseline HAQ DI score yielded a significantly lower likelihood of achieving MDA at ≥3 (odds ratio 0.514 [95% confidence interval 0.321–0.824]; P = 0.006) and ≥4 (odds ratio 0.480 [95% confidence interval 0.290–0.795]; P = 0.004) consecutive visits.

Conclusion

Among golimumab‐treated PsA patients, better long‐term functional improvement, patient global assessment, and radiographic outcomes were observed when patients achieved persistent MDA.
Childhood Physical Performance Measures and Adulthood Knee Cartilage Volume and Bone Area: A 25‐Year Cohort Study
Authors: Antony Benny , Jones Graeme , Venn Alison , Cicuttini Flavia , March Lyn , Blizzard Leigh , Dwyer Terence , Cross Marita , Ding Changhai
Published: March 2015

Objective

We aimed to determine the associations between childhood physical performance measures and tibial cartilage volume and tibial bone area in adults 25 years later.

Methods

Participants (n = 330, ages 31–41 years, female 47%) were selected from the Australian Schools Health and Fitness Survey of 1985. The participants underwent T1‐weighted fat‐suppressed magnetic resonance imaging (MRI) of their knees. Tibial bone area and cartilage volume were measured from MRI. Childhood measures, including physical work capacity at 170 beats per minute (PWC170), leg strength, number of sit‐ups, long‐run, and short‐run were measured in 1985. PWC170 and leg strength measures were repeated after 20 years in their adulthood. Linear regression analysis was used to determine the association of performance measures with cartilage volume.

Results

There were consistent positive associations of all childhood measures, including PWC170 (β = 0.38 cm2 per 10 watts, 95% confidence interval [95% CI] 0.15, 0.60), leg strength, long‐run, short‐run, and sit‐ups with adult medial and total tibial bone area. Similarly, there was an association of PWC170 and sit‐ups with adult medial tibial cartilage volume. After further adjustment for tibial bone area, the association between PWC170 and medial and total (β = 0.08 cm3 per 10 watts, 95% CI 0.02, 0.10) tibial cartilage volume decreased in magnitude but remained significant.

Conclusion

Childhood physical performance measures, especially PWC170, were associated with knee tibial bone area and cartilage volume in adulthood. The associations with cartilage volume appeared to be partially mediated by bone area. This suggests physical performance measures in childhood can independently influence adult knee structures.
Magnetic Resonance Imaging–Assessed Vastus Medialis Muscle Fat Content and Risk for Knee Osteoarthritis Progression: Relevance From a Clinical Trial
Authors: Raynauld Jean‐Pierre , Pelletier Jean‐Pierre , Roubille Camille , Dorais Marc , Abram François , Li Wei , Wang Yuanyuan , Fairley Jessica , Cicuttini Flavia M. , Martel‐Pelletier Johanne
Published: March 2015

Objective

Studies have proposed vastus medialis (VM) muscle cross‐sectional area change as a variable associated with cartilage volume loss in knee osteoarthritis (OA). However, the VM also includes fat (%Fat), which may influence knee function. This study analyzed the VM area and %Fat data, separately and in combination, to predict symptoms, cartilage volume loss, and bone marrow lesion (BML) change in knee OA.

Methods

This study included the according‐to‐protocol population (n = 143) of a 2‐year knee OA randomized clinical trial having magnetic resonance imaging at baseline and 2 years. Correlations used multivariate analyses.

Results

Greater baseline value for VM area and %Fat were significantly associated with sex (male, area; female, %Fat), higher body mass index (BMI), and Western Ontario and McMaster Universities Osteoarthritis Index stiffness, function, and total scores (better, high area; worse, high %Fat). Moreover, a VM %Fat increase of 1% at 2 years was associated with worsening of cartilage volume loss in the global knee (P = 0.015) and some subregions (P ≤ 0.030), and with an increment of BML global score change (P < 0.001). A 1% decrease in VM area at 2 years was associated with worsening of knee pain score (P = 0.048). Importantly, the concurrent presence of low VM area, high VM %Fat, and high BMI identified a subgroup of patients with greater cartilage volume loss in the medial femur (P = 0.028) than the rest of the cohort.

Conclusion

These data demonstrated, for the first time, that VM fat content is a strong predictor of cartilage volume loss and the occurrence and progression of BML. Importantly, the combined data of VM area, VM %Fat, and BMI identified patients at higher risk for OA progression.
The Relationship between Structural and Electrical Characteristics in Perylenecarboxydiimide‐Based Nanoarchitectures
Authors: Musumeci Chiara , Salzmann Ingo , Bonacchi Sara , Röthel Christian , Duhm Steffen , Koch Norbert , Samorì Paolo
Published: March 2015

The controlled assembly of the prototypical n‐type organic semiconductor N,N′‐1H,1H‐perfluorobutyl dicyanoperylenecarboxydiimide (PDIF‐CN2) into ordered nanoarchitectures and the multiscale analysis of the correlation between their structural and their electrical properties is reported. By making use of the Langmuir–Blodgett (LB) technique, monolayers of PDIF‐CN2 arranged in upright standing molecular packing on different substrates are formed. Postdeposition thermal treatment makes it possible to trigger a reorganization into layered ultrathin crystalline nanostructures, exhibiting structural and photophysical properties similar to those of microscopic crystals obtained by solvent‐induced precipitation. The controlled engineering of these molecular architectures on surfaces enables us to identify both a dependence of the monolayer resistance on the molecular tilt angle in vertical junctions and a pronounced charge‐transport anisotropy with enhanced transport along the π–π stacking direction of the PDI core. While a charge carrier mobility for electrons as high as 10–2 cm2 V–1 s–1 is determined in monolayer field‐effect transistors for the in‐plane direction, being the highest yet reported value for a n‐type LB monolayer, the out‐of‐plane mobility measured by conductive atomic force microscopy in multilayered structures is found to be one order of magnitude lower.
Self‐Repairable, High Permittivity Dielectric Elastomers with Large Actuation Strains at Low Electric Fields
Authors: Dünki Simon J. , Ko Yee Song , Nüesch Frank A. , Opris Dorina M.
Published: March 2015

A one‐step process for the synthesis of elastomers with high permittivity, excellent mechanical properties and increased electromechanical sensitivity is presented. It starts from a high molecular weight polymethylvinylsiloxane, P1, whose vinyl groups serve two functions: the introduction of polar nitrile moieties by reacting P1 with 3‐mercaptopropionitrile (1) and the introduction of cross‐links to fine tune mechanical properties by reacting P1 with 2,2′‐(ethylenedioxy)diethanethiol (2). This twofold chemical modification furnished a material, C2, with a powerful combination of properties: permittivity of up to 10.1 at 104 Hz, elastic modulus Y10% = 154 kPa, and strain at break of 260%. Actuators made of C2 show lateral actuation strains of 20.5% at an electric field as low as 10.8 V μm–1. Additionally, such actuators can self‐repair after a breakdown, which is essential for an improved device lifetime and an attractive reliability. The actuators can be operated repeatedly and reversibly at voltages below the first breakdown. Due to the low actuation voltage and the large actuation strain applications of this material in commercial products might become reality.
A Novel Bioinspired Switchable Adhesive with Three Distinct Adhesive States
Authors: Isla Paula Yagüe , Kroner Elmar
Published: March 2015

A novel switchable adhesive, inspired by the gecko's fibrillar dry attachment system, is introduced. It consists of a patterned surface with an array of mushroom‐shaped pillars having two distinct heights. The different pillar heights allow control of the pull‐off force in two steps by application of a low and a high preload. For low preload, only the long pillars form contact, resulting in a low pull‐off force. At higher preload, all pillars form contact, resulting in high pull‐off force. Even further loading leads to buckling induced detachment of the pillars which corresponds to extremely low pull‐off force. To achieve the respective samples a new fabrication method called double inking is developed, to achieve multiple‐height pillar structures. The adhesion performance of the two‐step switchable adhesive is analysed at varying preload and for different pillar aspect ratios and height relations. Finally, the deformation behavior of the samples is investigated by in situ monitoring.
Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine
Authors: Hinderer Svenja , Brauchle Eva , Schenke‐Layland Katja
Published: March 2015

Current clinically applicable tissue and organ replacement therapies are limited in the field of cardiovascular regenerative medicine. The available options do not regenerate damaged tissues and organs, and, in the majority of the cases, show insufficient restoration of tissue function. To date, anticoagulant drug‐free heart valve replacements or growing valves for pediatric patients, hemocompatible and thrombus‐free vascular substitutes that are smaller than 6 mm, and stem cell‐recruiting delivery systems that induce myocardial regeneration are still only visions of researchers and medical professionals worldwide and far from being the standard of clinical treatment. The design of functional off‐the‐shelf biomaterials as well as automatable and up‐scalable biomaterial processing methods are the focus of current research endeavors and of great interest for fields of tissue engineering and regenerative medicine. Here, various approaches that aim to overcome the current limitations are reviewed, focusing on biomaterials design and generation methods for myocardium, heart valves, and blood vessels. Furthermore, novel contact‐ and marker‐free biomaterial and extracellular matrix assessment methods are highlighted.
Anderson transition for Google matrix eigenstates
Authors: Zhirov O. V. , Shepelyansky D. L.
Published: March 2015

We introduce a number of random matrix models describing the Google matrix G of directed networks. The properties of their spectra and eigenstates are analyzed by numerical matrix diagonalization. We show that for certain models it is possible to have an algebraic decay of PageRank vector with the exponent similar to real directed networks. At the same time the spectrum has no spectral gap and a broad distribution of eigenvalues in the complex plain. The eigenstates of G are characterized by the Anderson transition from localized to delocalized states and a mobility edge curve in the complex plane of eigenvalues.

image
Synthesis, characterization, and in vitro drug release study of 3‐arm poly‐β‐alanine
Authors: Kumar Krishna , Adhikary Pubali , Tungala Kranthikumar , Azmeera Venkanna , Krishnamoorthi S.
Published: March 2015

Synthesis of three arms star‐shaped poly‐β‐alanine (3‐b‐ala) based on tri(prop‐2‐yn‐1‐yl) benzene‐1,3,5‐tricarboxylate (TBT) and azido terminated poly‐β‐alanine (N3‐P‐ala) was performed using click reaction. TBT was synthesized by nucleophilic substitution reaction between propargyl alcohol and 1,3,5‐benzenetricarbonyltrichloride. For the first time, N3‐P‐ala was synthesized through anionic polymerization of acrylamide using sodium azide as an initiator. TBT was characterized by FT‐IR and 1HNMR. N3‐p‐ala was characterized by FT‐IR, GPC, and 1HNMR and 3‐b‐ala was characterized by FT‐IR, GPC, 1HNMR, TGA, and XRD. The synthesized 3‐b‐ala was used for drug loading and releasing studies. Polymer loaded drug (3‐b‐ala‐D) hybrid was used in in vitro studies of drug (Diclofenac sodium) release in phosphate buffer solution (PBS) at 37 ± 0.5°C and pH 7.4. The drug loading and releasing studies were analyzed by UV‐visible spectrophotometer. 3‐b‐ala‐D was examined by AFM to analyze the surface morphology and roughness. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42124.
Interdisciplinary archaeological prospection, excavation and 3D documentation exemplified through the investigation of a burial at the Iron Age settlement site of Uppåkra in Sweden
Authors: Larsson Lars , Trinks Immo , Söderberg Bengt , Gabler Manuel , Dell'unto Nicolo , Neubauer Wolfgang , Ahlström Torbjörn
Published: March 2015

This paper presents the archaeological prospection, excavation and digital three‐dimensional documentation of a previously unknown neolithic grave, presumably late neolithic, at the outstanding Iron Age site of Uppåkra in southern Sweden, and exemplifies a multidisciplinary approach to modern archaeological fieldwork. In the framework of a large‐scale archaeological prospection pilot study conducted at the archaeological site of Uppåkra using remote sensing and large‐scale near‐surface geophysical prospection methods a peculiar circular structure was discovered and mapped using both manual and motorized high‐resolution ground‐penetrating radar (GPR) measurements. The structure, consisting of a ring ditch of ca. 10 m diameter, encloses an east–west oriented strongly reflecting rectangular body in the centre, which therefore was interpreted as being caused by the buried remains of a prehistoric barrow. Subsequent archaeological excavation was conducted across this structure in order to determine the exact cause of the GPR anomaly. This excavation resulted in detailed confirmation of the archaeological prospection results as well as in the discovery of dateable finds. The excavation was documented using the latest image‐based three‐dimensional modelling techniques. Copyright © 2015 John Wiley & Sons, Ltd.
Disease Activity in Rheumatoid Arthritis and the Risk of Cardiovascular Events
Authors: Solomon D. H. , Reed G. W. , Kremer J. M. , Curtis J. R. , Farkouh M. E. , Harrold L. R. , Hochberg M. C. , Tsao P. , Greenberg J. D.
Published: March 2015

Objective

Use of several immunomodulatory agents has been associated with reduced numbers of cardiovascular (CV) events in epidemiologic studies of rheumatoid arthritis (RA). However, it is unknown whether time‐averaged disease activity in RA correlates with CV events.

Methods

We studied patients with RA whose cases were followed in a longitudinal US‐based registry. Time‐averaged disease activity was assessed during followup using the area under the curve of the Clinical Disease Activity Index (CDAI), a validated measure of RA disease activity. Age, sex, presence of diabetes mellitus, hypertension, or hyperlipidemia, body mass index, family history of myocardial infarction (MI), use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), presence of CV disease, and baseline use of an immunomodulator were assessed at baseline. Cox proportional hazards regression models were examined to determine the risk of a composite CV end point that included MI, stroke, and death from CV causes.

Results

A total of 24,989 patients who had been followed up for a median of 2.7 years were included in these analyses. During followup, we observed 534 confirmed CV end points, for an incidence rate of 7.8 per 1,000 person‐years (95% confidence interval [95% CI] 6.7–8.9). In models adjusted for variables noted above, a 10‐point reduction in the time‐averaged CDAI was associated with a 21% reduction in CV risk (95% CI 13–29). These results were robust in subgroup analyses stratified by the presence of CV disease, use of corticosteroids, use of NSAIDs or selective cyclooxygenase 2 inhibitors, and change in RA treatment, as well as when restricted to events adjudicated as definite or probable.

Conclusion

Our findings showed that reduced time‐averaged disease activity in RA is associated with fewer CV events.
Outcomes of Nonsevere Relapses in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis Treated With Glucocorticoids
Authors: Miloslavsky E. M. , Specks U. , Merkel P. A. , Seo P. , Spiera R. , Langford C. A. , Hoffman G. S. , Kallenberg C. G. M. , St.Clair E. W. , Tchao N. K. , Ding L. , Iklé D. , Villareal M. , Lim N. , Brunetta P. , Fervenza F. C. , Monach P. A. , Stone J. H. ,   for the Rituximab in ANCA‐Associated Vasculitis–Immune Tolerance Network Research Group
Published: March 2015

Objective

Nonsevere relapses are more common than severe relapses in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), but their clinical course and treatment outcomes remain largely unexamined. We undertook this study to analyze the outcomes of patients with nonsevere relapses in the Rituximab in ANCA‐Associated Vasculitis (RAVE) trial who were treated with prednisone according to a prespecified protocol.

Methods

RAVE was a randomized, double‐blind, placebo‐controlled trial comparing rituximab (RTX) to cyclophosphamide (CYC) followed by azathioprine (AZA) for induction of remission. Patients who experienced nonsevere relapses between months 1 and 18 were treated with a prednisone increase without a concomitant change in their nonglucocorticoid immunosuppressants, followed by a taper.

Results

Forty‐four patients with a first nonsevere relapse were analyzed. In comparison to the 71 patients who maintained relapse‐free remission over 18 months, these patients were more likely to have proteinase 3–ANCAs, diagnoses of granulomatosis with polyangiitis (Wegener's), and a history of relapsing disease at baseline. A prednisone increase led to remission in 35 patients (80%). However, only 13 patients (30%) were able to maintain second remissions through the followup period (mean 12.5 months); 31 patients (70%) had a second disease relapse, 14 of them with severe disease. The mean time to second relapse was 9.4 months (4.7 months in the group treated with RTX versus 13.7 months in the group treated with CYC/AZA; P < 0.01). Patients who experienced nonsevere relapses received more glucocorticoids than those who maintained remission (6.7 grams versus 3.8 grams; P < 0.01).

Conclusion

Treatment of nonsevere relapses in AAV with an increase in glucocorticoids is effective in restoring temporary remission in the majority of patients, but recurrent relapses within a relatively short interval remain common. Alternative treatment approaches are needed for this important subset of patients.
Brief Report: Main Contribution of DRB1*04:05 Among the Shared Epitope Alleles and Involvement of DRB1 Amino Acid Position 57 in Association With Joint Destruction in Anti–Citrullinated Protein Antibody–Positive Rheumatoid Arthritis
Authors: Terao Chikashi , Yano Koichiro , Ikari Katsunori , Furu Moritoshi , Yamakawa Noriyuki , Yoshida Shinji , Hashimoto Motomu , Ito Hiromu , Fujii Takao , Ohmura Koichiro , Yurugi Kimiko , Miura Yasuo , Maekawa Taira , Taniguchi Atsuo , Momohara Shigeki , Yamanaka Hisashi , Mimori Tsuneyo , Matsuda Fumihiko
Published: March 2015

Objective

The shared epitope is associated with increased joint destruction in rheumatoid arthritis (RA) as well as susceptibility to RA and the production of anti–citrullinated protein antibody (ACPA). However, previous studies addressing whether the association of the shared epitope with joint destruction is independent of ACPA have shown different results in different populations. Different allele distributions in the shared epitope may explain this ethnic heterogeneity. This study was undertaken to assess the associations of the shared epitope and HLA–DRB1*04:05, the most common shared epitope allele in the Japanese population, with joint destruction in patients with ACPA‐positive RA.

Methods

A total of 861 patients with ACPA‐positive RA who had not received any biologic agents were recruited from the institute of Rheumatology, Rheumatoid Arthritis cohort (sets 1 and 2) and the Kyoto University Rheumatoid Arthritis Management Alliance cohort (set 3). Joint destruction was assessed using the modified Sharp/van der Heijde score (SHS). The associations of the shared epitope alleles, HLA–DRB1*04:05, and other shared epitope allele groups with the SHS were analyzed in a linear regression analysis. Amino acid variations associated with the SHS were also analyzed.

Results

The shared epitope was significantly associated with an increased SHS (P = 0.0017). Although HLA–DRB1*04:05 was significantly associated with an increased SHS (P = 2.7 × 10−5), the group of other shared epitope alleles, including HLA–DRB1*01:01, did not show an association with the SHS in spite of sufficient power (P = 0.67). HLA–DRB1*04:05 was associated with joint destruction in a dose‐dependent manner. Analyses of amino acid associations of HLA–DRB1 revealed that serine at position 57, recently shown to have a susceptibility effect for ACPA‐positive RA in Asian populations, showed a significant association (P = 5.0 × 10−6).

Conclusion

HLA–DRB1*04:05, characterized by serine at position 57, accounts for the detrimental association between the shared epitope and SHS in Japanese patients with ACPA‐positive RA.
Brief Report: IFIH1 Mutation Causes Systemic Lupus Erythematosus With Selective IgA Deficiency
Authors: Van Eyck Lien , De Somer Lien , Pombal Diana , Bornschein Simon , Frans Glynis , Humblet‐Baron Stéphanie , Moens Leen , de Zegher Francis , Bossuyt Xavier , Wouters Carine , Liston Adrian
Published: March 2015

Objective

To identify the underlying genetic defect in a 16‐year‐old girl with severe early‐onset and refractory systemic lupus erythematosus (SLE), IgA deficiency, and mild lower limb spasticity without neuroradiologic manifestations.

Methods

Whole‐exome sequencing and extensive immunologic analysis were performed on samples from the index patient.

Results

We identified a de novo p.R779H IFIH1 gain‐of‐function mutation in a patient with severe early‐onset SLE, selective IgA deficiency, and mild lower limb spasticity. The same mutation in IFIH1 was recently identified in patients with Aicardi‐Goutières syndrome, a rare neuroimmunologic disorder associated with elevated levels of type I interferon (IFN). IFN induced with helicase C domain 1 functions as an intracellular innate immune receptor that senses viral nucleic acids and leads to the induction of type I IFN and proinflammatory cytokines. Despite systemic immunosuppressive treatment, disease activity persisted in the patient and was associated with elevated serum levels of IFNα and up‐regulation of IFIH1 itself.

Conclusion

This finding adds a new genetic causation for Mendelian lupus and greatly extends the disease spectrum associated with mutations in IFIH1 (ranging from inflammatory encephalopathy to prototypic systemic autoimmune disease). This marked phenotypic heterogeneity, despite an identical mutation, demonstrates the importance of modifying factors in type I IFN–dependent pathologies caused by mutations in IFIH1.
Rosuvastatin‐Induced Carotid Plaque Regression in Patients With Inflammatory Joint Diseases: The Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases Study
Authors: Rollefstad S. , Ikdahl E. , Hisdal J. , Olsen I. C. , Holme I. , Hammer H. B. , Smerud K. T. , Kitas G. D. , Pedersen T. R. , Kvien T. K. , Semb A. G.
Published: March 2015

Objective

Patients with rheumatoid arthritis (RA) and carotid artery plaques have an increased risk of acute coronary syndromes. Statin treatment with the goal of achieving a low‐density lipoprotein (LDL) cholesterol level of ≤1.8 mmoles/liter (≤70 mg/dl) is recommended for individuals in the general population who have carotid plaques. The aim of the ROsuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases (RORA‐AS) study was to evaluate the effect of 18 months of intensive lipid‐lowering treatment with rosuvastatin with regard to change in carotid plaque height.

Methods

Eighty‐six patients (60.5% of whom were female) with carotid plaques and inflammatory joint disease (55 with RA, 21 with AS, and 10 with psoriatic arthritis) were treated with rosuvastatin to obtain the LDL cholesterol goal. Carotid plaque height was evaluated by B‐mode ultrasonography.

Results

The mean ± SD age of the patients was 60.8 ± 8.5 years, and the median compliance with rosuvastatin treatment was 97.9% (interquartile range [IQR] 96.0–99.4). At baseline, the median number and height of the carotid plaques were 1.0 (range 1–8) and 1.80 mm (IQR 1.60–2.10), respectively. The mean ± SD change in carotid plaque height after 18 months of treatment with rosuvastatin was −0.19 ± 0.35 mm (P < 0.0001). The mean ± SD baseline LDL cholesterol level was 4.0 ± 0.9 mmoles/liter (154.7 ± 34.8 mg/dl), and the mean reduction in the LDL cholesterol level was −2.3 mmoles/liter (95% confidence interval [95% CI] −2.48, −2.15) (−88.9 mg/dl [95% CI −95.9, −83.1]). The mean ± SD LDL cholesterol level during the 18 months of rosuvastatin treatment was 1.7 ± 0.4 mmoles/liter (area under the curve). After adjustment for age/sex/blood pressure, no linear relationship between a reduction in carotid plaque height and the level of LDL cholesterol exposure during the study period was observed. Attainment of the LDL cholesterol goal of ≤1.8 mmoles/liter (≤70 mg/dl) or the amount of change in the LDL cholesterol level during the study period did not influence the degree of carotid plaque height reduction.

Conclusion

Intensive lipid‐lowering treatment with rosuvastatin induced atherosclerotic regression and reduced the LDL cholesterol level significantly in patients with inflammatory joint disease.