bluuebunny/crossref_metadata_2025 huggingface dataset:
Out in the Mediation Field, and on the Mediation Carpet
Authors: Creo Robert A.
Published: October 2015

Editor's note: Longtime Alternatives columnist Bob Creo, a veteran Pittsburgh neutral, is revisiting his classic CPR Institute website columns of a decade ago in a Back to Basics Series that he has subtitled “Human Problems, Human Solutions.” These updated and expanded columns, in print for the first time, began late last year. He has revisited and re‐examined mediation‐room techniques and practice issues. This month, he returns to the first column he wrote at www.cpradr.org a decade ago, and brings it forward.
Controlling Electrical Conductance through a π‐Conjugated Cruciform Molecule by Selective Anchoring to Gold Electrodes
Authors: Huang Cancan , Chen Songjie , Baruël Ørnsø Kristian , Reber David , Baghernejad Masoud , Fu Yongchun , Wandlowski Thomas , Decurtins Silvio , Hong Wenjing , Thygesen Kristian Sommer , Liu Shi‐Xia
Published: October 2015

Tuning charge transport at the single‐molecule level plays a crucial role in the construction of molecular electronic devices. Introduced herein is a promising and operationally simple approach to tune two distinct charge‐transport pathways through a cruciform molecule. Upon in situ cleavage of triisopropylsilyl groups, complete conversion from one junction type to another is achieved with a conductance increase by more than one order of magnitude, and it is consistent with predictions from ab initio transport calculations. Although molecules are well known to conduct through different orbitals (either HOMO or LUMO), the present study represents the first experimental realization of switching between HOMO‐ and LUMO‐dominated transport within the same molecule.
Electrospun poly(vinyl alcohol) composite nanofibers with halloysite nanotubes for the sustained release of sodiumd‐pantothenate
Authors: Lee Il Woo , Li Jinglei , Chen Xiguang , Park Hyun Jin
Published: October 2015

Poly(vinyl alcohol) (PVA) nanofibers containing halloysite nanotubes (HNTs) loaded with sodiumd‐pantothenate (SDP) were successfully fabricated via simple blend‐electrospinning. SDP was efficiently loaded into the innate HNT lumen with an SDP/HNT mass ratio of 1.5:1 via vacuum treatment. The SDP‐loaded HNT‐inclusion complex was evaluated with drug‐loading efficiency testing, Fourier transform infrared (FTIR) spectroscopy, and X‐ray diffraction. The morphologies of the nanofibers were observed by scanning electron microscopy, which revealed uniform and smooth surfaces of the nanofibers. The addition of HNTs to the composite nanofibers increased the viscosity of the polymer solution, and this suggested shorter fiber diameters. FTIR spectroscopy verified the good compatibility of the SDP and HNTs with PVA. Moreover, the swelling properties were found to quantitatively correlate with weight loss.In vitrodrug‐release testing revealed that the HNTs and crosslinking reaction most dramatically affected the sustained release of SDP from the PVA and SDP‐loaded HNT complex. In the drug‐release kinetics model, SDP release depended on the diffusion caused by the deformation of the polymer‐based structures in the medium; it followed Fickian diffusion with acceptable coefficient of determination (r2) values between 0.88 and 0.94. Most importantly, the HNTs as natural biocontainers effectively modulated the release profile by loading the active compound in harmony with the electrospun nanofibers. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2016,133, 42900.
Isolating Visual and Proprioceptive Components of Motor Sequence Learning in ASD
Authors: Sharer Elizabeth A. , Mostofsky Stewart H. , Pascual‐Leone Alvaro , Oberman Lindsay M.
Published: October 2015

In addition to defining impairments in social communication skills, individuals with autism spectrum disorder (ASD) also show impairments in more basic sensory and motor skills. Development of new skills involves integrating information from multiple sensory modalities. This input is then used to form internal models of action that can be accessed when both performing skilled movements, as well as understanding those actions performed by others. Learning skilled gestures is particularly reliant on integration of visual and proprioceptive input. We used a modified serial reaction time task (SRTT) to decompose proprioceptive and visual components and examine whether patterns of implicit motor skill learning differ in ASD participants as compared with healthy controls. While both groups learned the implicit motor sequence during training, healthy controls showed robust generalization whereas ASD participants demonstrated little generalization when visual input was constant. In contrast, no group differences in generalization were observed when proprioceptive input was constant, with both groups showing limited degrees of generalization. The findings suggest, when learning a motor sequence, individuals with ASD tend to rely less on visual feedback than do healthy controls. Visuomotor representations are considered to underlie imitative learning and action understanding and are thereby crucial to social skill and cognitive development. Thus, anomalous patterns of implicit motor learning, with a tendency to discount visual feedback, may be an important contributor in core social communication deficits that characterize ASD. Autism Res 2016, 9: 563–569. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Neonatal brain abnormalities associated with autism spectrum disorder in children born very preterm
Authors: Ure Alexandra M. , Treyvaud Karli , Thompson Deanne K. , Pascoe Leona , Roberts Gehan , Lee Katherine J. , Seal Marc L. , Northam Elisabeth , Cheong Jeanie L. , Hunt Rod W. , Inder Terrie , Doyle Lex W. , Anderson Peter J.
Published: October 2015

Very preterm (VP) survivors are at increased risk of autism spectrum disorder (ASD) compared with term‐born children. This study explored whether neonatal magnetic resonance (MR) brain features differed in VP children with and without ASD at 7 years. One hundred and seventy‐two VP children (<30 weeks' gestation or <1250 g birth weight) underwent structural brain MR scans at term equivalent age (TEA; 40 weeks' gestation ±2 weeks) and were assessed for ASD at 7 years of age. The presence and severity of white matter, cortical gray matter, deep nuclear gray matter, and cerebellar abnormalities were assessed, and total and regional brain volumes were measured. ASD was diagnosed using a standardized parent report diagnostic interview and confirmed via an independent assessment. Eight VP children (4.7%) were diagnosed with ASD. Children with ASD had more cystic lesions in the cortical white matter at TEA compared with those without ASD (odds ratio [OR] 8.7, 95% confidence interval [CI] 1.5, 51.3, P = 0.02). There was also some evidence for smaller cerebellar volumes in children with ASD compared with those without ASD (OR = 0.82, CI = 0.66, 1.00, P = 0.06). Overall, the results suggest that VP children with ASD have different brain structure in the neonatal period compared with those who do not have ASD. Autism Res 2016, 9: 543–552. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Spontaneous Facial Mimicry is Modulated by Joint Attention and Autistic Traits
Authors: Neufeld Janina , Ioannou Christina , Korb Sebastian , Schilbach Leonhard , Chakrabarti Bhismadev
Published: October 2015

Joint attention (JA) and spontaneous facial mimicry (SFM) are fundamental processes in social interactions, and they are closely related to empathic abilities. When tested independently, both of these processes have been usually observed to be atypical in individuals with autism spectrum conditions (ASC). However, it is not known how these processes interact with each other in relation to autistic traits. This study addresses this question by testing the impact of JA on SFM of happy faces using a truly interactive paradigm. Sixty‐two neurotypical participants engaged in gaze‐based social interaction with an anthropomorphic, gaze‐contingent virtual agent. The agent either established JA by initiating eye contact or looked away, before looking at an object and expressing happiness or disgust. Eye tracking was used to make the agent's gaze behavior and facial actions contingent to the participants' gaze. SFM of happy expressions was measured by Electromyography (EMG) recording over the Zygomaticus Major muscle. Results showed that JA augments SFM in individuals with low compared with high autistic traits. These findings are in line with reports of reduced impact of JA on action imitation in individuals with ASC. Moreover, they suggest that investigating atypical interactions between empathic processes, instead of testing these processes individually, might be crucial to understanding the nature of social deficits in autism. Autism Res 2016, 9: 781–789. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research
Targeting tumor suppressor genes for cancer therapy
Authors: Liu Yunhua , Hu Xiaoxiao , Han Cecil , Wang Liana , Zhang Xinna , He Xiaoming , Lu Xiongbin
Published: October 2015

Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain‐of‐function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss‐of‐function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics.
On‐chip assessment of human primary cardiac fibroblasts proliferative responses to uniaxial cyclic mechanical strain
Authors: Ugolini Giovanni Stefano , Rasponi Marco , Pavesi Andrea , Santoro Rosaria , Kamm Roger , Fiore Gianfranco Beniamino , Pesce Maurizio , Soncini Monica
Published: October 2015

Cardiac cell function is substantially influenced by the nature and intensity of the mechanical loads the cells experience. Cardiac fibroblasts (CFs) are primarily involved in myocardial tissue remodeling: at the onset of specific pathological conditions, CFs activate, proliferate, differentiate, and critically alter the amount of myocardial extra‐cellular matrix with important consequences for myocardial functioning. While cyclic mechanical strain has been shown to increase matrix synthesis of CFs in vitro, the role of mechanical cues in CFs proliferation is unclear. We here developed a multi‐chamber cell straining microdevice for cell cultures under uniform, uniaxial cyclic strain. After careful characterization of the strain field, we extracted human heart‐derived CFs and performed cyclic strain experiments. We subjected cells to 2% or 8% cyclic strain for 24 h or 72 h, using immunofluorescence to investigate markers of cell morphology, cell proliferation (Ki67, EdU, phospho‐Histone‐H3) and subcellular localization of the mechanotransduction‐associated transcription factor YAP. Cell morphology was affected by cyclic strain in terms of cell area, cell and nuclear shape and cellular alignment. We additionally observed a strain intensity‐dependent control of cell growth: a significant proliferation increase occurred at 2% cyclic strain, while time‐dependent effects took place upon 8% cyclic strain. The YAP‐dependent mechano‐transduction pathway was similarly activated in both strain conditions. These results demonstrate a differential effect of cyclic strain intensity on human CFs proliferation control and provide insights into the YAP‐dependent mechano‐sensing machinery of human CFs. Biotechnol. Bioeng. 2016;113: 859–869. © 2015 Wiley Periodicals, Inc.
The Electrochemical Analysis using Critical Parameters in Li–S Battery
Authors: Park Jungjin , Kim Chunjoong , Sung Yung‐Eun
Published: October 2015

The electrochemically critical parameters in the Li–S battery, the overpotential (ΔV), the capacity from the dissolution region (Q
1), and the capacity from the precipitation region (Q
2), are identified to trace the electrochemical behavior of the electrode during the charge/discharge operation, which can aid in the deep understanding of the enhancement mechanism in the various model systems. The effects of cycling rate, conductive additive content, and oxygen functional group on the battery performance have been studied as the model systems. In this study, it is suggested that critical parameters should be carefully analyzed when exploring the performance of Li–S battery or designing batteries based on a new concept or novel architecture.
Writing throughout the biochemistry curriculum: Synergistic inquiry‐based writing projects for biochemistry students
Authors: Mertz Pamela , Streu Craig
Published: October 2015

This article describes a synergistic two‐semester writing sequence for biochemistry courses. In the first semester, students select a putative protein and are tasked with researching their protein largely through bioinformatics resources. In the second semester, students develop original ideas and present them in the form of a research grant proposal. Both projects involve multiple drafts and peer review. The complementarity of the projects increases student exposure to bioinformatics and literature resources, fosters higher‐order thinking skills, and develops teamwork and communication skills. Student feedback and responses on perception surveys demonstrated that the students viewed both projects as favorable learning experiences. © 2015 by The International Union of Biochemistry and Molecular Biology, 43:408–416, 2015.
Palladium‐Catalyzed sp2 C−H Arylation of Azoarenes with Arylhydrazines
Authors: Li Mingyang , Ye Yong
Published: October 2015

Transition‐metal‐catalyzed direct functionalization of C−H bonds is important for new compound synthesis, but usually needs special reagents and harsh conditions. With the aid of an azo directing group, the palladium‐catalyzed ortho‐sp2 C−H bond activation of azoarenes with hydrazines has been explored. In the reaction, the Pd catalyst reacts with azobenzene to form a palladacyclic intermediate, which reacts with a phenyl radical generated from phenylhydrazine under heating and oxygen to produce a PdIV or PdIII intermediate. This finally undergoes reductive elimination to give the ortho‐arylated products with the release of the PdII catalyst. This reaction provides a novel access to ortho‐aryl azoarenes under mild conditions in high yield.
One‐Pot Aminoethylation of Indoles/Pyrroles with Alkynes and Sulfonyl Azides
Authors: Rajasekar Shanmugam , Yadagiri Dongari , Anbarasan Pazhamalai
Published: October 2015

A general and efficient one‐pot aminoethylation of substituted indoles/pyrroles was accomplished for the synthesis of various tryptamine derivatives employing a combination of alkynes and sulfonyl azides as readily accessible aminoethylating agents. The reaction features a successful integration of copper‐catalyzed alkyne and azide cycloaddition to N‐sulfonyl‐1,2,3‐triazole, rhodium‐catalyzed selective insertion of α‐iminocarbenes onto the C3H bond of indoles, and reduction of the resultant enamides to tryptamine derivatives employing either NaCNBH3 or palladium catalyst, in one‐pot. The reaction also showed excellent functional‐group tolerance and allowed the synthesis of various substituted tryptamines in good to excellent yield. This transformation constitutes a one‐pot formal regioselective functionalization of terminal alkynes. Utility of the synthesized tryptamine was further demonstrated in the synthesis of dihydro‐β‐carboline and tryptoline.
The Diaza[5.5.6.6]fenestrane Skeleton—Synthesis of Leuconoxine Alkaloids
Authors: Pfaffenbach Magnus , Gaich Tanja
Published: October 2015

Among the Aspidosperma‐derived monoterpene indole alkaloids, the leuconoxine subgroup has drawn significant attention from the synthetic community during the past few years. This Minireview summarizes the hitherto six completed total syntheses of leuconoxines emphasizing the different strategies for assembling the key structural motif, an unprecedented diaza[5.5.6.6]fenestrane skeleton. In addition, the proposed biogenetic relationships within the group of these alkaloids are described.
Rational Design of a Lanthanide‐Based Complex Featuring Different Single‐Molecule Magnets
Authors: Pointillart F. , Guizouarn T. , Lefeuvre B. , Golhen S. , Cador O. , Ouahab L.
Published: October 2015

The rational synthesis of the 2‐{1‐methylpyridine‐N‐oxide‐4,5‐[4,5‐bis(propylthio)tetrathiafulvalenyl]‐1H‐benzimidazol‐2‐yl}pyridine ligand (L) is described. It led to the tetranuclear complex [Dy4(tta)12(L)2] (Dy‐Dy2‐Dy) after coordination reaction with the precursor Dy(tta)3⋅2 H2O (tta−=2‐thenoyltrifluoroacetonate). The X‐ray structure of Dy‐Dy2‐Dy can be described as two terminal mononuclear units bridged by a central antiferromagnetically coupled dinuclear complex. The terminal N2O6 and central O8 environments are described as distorted square antiprisms. The ac magnetism measurements revealed a strong out‐of‐phase signal of the magnetic susceptibility with two distinct sets of data. The high‐ and low‐frequency components were attributed to the two terminal mononuclear single‐molecule magnets (SMMs) and the central dinuclear SMM, respectively. A magnetic hysteresis loop was detected at very low temperature. From both structural and magnetic points of view, the tetranuclear SMM Dy‐Dy2‐Dy is a self‐assembly of two known mononuclear SMMs bridged by a known dinuclear SMM.
Design, Synthesis, and Biological Evaluation of Quercetagetin Analogues as JNK1 Inhibitors
Authors: Hierold Judith , Baek Sohee , Rieger Rene , Lim Tae‐Gyu , Zakpur Saman , Arciniega Marcelino , Lee Ki Won , Huber Robert , Tietze Lutz F.
Published: October 2015

The recent discovery of c‐Jun NH2‐terminal kinase JNK1 suppression by natural quercetagetin (1) is a promising lead for the development of novel anticancer agents. Using both X‐ray structure and docking analyses we predicted that 5′‐hydroxy‐ (2) and 5′‐hydroxymethyl‐quercetagetin (3) would inhibit JNK1 more actively than the parent compound 1. Notably, our drug design was based on the active enzyme–ligand complex as opposed to the enzyme’s relatively open apo structure. In this paper we test our theoretical predictions, aided by docking‐model experiments, and report the first synthesis and biological evaluation of quercetagetin analogues 2 and 3. As calculated, both compounds strongly suppress JNK1 activity. The IC50 values were determined to be 3.4 μM and 12.2 μM, respectively, which shows that 2 surpasses the potency of the parent compound 1 (IC50=4.6 μM). Compound 2 was also shown to suppress matrix metalloproteinase‐1 expression with high specificity after UV irradiation.
Palladium‐Catalyzed Arylation of Unactivated γ‐Methylene C(sp3)H and δ‐CH Bonds with an Oxazoline‐Carboxylate Auxiliary
Authors: Ling Peng‐Xiang , Fang Sheng‐Long , Yin Xue‐Song , Chen Kai , Sun Bo‐Zheng , Shi Bing‐Feng
Published: October 2015

A palladium‐catalyzed arylation of unactivated γ‐methylene C(sp3)H and remote δ‐CH bonds by using an oxazoline‐carboxylate directing group has been developed. Arylation occurs with a broad substrate scope and high tolerance of functional groups (i.e., halogen, nitro, cyano, ether, trifluoromethyl, amine, and ester). The oxazoline‐type auxiliary can be removed under acidic conditions.
Designing the Molybdopterin Core through Regioselective Coupling of Building Blocks
Authors: Pimkov Igor V. , Serli‐Mitasev Barbara , Peterson Antoinette A. , Ratvasky Stephen C. , Hammann Bernd , Basu Partha
Published: October 2015

Molybdopterin is an essential cofactor for all forms of life. The cofactor is composed of a pterin moiety appended to a dithiolene‐functionalized pyran ring, and through the dithiolene moiety it binds metal ions. Different synthetic strategies for dithiolene‐functionalized pyran precursors that have been designed and synthesized are discussed. These precursors also harbor 1,2‐diketone or osone functionality that has been condensed with 1,2‐diaminobenzene or other heterocycles resulting in several quinoxaline or pterin derivatives. Use of additives improves the regioselectivity of the complexes. The molecules have been characterized by 1H and 13C NMR and IR spectroscopies, as well as by mass spectrometry. In addition, several compounds have been crystallographically characterized. The geometries of the synthesized molecules are more planar than the geometry of the cofactor found in proteins.
Hierarchical Pore Development by Plasma Etching of Zr‐Based Metal–Organic Frameworks
Authors: DeCoste Jared B. , Rossin Joseph A. , Peterson Gregory W.
Published: October 2015

The typically stable Zr‐based metal–organic frameworks (MOFs) UiO‐66 and UiO‐66‐NH2 were treated with tetrafluoromethane (CF4) and hexafluoroethane (C2F6) plasmas. Through interactions between fluoride radicals from the perfluoroalkane plasma and the zirconium–oxygen bonds of the MOF, the resulting materials showed the development of mesoporosity, creating a hierarchical pore structure. It is anticipated that this strategy can be used as a post‐synthetic technique for developing hierarchical networks in a variety of MOFs.
Self‐Relay Gold(I)‐Catalyzed Pictet–Spengler/Cyclization Cascade Reaction for the Rapid Elaboration of Pentacyclic Indole Derivatives
Authors: Gobé Valérian , Retailleau Pascal , Guinchard Xavier
Published: October 2015

Gold‐catalyzed cascade reactions allow the rapid elaboration of pentacyclic indolo[2,3‐a]quinolizidines from N‐allyl tryptamines and ortho‐alkynylarylaldehydes. The tandem process combines a gold‐catalyzed Pictet‐Spengler reaction and a cyclization occurring concomitantly with an allyl transfer from the nitrogen atom to the stilbene function. Various substituted allyls were successfully transferred, furnishing the products in yields typically ranging from 60–98 % in high diastereoselectivity. Tryptamines bearing a butenol chain undergo an additional cyclization to chiral hemiaminals in high diastereoselectivities.
Asphaltene solubility in common solvents: A molecular dynamics simulation study
Authors: Amjad‐Iranagh Sepideh , Rahmati Mahmoud , Haghi Mahdi , Hoseinzadeh Mohsen , Modarress Hamid
Published: October 2015

Solubility of all proposed molecular models of asphaltene in various solvents is studied through molecular dynamics simulation to find the structural parameters which have a determining effect on asphaltene solubility. It is found that higher numbers of aromatic rings and heteroatoms such as oxygen, nitrogen, and sulphur in the molecular structure of asphaltenes raises their solubility in the solvents, whereas the length of aliphatic group, which increases the chain length, lowers their solubility. In addition, a cubic correlation equation for evaluating the asphaltene solubility parameter as a ratio of number of aromatic rings in the asphaltene molecular core to the number of carbon atoms in the asphaltene side chains is proposed. The results indicate that the relative energy difference (RED) of asphaltene models and isopropyl benzene, as a solvent, is the lowest compared with other solvents. To elucidate the mechanism of asphaltene dissolution in the common solvents the solubility of two asphaltene structural models in three solvents, including isopropyl benzene, toluene, and heptane, were studied by evaluating the radial distribution functions (RDFs) of the asphaltenes, and the results confirm that asphaltene has the highest solubility in isopropyl benzene.
DW‐MRI and 18F‐FLT PET for early assessment of response to radiation therapy associated with hypoxia‐driven interventions. Preclinical studies using manipulation of oxygenation and/or dose escalation
Authors: Tran Ly‐Binh‐An , Bol Anne , Labar Daniel , Karroum Oussama , Mignion Lionel , Bol Vanesa , Jordan Bénédicte F. , Grégoire Vincent , Gallez Bernard
Published: October 2015

Early markers of treatment response may help in the management of patients by predicting the outcome of a specific therapeutic intervention. Here, we studied the potential value of diffusion‐weighted MRI (DW‐MRI) and 18F‐fluorothymidine (18F‐FLT), markers of cell death and cell proliferation respectively, to predict the response to irradiation. In addition, dose escalation and/or carbogen breathing were used to modulate the response to irradiation. The studies were performed on two hypoxic rat tumor models: rhabdomyosarcoma and 9L‐glioma. The rats were imaged using MRI and PET before and two days after the treatment. In both tumor models, changes in ADC (apparent diffusion coefficient) and 18F‐FLT SUV (standardized uptake value) were significantly correlated with the tumor growth delay. For both tumor models, the ADC values increased in all irradiated groups two days after the treatment while they decreased in the untreated groups. At the same time, the uptake of 18F‐FLT increased in the untreated groups and decreased in all treated groups. Yet, ADC values were not sensitive enough to predict the added value of dose escalation or carbogen breathing in either model. Change in 18F‐FLT uptake was able to predict the higher tumor response when using increased dose of irradiation, but not when using a carbogen breathing challenge. Our results also emphasize that the magnitude of change in 18F‐FLT uptake was strongly dependent on the tumor model. Copyright © 2015 John Wiley & Sons, Ltd.
Topological design of all‐ceramic dental bridges for enhancing fracture resistance
Authors: Zhang Zhongpu , Chen Junning , Li Eric , Li Wei , Swain Michael , Li Qing
Published: October 2015

Layered all‐ceramic systems have been increasingly adopted in major dental prostheses. However, ceramics are inherently brittle, and they often subject to premature failure under high occlusion forces especially in the posterior region. This study aimed to develop mechanically sound novel topological designs for all‐ceramic dental bridges by minimizing the fracture incidence under given loading conditions. A bi‐directional evolutionary structural optimization (BESO) technique is implemented within the extended finite element method (XFEM) framework. Extended finite element method allows modeling crack initiation and propagation inside all‐ceramic restoration systems. Following this, BESO searches the optimum distribution of two different ceramic materials, namely porcelain and zirconia, for minimizing fracture incidence. A performance index, as per a ratio of peak tensile stress to material strength, is used as a design objective. In this study, the novel XFEM based BESO topology optimization significantly improved structural strength by minimizing performance index for suppressing fracture incidence in the structures. As expected, the fracture resistance and factor of safety of fixed partial dentures structure increased upon redistributing zirconia and porcelain in the optimal topological configuration. Dental CAD/CAM systems and the emerging 3D printing technology were commercially available to facilitate implementation of such a computational design, exhibiting considerable potential for clinical application in the future. Copyright © 2015 John Wiley & Sons, Ltd.
Revocable and anonymous searchable encryption in multi‐user setting
Authors: Miao Yinbin , Ma Jianfeng , Liu Zhiquan
Published: October 2015

With powerful storage and computing capacities provided by cloud server provider(CSP), cloud customers can relieve from heavy storage and maintenance burden in cloud computing. Therefore, searchable encryption(SE) technology becomes a fundamental solution to search over encrypted data in outsourcing service. However, the genuine safety of SE schemes should concentrate not only on keyword privacy but also on user privacy as information tracking may leak user identity. For example, in the personal health record system, the malicious CSP may match sensitive disease information(cancer or AIDS) with certain patient. In addition, practical SE scheme should not be confined to single‐user setting because of its limitations. While SE schemes applied to multi‐user setting may result in additional secret key and ciphertext updating burden due to frequent user revocation. Along this direction, we define a revocable and anonymous SE scheme in multiple‐user setting, which is scalable and efficient in user revocation and anonymity. Security analysis shows that our scheme is Anonymous‐Revocable‐ID‐CPA secure under Decision Bilinear Diffie–Hellman assumption and is able to effectively resist decryption key exposure threat. Copyright © 2015 John Wiley & Sons, Ltd.
Gaspar: a compositional aspect‐oriented approach for cluster applications
Authors: Medeiros B. , Silva R. , Sobral J. L.
Published: October 2015

This paper presents a framework that enables the development of Java applications that execute on CPUs, graphics processing units (GPUs) and clusters of CPUs/GPUs. Applications are specified in an OpenMP‐like fashion, accessing data through a framework‐provided data API. The framework enables the efficient execution of applications in CPU and/or GPU by relying on two key features: (i) parallelism exploitation patterns are specified by additional aspect modules; and (ii) data layout can be selected according to the target platform. This paper describes how the framework abstractions are mapped and how the framework intrinsically supports the development of applications with hybrid parallelism by composing aspect modules with a given base program. Performance results show that the framework provides a performance level similar to traditional approaches and enables better performance portability for a given base program. Copyright © 2015 John Wiley & Sons, Ltd.
Schisandrae Fructus Inhibits IL‐1β‐Induced Matrix Metalloproteinases and Inflammatory Mediators Production in SW1353 Human Chondrocytes by Suppressing NF‐κB and MAPK Activation
Authors: Jeong Jin‐Woo , Lee Hye Hyeon , Choi Eun‐Ok , Lee Ki Won , Kim Ki Young , Kim Sung Goo , Hong Su Hyun , Kim Gi‐Young , Park Cheol , Kim Ho Kyoung , Choi Young Whan , Choi Yung Hyun
Published: October 2015

Preclinical Research

Proinflammatory cytokine interleukin‐1 beta (IL‐1β) plays a crucial role in the pathogenesis of osteoarthritis (OA) by stimulating several mediators that contribute to cartilage degradation. Schisandrae Fructus (SF), the dried fruit of Schisandra chinensis (Turcz.) Baill. (Magnoliaceae), is widely used in traditional medicine for the treatment of a number of chronic inflammatory diseases. This study investigated the antiosteoarthritis properties of an ethanol extract of SF on IL‐1β‐stimulated SW1353 chondrocytes. SF attenuated IL‐1β‐induced expression and activity of matrix metalloproteinase (MMP)‐1, MMP‐3, and MMP‐13 and also reduced the elevated levels of cyclooxygenase‐2 and inducible nitric oxide synthase associated with the inhibition of prostaglandin E2 and nitric oxide production in IL‐1β‐stimulated SW1353 chondrocytes. In addition, SF markedly suppressed the nuclear translocation of nuclear factor‐kappa B (NF‐κB) by blocking inhibitor κB‐alpha degradation and inhibited the phosphorylation of c‐Jun N‐terminal kinase (JNK) and p38 mitogen‐activated protein kinase (MAPK). These results indicate that the inhibitory effect of SF on IL‐1β‐stimulated expression of MMPs and inflammatory mediators production in SW1353 cells were associated with the suppression of the NF‐κB and JNK/p38 MAPK signaling pathways. The results from this study indicate that SF may have therapeutic potential for the treatment of OA due to its anti‐inflammatory and chondroprotective features. Drug Dev Res 76 : 474–483, 2015. © 2015 Wiley Periodicals, Inc.
The perilipin 2 (PLIN2) gene Ser251Pro missense mutation is associated with reduced insulin secretion and increased insulin sensitivity in Italian obese subjects
Authors: Sentinelli Federica , Capoccia Danila , Incani Michela , Bertoccini Laura , Severino Anna , Pani Maria Grazia , Manconi Ettore , Cossu Efisio , Leonetti Frida , Baroni Marco G.
Published: October 2015

Background

Perilipin 2 (PLIN2), a member of the family of perilipin lipid droplets coating proteins, is very widely expressed.

The Ser251Pro (rs35568725) missense mutation in exon 6 of PLIN2 gene was previously associated with increased lipid accumulation, decreased lipolysis and increased number of small lipid droplets per cell. Furthermore, the Pro251 mutation was associated with decreased plasma triglyceride and very low density lipoprotein concentrations in population studies.

The aim of this study was to evaluate the effect of the Ser251Pro mutation of PLIN2 gene in a cohort with a higher predisposition to obesity‐associated metabolic alterations, such as insulin resistance, decreased insulin‐secretion, hyperglycaemia, and dyslipidaemia.

Methods

A large cohort (N = 1692) of Italian obese subjects (mean body mass index = 41 kg/m2) was genotyped for the Ser251Pro mutation. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance and of insulin secretion were also calculated. Clinical and biochemical parameters were collected for all participants.

Results

We observed that insulin concentration was significantly reduced at 120 min after the administration of glucose in Pro251 allele carriers, whereas glucose levels were similar in Pro251 allele carriers and non‐carriers throughout the OGTT. Furthermore, the CIR120 index of insulin secretion was significantly lower (P < 0.035) and the ISI index of insulin‐sensitivity was significantly higher (P < 0.031) in carriers of the Pro251 allele. When we analysed men and women separately to test for gender‐specific associations, we observed that in women insulin levels were significantly lower in Pro251 allele carriers compared with wild‐type subjects throughout the whole OGTT. In men, we confirmed a significant reduction in insulin concentration only at 120 min after the OGTT. No significant differences between genotype groups regarding triglyceride levels and anyother clinical and metabolic parameters were observed.

Conclusion

We observed a strong significant association between the PLIN2 Pro251 mutation and lower insulin secretion associated with an increased insulin sensitivity. Copyright © 2015 John Wiley & Sons, Ltd.
Kupffer's vesicle size threshold for robust left–right patterning of the zebrafish embryo
Authors: Gokey Jason J. , Ji Yongchang , Tay Hwee Goon , Litts Bridget , Amack Jeffrey D.
Published: October 2015

Background:

Motile cilia in the “organ of asymmetry” create directional fluid flows that are vital for left–right (LR) asymmetric patterning of vertebrate embryos. Organ function often depends on tightly regulated organ size control, but the role of organ of asymmetry size in LR patterning has remained unknown. Observations of the organ of asymmetry in the zebrafish, called Kupffer's vesicle (KV), have suggested significant variations in KV size in wild‐type embryos, raising questions about the impact of KV organ size on LR patterning.

Results:

To understand the relationship between organ of asymmetry size and its function, we characterized variations in KV at several developmental stages and in several different zebrafish strains. We found that the number of KV cilia and the size of the KV lumen were highly variable, whereas the length of KV cilia showed less variation. These variabilities were similar among different genetic backgrounds. By specifically modulating KV size and analyzing individual embryos, we identified a size threshold that is necessary for KV function.

Conclusions:

Together these results indicate the KV organ of asymmetry size is not tightly controlled during development, but rather must only exceed a threshold to direct robust LR patterning of the zebrafish embryo. Developmental Dynamics 245:22–33, 2016. © 2015 Wiley Periodicals, Inc.
Drosophilachitinous aECM and its cellular interactions during tracheal development
Authors: Öztürk‐Çolak Arzu , Moussian Bernard , Araújo Sofia J.
Published: October 2015

The morphology of organs, and hence their proper physiology, relies to a considerable extent on the extracellular matrix (ECM) secreted by their cells. The ECM is a structure contributed to and commonly shared by many cells in an organism that plays an active role in morphogenesis. Increasing evidence indicates that the ECM not only provides a passive contribution to organ shape but also impinges on cell behaviour and genetic programmes. The ECM is emerging as a direct modulator of many aspects of cell biology, rather than as a mere physical network that supports cells. Here, we review how the apical chitinous ECM is generated inDrosophilatrachea and how cells participate in the formation of this supracellular structure. We discuss recent findings on the molecular and cellular events that lead to the formation of this apical ECM (aECM) and how it is influenced and affects tracheal cell biology.Developmental Dynamics 245:259–267, 2016. © 2015 Wiley Periodicals, Inc.
Association of impaired left ventricular twisting‐untwisting with vascular dysfunction, neurohumoral activation and impaired exercise capacity in hypertensive heart disease
Authors: Ikonomidis Ignatios , Tzortzis Stavros , Triantafyllidi Helen , Parissis John , Papadopoulos Costas , Venetsanou Kyriaki , Trivilou Paraskevi , Paraskevaidis Ioannis , Lekakis John
Published: October 2015

Aims

We investigated the association between left ventricular (LV) torsional deformation and vascular dysfunction, fibrosis, neurohumoral activation, and exercise capacity in patients with normal ejection fraction

Methods and results

In 320 newly‐diagnosed untreated hypertensive patients and 160 controls, we measured: pulse wave velocity (PWV); coronary flow reserve (CFR) by Doppler echocardiography; global longitudinal strain and strain rate, peak twisting, the percentage changes between peak twisting, and untwisting at mitral valve opening (%dpTw – UtwMVO), at peak (%dpTw – UtwPEF), and the end of early LV diastolic filling (%dpTw – UtwEDF) by speckle tracking imaging; transforming growth factor (TGFb‐1), metalloproteinase‐9 (MMP‐9), tissue inhibitor of matrix metalloptoteinase‐1(TIMP‐1), markers of collagen synthesis, and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). Oxygen consumption (VO2), measured by means of cardiopulmonary exercise test, was assessed in a subset of 80 patients. The PWV, CFR, longitudinal strain and strain rate, %dpTw‐UtwMVO, %dpTw‐UtwPEF, and %dpTw‐UtwEDF were impaired in hypertensive patients compared with controls. In multivariable analysis, CFR, PWV, LV mass, and systolic blood pressure were independent determinants of longitudinal strain, strain rate, and untwisting markers (P < 0.05). Increased TGFb‐1 was related with increased collagen synthesis markers, TIMP‐1 and MMP‐9 and these biomarkers were associated with impaired longitudinal systolic strain rate, untwisting markers, CFR and PWV (P < 0.05). Delayed untwisting as assessed by reduced %dpTw – UtwEDF was related with increased NT‐proBNP and reduced VO2 (P < 0.05).

Conclusions

Impaired LV untwisting is associated with increased arterial stiffness and coronary microcirculatory dysfunction, and is linked to reduced exercise capacity and neurohumoral activation in hypertensive heart disease. A fibrotic process may be the common link between vascular dysfunction and abnormal myocardial deformation.
Enhancing our understanding of enhancers in T‐helper cells
Authors: Paiano Jacob J. , Johnson John L. , Vahedi Golnaz
Published: October 2015

A long‐standing question in immunology has been to understand how transcription factors (TF) determine cell‐type‐specific transcription programs. Traditionally, investigating TFs in immune cells has been limited to measuring the effect of a single TF on a limited number of gene targets. The advent of next generation sequencing methods makes it possible to measure the effects of multiple transcription factors on a genome‐wide scale. This holistic approach gives us a better understanding of the influence that multiple TFs have on cell‐specific programs. In this issue of European Journal of Immunology, Fang et al. [Eur. J. Immunol. 2015. 45: 3150–3157] show that genomic regions cooccupied with two or more TFs show increased epigenetic histone marks of active enhancers, which correspond to increased transcriptional activity.
Reinforcement learning‐based clustering protocols for a self‐organising cognitive radio network
Authors: Ramli Aizat , Grace David
Published: October 2015

This paper presents a methodology on how cognitive radio networks can form clusters by exploiting reinforcement learning‐based principles. Each node repeatedly senses the received signal strength indicator beacons given off by other nodes in the network. This information can be used by the nodes to learn about its positioning significance within the network and whether to become cluster heads thus forming a cluster. Extensive simulation results are presented, and it is shown that on average, the clustering performance (packing efficiency) can be improved when nodes have the ability to learn. The results are compared with that of a k‐means and node degree‐based approach for the formation of clusters. It is found that the node degree scheme can result in the clustering performance deteriorating, which is undesirable as it can lead to an increase in the total energy consumption of the network over time. It is shown that in a shadowing environment, that clusters formed via learning through received signal strength indicator can reduce their transmission power by up to 2 dBW (achieving a potential power saving of 37 per cent) while achieving the same signal‐to‐noise ratio as that of the no learning and node degree schemes. Further energy conservation can be obtained by restricting beacon transmissions to immediate neighbouring nodes. In certain geographical node distributions, a no learning scheme is preferred for the formation of clusters due to its lower overhead. Copyright © 2015 John Wiley & Sons, Ltd.
Examination of the Synthetic Control Method for Evaluating Health Policies with Multiple Treated Units
Authors: Kreif Noémi , Grieve Richard , Hangartner Dominik , Turner Alex James , Nikolova Silviya , Sutton Matt
Published: October 2015

This paper examines the synthetic control method in contrast to commonly used difference‐in‐differences (DiD) estimation, in the context of a re‐evaluation of a pay‐for‐performance (P4P) initiative, the Advancing Quality scheme. The synthetic control method aims to estimate treatment effects by constructing a weighted combination of control units, which represents what the treated group would have experienced in the absence of receiving the treatment. While DiD estimation assumes that the effects of unobserved confounders are constant over time, the synthetic control method allows for these effects to change over time, by re‐weighting the control group so that it has similar pre‐intervention characteristics to the treated group.

We extend the synthetic control approach to a setting of evaluation of a health policy where there are multiple treated units. We re‐analyse a recent study evaluating the effects of a hospital P4P scheme on risk‐adjusted hospital mortality. In contrast to the original DiD analysis, the synthetic control method reports that, for the incentivised conditions, the P4P scheme did not significantly reduce mortality and that there is a statistically significant increase in mortality for non‐incentivised conditions. This result was robust to alternative specifications of the synthetic control method. © 2015 The Authors. Health Economics published by John Wiley & Sons Ltd.
Reward memory relieves anxiety‐related behavior through synaptic strengthening and protein kinase C in dentate gyrus
Authors: Lei Zhuofan , Liu Bei , Wang Jin‐Hui
Published: October 2015

Anxiety disorders are presumably associated with negative memory. Psychological therapies are widely used to treat this mental deficit in human beings based on the view that positive memory competes with negative memory and relieves anxiety status. Cellular and molecular processes underlying psychological therapies remain elusive. Therefore, we have investigated its mechanisms based on a mouse model in which food reward at one open‐arm of the elevated plus‐maze was used for training mice to form reward memory and challenge the open arms. Mice with the reward training showed increased entries and stay time in reward open‐arm versus neutral open‐arm as well as in open‐arms versus closed‐arms. Accompanying with reward memory formation and anxiety relief, glutamatergic synaptic transmission in dentate gyrus in vivo and dendritic spines in granule cells became upregulated. This synaptic up‐regulation was accompanied by the expression of more protein kinase C (PKC) in the dendritic spines. The inhibition of PKC by chelerythrine impaired the formation of reward memory, the relief of anxiety‐related behavior and the up‐regulation of glutamate synapses. Our results suggest that reward‐induced positive memory relieves mouse anxiety‐related behavior by strengthening synaptic efficacy and PKC in the hippocampus, which imply the underlying cellular and molecular processes involved in the beneficial effects of psychological therapies treating anxiety disorders. © 2015 Wiley Periodicals, Inc.
Development of a bioavailability-based risk assessment approach for nickel in freshwater sediments
Authors: Schlekat Christian E , Garman Emily R , Vangheluwe Marnix LU , Burton G Allen
Published: October 2015

To assess nickel (Ni) toxicity and behavior in freshwater sediments, a large-scale laboratory and field sediment testing program was conducted. The program used an integrative testing strategy to generate scientifically based threshold values for Ni in sediments and to develop integrated equilibrium partitioning-based bioavailability models for assessing risks of Ni to benthic ecosystems. The sediment testing program was a multi-institutional collaboration that involved extensive laboratory testing, field validation of laboratory findings, characterization of Ni behavior in natural and laboratory conditions, and examination of solid phase Ni speciation in sediments. The laboratory testing initiative was conducted in 3 phases to satisfy the following objectives: 1) evaluate various methods for spiking sediments with Ni to optimize the relevance of sediment Ni exposures; 2) generate reliable ecotoxicity data by conducting standardized chronic ecotoxicity tests using 9 benthic species in sediments with low and high Ni binding capacity; and, 3) examine sediment bioavailability relationships by conducting chronic ecotoxicity testing in sediments that showed broad ranges of acid volatile sulfides, organic C, and Fe. A subset of 6 Ni-spiked sediments was deployed in the field to examine benthic colonization and community effects. The sediment testing program yielded a broad, high quality data set that was used to develop a Species Sensitivity Distribution for benthic organisms in various sediment types, a reasonable worst case predicted no-effect concentration for Ni in sediment (PNECsediment), and predictive models for bioavailability and toxicity of Ni in freshwater sediments. A bioavailability-based approach was developed using the ecotoxicity data and bioavailability models generated through the research program. The tiered approach can be used to fulfill the outstanding obligations under the European Union (EU) Existing Substances Risk Assessment, EU Registration, Evaluation, Authorisation, and Regulation of Chemicals (REACH), and other global regulatory initiatives. Integr Environ Assess Manag 2016;12:735–746. © 2015 SETAC