bluuebunny/crossref_metadata_2025 huggingface dataset:
A three step blind approach for improving high performance computing systems' energy performance
Authors: Tsafack Chetsa Ghislain Landry , Lefevrem Laurent , Stolf Patricia
Published: July 2014

Nowadays, there is no doubt that energy consumption has become a limiting factor in the design and operation of high performance computing (HPC) systems. This is evidenced by the rise of efforts both from the academia and the industry to reduce the energy consumption of those systems. Unlike hardware solutions, software initiatives targeting HPC systems' energy consumption reduction despite their effectiveness are often limited for reasons including (1) the program specific nature of the solution proposed; (2) the need of deep understanding of the application task at hand; and (3) proposed solutions are often difficult to use by novices and/or are designed for single task environments. This paper proposes a three step blind system‐wide, application independent, fine‐grain, and easy to use (user friendly) methodology for improving energy performance of HPC systems. The methodology typically breaks into phase detection, phase characterization, and phase identification and system reconfiguration. And it is blind in the sense that it does not require any knowledge from users. It relies upon reconfigurable capabilities offered by the majority of HPC subsystems—including the processor, storage, memory, and communication subsystems—to reduce the overall energy consumption of the system (excluding network equipments) at runtime. We also present an implementation of our methodology through which we demonstrate its effectiveness via static analyses and experiments using benchmarks representative of HPC workloads. The memory becoming one of the most power hungry HPC system this paper also introduces and investigates the relevance of a potential power saving scheme which we refer to as memory size scaling. It is destined to scale the memory size for saving energy in a CPU frequency scaling like fashion. Copyright © 2014 John Wiley & Sons, Ltd.
Failure analysis and tolerance strategies in web service ecosystems
Authors: Liu Yi , Fan Yushun , Huang Keman , Tan Wei
Published: July 2014

Service‐oriented computing and cloud computing are playing critical roles in supporting business collaboration over the Internet. Thanks to the latest development in computing technologies, various large‐scale, evolving, and rapidly growing service ecosystems emerge. However, service failures greatly hamper the usability and reputation of service ecosystems. In the previous work, service failure is not adequately studied from an ecosystem's perspective. To address this gap, we propose a service failure analysis framework based on a complex network model of service ecosystem. This framework comprises a feature model of failed services and several service failure impact indicators. By applying the framework, empirical analysis of failed service features and failure impact assessment can be implemented more easily and precisely. Moreover, to provide failure tolerance strategies for service ecosystems, a novel composition‐based service substitution method is designed to replace the failed services with functional similar ones, such that the service systems are more robust when a failure occurs. As the new substitution method requires fewer structural data of services, it is more convenient to be applied in present RESTful Representational State Transfer (REST) service environment. Both the framework and the service substitution method are tested on real‐world data set, and their usability and efficiency are demonstrated. Copyright © 2014 John Wiley & Sons, Ltd.
The power of circuit simulations for designing photonic integrated circuits
Authors: Arellano C. , Mingaleev S. F. , Sokolov E. S. , Richter A.
Published: July 2014

The emerging of circuit‐level simulators for photonic integrated circuits (PICs) is driven by recent developments in technologies for integration of large‐scale monolithic PICs in both, silicon and InP technologies. For that reason, powerful circuit‐level simulators should be capable to model on the same circuit different types of sub‐components performing photonic, electronic or opto‐electronic, active or passive functions. In comparison with device‐level simulations, the use of realistic circuit‐level abstracted models facilitates rapid functional design without going into technological fabrication details and subsequent design flow. This accelerates the design process and decreases the number of runs to achieve the desired results. Detailed physical modeling remains limited to the design of some specific individual sub‐elements. Large‐scale PICs might comprise several thousands of elements. The circuit‐level abstraction also ensures that the simulation speed to achieve a certain simulation accuracy decreases reasonably slowly with the total number of photonic components in the modeled PIC. In this work, we present our solution for modeling PICs in the framework of the circuit‐level simulation tool VPIcomponentMaker™Photonic Circuits (Carnotstr. 6, 10587, Berlin, Germany, www.VPIphotonics.com). We demonstrate the combination of different simulation approaches in time domain, frequency domain and time‐and‐frequency domain for fast and accurate simulations. We discuss several diverse modeling benefits by means of application examples on silicon photonic PICs. Copyright © 2014 John Wiley & Sons, Ltd.
Corporate Social Responsibility in Korea: How to Communicate Global Issues to Local Stakeholders
Authors: Park Gain , Park Hyun Soon
Published: July 2014

This paper examines how to get support and legitimation for global environmental CSR campaigns from local and domestic stakeholders using construal level theory. The paper develops communication strategies to enhance the persuasiveness of CSR campaigns. A survey was with 252 young adults in eight experimental groups. We argue that there exists a certain distance toward every CSR topic perceived by individuals and that each matches better with either desirability or feasibility message framing. The results show that desirability messages have a greater power of persuasion in a CSR campaign that yields consequences in a distant time and place, whereas feasibility messages have a greater persuasive power in a campaign that yields relatively immediate results in a nearby place. We propose some recommendations for businesses on how to apply the findings to a practical CSR message design in order to improve the persuasiveness of global CSR campaigns. Copyright © 2014 John Wiley & Sons, Ltd and ERP Environment
Examining Stakeholders' Perceptions of Mining Impacts and Corporate Social Responsibility
Authors: Viveros Hector
Published: July 2014

This paper aims to provide a better understanding of multistakeholder perceptions of corporate social responsibility (CSR) in connection with mining industry impacts. While there is significant research about CSR, there is a lack of understanding in the area of specific stakeholders' perceptions within the extractive industry, particularly in a developing country like Chile. The findings reveal that stakeholders perceive mining impacts on social and environmental domains negatively in contrast to a positive perception about economic impacts. CSR is addressed in terms of social and environmental responsibilities, but is also perceived negatively as mere rhetoric, or simply as a marketing campaign. These perceptions reflect an anti‐trade‐off sentiment, revealing that CSR cannot be used as a tool to compensate negative mining impacts. Copyright © 2014 John Wiley & Sons, Ltd and ERP Environment
Cultural Values and Ecosystem Management at the Subwatershed Level
Authors: Retallack Matthew , Schott Stephan
Published: July 2014

The valuation of ecosystem services is often centred on the proper integration of ecological and economic values but overlooks the social and cultural dimensions of ecosystem changes. We argue that these factors are essential for sustainable outcomes because they underlie preference formation, affect ownership over decision making and may help ensure that primary non‐market services needed to maintain ecosystem functions are sustained. In this study, we propose a conceptual framework for ecosystem service valuation at a local subwatershed scale that employs participatory democracy and discourse‐based methods to elicit and develop value systems while at the same time serving as a decision‐making process. Incorporating cultural theory and perceptions of risk tolerance, the framework discusses the importance of cultural considerations to achieving intergenerational equity, a precondition for sustainable development. The framework is applied to the case of Chelsea, Québec (Canada), and used to examine the community consultation component of a policy development process. Copyright © 2014 John Wiley & Sons, Ltd and ERP Environment
The Influence of Interests and Beliefs on the Use of Environmental Cost–Benefit Analysis in Water Policy: The case of German policy‐makers
Authors: Dehnhardt Alexandra
Published: July 2014

In recent decades cost–benefit analysis (CBA) and environmental benefit valuation have been assigned a significant role for environmental policy‐making and have been integrated as economic tools into the EC Water Framework Directive. The primary aim of the study is to explore the role that interests of bureaucratic actors as well as their beliefs might play in the application of environmental CBA. The paper draws on different analytical approaches derived from a political economy and a policy science perspective to explain the apparent reluctance to use the results of CBA and benefit estimates in policy‐making. The empirical findings of a qualitative survey among German water policy‐makers reveal that the self‐interested behaviour of bureaucratic actors impedes the use of CBA, but also suggest a considerable influence of beliefs that shape actors’ perception of the suitability of economic valuation approaches for environmental policy‐making. A differentiated view on these restraints might contribute to a reasonable use of procedural economic instruments in order to achieve environmental objectives. Copyright © 2014 John Wiley & Sons, Ltd and ERP Environment
Tetranuclear [2×2] Square‐Grid Lanthanide(III) Complexes: Syntheses, Structures, and Magnetic Properties
Authors: Biswas Sourav , Das Sourav , van Leusen Jan , Kögerler Paul , Chandrasekhar Vadapalli
Published: July 2014

The reactions of lanthanide(III) nitrate salts (DyIII, TbIII, GdIII, and ErIII) with the aroylhydrazone‐based multidentate ligand 6‐(hydroxymethyl)‐N′‐[1‐(pyridin‐2‐yl)ethylidene]picolinohydrazide (LH2) in the presence of Et3N in a molar ratio of 1:1:4 afforded a series of homometallic tetranuclear lanthanide(III) complexes, [Ln4(LH)4(μ2‐OH)3(μ2‐OMe)]4NO3·xMeOH·yH2O (1, Ln = Dy, x = 2, y = 4; 2, Ln = Tb, x = 2, y = 4; 3, Ln = Gd, x = 2, y = 5; and 4, Ln = Er, x = 3, y = 3). X‐ray diffraction studies revealed that all of the complexes contain a tetracationic [2×2] square‐grid‐like [Ln4(μ2‐OH)3(μ2‐OMe)(μ2‐O)4]4+ core, which is assembled by the concerted coordination action of four monoanionic [LH]– ligands along with three μ2‐OH ligands and a μ2‐OMe ligand. All of the lanthanide centers are eight‐coordinate and adopt distorted triangular‐dodecahedral coordination geometries with two different types of coordination environments (6O,2N and 4O,4N). The magnetic susceptibility measurements of the complexes reveal both the presence of all‐antiferromagnetic coupling interactions as well as both isotropic (3) and anisotropic (1, 2, 4) single‐ion contributions, which do not result in slow relaxation characteristics typical of single‐molecule magnets.
Polynuclear Copper(II) Complexes as Catalysts for the Peroxidative Oxidation of Cyclohexane in a Room‐Temperature Ionic Liquid
Authors: Jlassi Raja , Ribeiro Ana P. C. , Guedes da Silva M. Fátima C. , Mahmudov Kamran T. , Kopylovich Maximilian N. , Anisimova Tatiana B. , Naïli Houcine , Tiago Gonçalo A. O. , Pombeiro Armando J. L.
Published: July 2014

The reaction of copper(II) nitrate hydrate with sodium 2‐[2‐(2,4‐dioxopentan‐3‐ylidene)hydrazinyl]terephthalate (Na2HL1) in the absence or presence of imidazole (im) leads to the new complexes [(H2O)Cu0.5{(μ‐L1‐1κO:2κ3N,O′,O″)Cu(H2O)2}]2 (1) and [Cu(im)(μ‐HL1‐1κO:2κ3N,O,O′)]2 (2), respectively, whereas the 1D coordination polymer [Cu2(H2O)2(μ‐H2L2‐1κ3N,O,O′:2κO″)(μ‐L2‐1κ3N,O,O′:2κ2N′,O″)]n (3) is obtained from Cu(NO3)2·2.5H2O and sodium 2‐[2‐(4,4‐dimethyl‐2,6‐dioxocyclohexylidene)hydrazinyl]terephthalate (Na2HL2). All of the compounds were characterized by ESI‐MS, IR spectroscopy, elemental analysis and X‐ray diffraction analysis. Di‐ or tri‐deprotonated ligands display different coordination modes and lead to distinct nuclearities of the CuII complexes depending on the conditions used for the syntheses. Complexes 1–3 were successfully tested as dual‐role catalysts for cyclohexane oxidation under acid‐free conditions in the ionic liquid [1‐butyl‐3‐methylimidazolium tetrafluoroborate, (bmim)(BF4)] as well as in acetonitrile. The application of the ionic liquid (IL) increased the product yield and turnover number and decreased the reaction time, in comparison with those for the use of the conventional acetonitrile solvent. Easy recycling of the catalyst, with preservation of almost the initial activity and selectivity, was also achieved by using the IL medium.
Hydrophilic Pd0 Complexes Based on Sugars for Efficient Suzuki–Miyaura Coupling in Aqueous Systems
Authors: Tarantino Giulia , Curcio Massimiliano , Pica Andrea , Carpentieri Andrea , Cucciolito Maria E. , Ruffo Francesco , Vitagliano Aldo , Lega Matteo
Published: July 2014

Two classes of hydrophilic Pd0 complexes containing P,N and N,N sugar‐based ligands were prepared and tested in the Suzuki–Miyaura cross‐coupling reaction under environmentally friendly aqueous conditions. The best catalyst was tolerant towards different substrates, and its activity is comparable with the highest values reported so far for reactions in aqueous media [loading 0.0010 %, turnover frequency (TOF) 3.5 × 104 h–1].
Synthesis of the Spiroketal Fragment of (–)‐Ushikulide A
Authors: Yadav Jhillu S. , Reddy N. Mallikarjuna , Rahman Md. Ataur , Prasad Attaluri R.
Published: July 2014

The stereoselective synthesis of the spiroketal fragment of the immunosuppressant (–)‐ushikulide A is described. The salient feature of this synthesis is the construction of the spiroketal moiety by hydrolysis of a dialkylated tosylmethyl isocyanide derivative derived from alkylation of tosylmethyl isocyanide (TosMIC) with suitably substituted halohydrin derivatives. The key functionalized tetrahydropyran ring was constructed by using Prins cyclization of the α‐acetoxy ether.
Dual Catalysis in Domino N‐Benzylation/Intramolecular C–H Arylation: Regio‐ and Chemoselective Synthesis of Annelated Nitrogen Heterocycles
Authors: Laha Joydev K. , Dayal Neetu , Singh Swati , Bhimpuria Rohan
Published: July 2014

A general method has been developed for the synthesis of fused nitrogen heterocycles by using a domino N‐benzylation/C–H arylation reaction sequence. The details and yields of the domino process were compared with those of the two‐step literature protocol. Fused azaindoles, which are otherwise difficult to obtain, were synthesized by using this process. The unprecedented catalytic role of PPh3 in this N‐benzylation is described.
Biocatalytic Synthesis of Enantiopure β‐Methoxy‐β‐arylalanine Derivatives
Authors: Fan Shiming , Liu Shouxin , Zhang Hubo , Liu Ying , Yang Yihuang , Jin Longyi
Published: July 2014

Chiral β‐hydroxy‐β‐arylalanine and β‐methoxy‐β‐arylalanine derivatives, which occur widely in marine nature products, were stereoselectively synthesized with 99 % ee values. The two erythro isomers were prepared by L‐ or D‐aminoacylase‐catalyzed resolution of the corresponding N‐acetyl derivatives, whereas the two threo isomers were obtained only by D‐aminoacylase‐catalyzed resolution of the derivatives. erythro‐β‐Hydroxy‐β‐arylalanine derivatives were prepared by diastereoselective hydrogenation of ethyl 2‐(hydroxyimino)‐3‐oxo‐3‐arylpropanoates, which were in turn acquired by the oximation of ethyl 3‐oxo‐3‐arylpropanoates with ethyl nitrite in the presence of nano‐K2CO3 with yields of 72 % to 80 %. β‐Methoxy‐β‐arylalanine derivatives were synthesized through Williamson reactions between the corresponding β‐hydroxy‐β‐arylalanines and iodomethane with silver oxide as base.
Spiroaminals – Crystal Structure and Computational Investigation of Conformational Preferences and Tautomerization Reactions
Authors: Loerbroks Claudia , Böker Birte , Cordes Jens , Barrett Anthony G. M. , Thiel Walter
Published: July 2014

We report the first X‐ray structure of a spiroaminal hydrochloride. The chiral spiroaminal crystallizes as a racemic hydrochloride in the monoclinic space group P21/n and adopts the thermodynamically most stable conformation. Density functional calculations on several spiroaminals were used to establish correlations between trends in conformational energies, steric repulsions, and anomeric effects and to reveal the mechanism of the ring‐opening tautomerization reaction. In the unsubstituted and backbone‐substituted spiroaminals, the aminal tautomer is thermodynamically preferred. N‐Substituted spiroaminals favor the amine/imine form for steric reasons, except for those with bridging N,N′ groups. The tautomerization from the aminal to the amine/imine is endergonic and kinetically hindered in the neutral species but quite facile after protonation. Anomeric effects lower the barriers but are less important than steric factors for relative energies.
Stereoselective Synthesis of Lignans of Three Structural Types from a Common Intermediate, Enantioselective Synthesis of (+)‐Yangambin
Authors: Syed Majid Khalil , Murray Cian , Casey Mike
Published: July 2014

Enantioselective total synthesis of (+)‐yangambin was achieved. The key transformation is one‐pot conjugate addition/aldol reaction that involves an enantioenriched benzyl tert‐butyl sulfoxide, an enone, and gaseous formaldehyde to construct the bis(phenylpropanoid) backbone with excellent stereoselectivity and in good yield. Reduction of the ketone with diisobutylaluminium hydride and acid‐catalysed cyclisation in EtOH furnished (+)‐yangambin in good yield. The resulting synthesis is short, efficient and highly selective. Formation of 2,5‐diaryltetrahydrofuran lignans was observed as a side reaction in the final step of yangambin synthesis. Acid‐catalysed cyclisation of the aldol intermediate gave a completely different outcome. Dehydration to give an enone was followed by two electrophilic aromatic substitution reactions to furnish a derivative of the lignan lirionol.
Seismic performance and damage evaluation of a reinforced concrete frame with hysteretic dampers through shake‐table tests
Authors: Benavent‐Climent Amadeo , Morillas Leandro , Escolano‐Margarit David
Published: July 2014

Passive energy dissipation devices are increasingly implemented in frame structures to improve their performance under seismic loading. Most guidelines for designing this type of system retain the requirements applicable to frames without dampers, and this hinders taking full advantage of the benefits of implementing dampers. Further, assessing the extent of damage suffered by the frame and by the dampers for different levels of seismic hazard is of paramount importance in the framework of performance‐based design. This paper presents an experimental investigation whose objectives are to provide empirical data on the response of reinforced concrete (RC) frames equipped with hysteretic dampers (dynamic response and damage) and to evaluate the need for the frame to form a strong column‐weak beam mechanism and dissipate large amounts of plastic strain energy. To this end, shake‐table tests were conducted on a 2/5‐scale RC frame with hysteretic dampers. The frame was designed only for gravitational loads. The dampers provided lateral strength and stiffness, respectively, three and 12 times greater than those of the frame. The test structure was subjected to a sequence of seismic simulations that represented different levels of seismic hazard. The RC frame showed a performance level of ‘immediate occupancy’, with maximum rotation demands below 20% of the ultimate capacity. The dampers dissipated most of the energy input by the earthquake. It is shown that combining hysteretic dampers with flexible reinforced concrete frames leads to structures with improved seismic performance and that requirements of conventional RC frames (without dampers) can be relieved. Copyright © 2014 John Wiley & Sons, Ltd.
An embedded boundary framework for compressible turbulent flow and fluid–structure computations on structured and unstructured grids
Authors: Lakshminarayan V. , Farhat C. , Main A.
Published: July 2014

The finite volume method with exact two‐phase Riemann problems (FIVER) is a two‐faceted computational method for compressible multi‐material (fluid–fluid, fluid–structure, and multi‐fluid–structure) problems characterized by large density jumps, and/or highly nonlinear structural motions and deformations. For compressible multi‐phase flow problems, FIVER is a Godunov‐type discretization scheme characterized by the construction and solution at the material interfaces of local, exact, two‐phase Riemann problems. For compressible fluid–structure interaction (FSI) problems, it is an embedded boundary method for computational fluid dynamics (CFD) capable of handling large structural deformations and topological changes. Originally developed for inviscid multi‐material computations on nonbody‐fitted structured and unstructured grids, FIVER is extended in this paper to laminar and turbulent viscous flow and FSI problems. To this effect, it is equipped with carefully designed extrapolation schemes for populating the ghost fluid values needed for the construction, in the vicinity of the fluid–structure interface, of second‐order spatial approximations of the viscous fluxes and source terms associated with Reynolds averaged Navier–Stokes (RANS)‐based turbulence models and large eddy simulation (LES). Two support algorithms, which pertain to the application of any embedded boundary method for CFD to the robust, accurate, and fast solution of FSI problems, are also presented in this paper. The first one focuses on the fast computation of the time‐dependent distance to the wall because it is required by many RANS‐based turbulence models. The second algorithm addresses the robust and accurate computation of the flow‐induced forces and moments on embedded discrete surfaces, and their finite element representations when these surfaces are flexible. Equipped with these two auxiliary algorithms, the extension of FIVER to viscous flow and FSI problems is first verified with the LES of a turbulent flow past an immobile prolate spheroid, and the computation of a series of unsteady laminar flows past two counter‐rotating cylinders. Then, its potential for the solution of complex, turbulent, and flexible FSI problems is also demonstrated with the simulation, using the Spalart–Allmaras turbulence model, of the vertical tail buffeting of an F/A‐18 aircraft configuration and the comparison of the obtained numerical results with flight test data. Copyright © 2014 John Wiley & Sons, Ltd.
Numerical comparison of hybridized discontinuous Galerkin and finite volume methods for incompressible flow
Authors: Ahnert T. , Bärwolff G.
Published: July 2014

In this study, a hybridizable discontinuous Galerkin method is presented for solving the incompressible Navier–Stokes equation. In our formulation, the convective part is linearized using a Picard iteration, for which there exists a necessary criterion for convergence. We show that our novel hybridized implementation can be used as an alternative method for solving a range of problems in the field of incompressible fluid dynamics. We demonstrate this by comparing the performance of our method with standard finite volume solvers, specifically the well‐established finite volume method of second order in space, such as the icoFoam and simpleFoam of the OpenFOAM package for three typical fluid problems. These are the Taylor–Green vortex, the 180‐degree fence case and the DFG benchmark. Our careful comparison yields convincing evidence for the use of hybridizable discontinuous Galerkin method as a competitive alternative because of their high accuracy and better stability properties. Copyright © 2014 John Wiley & Sons, Ltd.
An Fc‐optimized NKG2D‐immunoglobulin G fusion protein for induction of natural killer cell reactivity against leukemia
Authors: Steinbacher Julia , Baltz‐Ghahremanpour Katrin , Schmiedel Benjamin Joachim , Steinle Alexander , Jung Gundram , Kübler Ayline , André Maya Caroline , Grosse‐Hovest Ludger , Salih Helmut Rainer
Published: July 2014

Recruitment of Fc‐receptor‐bearing effector cells, such as natural killer (NK) cells, is a feature critical for the therapeutic success of antitumor antibodies and can be improved by the modifications of an antibody's Fc part. The various ligands of the activating immunoreceptor NKG2D, NKG2DL) are selectively expressed on malignant cells including leukemia. We here took advantage of the tumor‐associated expression of NKG2DL for targeting leukemic cells by NKG2D–immunoglobulin G (IgG)1 fusion proteins containing modified Fc parts. Compared to NKG2D–Fc containing a wild‐type Fc part (NKG2D–Fc–WT), our mutants (S239D/I332E and E233P/L234V/L235A/ΔG236/A327G/A330S) displayed highly enhanced (NKG2D–Fc–ADCC) and abrogated (NKG2D–Fc–KO) affinity to the NK cell Fc receptor, respectively. Functional analyses with allogenic as well as autologous NK cells and primary malignant cells of leukemia patients revealed that NKG2D–Fc–KO significantly reduced NK reactivity by blocking immunostimulatory NKG2D–NKG2DL interaction. NKG2D–Fc–WT already enhanced antileukemia reactivity by inducing antibody‐dependent cellular cytotoxicity (ADCC) with NKG2D–Fc–ADCC mediating significantly stronger effects. Parallel application of NKG2D–Fc–ADCC with Rituximab caused additive effects in lymphoid leukemia. In line with the tumor‐associated expression of NKG2DL, no NK cell ADCC against resting healthy blood cells was induced. Thus, NKG2D–Fc–ADCC potently enhances NK antileukemia reactivity despite the inevitable reduction of activating signals upon binding to NKG2DL and may constitute an attractive means for immunotherapy of leukemia.
Human natural killer cells promote cross‐presentation of tumor cell‐derived antigens by dendritic cells
Authors: Deauvieau Florence , Ollion Vincent , Doffin Anne‐Claire , Achard Carole , Fonteneau Jean‐François , Verronese Estelle , Durand Isabelle , Ghittoni Raffaella , Marvel Jacqueline , Dezutter‐Dambuyant Colette , Walzer Thierry , Vie Henri , Perrot Ivan , Goutagny Nadège , Caux Christophe , Valladeau‐Guilemond Jenny
Published: July 2014

Dendritic cells (DCs) cross‐present antigen (Ag) to initiate T‐cell immunity against most infections and tumors. Natural killer (NK) cells are innate cytolytic lymphocytes that have emerged as key modulators of multiple DC functions. Here, we show that human NK cells promote cross‐presentation of tumor cell‐derived Ag by DC leading to Ag‐specific CD8+ T‐cell activation. Surprisingly, cytotoxic function of NK cells was not required. Instead, we highlight a critical and nonredundant role for IFN‐γ and TNF‐α production by NK cells to enhance cross‐presentation by DC using two different Ag models. Importantly, we observed that NK cells promote cell‐associated Ag cross‐presentation selectively by monocytes‐derived DC (Mo‐DC) and CD34‐derived CD11bnegCD141high DC subsets but not by myeloid CD11b+ DC. Moreover, we demonstrate that triggering NK cell activation by monoclonal antibodies (mAbs)‐coated tumor cells leads to efficient DC cross‐presentation, supporting the concept that NK cells can contribute to therapeutic mAbs efficiency by inducing downstream adaptive immunity. Taken together, our findings point toward a novel role of human NK cells bridging innate and adaptive immunity through selective induction of cell‐associated Ag cross‐presentation by CD141high DC, a process that could be exploited to better harness Ag‐specific cellular immunity in immunotherapy.
Colorectal liver metastases with a disrupted circadian rhythm phase shift the peripheral clock in liver and kidney
Authors: Huisman Sander A. , Oklejewicz Malgorzata , Ahmadi Ali R. , Tamanini Filippo , Ijzermans Jan N.M. , van der Horst Gijsbertus T.J. , de Bruin Ron W.F.
Published: July 2014

Circadian clock genes regulate 10–15% of the transcriptome, and might function as tumor suppressor genes. Relatively little is known about the circadian clock in tumors and its effect on surrounding healthy tissues. Therefore, we compared the 24‐hr expression levels of key circadian clock genes in liver and kidney of healthy control mice with those of mice bearing C26 colorectal tumor metastases in the liver. Metastases were induced by injection of C26 colorectal carcinoma cells into the spleen. Subsequently, tumor, liver and kidney tissue was collected around the clock to compare circadian rhythmicity. Expression levels of five clock genes (Rev‐Erbα, Per1, Per2, Bmal1 and Cry1) and three clock‐controlled genes (CCGs; Dbp, p21 and Wee1) were determined by qRT‐PCR. Liver and kidney tissue of healthy control mice showed normal 24‐hr oscillations of all clock genes and CCGs, consistent with normal circadian rhythmicity. In colorectal liver metastases, however, 24‐hr oscillations were completely absent for all clock genes and CCGs except Cry1. Liver and kidney tissue of tumor‐bearing mice showed a shift in clock periodicity relative to control mice. In the liver we observed a phase advance, whereas in the kidney the phase was delayed. These data show that hepatic metastases of C26 colon carcinoma with a disrupted circadian rhythm phase shift liver and kidney tissue clocks, which strongly suggests a systemic effect on peripheral clocks. The possibility that tumors may modify peripheral clocks to escape from ordinary circadian rhythms and in this way contribute to fatigue and sleep disorders in cancer patients is discussed.
The metastatic microenvironment: Claudin‐1 suppresses the malignant phenotype of melanoma brain metastasis
Authors: Izraely Sivan , Sagi‐Assif Orit , Klein Anat , Meshel Tsipi , Ben‐Menachem Shlomit , Zaritsky Assaf , Ehrlich Marcelo , Prieto Victor G. , Bar‐Eli Menashe , Pirker Christine , Berger Walter , Nahmias Clara , Couraud Pierre‐Olivier , Hoon Dave S.B. , Witz Isaac P.
Published: July 2014

Brain metastases occur frequently in melanoma patients with advanced disease whereby the prognosis is dismal. The underlying mechanisms of melanoma brain metastasis development are not well understood. Identification of molecular determinants regulating melanoma brain metastasis would advance the development of prevention and therapy strategies for this disease. Gene expression profiles of cutaneous and brain‐metastasizing melanoma variants from three xenograft tumor models established in our laboratory revealed that expression of tight junction component CLDN1 was lower in the brain‐metastasizing variants than in cutaneous variants from the same melanoma. The objective of our study was to determine the significance of CLDN1 downregulation/loss in metastatic melanoma and its role in melanoma brain metastasis. An immunohistochemical analysis of human cells of the melanocyte lineage indicated a significant CLDN1 downregulation in metastatic melanomas. Transduction of melanoma brain metastatic cells expressing low levels of CLDN1 with a CLDN1 retrovirus suppressed their metastatic phenotype. CLDN1‐overexpressing melanoma cells expressed a lower ability to migrate and adhere to extracellular matrix, reduced tumor aggressiveness in nude mice and, most importantly, eliminated the formation of micrometastases in the brain. In sharp contrast, the ability of the CLDN1‐overexpressing cells to form lung micrometastases was not impaired. CLDN1‐mediated interactions between these cells and brain endothelial cells constitute the mechanism underlying these results. Taken together, we demonstrated that downregulation or loss of CLDN1 supports the formation of melanoma brain metastasis, and that CLDN1 expression could be a useful prognostic predictor for melanoma patients with a high risk of brain metastasis.
miR‐542‐3p exerts tumor suppressive functions in neuroblastoma by downregulating Survivin
Authors: Althoff Kristina , Lindner Sven , Odersky Andrea , Mestdagh Pieter , Beckers Anneleen , Karczewski Sarah , Molenaar Jan J. , Bohrer Anna , Knauer Shirley , Speleman Frank , Epple Matthias , Kozlova Diana , Yoon Sena , Baek Kwanghee , Vandesompele Jo , Eggert Angelika , Schramm Alexander , Schulte Johannes H.
Published: July 2014

MicroRNAs (miRNAs) are deregulated in a variety of human cancers, including neuroblastoma, the most common extracranial tumor of childhood. We previously reported a signature of 42 miRNAs to be highly predictive of neuroblastoma outcome. One miRNA in this signature, miR‐542, was downregulated in tumors from patients with adverse outcome. Reanalysis of quantitative PCR and next‐generation sequencing transcript data revealed that miR‐542‐5p as well as miR‐542‐3p expression is inversely correlated with poor prognosis in neuroblastoma patients. We, therefore, analyzed the function of miR‐542 in neuroblastoma tumor biology. Ectopic expression of miR‐542‐3p in neuroblastoma cell lines reduced cell viability and proliferation, induced apoptosis and downregulated Survivin. Survivin expression was also inversely correlated with miR‐542‐3p expression in primary neuroblastomas. Reporter assays confirmed that miR‐542‐3p directly targeted Survivin. Downregulating Survivin using siRNA copied the phenotype of miR‐542‐3p expression in neuroblastoma cell lines, while cDNA‐mediated ectopic expression of Survivin partially rescued the phenotype induced by miR‐542‐3p expression. Treating nude mice bearing neuroblastoma xenografts with miR‐542‐3p‐loaded nanoparticles repressed Survivin expression, decreased cell proliferation and induced apoptosis in the respective xenograft tumors. We conclude that miR‐542‐3p exerts its tumor suppressive function in neuroblastoma, at least in part, by targeting Survivin. Expression of miR‐542‐3p could be a promising therapeutic strategy for treating aggressive neuroblastoma.
Family Therapy and Young Children A Case of Potential Child Abuse
Authors: Prior Graham
Published: July 2014

Parental distress often places young children in grave danger of physical abuse. In this paper a family therapy approach is used with a single parent family with young children where physical abuse is a distinct possibility.

The paper outlines some of the basic concepts used in the therapy and focuses on the effective use of relabelling as a means to diffuse anger and open the way for constructive change within the family system.
Towards a Multicultural Society: Family Therapy with Greek Families†
Authors: Stagoll Brian
Published: July 2014

Language and cultural differences can pose barriers to effective intervention in migrant families in conflict. Family therapy approaches can provide some useful strategies for overcoming these obstacles. A family therapy approach can (1) emphasise the value of utilizing natural network support systems; (2) provide a model which helps clarify communication problems arising in the relay of information through a third person acting as an interpreter; (3) underline the importance of non‐verbal and process aspects of family communication; (4) suggest techniques for negotiating, joining, and finding commonalities of family experience between a therapist and family of different ethnic background.

The therapist needs to develop sensitivity to both the universal and specific ethno‐cultural structures, norms and problems of families; when this sensitivity is achieved powerful and culturally syntonic healing forces can be released. Examples of successful family therapy interventions in some Greek families in conflict are given.
The Structure of the Families of Schizophrenics
Authors: Davis John Mark
Published: July 2014

In the families of schizophrenic patients everything is subordinated to the neurotic or psychotic needs of one of the parents, and the whole family then works together to stop that parent from becoming psychotic. The other parent must become completely subjugated or withdrawn and leave the family under the domination of his spouse. This becomes a rigid system in which the patient's role is to “feel nothing, do nothing, and be nothing”, and any minor change in him becomes a major threat to the integrity of the whole family. It is when he can no longer maintain this role that the person becomes clinically schizophrenic. Some of the difficulties in treating schizophrenic patients in individual or family therapy are discussed.
Group Therapy with Couples in Conflict
Authors: Kaslow Florence W.
Published: July 2014

This article describes a psychoanalytically based time limited model of couples group therapy, using live clinical material to illustrate the process and flow of therapy. Because of the pre‐therapy clear agreement regarding number of sessions, it is important that the contract be adhered to by all parties, underscoring issues of reliability regarding commitment and fostering completion. Critical themes such as dependence and independence rapidly become focal issues in treatment. Mirroring, reflecting, confronting, supporting and interpreting are among the treatment techniques utilized. A heterosexual co‐therapy team is recommended as the optimal therapeutic pair for group leadership.
Consumer Feedback from Short Courses in Family Therapy: a New Zealand Report
Authors: Pilalis Jennie K.
Published: July 2014

Questions are emerging regarding the usefulness and efficiency of the present ad hoc and haphazard manner of providing short courses in family therapy. This paper reports on the responses of 105 participants in different types of short seminar‐workshops to a mailed, evaluation questionnaire. The characteristics of those attending, their expectations, reported satisfaction and changes in practice following attendance are explored. Felt needs for further training are also reported. Suggestions are made to consumers, organisers and leaders of courses and to all interested in family therapy training regarding possible future directions in short, informal course provision. The need for more detailed study to test out these suggestions and other issues raised is highlighted.
Step‐Families and the Marriage Counsellor*
Authors: Harvey Les
Published: July 2014

Marital breakdown and the threat of it affects all members of the family. When a stepfamily is involved more people are affected. Marriage counsellors will now encounter more clients who are in stepfamilies. Stepfamily formation is different from nuclear family formation. These differences and their relevance to marriage counselling are discussed. Utilising family system, small group learning and organisational development concepts a number of tasks for the marriage counsellor and others dealing with stepfamilies are discussed.
Family Law and Family Systems: Multidisciplinary Training for Professionals
Authors: Topham Margaret , Davidson Paul
Published: July 2014

The Family Court in New Zealand has become the crucible for the mixing of legal and mental health professionals. Low key workshops convened by family therapists for multidisciplinary groups have made successful use of family therapy models and expertise to provide a base for the conciliation and mediation alternative to the adversary system so common in law and in earlier family litigation. Enhanced cross‐disciplinary understanding and morale appear to have accompanied the more formal learnings in family therapy, and the programme as detailed is included as one possible structure on which such experiences might be offered by other therapists in other places.
The Practice of Change: A Working MRI/Brief Therapy Clinic
Authors: Chubb Hendon , Nauts Phyllis L. , Evans Eldon L.
Published: July 2014

This paper describes the application of the M.R.I.'s brief therapy model in a new clinic in California. It discusses certain aspects of the model that are particularly important to the clinic's work and presents statistics for the early months of operation. Three case descriptions are offered as examples of the clinic's working style. A brief discussion of the model's effectiveness in a clinic setting is included.
Blackmail is Against the Law — Part Four: We Don't Need it Anymore!
Authors: Lang Moshe , McCallum Peter
Published: July 2014

This paper reports in detail on the fourth session of family therapy which began after both mother and 14‐year old daughter attempted suicide. The transcript demonstrates how the family in some ways stays the same while at the same time responding to therapy by some changes. Considerable background information emerges which makes previously recognized problems in the family much more comprehensible. Complex negotiations occur which lead to agreement that the children will withdraw from therapy and their parents will continue in marital therapy.
Cytotoxic and apoptotic activities of the plancitoxin I from the venom of crown‐of‐thorns starfish (Acanthaster planci) on A375.S2 cells
Authors: Lee Chi‐Chiu , Hsieh Hernyi Justin , Hwang Deng‐Fwu
Published: July 2014

This study reports on a cytotoxic toxin derived from the venom of the crown‐of‐thorns starfish Acanthaster planci (CAV). The protein toxin was isolated through both ion‐exchange and gel‐filtration chromatography, and characterized by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) and mass spectrum analyzes. The CAV was identified as plancitoxin I protein. The mechanistic role of the CAV toxin was explored in human malignant melanoma A375.S2 cell death. The results indicated that after incubation with CAV toxin, cells significantly decreased in A375.S2 cell viability and increased in the lactate dehydrogenase (LDH) level in a dose‐dependent manner. The assays indicated that CAV toxin promoted reactive oxygen species (ROS) production, induced nitric oxide (NO) formation, lost mitochondrial membrane potential (ΔΨm) and induced inter‐nucleosomal DNA fragmentation in A375.S2 cells. The molecular cytotoxicity of the CAV toxin was tested through evaluation of the apoptosis/necrosis ratio by double staining with annexin V‐FITC and a propidium iodide (PI) assay. The results suggested that CAV toxin induced a cytotoxic effect in A375.S2 cells via the apoptotic procedure, and may be associated with the regulation of the p38 pathways. Copyright © 2014 John Wiley & Sons, Ltd.
Coarse‐grained molecular dynamics simulations of protein–ligand binding
Authors: Negami Tatsuki , Shimizu Kentaro , Terada Tohru
Published: July 2014

Coarse‐grained molecular dynamics (CGMD) simulations with the MARTINI force field were performed to reproduce the protein–ligand binding processes. We chose two protein–ligand systems, the levansucrase–sugar (glucose or sucrose), and LinB–1,2‐dichloroethane systems, as target systems that differ in terms of the size and shape of the ligand‐binding pocket and the physicochemical properties of the pocket and the ligand. Spatial distributions of the Coarse‐grained (CG) ligand molecules revealed potential ligand‐binding sites on the protein surfaces other than the real ligand‐binding sites. The ligands bound most strongly to the real ligand‐binding sites. The binding and unbinding rate constants obtained from the CGMD simulation of the levansucrase–sucrose system were approximately 10 times greater than the experimental values; this is mainly due to faster diffusion of the CG ligand in the CG water model. We could obtain dissociation constants close to the experimental values for both systems. Analysis of the ligand fluxes demonstrated that the CG ligand molecules entered the ligand‐binding pockets through specific pathways. The ligands tended to move through grooves on the protein surface. Thus, the CGMD simulations produced reasonable results for the two different systems overall and are useful for studying the protein–ligand binding processes. © 2014 Wiley Periodicals, Inc.
Functional morphology of the bovid astragalus in relation to habitat: Controlling phylogenetic signal in ecomorphology
Authors: Barr W. Andrew
Published: July 2014

Bovid astragali are one of the most commonly preserved bones in the fossil record. Accordingly, astragali are an important target for studies seeking to predict the habitat preferences of fossil bovids based on bony anatomy. However, previous work has not tested functional hypotheses linking astragalar morphology with habitat while controlling for body size and phylogenetic signal. This article presents a functional framework relating the morphology of the bovid astragalus to habitat‐specific locomotor ecology and tests four hypotheses emanating from this framework. Highly cursorial bovids living in structurally open habitats are hypothesized to differ from their less cursorial closed‐habitat dwelling relatives in having (1) relatively short astragali to maintain rotational speed throughout the camming motion of the rotating astragalus, (2) a greater range of angular excursion at the hock, (3) relatively larger joint surface areas, and (4) a more pronounced “spline‐and‐groove” morphology promoting lateral joint stability. A diverse sample of 181 astragali from 50 extant species was scanned using a Next Engine laser scanner. Species were assigned to one of four habitat categories based on the published ecological literature. A series of 11 linear measurements and three joint surface areas were measured on each astragalus. A geometric mean body size proxy was used to size‐correct the measurement data. Phylogenetic generalized least squares (PGLS) was used to test for differences between habitat categories while controlling for body size differences and phylogenetic signal. Statistically significant PGLS results support Hypotheses 1 and 2 (which are not mutually exclusive) as well as Hypothesis 3. No support was found for Hypothesis 4. These findings confirm that the morphology of the bovid astragalus is related to habitat‐specific locomotor ecology, and that this relationship is statistically significant after controlling for body size and phylogeny. Thus, this study validates the use of this bone as an ecomorphological indicator. J. Morphol. 275:1201–1216, 2014. © 2014 Wiley Periodicals, Inc.
Simulating direct effects of dust aerosol on arid and semi‐arid regions using an aerosol–climate coupled system
Authors: Zhao Shuyun , Zhang Hua , Feng Song , Fu Qiang
Published: July 2014

This work uses an aerosol–climate coupled system to study the direct climatic effects of dust aerosol on global arid (including hyper‐arid) and semi‐arid regions. Results show that dust aerosol can cause surface cooling over these regions. The cooling effects of dust aerosol are larger in the Northern Hemisphere (NH) than in the Southern Hemisphere (SH). This asymmetric cooling leads to a severer reduction in evaporation over the low latitudes of the NH compared with their counterpart areas in the SH. In addition, air descent is enhanced (or ascent is weakened) by dust aerosol over the low latitudes of the NH, whereas the reverse happens in the SH. With the anomalous in evaporation and circulation, precipitation is decreased (increased) over the arid and semi‐arid areas in the NH (SH) by dust aerosol. Dust aerosol can decrease the potential evapotranspiration in arid and semi‐arid regions mainly by decreasing the net radiation flux at the top of the atmosphere, which compensates for the decrease in precipitation caused by dust aerosol. Therefore, as the dominant aerosol in the arid and semi‐arid regions, dust aerosol does not exacerbate the aridity over most of these regions. The effects of dust aerosol are indiscernible in the expansion of arid and semi‐arid areas on a global scale.