bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction sociale et usages d'Internet au Cameroun
Authors: Fambeu Ariel Herbert , Bakehe Novice Patrick
Published: September 2016

Le comportement des individus est très souvent influencé par leur environnement, notamment le comportement de leurs pairs. À partir des données issues de l’enquête sur les usages des Technologies de l’Information et de la Communication (TIC) par les ménages et citoyens camerounais, nous estimons les effets des pairs et les multiplicateurs sociaux des usages d’Internet. L’estimation du modèle linéaire en moyenne par la méthode de variables instrumentales (VI) fondée sur des restrictions d’exclusion confirme l’influence positive du voisinage social sur les usages d’Internet. Cette approche permet ainsi de trouver les multiplicateurs sociaux de 4,167 pour l’usage de la communication interpersonnelle, 10,204 pour la recherche et 7,692 pour le téléchargement en ligne.
Projections de l’état de santé de la population québécoise et impacts sur le risque de longévité d’un régime de retraite à prestations déterminées
Authors: Côté-Sergent Aurélie , Duclos Jean-Yves , Lekina Alexandre , Marchand Steeve , Michaud Pierre-Carl
Published: September 2016

Nous nous intéressons au risque futur de longévité étant donné l’augmentation de l’espérance de vie due au progrès technologique et la hausse de la prévalence de maladies liées à l’obésité et à la sédentarité. Nous utilisons dans un premier temps des techniques de microsimulation afin de projeter l’état de santé de la population québécoise dans divers scénarios, en incluant dans cette microsimulation une hypothèse d’amélioration exogène de la mortalité semblable à celle faite par la Régie des rentes du Québec (RRQ). Nous évaluons dans un deuxième temps les implications des tendances en santé fournies par ces simulations pour le ratio de financement de régimes de retraite à prestations déterminées (hypothétiques). Il s’avère qu’en 2050, le ratio de financement des scénarios alternatifs pourrait être entre 3 % et 18 % plus faible que celui du scénario de référence, indiquant que des changements dans l’évolution de l’état de santé pourraient avoir des effets importants sur les régimes de retraite dans le futur. Nous analysons dans un dernier temps les hypothèses de mortalité faites par la RRQ en considérant des scénarios alternatifs associés à des avancées médicales susceptibles de se produire dans les 10 prochaines années. Il s’avère selon cette analyse que les hypothèses de la RRQ pourraient surestimer significativement la croissance de l’espérance de vie future, en particulier celle des individus de 30 à 65 ans.
Un feuillet paroissial polémiste : La Bonne Nouvelle du curé Lavergne (1931-1935)
Authors: Dumas Alexandre
Published: September 2016

Les publications religieuses ont parfois été impliquées dans des polémiques politiques et sociales. La Bonne Nouvelle, bulletin paroissial de Notre-Dame de Grâce de Québec, présente la particularité d’avoir résisté pendant quatre ans aux plaintes répétées du premier ministre Louis-Alexandre Taschereau tout en ignorant les mises en garde continues du cardinal Villeneuve. Comment expliquer qu’un périodique contesté par de si hautes instances ait pu survivre aussi longtemps ? Cet article vise à mieux comprendre les mécanismes de la discipline ecclésiastique et la façon dont elle a pu être affectée par les rapports de l’Église à la politique.
A model for regulation by SynGAP-α1 of binding of synaptic proteins to PDZ-domain 'Slots' in the postsynaptic density
Authors: Walkup Ward G , Mastro Tara L , Schenker Leslie T , Vielmetter Jost , Hu Rebecca , Iancu Ariella , Reghunathan Meera , Bannon Barry Dylan , Kennedy Mary B
Published: September 2016

SynGAP is a Ras/Rap GTPase-activating protein (GAP) that is a major constituent of postsynaptic densities (PSDs) from mammalian forebrain. Its α1 isoform binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95, the principal PSD scaffold, and can occupy as many as 15% of these PDZ domains. We present evidence that synGAP-α1 regulates the composition of the PSD by restricting binding to the PDZ domains of PSD-95. We show that phosphorylation by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Polo-like kinase-2 (PLK2) decreases its affinity for the PDZ domains by several fold, which would free PDZ domains for occupancy by other proteins. Finally, we show that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present in higher concentration in PSDs isolated from mice with a heterozygous deletion of synGAP.
Platelet-rich concentrate in serum free medium enhances osteogenic differentiation of bone marrow-derived human mesenchymal stromal cells
Authors: Samuel Shani , Ahmad Raja Elina , Ramasamy Thamil Selvee , Karunanithi Puvanan , Naveen Sangeetha Vasudevaraj , Murali Malliga Raman , Abbas Azlina A. , Kamarul Tunku
Published: September 2016

Previous studies have shown that platelet concentrates used in conjunction with appropriate growth media enhance osteogenic differentiation of human mesenchymal stromal cells (hMSCs). However, their potential in inducing osteogenesis of hMSCs when cultured in serum free medium has not been explored. Furthermore, the resulting osteogenic molecular signatures of the hMSCs have not been compared to standard osteogenic medium. We studied the effect of infrequent supplementation (8-day interval) of 15% non-activated platelet-rich concentrate (PRC) in serum free medium on hMSCs proliferation and differentiation throughout a course of 24 days, and compared the effect with those cultured in a standard osteogenic medium (OM). Cell proliferation was analyzed by alamar blue assay. Gene expression of osteogenic markers (Runx2, Collagen1, Alkaline Phosphatase, Bone morphogenetic protein 2, Osteopontin, Osteocalcin, Osteonectin) were analyzed using Q-PCR. Immunocytochemical staining for osteocalcin, osteopontin and transcription factor Runx2 were done at 8, 16 and 24 days. Biochemical assays for the expression of ALP and osteocalcin were also performed at these time-points. Osteogenic differentiation was further confirmed qualitatively by Alizarin Red S staining that was quantified using cetylpyridinium chloride. Results showed that PRC supplemented in serum free medium enhanced hMSC proliferation, which peaked at day 16. The temporal pattern of gene expression of hMSCs under the influence of PRC was comparable to that of the osteogenic media, but at a greater extent at specific time points. Immunocytochemical staining revealed stronger staining for Runx2 in the PRC-treated group compared to OM, while the staining for Osteocalcin and Osteopontin were comparable in both groups. ALP activity and Osteocalcin/DNA level were higher in the PRC group. Cells in the PRC group had similar level of bone mineralization as those cultured in OM, as reflected by the intensity of Alizarin red stain. Collectively, these results demonstrate a great potential of PRC alone in inducing proliferation of hMSCs without any influence from other lineage-specific growth media. PRC alone has similar capacity to enhance hMSC osteogenic differentiation as a standard OM, without changing the temporal profile of the differentiation process. Thus, PRC could be used as a substitute medium to provide sufficient pool of pre-differentiated hMSCs for potential clinical application in bone regeneration.
Testing the link between genome size and growth rate in maize
Authors: Tenaillon Maud I. , Manicacci Domenica , Nicolas Stéphane D. , Tardieu Francois , Welcker Claude
Published: September 2016

Little is known about the factors driving within species Genome Size (GS) variation. GS may be shaped indirectly by natural selection on development and adaptative traits. Because GS variation is particularly pronounced in maize, we have sampled 83 maize inbred lines from three well described genetic groups adapted to contrasted climate conditions: inbreds of tropical origin, Flint inbreds grown in temperate climates, and Dent inbreds distributed in the Corn Belt. As a proxy for growth rate, we measured the Leaf Elongation Rate maximum during nighttime (LERmax) as well as GS in all inbred lines. In addition we combined available and new nucleotide polymorphism data at 29,090 sites to characterize the genetic structure of our panel. We found significant variation for both LERmaxand GS among groups defined by our genetic structuring. Tropicals displayed larger GS than Flints while Dents exhibited intermediate values. LERmaxfollowed the opposite trend with greater growth rate in Flints than in Tropicals. In other words, LERmaxand GS exhibited a significantly negative correlation (r= − 0.27). However, this correlation was driven by among-group variation rather than within-group variation—it was no longer significant after controlling for structure and kinship among inbreds. Our results indicate that selection on GS may have accompanied ancient maize diffusion from its center of origin, with large DNA content excluded from temperate areas. Whether GS has been targeted by more intense selection during modern breeding within groups remains an open question.
Genome-wide identification and characterization of WRKY gene family inSalix suchowensis
Authors: Bi Changwei , Xu Yiqing , Ye Qiaolin , Yin Tongming , Ye Ning
Published: September 2016

WRKY proteins are the zinc finger transcription factors that were first identified in plants. They can specifically interact with the W-box, which can be found in the promoter region of a large number of plant target genes, to regulate the expressions of downstream target genes. They also participate in diverse physiological and growing processes in plants. Prior to this study, a plenty of WRKY genes have been identified and characterized in herbaceous species, but there is no large-scale study of WRKY genes in willow. With the whole genome sequencing ofSalix suchowensis, we have the opportunity to conduct the genome-wide research for willow WRKY gene family. In this study, we identified 85 WRKY genes in the willow genome and renamed them from SsWRKY1 to SsWRKY85 on the basis of their specific distributions on chromosomes. Due to their diverse structural features, the 85 willow WRKY genes could be further classified into three main groups (group I–III), with five subgroups (IIa–IIe) in group II. With the multiple sequence alignment and the manual search, we found three variations of the WRKYGQK heptapeptide: WRKYGRK, WKKYGQK and WRKYGKK, and four variations of the normal zinc finger motif, which might execute some new biological functions. In addition, the SsWRKY genes from the same subgroup share the similar exon–intron structures and conserved motif domains. Further studies of SsWRKY genes revealed that segmental duplication events (SDs) played a more prominent role in the expansion of SsWRKY genes. Distinct expression profiles of SsWRKY genes with RNA sequencing data revealed that diverse expression patterns among five tissues, including tender roots, young leaves, vegetative buds, non-lignified stems and barks. With the analyses of WRKY gene family in willow, it is not only beneficial to complete the functional and annotation information of WRKY genes family in woody plants, but also provide important references to investigate the expansion and evolution of this gene family in flowering plants.
Revised single‐spacecraft method for determining wave vector k and resolving space‐time ambiguity
Authors: Bellan P. M.
Published: September 2016

A practical method is proposed for determining the wave vector of waves from single‐spacecraft measurements. This wave vector knowledge can then be used to remove the space‐time ambiguity produced by frequency Doppler shift associated with spacecraft motion. The method involves applying the Wiener‐Khinchin theorem to cross correlations of the current and magnetic field oscillations and to autocorrelations of the magnetic field oscillations. The method requires that each wave frequency component map to a unique wave vector, a condition presumed true in many spacecraft measurement situations. Examples validating the method are presented.
On The Superior High Temperature Hardness of Precipitation Strengthened High Entropy Ni‐Based Alloys
Authors: Tsao Te‐Kang , Yeh An‐Chou , Kuo Chen‐Ming , Murakami Hideyuki
Published: September 2016

The microstructure and high temperature hardness of two face‐centered cubic high entropy Ni‐based alloys with L12 γ′ precipitates have been studied. Both alloys exhibit higher mixing entropy and with the advantages in lower density and lower cost of raw materials than conventional Ni‐based superalloys. Their γ′ solvus are above 1 150 °C, and the γ–γ′ microstructure can be thermodynamically stable after isothermal ageing from 700 to 1 100 °C for at least 500 h. By XRD peak deconvolution, positive lattice misfits between γ and γ′ have been shown till elevated temperatures. The results from nano‐indentation test indicate that their highly alloyed γ′ phase have rendered more significant strengthening, and the underlying mechanism can be attributed to the higher anti‐phase boundary energy. Therefore, with minor refractory additions, the bulk hardness of present alloys can surpass that of commercial superalloy from room to high temperature.
Hollow Manganese Silicate Nanotubes with Tunable Secondary Nanostructures as Excellent Fenton‐Type Catalysts for Dye Decomposition at Ambient Temperature
Authors: Hao Shu‐Meng , Qu Jin , Zhu Zhong‐Shuai , Zhang Xiao‐Ying , Wang Qian‐Qian , Yu Zhong‐Zhen
Published: September 2016

Fast diffusion rate of ions and sufficiently exposed active sites are important for catalysts. As a superior but rarely studied Fenton‐type catalyst, unsatisfactory ion diffusion rate of manganese silicate is the exact obstacle for improving its catalytic activity. Here, hierarchical manganese silicate hollow nanotubes (MnSNTs) assembled by tunable secondary structures are precisely fabricated by an efficient hydrothermal method and systematically investigated as Fenton‐type catalysts for the first time. The open end and thin mesoporous walls of the hollow nanotubes help shorten the diffusion pathway of ions and enhance the mass transport. Moreover, the numerous standing small nanosheets endow MnSNTs with higher specific surface area and larger pore volume than the large nanosheets and nanoparticles, and thus expose more active sites for adsorption and catalytic decomposition. MnSNTs are highly efficient in adsorption and catalytic decomposition of cationic dyes with an excellent recycling stability. About 98.1% of methylene blue is catalytically decomposed in 45 min at an ambient temperature of 25 °C. When the temperature increases to 60 °C, only 2 min are required, with a 530% higher kinetic constant than reported.
Engineered Breast Cancer Cell Spheroids Reproduce Biologic Properties of Solid Tumors
Authors: Ham Stephanie L. , Joshi Ramila , Luker Gary D. , Tavana Hossein
Published: September 2016

Solid tumors develop as 3D tissue constructs. As tumors grow larger, spatial gradients of nutrients and oxygen and inadequate diffusive supply to cells distant from vasculature develops. Hypoxia initiates signaling and transcriptional alterations to promote survival of cancer cells and generation of cancer stem cells (CSCs) that have self‐renewal and tumor‐initiation capabilities. Both hypoxia and CSCs are associated with resistance to therapies and tumor relapse. This study demonstrates that 3D cancer cell models, known as tumor spheroids, generated with a polymeric aqueous two‐phase system (ATPS) technology capture these important biological processes. Similar to solid tumors, spheroids of triple negative breast cancer cells deposit major extracellular matrix proteins. The molecular analysis establishes presence of hypoxic cells in the core region and expression of CSC gene and protein markers including CD24, CD133, and Nanog. Importantly, these spheroids resist treatment with chemotherapy drugs. A combination treatment approach using a hypoxia‐activated prodrug, TH‐302, and a chemotherapy drug, doxorubicin, successfully targets drug resistant spheroids. This study demonstrates that ATPS spheroids recapitulate important biological and functional properties of solid tumors and provide a unique model for studies in cancer research.
FeNi3/NiFeOx Nanohybrids as Highly Efficient Bifunctional Electrocatalysts for Overall Water Splitting
Authors: Yan Xiaodong , Tian Lihong , Li Kexue , Atkins Samuel , Zhao Haifeng , Murowchick James , Liu Lei , Chen Xiaobo
Published: September 2016

Earth‐abundant, low‐cost, and highly active bifunctional electrocatalysts are of significant importance to the large‐scale production of hydrogen from water electrolysis. Herein, it is reported that novel FeNi3/NiFeOx nanohybrids display high electrocatalytic activities in both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). These FeNi3/NiFeOx nanohybrids are obtained with the unique hydrogenation treatment of NiFeOx nanosheets. Small onset potentials of ≈20 and 240 mV are obtained for HER and OER, respectively, benefited from the synergistic effect of FeNi3 and NiFeOx. Only a small voltage of 1.55 V is needed to reach a current density of 10 mA cm−2 for the overall water splitting in an alkaline electrolyzer when using FeNi3/NiFeOx as both cathode and anode catalysts. This is one of the best performance of electrocatalysts for HER and OER, shining the bright future for earth‐abundant, low‐cost bifunctional electrocatalysts for large‐scale production of hydrogen from water electrolysis.
Halloysites Stabilized Emulsions for Hydroformylation of Long Chain Olefins
Authors: von Klitzing Regine , Stehl Dimitrij , Pogrzeba Tobias , Schomäcker Reinhard , Minullina Renata , Panchal Abhishek , Konnova Svetlana , Fakhrullin Rawil , Koetz Joachim , Möhwald Helmuth , Lvov Yuri
Published: September 2016

Halloysites as tubular alumosilicates are introduced as inexpensive natural nanoparticles to form and stabilize oil–water emulsions. This stabilized emulsion is shown to enable efficient interfacial catalytic reactions. Yield, selectivity, and product separation can be tremendously enhanced, e.g., for the hydroformylation reaction of dodecene to tridecanal. In perspective, this type of formulation may be used for oil spill dispersions. The key elements of the described formulations are clay nanotubes (halloysites) which are highly anisometric, can be filled by helper molecules, and are abundantly available in thousands of tons, making this technology scalable for industrial applications.
Exfoliated Metal Oxide Nanosheets as Effective and Applicable Substrates for Atomically Dispersed Metal Nanoparticles with Tailorable Functionalities
Authors: Seo Jiyoon , Jin Xiaoyan , Kim Minho , Kim In Young , Jo Yun Kyung , Bera Sandipan , Lee Nam‐Suk , Lee Wan In , Kim Hyungjun , Hwang Seong‐Ju
Published: September 2016

An effective methodology to stabilize highly dispersed metal nanoparticles is developed by employing the exfoliated 2D metal oxide nanosheets with variable surface structures as substrates. The selection of appropriate crystal structure of titanate nanosheet is very crucial in stabilizing atomically dispersed Pt nanoparticles through the tuning of chemical interaction between Pt and titanate substrate. A theoretical study using density functional theory calculations confirms the significant influence of the crystal structure of layered titanate nanosheet on the crystal growth behavior of immobilized metal nanoparticle. As a consequence of the good dispersion of Pt nanoparticles, the Pt–trititanate nanohybrids with stronger interaction show much higher content of atomically dispersed Pt and better catalyst performances than do the Pt–lepidocrocite titanate ones. The applicability of the present method for other metal species is evidenced by the successful tuning of the crystal size and functionality of Au nanoparticles via immobilization on layered titanate nanosheets. The functionality of Au for surface‐enhanced Raman spectroscopy becomes improved by the anchoring on the lepidocrocite‐type titanate nanosheet. The present study underscores that the use of the metal oxide 2D nanosheets with appropriate surface structure as substrates is effective in tailoring the crystal growth and the functionalities of immobilized metal nanoparticles.
On Emotions and Decisions
Authors: Creo Robert A.
Published: September 2016

Last month, Master Mediator columnist Bob Creo looked at the role of emotions in conflict resolution decision making. In Part 2 this month, he factors in the effects of shame and guilt.
Construction of Tropane Derivatives by the Organocatalytic Asymmetric Dearomatization of Isoquinolines
Authors: Xu Jin‐Hui , Zheng Sheng‐Cai , Zhang Ji‐Wei , Liu Xin‐Yuan , Tan Bin
Published: September 2016

A chiral‐NHC‐catalyzed highly diastereo‐ and enantioselective dearomatizing double Mannich reaction of isoquinolines was developed that provides a powerful and straightforward synthetic route toward substituted tropane derivatives with four contiguous stereocenters. A unique feature of this strategy is the use of readily available isoquinolines to provide two reactive sites for dearomatization, thus opening up an unprecedented approach to tropane derivatives with excellent stereoselectivity. The four‐component reactions proceeded smoothly with good results. Thus, the present method is suitable for the diversity‐oriented synthesis of useful tropane derivatives with high efficiency.
Mit variablem Abstand gestapelte lineare Ketten magnetischer Ionen: ferromagnetische Ordnung mit einer Curie‐Temperatur von über 20 K
Authors: Friedländer Stefan , Liu Jinxuan , Addicoat Matt , Petkov Petko , Vankova Nina , Rüger Robert , Kuc Agnieszka , Guo Wei , Zhou Wencai , Lukose Binit , Wang Zhengbang , Weidler Peter G. , Pöppl Andreas , Ziese Michael , Heine Thomas , Wöll Christof
Published: September 2016

Die magnetischen Eigenschaften Metall‐organischer Gerüste (MOFs) der SURMOF‐2‐Serie wurden untersucht. Anders als bei Volumen‐MOF‐2‐Kristallen, bei denen Cu2+‐Ionen in einer Schaufelrad‐Anordnung vorliegen und antiferromagnetisch gekoppelt sind, zeigen die Carboxylatgruppen hier eine reißverschlussartige Anordnung. Eine theoretische Analyse ergibt, dass diese ungewöhnliche Kopplung der Spin‐
‐Ionen innerhalb der entstehenden, eindimensionalen Ketten bei niedriger Temperatur eine ferromagnetische Phase (FM‐Phase) stabilisiert. Anders als bei anderen geordneten 1D‐Systemen sind zum Induzieren des Ferromagnetismus keine starken Magnetfelder erforderlich. Die Konstanten der magnetischen Kopplung zur Beschreibung der Wechselwirkung zwischen den einzelnen Metallionen wurden in SQUID‐Versuchen bestimmt. Sie stimmen ausgezeichnet mit den Ergebnissen von Ab‐initio‐DFT‐Elektronenstruktur‐Berechnungen überein. Die theoretischen Ergebnisse ermöglichen eine detaillierte Beschreibung des ungewöhnlichen Verhaltens dieses exotischen, aber dennoch leicht herstellbaren Materials.
Selective Synthesis of Cyclooctanoids by Radical Cyclization of Seven‐Membered Lactones: Neutron Diffraction Study of the Stereoselective Deuteration of a Chiral Organosamarium Intermediate
Authors: Just‐Baringo Xavier , Clark Jemma , Gutmann Matthias J. , Procter David J.
Published: September 2016

Seven‐membered lactones undergo selective SmI2–H2O‐promoted radical cyclization to form substituted cyclooctanols. The products arise from an exo‐mode of cyclization rather than the usual endo‐attack employed in the few radical syntheses of cyclooctanes. The process is terminated by the quenching of a chiral benzylic samarium. A labeling experiment and neutron diffraction study have been used for the first time to probe the configuration and highly diastereoselective deuteration of a chiral organosamarium intermediate.
Aptamers against Cells Overexpressing Glypican 3 from Expanded Genetic Systems Combined with Cell Engineering and Laboratory Evolution
Authors: Zhang Liqin , Yang Zunyi , Le Trinh Thu , Teng I‐Ting , Wang Sai , Bradley Kevin M. , Hoshika Shuichi , Wu Qunfeng , Cansiz Sena , Rowold Diane J. , McLendon Christopher , Kim Myong‐Sang , Wu Yuan , Cui Cheng , Liu Yuan , Hou Weijia , Stewart Kimberly , Wan Shuo , Liu Chen , Benner Steven A. , Tan Weihong
Published: September 2016

Laboratory in vitro evolution (LIVE) might deliver DNA aptamers that bind proteins expressed on the surface of cells. In this work, we used cell engineering to place glypican 3 (GPC3), a possible marker for liver cancer theranostics, on the surface of a liver cell line. Libraries were then built from a six‐letter genetic alphabet containing the standard nucleobases and two added nucleobases (2‐amino‐8H‐imidazo[1,2‐a][1,3,5]triazin‐4‐one and 6‐amino‐5‐nitropyridin‐2‐one), Watson–Crick complements from an artificially expanded genetic information system (AEGIS). With counterselection against non‐engineered cells, eight AEGIS‐containing aptamers were recovered. Five bound selectively to GPC3‐overexpressing cells. This selection–counterselection scheme had acceptable statistics, notwithstanding the possibility that cells engineered to overexpress GPC3 might also express different off‐target proteins. This is the first example of such a combination.
Linear Chains of Magnetic Ions Stacked with Variable Distance: Ferromagnetic Ordering with a Curie Temperature above 20 K
Authors: Friedländer Stefan , Liu Jinxuan , Addicoat Matt , Petkov Petko , Vankova Nina , Rüger Robert , Kuc Agnieszka , Guo Wei , Zhou Wencai , Lukose Binit , Wang Zhengbang , Weidler Peter G. , Pöppl Andreas , Ziese Michael , Heine Thomas , Wöll Christof
Published: September 2016

We have studied the magnetic properties of the SURMOF‐2 series of metal–organic frameworks (MOFs). Contrary to bulk MOF‐2 crystals, where Cu2+ ions form paddlewheels and are antiferromagnetically coupled, in this case the Cu2+ ions are connected via carboxylate groups in a zipper‐like fashion. This unusual coupling of the spin
ions within the resulting one‐dimensional chains is found to stabilize a low‐temperature, ferromagnetic (FM) phase. In contrast to other ordered 1D systems, no strong magnetic fields are needed to induce the ferromagnetism. The magnetic coupling constants describing the interaction between the individual metal ions have been determined in SQUID experiments. They are fully consistent with the results of ab initio DFT electronic structure calculations. The theoretical results allow the unusual magnetic behavior of this exotic, yet easy‐to‐fabricate, material to be described in a detailed fashion.
A Kinetic Self‐Sorting Approach to Heterocircuit [3]Rotaxanes
Authors: Neal Edward A. , Goldup Stephen M.
Published: September 2016

In this proof‐of‐concept study, an active‐template coupling is used to demonstrate a novel kinetic self‐sorting process. This process iteratively increases the yield of the target heterocircuit [3]rotaxane product at the expense of other threaded species.
ESOA modified unsaturated polyester hybrid networks: A new perspective
Authors: Panda Shivkumari , Mohanty Priyabrata , Behera Dibakar , Kumar Bastia Tapan
Published: September 2016

Hybrid polymer networks based on unsaturated polyester (UPE) and epoxidized soybean oil acrylate (ESOA) were synthesized by reactive blending through free radical addition polymerization reaction. ESOA was prepared by acrylation of epoxidized soybean oil (ESO). The physical, mechanical, thermal and electrical properties of the cured blends were compared with the neat resin. ESOA resin bearing reactive functional groups showed good miscibility and compatibility with the UPE resin. The co‐cured resin showed substantial upgrading in the toughness, impact resistance, thermal properties, and downgrading brittleness up to the addition of 20 wt % of ESOA content. The muddled phase structure was corroborated by Fourier transform infrared spectroscopy, scanning electron microscope, and transmission electron microscopy and proved the formation of excellent hybrid polymer network. An improvement in overall properties has been achieved without seriously affecting any other properties. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44345.
Synthesis, Cyclooxygenase Inhibition, Anti‐Inflammatory Evaluation, and Ulcerogenic Liability of New 1,3,5‐Triarylpyrazoline Derivatives Possessing a Methanesulfonyl Pharmacophore
Authors: Abdellatif Khaled R. A. , Fadaly Wael A. A. , Azouz Amany A.
Published: September 2016

A new series of 1,3,5‐triarylpyrazolines 13a–l was synthesized and all prepared compounds were evaluated for their in vitro COX‐1/COX‐2 inhibitory activity and in vivo anti‐inflammatory activity. All test compounds were more selective for the COX‐2 isozyme and showed good in vivo anti‐inflammatory activity. Compound 13h was the most COX‐2 selective compound (COX‐2 selectivity index (SI) = 10.23) and the most potent anti‐inflammatory derivative (ED50 = 60.1 µmol/kg) in comparison with celecoxib (COX‐2 SI = 9.29 and ED50 = 81.4 µmol/kg). All screened compounds were less ulcerogenic (ulcer indexes (UI) = 0.33–1.33) than aspirin (UI = 2.33) and comparable to celecoxib (UI = 0.33).
Observable Degree Analysis to Match Estimation Performance for Wireless Tracking Networks
Authors: Ge Quanbo , Ma Jinyan , Chen Shaodong , Wang Yongting , Bai Liang
Published: September 2016

State estimation suffers some new challenging problems when wireless sensor networks (WSNs) are used in mobile target tracking systems. An important problem among them is low observability, which makes it necessary to further study performance of tracking estimators from an observable degree point of view. This paper studies observable degree analysis (ODA) to formulate the estimator performance for a kind of wireless tracking filter. For a kind of time‐varying Kalman estimator, an improved ODA method is proposed by using weighted least square, Cauchy Schwarz inequality and normalization processing. The main contributions are that the relation is firstly analytically established between the observable degree and the estimation performance, and finally the observable degree is normalized in [0,1]. Meanwhile, observable degrees are both given for local state components and the global state. Thereby, we have the conclusion that higher observable degree corresponds to better estimation performance of the Kalman filter. Accordingly, it is potentially hopeful to achieve an effective function to study estimation performance of tracking estimators by directly using the observable degree. Simulation is provided to verify the results on real‐time and generality, completeness and consistency/matching of the proposed observable degree analysis.
Pre‐incubation with cyclosporine A potentiates its inhibitory effects on pitavastatin uptake mediated by recombinantly expressed cynomolgus monkey hepatic organic anion transporting polypeptide
Authors: Takahashi Tsuyoshi , Ohtsuka Tatsuyuki , Uno Yasuhiro , Utoh Masahiro , Yamazaki Hiroshi , Kume Toshiyuki
Published: September 2016

Cyclosporine A, an inhibitor of hepatic organic anion transporting polypeptides (OATPs), reportedly increased plasma concentrations of probe substrates, although its maximum unbound blood concentrations were lower than the experimental half‐maximal inhibitory (IC50) concentrations. Pre‐incubation with cyclosporine A in vitro before simultaneous incubation with probes has been reported to potentiate its inhibitory effects on recombinant human OATP‐mediated probe uptake. In the present study, the effects of cyclosporine A and rifampicin on recombinant cynomolgus monkey OATP‐mediated pitavastatin uptake were investigated in pre‐ and simultaneous incubation systems. Pre‐incubation with cyclosporine A, but not with rifampicin, decreased the apparent IC50 values on recombinant cynomolgus monkey OATP1B1‐ and OATP1B3‐mediated pitavastatin uptake. Application of the co‐incubated IC50 values toward R values (1 + [unbound inhibitor]inlet to the liver, theoretically maximum/inhibition constant) in static models, 1.1 in monkeys and 1.3 in humans, for recombinant cynomolgus monkey and human OATP1B1‐mediated pitavastatin uptake might result in the poor prediction of drug interaction magnitudes. In contrast, the lowered IC50 values after pre‐incubation with cyclosporine A provided better prediction with R values of 3.9 for monkeys and 2.7 for humans when the estimated maximum cyclosporine A concentrations at the inlet to the liver were used. These results suggest that the enhanced inhibitory potential of perpetrator medicines by pre‐incubation on cynomolgus monkey OATP‐mediated pitavastatin uptake in vitro could be of value for the precise estimation of drug interaction magnitudes in silico, in accordance with the findings from pre‐administration of inhibitors on pitavastatin pharmacokinetics validated in monkeys. Copyright © 2016 John Wiley & Sons, Ltd.
On‐site remodeling at chromatin: How multiprotein complexes are rebuilt during DNA repair and transcriptional activation
Authors: Papadopoulou Thaleia , Richly Holger
Published: September 2016

In this review, we discuss a novel on‐site remodeling function that is mediated by the H2A‐ubiquitin binding protein ZRF1. ZRF1 facilitates the remodeling of multiprotein complexes at chromatin and lies at the heart of signaling processes that occur at DNA damage sites and during transcriptional activation. In nucleotide excision repair ZRF1 remodels E3 ubiquitin ligase complexes at the damage site. During embryonic stem cell differentiation, it contributes to retinoic acid‐mediated gene activation by altering the subunit composition of the Mediator complex. We postulate that ZRF1 operates in conjunction with cellular remodeling machines and suggest that on‐site remodeling might be a hallmark of many chromatin‐associated signaling pathways. We discuss yet unexplored functions of ZRF1‐mediated remodeling in replication and double strand break repair. In conclusion, we postulate that on‐site remodeling of multiprotein complexes is essential for the timing of chromatin signaling processes.
Interactions of donor sources and media influence the histo‐morphological quality of full‐thickness skin models
Authors: Lange Julia , Weil Frederik , Riegler Christoph , Groeber Florian , Rebhan Silke , Kurdyn Szymon , Alb Miriam , Kneitz Hermann , Gelbrich Götz , Walles Heike , Mielke Stephan
Published: September 2016

Human artificial skin models are increasingly employed as non‐animal test platforms for research and medical purposes. However, the overall histopathological quality of such models may vary significantly. Therefore, the effects of manufacturing protocols and donor sources on the quality of skin models built‐up from fibroblasts and keratinocytes derived from juvenile foreskins is studied. Histo‐morphological parameters such as epidermal thickness, number of epidermal cell layers, dermal thickness, dermo‐epidermal adhesion and absence of cellular nuclei in the corneal layer are obtained and scored accordingly. In total, 144 full‐thickness skin models derived from 16 different donors, built‐up in triplicates using three different culture conditions were successfully generated. In univariate analysis both media and donor age affected the quality of skin models significantly. Both parameters remained statistically significant in multivariate analyses. Performing general linear model analyses we could show that individual medium‐donor‐interactions influence the quality. These observations suggest that the optimal choice of media may differ from donor to donor and coincides with findings where significant inter‐individual variations of growth rates in keratinocytes and fibroblasts have been described. Thus, the consideration of individual medium‐donor‐interactions may improve the overall quality of human organ models thereby forming a reproducible test platform for sophisticated clinical research.
Biological activity of peptide‐conjugated polyion complex matrices consisting of alginate and chitosan
Authors: Fujimori Chikara , Kumai Jun , Nakamura Kyotaro , Gu Yingzi , Katagiri Fumihiko , Hozumi Kentaro , Kikkawa Yamato , Nomizu Motoyoshi
Published: September 2016

Peptide‐conjugated polysaccharide matrices using bioactive laminin‐derived peptides are useful biomaterials for tissue and cell engineering. Here, we demonstrate an easy handling preparation method for peptide‐polysaccharide matrices using polyion complex with both alginate and chitosan. First, aldehyde‐alginate was synthesized by oxidization of alginate using NaIO4, and then, reacted with Cys‐peptides. Next, the peptide‐alginate solution was added to a chitosan‐coated plate, and the peptide‐polyion complex matrices (peptide‐PCMs) were prepared. The peptide‐PCMs using an integrin αvβ3‐binding peptide (A99a: ALRGDN, mouse laminin α1 chain 1145‐1150) and an integrin α2β1‐binding peptide (EF1XmR: RLQLQEGRLHFXFD, X = Nle, mouse laminin α1 chain 2751‐2763) showed strong cell attachment activity in a dose‐dependent manner. When we examined the effect of various spacers on the biological activity of A99a‐PCM, hydrophobic and long spacers enhanced the cell attachment activity. Further, the A99a‐PCM with the spacers strongly promoted neurite outgrowth. The polyion complex method is an easy way to obtain insolubilized matrix and is widely applicable for various polysaccharides. The peptide‐PCM is useful as a biomaterial for cell and tissue engineering.
Development of downstream processing to minimize beta‐glucan impurities in GMP‐manufactured therapeutic antibodies
Authors: Vigor Kim , Emerson John , Scott Robert , Cheek Julia , Barton Claire , Bax Heather J. , Josephs Debra H. , Karagiannis Sophia N. , Spicer James F. , Lentfer Heike
Published: September 2016

The presence of impurities or contaminants in biological products such as monoclonal antibodies (mAb) could affect efficacy or cause adverse reactions in patients. ICH guidelines (Q6A and Q6B) are in place to regulate the level of impurities within clinical drug products. An impurity less often reported and, therefore, lacking regulatory guideline is beta‐glucan. Beta‐glucans are polysaccharides of d‐glucose monomers linked by (1‐3) beta‐glycosidic bonds, and are produced by prokaryotic and eukaryotic organisms, including plants. They may enter manufacturing processes via raw materials such as cellulose‐based membrane filters or sucrose. Here we report the detection of beta‐glucan contamination of a monoclonal IgE antibody (MOv18), manufactured in our facility for a first‐in‐human, first‐in‐class clinical trial in patients with cancer. Since beta‐glucans have potential immunostimulatory properties and can cause symptomatic infusion reactions, it was of paramount importance to identify the source of beta‐glucans in our product and to reduce the levels to clinically insignificant concentrations. We identified beta‐glucans in sucrose within the formulation buffer and within the housing storage buffer of the virus removal filter. We also detected low level beta‐glucan contamination in two of four commercially available antibodies used in oncology. Both formulation buffers contained sucrose. We managed to reduce levels of beta‐glucan in our product 10‐fold, by screening all sucrose raw material, filtering the sucrose by Posidyne® membrane filtration, and by incorporating extra wash steps when preparing the virus removal filter. The beta‐glucan levels now lie within a range that is unlikely to cause clinically significant immunological effects. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1494–1502, 2016
Self‐Assembly of a [2]Pseudorotaxane by an Inchworm‐Motion Mechanism
Authors: Meng Zheng , Wang Bo‐Yang , Xiang Jun‐Feng , Shi Qiang , Chen Chuan‐Feng
Published: September 2016

The threading of biomolecules through pores or channels in membranes is important to validate the physiological activities of cells. To aid understanding of the controlling factors required for the translocation in space with confined size and distorted conformation, it is desirable to identify experimental systems with minimized complexity. We demonstrate the mechanism of a linear guest L1 threading into a tris(crown ether) host TC with a combinational distorted cavity to form a triply interlocked [2]pseudorotaxane 3in‐[L1⊂TC]. An inchworm‐motion mechanism is proposed for the process. For the forward‐threading steps that lead to the formation of higher‐order interlocked species, guest L1 must adopt a bent conformation to find the next crown ether cavity. Two simplified models are applied to investigate the self‐assembly dynamic of 3in‐[L1⊂TC]. Kinetic NMR spectroscopic and molecular dynamics (MD) studies show that formation of the singly penetrated species is fast, whereas formation of the doubly and triply threaded species is several orders of magnitude slower. During threading the freedom of both the guest L1 and host TC gradually decrease due to their interactions. This results in a significant entropy effect for the threading dynamic, which is also observed for the threading of a biomolecular chain through a channel.
Obtaining miRNA‐Target Interaction Information from miRWalk2.0
Authors: Parveen Alisha , Gretz Norbert , Dweep Harsh
Published: September 2016

miRWalk2.0 (http://zmf.umm.uni‐heidelberg.de/mirwalk2) is a freely accessible, regularly updated comprehensive archive supplying the largest available collection of predicted and experimentally verified miRNA‐target interactions, with various novel and unique features to assist the scientific community. Approximately 949 million interactions between 11,748 miRNAs, 308,700 genes, and 68,460 lncRNAs are documented in miRWalk2.0 with 5,146,217 different kinds of identifiers to offer a one‐stop site to collect an abundance of information. This article describes a schematic workflow on how to obtain miRNA‐target interactions from miRWalk2.0. © 2016 by John Wiley & Sons, Inc.
Social‐ecological outcomes in recreational fisheries: the interaction of lakeshore development and stocking
Authors: Ziegler Jacob P. , Golebie Elizabeth J. , Jones Stuart E. , Weidel Brian C. , Solomon Christopher T.
Published: September 2016

Many ecosystems continue to experience rapid transformations due to processes like land use change and resource extraction. A systems approach to maintaining natural resources focuses on how interactions and feedbacks among components of complex social‐ecological systems generate social and ecological outcomes. In recreational fisheries, residential shoreline development and fish stocking are two widespread human behaviors that influence fisheries, yet emergent social‐ecological outcomes from these potentially interacting behaviors remain under explored. We applied a social‐ecological systems framework using a simulation model and empirical data to determine whether lakeshore development is likely to promote stocking through its adverse effects on coarse woody habitat and thereby also on survival of juvenile and adult fish. We demonstrate that high lakeshore development is likely to generate dependency of the ecosystem on the social system, in the form of stocking. Further, lakeshore development can interact with social‐ecological processes to create deficits for state‐level governments, which threatens the ability to fund further ecosystem subsidies. Our results highlight the value of a social‐ecological framework for maintaining ecosystem services like recreational fisheries.
Osteopontin has a protective role in prostate tumor development in mice
Authors: Danzaki Keiko , Kanayama Masashi , Alcazar Oscar , Shinohara Mari L.
Published: September 2016

Osteopontin (OPN) is a protein, generally considered to play a pro‐tumorigenic role, whereas several reports have demonstrated the anti‐tumorigenic function of OPN during tumor development. These opposing anti‐ and pro‐tumorigenic functions are not fully understood. Here, we report that host‐derived OPN plays an anti‐tumorigenic role in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model and a TRAMP tumor transplant model. Tumor suppression mediated by OPN in Rag2−/− mice suggests that OPN is dispensable in the adaptive immune response. We found that host‐derived OPN enhanced infiltration of natural killer (NK) cells into TRAMP tumors. The requirement of OPN in NK cell migration towards TRAMP cells was confirmed by an ex vivo cell migration assay. In contrast to TRAMP cells, in vivo B16 tumor development was not inhibited by OPN, and B16 tumors did not show OPN‐mediated cell recruitment. It is possible that low levels of chemokine expression by B16 cells do not allow OPN to enhance immune cell recruitment. In addition to demonstrating the anti‐tumorigenic role of OPN in TRAMP tumor development, this study also suggests that the contribution of OPN to tumor development depends on the type of tumor as well as the source and isoform of OPN.
The transcriptional repressor Gfi1 prevents lupus autoimmunity by restraining TLR7 signaling
Authors: Desnues Benoit , Macedo Amanda B. , Ordoñez‐Rueda Diana , Roussel‐Queval Annie , Malissen Bernard , Bruhns Pierre , Malissen Marie , Alexopoulou Lena
Published: September 2016

The transcriptional repressor growth factor independence 1 (Gfi1) is important in myeloid and lymphoid differentiation. In the current study we evaluated the involvement of Gfi1 in systemic lupus erythematosus (SLE). We found that Genista mice, which carry a hypomorphic mutation in the gfi1 gene or Gfi1‐deficient (Gfi1−/−) mice develop signs of spontaneous lupus autoimmunity, including increased serum levels of IgM and IgG2a, autoantibodies against RNA and DNA, glomerular immunodeposits and increased frequencies of plasmablasts, germinal center (GC) B cells and age‐associated B cells (ABCs). On the contrary, Genista mice deprived of TLR7 did not show any of these phenotypes, suggesting that the observed lupus autoimmunity in Genista mice is TLR7‐dependent. Moreover, Genista mice showed an increased activation of dendritic cells (DCs), B and T cells that was dependent on TLR7 for DCs and B cells, but not for T cells. Upon TLR7 or TLR4 stimulation Genista DCs produced increased amounts of TNF, IL‐6 and IFN‐β and showed increased NF‐κB phosphorylation and IRF7 nuclear translocation, suggesting that Gfi1 controls the NF‐κB and type I IFN signaling pathway downstream of TLRs. Our data reveal that Gfi1 plays a critical role in the prevention of spontaneous lupus autoimmunity by negatively regulating TLR7 signaling.
Extended Naphthalene Diimides with Donor/Acceptor Hydrogen‐Bonding Properties Targeting G‐Quadruplex Nucleic Acids
Authors: Doria Filippo , Nadai Matteo , Costa Giosuè , Sattin Giovanna , Gallati Caroline , Bergamaschi Greta , Moraca Federica , Alcaro Stefano , Freccero Mauro , Richter Sara N.
Published: September 2016

Naphthalene diimides with one or two centrosymmetric arylethynyl moieties capable of synergic donor and acceptor hydrogen bonding exhibit promising binding properties and selectivity towards parallel G‐quadruplex (G4) nucleic acids (c‐myc, bcl‐2 and parallel hTel22). The hydrogen‐bonding network involving the phosphate backbone and outside rim of the G‐quartet represents an opportunity to exploit G4 selectivity for extended aromatics.