bluuebunny/crossref_metadata_2025 huggingface dataset:
Everolimus for subependymal giant cell astrocytoma: 5‐year final analysis
Authors: Franz David N. , Agricola Karen , Mays Maxwell , Tudor Cindy , Care Marguerite M. , Holland‐Bouley Katherine , Berkowitz Noah , Miao Sara , Peyrard Séverine , Krueger Darcy A.
Published: September 2015

Objective

To analyze the cumulative efficacy and safety of everolimus in treating subependymal giant cell astrocytomas (SEGA) associated with tuberous sclerosis complex (TSC) from an open‐label phase II study (NCT00411619). Updated data became available from the conclusion of the extension phase and are presented in this ≥5‐year analysis.

Methods

Patients aged ≥ 3 years with a definite diagnosis of TSC and increasing SEGA lesion size (≥2 magnetic resonance imaging scans) received everolimus starting at 3mg/m2/day (titrated to target blood trough levels of 5–15ng/ml). The primary efficacy endpoint was reduction from baseline in primary SEGA volume.

Results

As of the study completion date (January 28, 2014), 22 of 28 (78.6%) initially enrolled patients finished the study per protocol. Median (range) duration of exposure to everolimus was 67.8 (4.7–83.2) months; 12 (52.2%) and 14 (60.9%) of 23 patients experienced SEGA volume reductions of ≥50% and ≥30% relative to baseline, respectively, after 60 months of treatment. The proportion of patients experiencing daily seizures was reduced from 7 of 26 (26.9%) patients at baseline to 2 of 18 (11.1%) patients at month 60. Most commonly reported adverse events (AEs) were upper respiratory tract infection and stomatitis of mostly grade 1 or 2 severity. No patient discontinued treatment due to AEs. The frequency of emergence of most AEs decreased over the course of the study.

Interpretation

Everolimus continues to demonstrate a sustained effect on SEGA tumor reduction over ≥5 years of treatment. Everolimus remained well‐tolerated, and no new safety concerns were noted. Ann Neurol 2015;78:929–938
Influence of Arrestin on the Photodecay of Bovine Rhodopsin
Authors: Chatterjee Deep , Eckert Carl Elias , Slavov Chavdar , Saxena Krishna , Fürtig Boris , Sanders Charles R. , Gurevich Vsevolod V. , Wachtveitl Josef , Schwalbe Harald
Published: September 2015

Continued activation of the photocycle of the dim‐light receptor rhodopsin leads to the accumulation of all‐trans‐retinal in the rod outer segments (ROS). This accumulation can damage the photoreceptor cell. For retinal homeostasis, deactivation processes are initiated in which the release of retinal is delayed. One of these processes involves the binding of arrestin to rhodopsin. Here, the interaction of pre‐activated truncated bovine visual arrestin (ArrTr) with rhodopsin in 1,2‐diheptanoyl‐sn‐glycero‐3‐phosphocholine (DHPC) micelles is investigated by solution NMR techniques and flash photolysis spectroscopy. Our results show that formation of the rhodopsin–arrestin complex markedly influences partitioning in the decay kinetics of rhodopsin, which involves the simultaneous formation of a meta II and a meta III state from the meta I state. Binding of ArrTr leads to an increase in the population of the meta III state and consequently to an approximately twofold slower release of all‐trans‐retinal from rhodopsin.
Palladium‐Catalyzed Synthesis of (Hetero)Aryl Alkyl Sulfones from (Hetero)Aryl Boronic Acids, Unactivated Alkyl Halides, and Potassium Metabisulfite
Authors: Shavnya Andre , Hesp Kevin D. , Mascitti Vincent , Smith Aaron C.
Published: September 2015

A palladium‐catalyzed one‐step synthesis of (hetero)aryl alkyl sulfones from (hetero)arylboronic acids, potassium metabisulfite, and unactivated or activated alkylhalides is described. This transformation is of broad scope, occurs under mild conditions, and employs readily available reactants. A stoichiometric experiment has led to the isolation of a catalytically active dimeric palladium sulfinate complex, which was characterized by X‐ray diffraction analysis.
Cobalt‐Catalyzed Allylation of Heterobicyclic Alkenes: Ligand‐Induced Divergent Reactivities
Authors: Huang Yuan , Ma Chao , Lee Yi Xin , Huang Rui‐Zhi , Zhao Yu
Published: September 2015

The allylation of heterobicyclic alkenes is presented for the first time. By using an inexpensive cobalt salt as the catalyst and easy‐to‐handle potassium allyltrifluoroborate as the reagent, an unprecedented formal hydroallylation of the bicyclic alkenes is realized in high efficiency. When a chiral cobalt/bis(phosphine) complex is used instead, the alternative ring‐opening products can be obtained in high yield and excellent enantioselectivity.
Die Existenz von Tricyanomethan
Authors: Soltner Theresa , Häusler Jonas , Kornath Andreas J.
Published: September 2015

Die Umsetzung von Calciumtricyanomethanid mit Fluorwasserstoff führt zur Bildung von Tricyanomethan und Ca(HF2)2. Tricyanomethan ist bis zu einer Temperatur von −40 °C beständig. Es wurde mittels Infrarot‐, Raman‐ und NMR‐Spektroskopie charakterisiert. Die Schwingungsspektren sind mit den quantenchemisch berechneten Frequenzen auf PBE1PBE/6‐311G(3df,3dp)‐Niveau verglichen und bestätigen die erwartete C3v‐Symmetrie des Moleküls mit regulären C‐H‐ (109.8 pm), C‐C‐ (146.7 pm) und CN‐Bindungen (114.7 pm).
Synthesis and Structure of Hypervalent Iodine(III) Reagents Containing Phthalimidate and Application to Oxidative Amination Reactions
Authors: Kiyokawa Kensuke , Kosaka Tomoki , Kojima Takumi , Minakata Satoshi
Published: September 2015

A new class of hypervalent iodine reagents containing phthalimidate was synthesized, and structurally characterized by X‐ray analysis. The benziodoxole‐based reagent displays satisfactory solubility in common organic solvents and is reasonably stable in solution as well as in the solid state. The reagent was used for the oxidative amination of the C(sp3)H bond of N,N‐dimethylanilines. In addition, the reagent was also applicable to oxidative amination with rearrangement of trialkylamines as well as enamines that were prepared in situ from secondary amines and aldehydes.
A Bioinspired Switchable and Tunable Carbonate‐Activated Nanofluidic Diode Based on a Single Nanochannel
Authors: Xie Ganhua , Xiao Kai , Zhang Zhen , Kong Xiang‐Yu , Liu Qian , Li Pei , Wen Liping , Jiang Lei
Published: September 2015

A smart nanofluidic diode that exhibits both ion gating and ion current rectification has been developed using a 1‐(4‐amino‐phenyl)‐2,2,2‐trifluoro‐ethanone‐functionalized, conical nanochannel in a polyimide (PI) membrane. The switch‐like property can be tuned by controlling the wettability and charge distribution with carbonate ions. Such a nanodevice is advantageous for precisely controlling conductive states with an ultrahigh gating ratio of up to 5000, and a high rectification ratio of 27. By virtue of the high selectivity and sensitivity for carbonate ions, this nanofluidic diode may find applications in carbonate or carbon dioxide detection.
Hydrolytic Transformation of Microporous Metal–Organic Frameworks to Hierarchical Micro‐ and Mesoporous MOFs
Authors: Kim Yonghwi , Yang Tao , Yun Gyeongwon , Ghasemian Mohammad Bagher , Koo Jaehyoung , Lee Eunsung , Cho Sung June , Kim Kimoon
Published: September 2015

A new approach to the synthesis of hierarchical micro‐ and mesoporous MOFs from microporous MOFs involves a simple hydrolytic post‐synthetic procedure. As a proof of concept, a new microporous MOF, POST‐66(Y), was synthesized and its transformation into a hierarchical micro‐ and mesoporous MOF by water treatment was studied. This method produced mesopores in the range of 3 to 20 nm in the MOF while maintaining the original microporous structure, at least in part. The degree of micro‐ and mesoporosity can be controlled by adjusting the time and temperature of hydrolysis. The resulting hierarchical porous MOF, POST‐66(Y)‐wt, can be utilized to encapsulate nanometer‐sized guests such as proteins, and the enhanced stability and recyclability of an encapsulated enzyme is demonstrated.
Synthesis of a branched photosensitive copolymer and its application for negative‐type photoresists
Authors: Li Hu , Liu Jingcheng , Zheng Xiangfei , Ji Changwei , Mu Qidao , Liu Ren , Liu Xiaoya
Published: September 2015

Novel branched copolymers, poly(styrene‐alt‐maleic anhydride) (BPSMA), were synthesized through mercapto chain‐transfer polymerization with styrene, maleic anhydride (MA), and 4‐vinyl benzyl thiol (VBT). Then, the hydroxyl of hydroxyethyl methacrylate was reacted with MA to synthesize branched photosensitive copolymers, p‐BPSMAs. Fourier transform IR spectroscopy and 1H‐NMR indicated that the synthesis was successful. Gel permeation chromatography indicated that the molecular weight decreased with increasing content of VBT. The thermal properties were characterized by thermogravimetric analysis; the results show that the thermal decomposition temperature of the BPSMAs was greatly enhanced. Real‐time IR was used to evaluate the UV‐curable kinetics of the p‐BPSMAs; the results show that the p‐BPSMAs could rapidly photopolymerize under UV irradiation in the presence of photoinitiators. Moreover, the photoresist based on the p‐BPSMAs exhibited improved photosensitivity when the VBT content increased, and the photoresist with 12 mol % VBT content had a low value of the dose that retained 50% of the original film thickness (10 mJ/cm2), and a 50‐μm resolution could be achieved compared to a linear photoresist. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42838.
Development of nanocomposites based on organically modified montmorillonite and plasticized PVC with improved barrier properties
Authors: Petersen Henrik , Jakubowicz Ignacy , Enebro Jonas , Yarahmadi Nazdaneh
Published: September 2015

Montmorillonite (MMT) was organically modified with tributyl citrate (TBC). Organoclays (OMMTs) were processed with diisononyl phthalate (DINP)‐plasticized polyvinyl chloride (PVC) to form polymer nanocomposites. The produced composite materials showed a contradictory change in properties to that expected of a layered silicate nanocomposite, with a decreased E‐modulus and increased gas permeability compared with a material without OMMT. It was experimentally shown that the TBC modifier was extracted from the OMMT and was dispersed in the PVC/DINP matrix, whereupon the OMMT collapsed and formed micrometer‐sized agglomerates. Further investigation revealed that TBC has a significant effect on the gas permeability and the E‐modulus, even at low additions to a DINP‐plasticized PVC. A PVC nanocomposite with the TBC acting as both the OM for MMT and as the primary plasticizer was produced. This material showed a significantly increased E‐modulus as well as a decrease in gas permeability, confirming that it is possible to develop a nanocomposite based on plasticized PVC, if both the organo‐modification of the MMT and the formulation of the matrix are carefully selected. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42876.
Enhancing the electrical conductivity of carbon black/graphite nanoplatelets: Poly(ethylene‐butyl acrylate) composites by melt extrusion
Authors: Ariño Ruth , Álvarez Elena , Rigdahl Mikael
Published: September 2015

The influence of processing parameters such as screw geometry, temperature profile, and screw speed on the electrical properties of hybrid composites consisting of graphite nanoplatelets and carbon black in ethyl butyl acrylate was studied. Two different screws were used to compound the hybrid composites at two different temperatures and two different screw speeds. A beneficial effect was noted with regard to the electrical properties when adding nanoplatelets to the filler system. The cause could be a synergistic effect due to the difference in particle shape of the two fillers. Lower percolation thresholds were obtained with the conventional screw due to less breakage of the graphite nanoplatelets compared to the barrier screw. No significant changes of the electrical properties were observed when changing the temperature profiles or the screw speeds. Furthermore, the melt viscosity of the compounds was not appreciably affected at the rather low filler contents used here. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42897.
Preparation of Porous Three‐Dimensional Quaternary Thioantimonates(III) ACuSb2S4 (A=Rb, Cs) through a Surfactant‐Thermal Method
Authors: Shen Yaying , Liu Chang , Hou Peipei , Zhi Mingjia , Zhou Chunmei , Chai Wenxiang , Cheng Jian‐Wen , Liu Yi , Zhang Qichun
Published: September 2015

Two novel porous three‐dimensional (3D) quaternary thioantimonates(III) ACuSb2S4 (A=Rb, Cs) were successfully synthesized by employing the neutral surfactant PEG‐400 (PEG=polyethyleneglycol) as reaction media, these are significantly different from the known quaternary A−Cu−Sb−S thioantimonates(III) with two‐dimensional (2D) crystal structures. This is the first time that crystalline quaternary chalcogenides have been prepared in surfactant media. Both experimental and theoretical studies confirm they are semiconductors with narrow band gaps. Our results demonstrated that the surfactant‐thermal strategy could offer a new opportunity to explore novel chalcogenides with diverse crystal structures and interesting physicochemical properties.
Thrombosis in pregnancy and maternal outcomes
Authors: James Andra H.
Published: September 2015

Pregnancy increases the risk of thrombosis four‐ to five‐fold. Seventy‐five to eighty percent of pregnancy‐related thrombotic events are venous and twenty to –twenty‐five percent are arterial. The main reason for the increased risk is hypercoagulability. Women are hypercoagulable because they have evolved so that they are protected against the bleeding challenges of pregnancy, miscarriage, or childbirth. Both genetic and acquired risk factors can further increase the risk of thrombosis. The maternal consequences of thrombosis of pregnancy include permanent vascular damage, disability, and death. While the maternal outcomes of thrombosis can be modified by anticoagulation therapy, management of thrombosis during pregnancy is the subject of another paper in this issue (see paper by B. Konkle). This review will focus on the epidemiology, pathophysiology, risk factors, and maternal consequences of thrombosis in pregnancy. Birth Defects Research (Part C) 105:159–166, 2015. © 2015 Wiley Periodicals, Inc.
Affirming Control by Multiple Reinforcers via Progressive Treatment Analysis
Authors: Ghaemmaghami Mahshid , Hanley Gregory P. , Jin Sandy C. , Vanselow Nicholas R.
Published: September 2015

It is common to isolate reinforcement contingencies across several test conditions in functional analyses of problem behavior; however, synthesizing all reinforcement contingencies in a single test condition may also have merit and even be necessary in some cases. Following a differentiated functional analysis, which relied on an interview‐informed synthesized test condition, functional communication training (FCT) was applied across the three suspected contingencies of reinforcement, partly in an attempt to understand the relevance of each. Communication responses were acquired for all three reinforcers, and problem behavior ceased only when all contingencies were addressed via FCT, suggesting that problem behavior was controlled by multiple contingencies of reinforcement. These analyses suggest that control by multiple contingencies of reinforcement can be understood during the treatment development process following a highly efficient functional analysis. Copyright © 2015 John Wiley & Sons, Ltd.
Synthesis, characterization and properties of salicylhydrazide–salicylacylhydrazone derivatives and their terbium complexes
Authors: Meng Defen , Liu Fen , Li Yingying , Yang Zehui , Li Guizhi , Guo Dongcai
Published: September 2015

A series of terbium complexes with salicylhydrazide–salicylacylhydrazone derivatives were synthesized and characterized by elemental analysis, IR spectra, UV/vis spectra and thermal analysis. The luminescence and electrochemical properties of the terbium complexes were investigated. The results show that all the target complexes exhibited characteristic emissions of terbium ions and the complex substituted by the chlorine has the strongest luminescence intensity with the highest quantum yield at 0.609. The introduction of donating electron groups could increase the oxidation potential and the highest occupied molecular orbital energy level of the terbium complex; however, the introduction of accepting electron groups gave the opposite result. Copyright © 2015 John Wiley & Sons, Ltd.
Behavioral Effects of Sustainability‐Oriented Incentive Systems
Authors: Huber Robert , Hirsch Bernhard
Published: September 2015

Companies increasingly extend their existing incentive systems by integrating several sustainable performance indicators. Although these ‘sustainability‐oriented’ incentive systems clearly highlight which business objectives should be attained, little is known about the effects that these incentive systems have on employee behavior. Based on signaling theory, social identity theory and a person–organization fit (PO‐fit) perspective, we assume positive relations between sustainability‐oriented incentive systems and employee attraction, motivation and cooperation. Furthermore, we examine whether these relations are moderated by personal attitudes toward corporate sustainability activities as well as the underlying mechanisms at the moderation (mediated moderation). Our experimental results (with students as future employees) do not give support for a general positive relation between sustainability‐oriented incentive systems and employee behavior. However, our data show that a person's attitude toward corporate sustainability activities moderates the link between sustainability‐oriented incentive systems and employee behavior. Additionally, we find PO‐fit perceptions to mediate the interaction effects. Copyright © 2015 John Wiley & Sons, Ltd and ERP Environment
Acceleration of the Rate‐Limiting Step of Thioredoxin Folding by Replacement of its Conserved cis‐Proline with (4 S)‐Fluoroproline
Authors: Roderer Daniel , Glockshuber Rudi , Rubini Marina
Published: September 2015

The incorporation of the non‐natural amino acids (4R)‐ and (4S)‐fluoroproline (Flp) has been successfully used to improve protein stability, but little is known about their effect on protein folding kinetics. Here we analyzed the influence of (4R)‐ and (4S)‐Flp on the rate‐limiting trans‐to‐cis isomerization of the Ile75–Pro76 peptide bond in the folding of Escherichia coli thioredoxin (Trx). While (4R)‐Flp at position 76 had essentially no effect on the isomerization rate in the context of the intact tertiary structure, (4S)‐Flp accelerated the folding reaction ninefold. Similarly, tenfold faster trans‐to‐cis isomerization of Ile75–(4S)‐Flp76 relative to Ile75–Pro76 was observed in the unfolded state of Trx. Our results show that the replacement of cis prolines by non‐natural proline analogues can be used for modulating the folding rates of proteins with cis prolyl‐peptide bonds in the native state.
An Investigation of the Interaction of Co‐Solvent with Substrates in the Pig Liver Esterase‐Catalyzed Hydrolysis of Malonate Esters
Authors: Smith Maureen E. , Fibinger Michael P. C. , Bornscheuer Uwe T. , Masterson Douglas S.
Published: September 2015

Previously, we have reported the effect of several co‐solvents, including ethanol, on the enantioselective outcome of pig liver esterase (PLE) hydrolysis reactions. The greatest improvements were observed in those substrates that contained an atom capable of forming a hydrogen bond in the sidechain portion of the molecule. To further explore the interaction between substrate and ethanol, a second series of substrates were synthesized, in which the hydrogen bonding atoms of the side chain were modified, and subjected to PLE hydrolysis. Substrates containing atoms capable of forming hydrogen bonds showed the largest equilibrium constants. However, a large equilibrium constant did not always produce significant changes in enantioselectivity as hypothesized. Finally, molecular modeling experiments were performed to obtain a better understanding of the interactions. These experiments revealed that there are substrate–enzyme interactions that can be influenced by the addition of ethanol.
Ruthenium‐Catalyzed Asymmetric Transfer Hydrogenation of Propargylic Ketones
Authors: Shatskiy Andrey , Kivijärvi Tove , Lundberg Helena , Tinnis Fredrik , Adolfsson Hans
Published: September 2015

The asymmetric transfer hydrogenation of α,β‐propargyl ketones catalyzed by an in situ formed ruthenium–hydroxyamide complex was explored. The acetylenic alcohols were isolated in good to excellent yields with excellent ee values (typically >90 %) after short reaction times at room temperature.
THEME: THEmatic model exploration through multiple co‐structure maximization
Authors: Bry X. , Verron T.
Published: September 2015

After showing that plain covariance or correlation‐based criteria are generally not suitable to deal with multiple‐block component models in an exploratory framework, we propose an extended criterion: multiple co‐structure (MCS). MCS combines the goodness‐of‐fit indicator of the component model to a flexible measure of structural relevance of the components. Thus, it allows to track various kinds of interpretable structures within the data, on top of variance–maximizing components: variable‐bundles, components close to satisfying relevant structural constraints, and so on. MCS is to be maximised under unit‐norm constraints on coefficient‐vectors. We provide a dedicated ascent algorithm for it. This algorithm is nested into a more general one, named THEME (thematic equation model explorator), which calculates several components per data‐array and extracts nested structural component models. The method is tested on simulated data and applied to physicochemical data. Copyright © 2015 John Wiley & Sons, Ltd.
Iron(III)‐Catalyzed Cycloisomerizations of Acetal–Vinylidenecyclopropanes: An Efficient Synthetic Route to 1,2‐Disubstituted Cyclobutenes
Authors: Yang Song , Yuan Wei , Xu Qin , Shi Min
Published: September 2015

A novel iron(III)‐catalyzed intramolecular cycloisomerization of acetal–vinylidenecyclopropanes to afford a series of halogenated 1,2‐disubstituted cyclobutenes tethered with a tetrahydropyrrole has been developed. The reaction is thought to proceed through a formal iron‐catalyzed Prins cyclization followed by a ring‐enlarging rearrangement of the methylenecyclopropane carbocation. The present protocol provides an alternative route to functionalized disubstituted cyclobutenes and the corresponding products could be successfully transformed into eight‐membered oxacyclic products.
Single‐Molecule Magnetism, Enhanced Magnetocaloric Effect, and Toroidal Magnetic Moments in a Family of Ln4 Squares
Authors: Das Chinmoy , Vaidya Shefali , Gupta Tulika , Frost Jamie M. , Righi Mattia , Brechin Euan K. , Affronte Marco , Rajaraman Gopalan , Shanmugam Maheswaran
Published: September 2015

Three cationic [Ln4] squares (Ln=lanthanide) were isolated as single crystals and their structures solved as [Dy4(μ4‐OH)(HL)(H2L)3(H2O)4]Cl2⋅(CH3OH)4⋅(H2O)8 (1), [Tb4(μ4‐OH)(HL)(H2L)3(MeOH)4]Cl2⋅(CH3OH)4⋅(H2O)4 (2) and [Gd4(μ4‐OH)(HL)(H2L)3(H2O)2(MeOH)2]Br2⋅(CH3OH)4⋅(H2O)3 (3). The structures are described as hydroxo‐centered squares of lanthanide ions, with each edge of the square bridged by a doubly deprotonated H2L2− ligand. Alternating current magnetic susceptibility measurements show frequency‐dependent out‐of‐phase signals with two different thermally assisted relaxation processes for 1, whereas no maxima in χM“ appears above 2.0 K for complex 2. For 1, the estimated effective energy barrier for these two relaxation processes is 29 and 100 K. Detailed ab initio studies reveal that complex 1 possesses a toroidal magnetic moment. The ab initio calculated anisotropies of the metal ions in complex 1 were employed to simulate the magnetic susceptibility by using the Lines model (POLY_ANISO) and this procedure yields J1=+0.01 and J2=−0.01 cm−1 for 1 as the two distinct exchange interactions between the DyIII ions. Similar parameters are also obtained for complex 1 (and 2) from specific heat measurements. A very weak antiferromagnetic super‐exchange interaction (J1=−0.043 cm−1 and g=1.99) is observed between the metal centers in 3. The magnetocaloric effect (MCE) was estimated by using field‐dependent magnetization and temperature‐dependent heat‐capacity measurements. An excellent agreement is found for the −ΔSm values extracted from these two measurements for all three complexes. As expected, 3 shows the largest −ΔSm variation (23 J Kg−1 K−1) among the three complexes. The negligible magnetic anisotropy of Gd indeed ensures near degeneracy in the (2S+1) ground state microstates, and the weak super‐exchange interaction facilitates dense population of low‐lying excited states, all of which are likely to contribute to the MCE, making complex 3 an attractive candidate for cryogenic refrigeration.
Loss of retinitis pigmentosa 2 (RP2) protein affects cone photoreceptor sensory cilium elongation in mice
Authors: Li Linjing , Rao Kollu Nageswara , Zheng‐Le Yun , Hurd Toby W. , Lillo Concepción , Khanna Hemant
Published: September 2015

Degeneration of photoreceptors (rods and cones) results in blindness. As we rely almost entirely on our daytime vision mediated by the cones, it is the loss of these photoreceptors that results in legal blindness and poor quality of life. Cone dysfunction is usually observed due to two mechanisms: noncell‐autonomous due to the secondary effect of rod death if the causative gene is specifically expressed in rods and cell autonomous, if the mutation is in a cone‐specific gene. However, it is difficult to dissect cone autonomous effect of mutations in the genes that are expressed in both rods and cones. Here we report a property of murine cone photoreceptors, which is a cone‐autonomous effect of the genetic perturbation of the retinitis pigmentosa 2 (Rp2) gene mutated in human X‐linked RP. Constitutive loss of Rp2 results in abnormal extension of the cone outer segment (COS). This effect is phenocopied when the Rp2 gene is ablated specifically in cones but not when ablated in rods. Furthermore, the elongated COS exhibits abnormal ultrastructure with disorganized lamellae. Additionally, elongation of both the outer segment membrane and the microtubule cytoskeleton was observed in the absence of RP2. Taken together, our studies identify a cone morphological defect in retinal degeneration due to ablation of RP2 and will assist in understanding cone‐autonomous responses during disease and develop targeted therapies. © 2015 Wiley Periodicals, Inc.
Evaluation of the expression pattern of rAAV2/1, 2/5, 2/7, 2/8, and 2/9 serotypes with different promoters in the mouse visual cortex
Authors: Scheyltjens Isabelle , Laramée Marie‐Eve , Van den Haute Chris , Gijsbers Rik , Debyser Zeger , Baekelandt Veerle , Vreysen Samme , Arckens Lutgarde
Published: September 2015

This study compared the expression pattern, laminar distribution, and cell specificity of several rAAV serotypes (2/1, 2/5, 2/7, 2/8, and 2/9) injected in the primary visual cortex (V1) of adult C57Bl/6J mice. In order to obtain specific expression in certain neuron subtypes, different promoter sequences were evaluated for excitatory cell specificity: a universal cytomegalovirus (CMV) promoter, and two versions of the excitatory neuron‐specific Ca2+/calmodulin‐dependent kinase subunit α (CaMKIIα) promoter, CaMKIIα 0.4 and CaMKIIα 1.3. The spatial distribution as well as the cell type specificity was immunohistochemically verified. Depending on the rAAV serotype used, the transduced volume expressing reporter protein differed substantially (rAAV2/5 ≫ 2/7 ≈ 2/9 ≈ 2/8 ≫ 2/1). Excitatory neuron‐specific targeting was promoter‐dependent, with a surprising difference between the 1.3 kb and 0.4 kb CaMKIIα promoters. While CaMKIIα 1.3 and CMV carrying vectors were comparable, with 78% of the transduced neurons being excitatory for CMV and 82% for CaMKIIα 1.3, the shorter CaMKIIα 0.4 version resulted in 95% excitatory specificity. This study therefore puts forward the CaMKIIα 0.4 promoter as the best choice to target excitatory neurons with rAAVs. Together, these results can be used as an aid to select the most optimal vector system to deliver transgenes into specific rodent neocortical circuits, allowing further elucidation of their functions. J. Comp. Neurol. 523:2019–2042, 2015. © 2015 Wiley Periodicals, Inc.
The mummified brain of a pleistocene woolly mammoth (Mammuthus primigenius) compared with the brain of the extant African elephant (Loxodonta africana)
Authors: Kharlamova Anastasia S. , Saveliev Sergei V. , Protopopov Albert V. , Maseko Busisiwe C. , Bhagwandin Adhil , Manger Paul R.
Published: September 2015

This study presents the results of an examination of the mummified brain of a pleistocene woolly mammoth (Mammuthus primigenius) recovered from the Yakutian permafrost in Siberia, Russia. This unique specimen (from 39,440–38,850 years BP) provides the rare opportunity to compare the brain morphology of this extinct species with a related extant species, the African elephant (Loxodonta africana). An anatomical description of the preserved brain of the woolly mammoth is provided, along with a series of quantitative analyses of various brain structures. These descriptions are based on visual inspection of the actual specimen as well as qualitative and quantitative comparison of computed tomography imaging data obtained for the woolly mammoth in comparison with magnetic resonance imaging data from three African elephant brains. In general, the brain of the woolly mammoth specimen examined, estimated to weigh between 4,230 and 4,340 g, showed the typical shape, size, and gross structures observed in extant elephants. Quantitative comparative analyses of various features of the brain, such as the amygdala, corpus callosum, cerebellum, and gyrnecephalic index, all indicate that the brain of the woolly mammoth specimen examined has many similarities with that of modern African elephants. The analysis provided here indicates that a specific brain type representative of the Elephantidae is likely to be a feature of this mammalian family. In addition, the extensive similarities between the woolly mammoth brain and the African elephant brain indicate that the specializations observed in the extant elephant brain are likely to have been present in the woolly mammoth. J. Comp. Neurol. 523:2326–2343, 2015. © 2015 Wiley Periodicals, Inc.
A Comparative Study of CO Oxidation on Nitrogen‐ and Phosphorus‐Doped Graphene
Authors: Esrafili Mehdi D. , Mohammad‐Valipour Ramin , Mousavi‐Khoshdel Seyed Morteza , Nematollahi Parisa
Published: September 2015

The geometry, electronic structure, and catalytic properties of nitrogen‐ and phosphorus‐doped graphene (N‐/P‐graphene) are investigated by density functional theory calculations. The reaction between adsorbed O2 and CO molecules on N‐ and P‐graphene is comparably studied via Langmuir–Hinshelwood (LH) and Eley–Rideal (ER) mechanisms. The results indicate that a two‐step process can occur, namely, CO+O2→CO2+Oads and CO+Oads→CO2. The calculated energy barriers of the first step are 15.8 and 12.4 kcal mol−1 for N‐ and P‐graphene, respectively. The second step of the oxidation reaction on N‐graphene proceeds with an energy barrier of about 4 kcal mol−1. It is noteworthy that this reaction step was not observed on P‐graphene because of the strong binding of Oads species on the P atoms. Thus, it can be concluded that low‐cost N‐graphene can be used as a promising green catalyst for low‐temperature CO oxidation.
In Situ Small‐Angle X‐ray Scattering Investigation of the Formation of Dual‐Mesoporous Materials
Authors: Schmitt Julien , Canilho Nadia , Impéror‐Clerc Marianne , Blin Jean‐Luc , Pedersen Jan Skov , Pérez Javier , Lebeau Bénédicte , Vidal Loic , Stébé Marie‐José
Published: September 2015

The formation of a 2D‐hexagonal (p6m) silica‐based hybrid dual‐mesoporous material is investigated in situ by using synchrotron time‐resolved small‐angle X‐ray scattering (SAXS). The material is synthesized from a mixed micellar solution of a nonionic fluorinated surfactant, RF8(EO)9 (EO=ethylene oxide) and a nonionic triblock copolymer, P123. Both mesoporous networks, with pore dimensions of 3.3 and 8.5 nm respectively, are observed by nitrogen sorption, transmission electron microscopy (TEM), and SAXS. The in situ SAXS experiments reveal that mesophase formation occurs in two steps. First the nucleation and growth of a primary 2D‐hexagonal network (N1), associated with mixed micelles containing P123, then subsequent formation of a second network (N2), associated with micelles of pure RF8(EO)9. The data obtained from SAXS and TEM suggest that the N1 network is used as a nucleation center for the formation of the N2 network, which would result in the formation of a grain with two mesopore sizes. Understanding the mechanism of the formation of such materials is an important step towards the synthesis of more‐complex materials by fine tuning the porosity.
The Economic Impact of Environmentally Responsible Practices
Authors: Tebini Hajer , M'Zali Bouchra , Lang Pascal , Perez‐Gladish Blanca
Published: September 2015

The objective of this paper is to present a dynamic analysis of the relationship between environmental (EP) and financial performance (FP). More precisely, we have analysed this relationship by considering the measurement of EP lagged by one, two, and three periods. The introduction of lagged variables at both an aggregate and non‐aggregate level, aims to capture the effects of EP on FP over time. Our results show that the aggregate measure of the lagged EP has a persistent positive effect on FP, extended over three years. This effect appears to be more marked for large size companies, for companies with low risk levels and for those spending less on investment. Results for non‐aggregate measurements reveal an asymmetric relationship between FP and KLD's concerns score, of which the impact is negative and persistent, and between FP and KLD's strengths score, where the effect is positive and limited to one year. Copyright © 2015 John Wiley & Sons, Ltd and ERP Environment
Mass‐transport Control on the Discharge Mechanism in Li–O2 Batteries Using Carbon Cathodes with Varied Porosity
Authors: Aklalouch Mohamed , Olivares‐Marín Mara , Lee Rung‐Chuan , Palomino Pablo , Enciso Eduardo , Tonti Dino
Published: September 2015

By comparing carbon electrodes with varying porosity in Li–O2 cells, we show that the effect of electrolyte stirring at a given current density can result in a change from 2D to 3D growth of discharged deposits. The change of morphology is evident using electron microscopy and by analyzing electrode pore size distribution with respect to discharge capacity. As a consequence, carbon electrodes with different textural properties exhibit different capacity enhancements in stirred‐electrolyte cells. We demonstrate that mass transport can directly control the discharge mechanism, similar to the electrolyte composition and current density, which have already been recognized as determining factors.
Methyltriphenylphosphonium Methylcarbonate, an All‐In‐One Wittig Vinylation Reagent
Authors: Cattelan Lisa , Noè Marco , Selva Maurizio , Demitri Nicola , Perosa Alvise
Published: September 2015

The methyltriphenylphosphonium methylcarbonate salt [Ph3PCH3][CH3OCO2], obtained directly by quaternarization of triphenylphosphine with dimethylcarbonate, is a latent ylide that promotes Wittig vinylation of aldehydes and ketones. Alkenes are obtained simply by mixing [Ph3PCH3][CH3OCO2] and the carbonyl and heating in a solvent (no base, no halides, and no inorganic byproducts). Deuterium exchange experiments and the particularly short anion‐cation distance measured by XRD in [Ph3PCH3][CH3OCO2] allowed to explain the nature and reactivity of this species. Green chemistry metrics (atom economy, mass index, environmental factor) indicate that this vinylation procedure is more efficient than comparable ones. Deuterated [Ph3PCD3][CH3OCO2] promoted the synthesis of deuterated olefins.
A Systematic Comparative Study of Hydrogen‐Evolving Molecular Catalysts in Aqueous Solutions
Authors: Roy Souvik , Bacchi Marine , Berggren Gustav , Artero Vincent
Published: September 2015

We describe here a systematic, reliable, and fast screening method that allows the comparison of H2‐forming catalysts that work under aqueous conditions with two readily prepared chemical reductants and two commonly used photosensitizers. This method uses a Clark‐type microsensor for H2 detection and complements previous methods based on rotating disk electrode measurements. The efficiencies of a series of H2‐producing catalysts based on Co, Ni, Fe, and Pt were investigated in aqueous solutions under thermal conditions with europium(II) reductants and under photochemical conditions in the presence of two different photosensitizers {[Ru(bipy)3]Cl2 (bipy=2,2‐bipyridine) and eosin‐Y} and sacrificial electron donors (ascorbate and triethanolamine, respectively). The majority of catalysts tested were active only under specific conditions. However, our results also demonstrate the impressive versatility of a group of Co catalysts, which were able to produce H2 under different reducing conditions and at various pH values. In particular, a cobaloxime, [Co(dmgH)2(H2O)2] (dmgH2=dimethylglyoxime), and a cobalt tetraazamacrocyclic complex, {Co(CR)Cl2}+ [CR=2,12‐dimethyl‐3,7,11,17‐tetraazabicylo(11.3.1)heptadeca‐1(17),2,11,13,15‐pentaene], displayed excellent catalytic rates under the studied conditions, and the best rates were observed under thermal conditions.
3D Woven‐Like Carbon Micropattern Decorated with Silicon Nanoparticles for Use in Lithium‐Ion Batteries
Authors: Kang Da‐Young , Kim Cheolho , Gueon Donghee , Park Gyulim , Kim Jung Sub , Lee Joong Kee , Moon Jun Hyuk
Published: September 2015

Carbon/silicon composite materials are a promising anode substrate for use in lithium‐ion batteries. In this study, we suggest a new architecture for a composite electrode made of a woven‐like carbon material decorated with silicon nanoparticles. The 3D woven‐like carbon (WLC) structure was fabricated using direct carbonization of multi‐beam interference lithography polymer patterns. Subsequent solution coating was applied to decorate the WLC with silicon nanoparticles (SiNPs). The SiNP/WLC electrode exhibited a specific capacity of 930 mAh g−1, which is three times higher than the specific capacity of the bare electrode. Specifically, the SiNP/WLC electrode exhibited an outstanding retention capacity of 81 % after 50 cycles and a Coulombic efficiency of more than 98 %. This rate capability performance was attributed to the WLC structure and the uniform decoration of the SiNPs.
Charge Modulation in Graphitic Carbon Nitride as a Switchable Approach to High‐Capacity Hydrogen Storage
Authors: Tan Xin , Kou Liangzhi , Tahini Hassan A. , Smith Sean C.
Published: September 2015

Electrical charging of graphitic carbon nitride nanosheets (g‐C4N3 and g‐C3N4) is proposed as a strategy for high‐capacity and electrocatalytically switchable hydrogen storage. Using first‐principle calculations, we found that the adsorption energy of H2 molecules on graphitic carbon nitride nanosheets is dramatically enhanced by injecting extra electrons into the adsorbent. At full hydrogen coverage, the negatively charged graphitic carbon nitride achieves storage capacities up to 6–7 wt %. In contrast to other hydrogen storage approaches, the storage/release occurs spontaneously once extra electrons are introduced or removed, and these processes can be simply controlled by switching on/off the charging voltage. Therefore, this approach promises both facile reversibility and tunable kinetics without the need of specific catalysts. Importantly, g‐C4N3 has good electrical conductivity and high electron mobility, which can be a very good candidate for electron injection/release. These predictions may prove to be instrumental in searching for a new class of high‐capacity hydrogen storage materials.
Simultaneous determination of tanshinones and polyphenolics in rat plasma by UPLC‐MS/MS and its application to the pharmacokinetic interaction between them
Authors: Ren Hao , Qian Dawei , Su Shulan , Guan Hanliang , Zhang Wei , Shang Erxin , Duan Jinao
Published: September 2015

The aim of this study was to investigate the pharmacokinetic interaction between tanshinones and polyphenolics which act as the main bioactive compounds in Saliva miltiorrhiza Bunge (SMB). Thus, a rapid and highly sensitive ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) method was developed and validated to determine the concentrations of Tanshinone IIA (TSIIA), Tanshinone I (TI), Cryptotanshinone (CT), Salvianolic acid B (Sal B), Protocatechuic aldehyde (PAL), Rosmarinic acid (RA), and Danshensu (DSS) in rat plasma. The Sprague–Dawley rats were allocated to three groups which orally administered tanshinones (DST), polyphenolics (DFS), and a mixture of tanshinones and polyphenolics (DTF). These samples were processed by a simple liquid‐liquid extraction (LLE) method with ethyl acetate. Chromatographic separation was achieved on an Acquity BEH C18 column (100 mm × 2. 1 mm, 1.7 µm) with the mobile phase consisting of 0.1% (v/v) formic acid and acetonitrile by gradient elution at a flow rate of 0.4 mL/min. The detection was performed on a triple quadrupole‐tandem mass spectrometer TQ‐MS/MS equipped with negative and positive electrospray ionization (ESI) interface in multiple reaction monitoring (MRM) mode. The statistical analysis was performed by the Student's t‐test with P ≤ 0.05 as the level of significance. The method showed good precision, accuracy, recovery, sensitivity, linearity, and stability. The pharmacokinetic profiles and parameters of these polyphenolics changed when co‐administrated with tanshinones. The tanshinones improved the bioavailability of DSS, accelerated the eliminating rate of RA and Sal B and promoted their distribution in vivo. They also contributed to promoting the biotransformation of Sal B to DSS. The polyphenolics could affect the pharmacokinetic of tanshinones, especially CT and TSIIA. Furthermore, the biotransformation of CT to TSIIA and the bioavailability of TSIIA were both improved. This study may provide useful information to avoid unexpected increase of the plasma drug concentration in the clinical practice. Copyright © 2015 John Wiley & Sons, Ltd.
In vitro characterization of potential CYP‐ and UGT‐derived metabolites of the psychoactive drug 25B‐NBOMe using LC‐high resolution MS
Authors: Boumrah Yacine , Humbert Luc , Phanithavong Melodie , Khimeche Kamel , Dahmani Abdallah , Allorge Delphine
Published: September 2015

One of the main challenges posed by the emergence of new psychoactive substances is their identification in human biological samples. Trying to detect the parent drug could lead to false‐negative results when the delay between consumption and sampling has been too long. The identification of their metabolites could then improve their detection window in biological matrices. Oxidative metabolism by cytochromes P450 and glucuronidation are two major detoxification pathways in humans. In order to characterize possible CYP‐ and UGT‐dependent metabolites of the 2‐(4‐bromo‐2,5‐dimethoxy‐phenyl)‐N‐[(2‐methoxyphenyl)methyl]ethanamine (25B‐NBOMe), a synthetic psychoactive drug, analyses of human liver microsome (HLM) incubates were performed using an ultra‐high performance liquid chromatography system coupled with a quadrupole‐time of flight mass spectrometry detector (UHPLC‐Q‐TOF/MS). On‐line analyses were performed using a Waters OASIS HLB column (30 x 2.1 mm, 20 µm) for the automatic sample loading and a Waters ACQUITY HSS C18 column (150 x 2 mm, 1.8 µm) for the chromatographic separation. Twenty‐one metabolites, consisting of 12 CYP‐derived and 9 UGT‐derived metabolites, were identified. O‐Desmethyl metabolites were the most abundant compounds after the phase I process, which appears to be in accordance with data from previously published NBOMe‐intoxication case reports. Although other important metabolic transformations, such as sulfation, acetylation, methylation or glutathione conjugation, were not studied and artefactual metabolites might have been produced during the HLM incubation process, the record of all the metabolite MS spectra in our library should enable us to characterize relevant metabolites of 25B‐NBOMe and allow us to detect 25B‐MBOMe users. Copyright © 2015 John Wiley & Sons, Ltd.
A novel experimental model of Cryptococcus neoformans‐related immune reconstitution inflammatory syndrome (IRIS) provides insights into pathogenesis
Authors: Eschke Maria , Piehler Daniel , Schulze Bianca , Richter Tina , Grahnert Andreas , Protschka Martina , Müller Uwe , Köhler Gabriele , Höfling Corinna , Rossner Steffen , Alber Gottfried
Published: September 2015

Antiretroviral therapy (ART) has yielded major advances in fighting the HIV pandemic by restoring protective immunity. However, a significant proportion of HIV patients co‐infected with the opportunistic fungal pathogen Cryptococcus neoformans paradoxically develops a life‐threatening immune reconstitution inflammatory syndrome (IRIS) during antiretroviral therapy. Despite several clinical studies, the underlying pathomecha‐nisms are poorly understood. Here, we present the first mouse model of cryptococcal IRIS that allows for a detailed analysis of disease development. Lymphocyte‐deficient RAG‐1−/− mice are infected with C. neoformans and 4 weeks later adoptively transferred with purified CD4+ T cells. Reconstitution of CD4+ T cells is sufficient to induce a severe inflammatory disease similar to clinical IRIS in C. neoformans‐infected RAG‐1−/− mice of different genetic backgrounds and immunological phenotypes (i.e. C57BL/6 and BALB/c). Multiorgan inflammation is accompanied by a systemic release of distinct proinflammatory cytokines, i.e. IFN‐γ, IL‐6, and TNF‐α. IRIS development is characterized by infection‐dependent activation of donor CD4+ T cells, which are the source of IFN‐γ. Interestingly, IFN‐γ‐mediated effects are not required for disease induction. Taken together, this novel mouse model of cryptococcal IRIS provides a useful tool to verify potential mechanisms of pathogenesis, revealing targets for diagnosis and therapeutic interventions.
Rhodium‐Catalyzed Sequential Dehydrogenation/Deoxygenation in One‐Pot: Efficient Synthesis of Dibenzothiophene Derivatives from Diaryl Sulfoxides
Authors: Huang Qiufeng , Fu Shurong , Ke Shaojia , Xiao Hanbing , Zhang Xiaofeng , Lin Shen
Published: September 2015

A novel strategy for the synthesis of dibenzothiophene derivatives is established through a one‐pot intramolecular cross‐dehydrogenative‐coupling reaction of diaryl sulfoxides followed by deoxygenation with a Rh/Ag catalytic system. The yields obtained were good to excellent (up to 96 %), therefore making the described protocol an attractive option for building dibenzothiophene compounds.
Hydrophilic strips for preventing air bubble formation in a microfluidic chamber
Authors: Choi Munseok , Na Yang , Kim Sung‐Jin
Published: September 2015

In a microfluidic chamber, unwanted formation of air bubbles is a critical problem. Here, we present a hydrophilic strip array that prevents air bubble formation in a microfluidic chamber. The array is located on the top surface of the chamber, which has a large variation in width, and consists of a repeated arrangement of super‐ and moderately hydrophilic strips. This repeated arrangement allows a flat meniscus (i.e. liquid front) to form when various solutions consisting of a single stream or two parallel streams with different hydrophilicities move through the chamber. The flat meniscus produced by the array completely prevents the formation of bubbles. Without the array in the chamber, the meniscus shape is highly convex, and bubbles frequently form in the chamber. This hydrophilic strip array will facilitate the use of a microfluidic chamber with a large variation in width for various microfluidic applications.