bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of marine boundary layer cloud simulations in the CAM with CLUBB and updated microphysics scheme based on ARM observations from the Azores
Authors: Zheng X. , Klein S. A. , Ma H.‐Y. , Bogenschutz P. , Gettelman A. , Larson V. E.
Published: June 2016

To assess marine boundary layer (MBL) cloud simulations in three versions of the Community Atmosphere Model (CAM), three sets of short‐term global hindcasts are performed and compared to Atmospheric Radiation Measurement Program (ARM) observations on Graciosa Island in the Azores from June 2009 to December 2010. The three versions consist of CAM5.3 with default schemes (CAM5.3), CAM5.3 with Cloud Layers Unified By Binormals (CLUBB‐MG1), and CAM5.3 with CLUBB and updated microphysics scheme (CLUBB‐MG2). Our results show that relative to CAM5.3 default schemes, simulations with CLUBB better represent MBL cloud base height, the height of the major cloud layer, and the daily cloud cover variability. CLUBB also better simulates the relationship of cloud fraction to cloud liquid water path (LWP) most likely due to CLUBB's consistent treatment of these variables through a probability distribution function (PDF) approach. Subcloud evaporation of precipitation is substantially enhanced in simulations with CLUBB‐MG2 and is more realistic based on the limited observational estimate. Despite these improvements, all model versions underestimate MBL cloud cover. CLUBB‐MG2 reduces biases in in‐cloud LWP (clouds are not too bright) but there are still too few of MBL clouds due to an underestimate in the frequency of overcast scenes. Thus, combining CLUBB with MG2 scheme better simulates MBL cloud processes, but because biases remain in MBL cloud cover CLUBB‐MG2 does not improve the simulation of the surface shortwave cloud radiative effect (CRESW).
Aspects of the Chemical Energetics of Carbon–Aluminum Bonded Species
Authors: Slayden Suzanne W. , Liebman Joel F.
Published: June 2016

The current chapter discusses the chemical energetics of carbon‐aluminum bonded species, both the “conventional” trivalent organoaluminum compounds such as monomeric Me
3
Al and its dimer and a variety of species of often surprising stoichiometry and structure.

The study begins with the “simple” binary aluminum carbides, starting with AlC (neutral and ions). Incorporation of hydrogen leads to consideration of dimethylaluminum ionic compounds derived from the cationic [Me
2
Al]
+
and anionic [Me
2
AlO]
−
.

Methyldialuminum species with one Al–Al bond and at least one Al–C bond, ranging from [Al
2
Me]
+
to [Al
2
Me
7
]
−
, are then examined.

The experimental enthalpies of formation, vaporization and dimerization of trialkylalanes are tabulated. The most recent enthalpy of formation value for Et3Al is used to recommend slightly revised enthalpies of formation for trialkylalanes and the related alkylaluminum hydrides and halides.

The interplay of aluminum and aromaticity is reviewed in the context of aluminum rich rings and clusters, relatively classical heterocycles such as aluminoles, and binding of neutral and cationic monoatomic Al with aromatics.

The chapter closes with a discussion of aluminum halide complexes of benzene and cyclobutadiene derivatives.
Neurologic syndrome associated with homozygous mutation at MAG sialic acid binding site
Authors: Roda Ricardo H. , FitzGibbon Edmond J. , Boucekkine Houda , Schindler Alice B. , Blackstone Craig
Published: June 2016

The MAG gene encodes myelin‐associated glycoprotein (MAG), an abundant protein involved in axon–glial interactions and myelination during nerve regeneration. Several members of a consanguineous family with a clinical syndrome reminiscent of Pelizaeus–Merzbacher disease and demyelinating leukodystrophy on brain MRI were recently found to harbor a homozygous missense p.Ser133Arg MAG mutation. Here, we report two brothers from a nonconsanguineous family afflicted with progressive cognitive impairment, neuropathy, ataxia, nystagmus, and gait disorder. Exome sequencing revealed the homozygous missense mutation p.Arg118His in MAG. This Arg118 residue in immunoglobulin domain 1 is critical for sialic acid binding, providing a compelling mechanistic basis for disease pathogenesis.
Giant Anisotropic Raman Response of Encapsulated Ultrathin Black Phosphorus by Uniaxial Strain
Authors: Li Yanyong , Hu Zhixin , Lin Shenghuang , Lai Sin Ki , Ji Wei , Lau Shu Ping
Published: June 2016

The giant anisotropic Raman response of encapsulated ultrathin black phosphorus (BP) is reported by uniaxial strain. A modified bending technique is employed to apply precise uniaxial tensile strain along the zigzag or armchair direction of the ultrathin BP encapsulated by a layer of polymethyl methacrylate. The Raman shift rates of the A
1
g, B
2g, and A
2
g modes are significantly distinct for strain applied along different directions. For the strain applied along zigzag direction, the Raman shift rate of the B
2g mode can reach a remarkable value of ≈−11 cm−1/% strain. In addition, the Grüneisen parameter is as high as ≈2.5, which is the largest among all the reported common 2D materials. Density functional perturbation theory calculations are performed to understand the exceptional anisotropic strain response discovering that not only the bond lengths but also the bond angels are changed in the strained ultrathin BP, which lead to the giant anisotropic Raman response. Furthermore, an alternative method based entirely on the strained ultrathin BP and nonpolarized Raman spectroscopy is demonstrated to determine the crystallographic orientations of ultrathin BP. This work paves a way to study the strain‐induced anisotropic electrical conductance and magnetotransport properties of BP.
Anomalous Anisotropic Magnetoresistance of Antiferromagnetic Epitaxial Bimetallic Films: Mn2Au and Mn2Au/Fe Bilayers
Authors: Wu Han‐Chun , Abid Mohamed , Kalitsov Alan , Zarzhitsky Pavel , Abid Mourad , Liao Zhi‐Min , Coileáin Cormac Ó , Xu Hongjun , Wang Jing‐Jing , Liu Huajun , Mryasov Oleg N. , Chang Ching‐Ray , Shvets Igor V.
Published: June 2016

Recently intensive efforts have been devoted to the emerging field of antiferromagnetic (AFM) spintronics, where ferromagnetic electrodes are substituted by antiferromagnets. This study investigates the anisotropic magnetoresistance (AMR) of epitaxial tetragonal antiferromagnetic bimetallic films: Mn2Au and Mn2Au/Fe bilayers. An anomalous AMR effect with additional peaks is observed. This study theoretically and experimentally demonstrates that the AFM spins of Mn2Au can be viewed and controlled at room temperature, and this is achievable with a notably relatively small magnetic field of 200 mT. Strong hybridization between Au and Mn, and strong modification of the intrinsic quadratic anisotropy of Mn2Au from interfacial biquadratic anisotropy result in an additional anomalous AMR component of 1%. The findings suggest that Mn2Au films can be used in room temperature antiferromagnetic spintronics.
Self‐Assembly of Chiral Plasmonic Nanostructures
Authors: Lan Xiang , Wang Qiangbin
Published: June 2016

Plasmonic chiroptical effects have attracted significant attention for their widespread potential applications in negative‐refractive‐index materials, advanced light‐polarization filters, and ultrasensitive sensing devices, etc. As compared to top‐down fabrication methods, the bottom‐up self‐assembly strategy provides nanoscale resolution, parallel production, and isotropic optical response, and therefore plays an indispensable role in the fabrication of chiral plasmonic nanostructures. The optical properties of these chiral structures can be predicted based on the near‐field coupling of localized surface plasmons in structural components, which offers a route to tune or enhance optical activity by selecting building blocks and designing structural configurations. To date, three main types of chiral plasmonic nanostructures, i.e., chiral “plasmonic molecules”, chiral superstructures, and chiral‐molecule–metal hybrid complexes, are usually assembled, in which metal nanoparticles with various sizes, shapes, and compositions, and/or chiral molecules are employed as building blocks. Here, recent achievements in the self‐assembly of chiral plasmonic nanostructures are highlighted and perspectives on the future directions of chiral plasmonics integrated with bottom‐up self‐assembly are presented, showing three typical examples, including chiral plasmonic switches, chiral nanoparticles, and chiral metamaterials.
Advanced Colloidal Lithography Beyond Surface Patterning
Authors: Ai Bin , Möhwald Helmuth , Wang Dayang , Zhang Gang
Published: June 2016

This Review presents an overview of recent development of colloidal lithography (CL) and its applications in fabrication of various nanostructures consisted of orderly arranged, dots, holes, bowls, cones, pillars, rings, shells and triangles. These structures have been widely exploited in various fields, including plasmonics, optics, wettability, sensors, solar cells, organic light‐emitting diode (OLEDs), biology and many others. The recent successes in the technical applications of the nanostructures fabricated via CL will be summarized. Hopefully, the present review will inspire more ingenious designs and execution of CL for advanced, smart applications.
Acetyl Bromide Promoted Sequence via Allene Intermediates: Metal‐Free Construction of 2,3‐Dihydroindenes and Isoindolines
Authors: Liu Le , Yao Jinzhong , Chen Dianpeng , Zhou Hongwei
Published: June 2016

2,3‐Dihydroindenes and isoindolines are important skeletons present in medicinal and synthetic chemistry. In this paper, an acetyl bromide promoted metal‐free construction of 2,3‐dihydroindenes and isoindolines with high synthetic efficiency is developed.

magnified image
All‐Copper Nanocluster Based Down‐Conversion White Light‐Emitting Devices
Authors: Wang Zhenguang , Chen Bingkun , Susha Andrei S. , Wang Weihua , Reckmeier Claas J. , Chen Rui , Zhong Haizheng , Rogach Andrey L.
Published: June 2016

Most of the present‐day down‐conversion white light‐emitting devices (WLEDs) utilize rare‐earth elements, which are expensive and facing the problem of shortage in supply. WLEDs based on the combination of orange and blue emitting copper nanoclusters are introduced, which are easy to produce and low in cost. Orange emitting Cu nanoclusters (NCs) are synthesized using glutathione as both the reduction agent and stabilizer, followed by solvent induced aggregation leading to the emission enhancement. Photoluminescence quantum yields (PL QY) of 24% and 43% in solution and solid state are achieved, respectively. Blue emitting Cu nanoclusters are synthesized by reduction of polyvinylpyrrolidone supported Cu(II) ions using ascorbic acid, followed by surface treatment with sodium citrate which improves both the emission intensity and stability of the clusters, resulting in the PL QY of 14% both in solution and solid state. All‐copper nanocluster based down‐conversion WLEDs are fabricated by integrating powdered orange and blue emitting Cu NC samples on a commercial GaN LED chip providing 370 nm excitation. They show favorable white light characteristics with Commission Internationale de l'Eclairage color coordinates, color rendering index, and correlated color temperature of (0.36, 0.31), 92, and 4163 K, respectively.
The Progress of Interface Design in Perovskite‐Based Solar Cells
Authors: Fan Rundong , Huang Yuan , Wang Ligang , Li Liang , Zheng Guanhaojie , Zhou Huanping
Published: June 2016

Organic–inorganic halide perovskite has received extensive attention as a light harvester for next‐generation low‐cost and high‐performance photovoltaics. Its superior optoelectronic properties are attractive among most thin film absorber materials, such as an extremely high absorption coefficient, optimal band gap, ambipolar carrier transport property, and high defects tolerance. However, it requires suitable electrodes and carrier transport materials to fulfill efficient photovoltaic process within an entire device. Thus, the interfaces along the device play a crucial role in determining device photovoltaic performance. Here, the progress of understanding interfaces in perovskite photovoltaics is reviewed from the perspective of processing chemistry and photophysics of carriers, which are the key parameters for the corresponding device photovoltaic behavior. This study is mainly focused on the relevant working mechanism, interface design fundamentals, and the resulting carrier dynamic control over the entire architecture. The study of the interfaces with appropriate materials design provides a fundamental understanding of the photocarrier behavior, including separation, transportation, and collection. The accumulative efforts will contribute to the construction of high‐efficiency perovskite‐based single junction and multijunction photovoltaic devices. It also affects other properties of perovskite solar cells, including J–V hysteresis phenomenon, and long‐term stability. Suggestions with respect to required improvements and future research directions are provided based on the current field of available literature.
Two novel EIF2S3 mutations associated with syndromic intellectual disability with severe microcephaly, growth retardation, and epilepsy
Authors: Moortgat Stéphanie , Désir Julie , Benoit Valérie , Boulanger Sébastien , Pendeville Hélène , Nassogne Marie‐Cécile , Lederer Damien , Maystadt Isabelle
Published: June 2016

X‐chromosome exome sequencing was performed to identify the genetic cause of syndromic intellectual disability in two unrelated families with suspected X‐linked inheritance. In both families, affected males presented with severe intellectual disability, microcephaly, growth retardation, and epilepsy. A missense mutation (c.777T>G p.(Ile259Met)) and a frameshift mutation (c.1394_1397del p.(Ile465Serfs*4)) were identified in the EIF2S3 gene in the hemizygous state in affected patients, and in the heterozygous states female obligate carriers. A missense mutation in EIF2S3, coding for the gamma‐subunit of the translation initiation factor eIF2, was reported once in a family presenting with similar clinical features. Morpholino‐based knockdown of the zebrafish EIF2S3 ortholog (eif2s3) recapitulates the human microcephaly and short stature phenotype, supporting the pathogenicity of the identified variants. Our data confirm that EIF2S3 mutation is implicated in a rare, but recognizable, form of syndromic intellectual disability. © 2016 Wiley Periodicals, Inc.
Fragile X syndrome screening in pregnant women and women planning pregnancy shows a remarkably high FMR1 premutation prevalence in the Balearic Islands
Authors: Alfaro Arenas Ramona , Rosell Andreo Jordi , Heine Suñer Dami ,   Group for the study of FXS in the Balearic Islands
Published: June 2016

There are no reported studies to determine incidence of Fragile X Syndrome (FXS) in women within the Spanish population. For this reason, together with the high incidence of FXS in the general population, the exclusively maternal expansion, the familial and social impact of the syndrome, and the ease of use and level of detection of current PCR‐based techniques, we have conducted a population‐based screening pilot program of which we present here the molecular results. We typed prospectively 3,413 pregnant and 318 non‐pregnant women and found a prevalence of premutation (PM) carriers of 1 in 106, which is the highest described to date in any population. We also found 230 different alleles of which the most frequent are 10A9A9 (38.4%), 9A9A9 (15.1%), and 10A9 (10.5%). Furthermore, alleles with 0 AGG interruptions or with a pure (uninterrupted) CGG repeat run larger than 34 (presumably more unstable), were more frequent among PM alleles compared to normal alleles. Theà unexpected high frequency of expanded PM alleles in females in the general population makes a very compelling argument for the need for prenatal or preconceptional FXS screening in our community. Furthermore, we find FMR1 triplet primed PCR (TP‐PCR) confidently and precisely determines sizes for both alleles of the CGG repeat in women and offers AGG information which greatly improves CGG expansion risk estimations for genetic counselling. Thus, TP‐PCR is an informative, efficient and robust method for FXS screening in the female population. © 2016 Wiley Periodicals, Inc.
Detection of viruses using discarded plants from wild mountain gorillas and golden monkeys
Authors: Smiley Evans Tierra , Gilardi Kirsten V.K. , Barry Peter A. , Ssebide Benard Jasper , Kinani Jean Felix , Nizeyimana Fred , Noheri Jean Bosco , Byarugaba Denis K. , Mudakikwa Antoine , Cranfield Michael R. , Mazet Jonna A.K. , Johnson Christine K.
Published: June 2016

Infectious diseases pose one of the most significant threats to the survival of great apes in the wild. The critically endangered mountain gorilla (Gorilla beringei beringei) is at high risk for contracting human pathogens because approximately 60% of the population is habituated to humans to support a thriving ecotourism program. Disease surveillance for human and non‐human primate pathogens is important for population health and management of protected primate species. Here, we evaluate discarded plants from mountain gorillas and sympatric golden monkeys (Cercopithecus mitis kandti), as a novel biological sample to detect viruses that are shed orally. Discarded plant samples were tested for the presence of mammalian‐specific genetic material and two ubiquitous DNA and RNA primate viruses, herpesviruses, and simian foamy virus. We collected discarded plant samples from 383 wild human‐habituated mountain gorillas and from 18 habituated golden monkeys. Mammalian‐specific genetic material was recovered from all plant species and portions of plant bitten or chewed by gorillas and golden monkeys. Gorilla herpesviral DNA was most consistently recovered from plants in which leafy portions were eaten by gorillas. Simian foamy virus nucleic acid was recovered from plants discarded by golden monkeys, indicating that it is also possible to detect RNA viruses from bitten or chewed plants. Our findings show that discarded plants are a useful non‐invasive sampling method for detection of viruses that are shed orally in mountain gorillas, sympatric golden monkeys, and potentially other species. This method of collecting specimens from discarded plants is a new non‐invasive sampling protocol that can be combined with collection of feces and urine to evaluate the most common routes of viral shedding in wild primates. Am. J. Primatol. 78:1222–1234, 2016. © 2016 Wiley Periodicals, Inc.
Lösungsprozessierte MoS2‐Nanoplättchen: Herstellung, Hybridisierung und Anwendungen
Authors: Zhang Xiao , Lai Zhuangchai , Tan Chaoliang , Zhang Hua
Published: June 2016

MoS2‐Nanoplättchen gehören zu einer neuen Klasse dünner zweidimensionaler Übergangsmetalldichalkogenid‐Nanomaterialien. Aufgrund ihrer einzigartigen Struktur und faszinierenden Eigenschaften sind sie sehr interessant für die Forschung. Lösungsbasierte Verfahren sind vielversprechende Methoden für die skalierbare Herstellung, Funktionalisierung und Hybridisierung von MoS2‐Nanoplättchen und ermöglichen so die Erforschung von MoS2‐Nanomaterialien für verschiedene interessante Anwendungen. Dieser Aufsatz gibt einen Überblick über die aktuellen Fortschritte bei der Herstellung und Weiterverarbeitung von MoS2‐Nanoplättchen in Lösung. Besonderes Augenmerk gilt den Synthesestrategien, der Funktionalisierung und Hybridisierung sowie Eigenschaften und Anwendungen. Abschließend werden die Herausforderungen und Zukunftsaussichten dieses sehr aktuellen Forschungsgebiets besprochen.
Oxidationsreaktionen mit bioinspirierten einkernigen Nicht‐Häm‐Oxidometallkomplexen
Authors: Engelmann Xenia , Monte‐Pérez Inés , Ray Kallol
Published: June 2016

Die selektive Funktionalisierung starker C‐H‐Bindungen sowie die Oxidation von Wasser durch preiswerte und ungiftige Metalle sind einige der Schlüsselziele der heutigen chemischen Forschung. Es wurde vorgeschlagen, dass hochvalente Eisen‐, Mangan‐ und Kupferkerne als reaktive Intermediate an diesen wichtigen Oxidationsreaktionen, die von biologischen Systemen ausgeführt werden, beteiligt sind, was sie zu begehrten Zielobjekten für biomimetische Synthesestudien macht. Die Herstellung und Charakterisierung von Modell‐Oxidometallkomplexen von Eisen, Mangan und Kupfer, zusammen mit detaillierten Reaktivitätsstudien, kann dazu beitragen, die Rolle der sterischen und elektronischen Eigenschaften der Metallzentren zur Regulierung der Reaktivität entsprechender Metalloenzyme zu verstehen. Dieser Aufsatz bietet einen fokussierten Rückblick auf die jüngsten Fortschritte in der biomimetischen Komplexchemie hochvalenter Oxidometallkerne der letzten fünf bis zehn Jahre, die mit unserem Verständnis von biologischen Systemen in Beziehung gebracht werden können.
Synthese von Aeruginosin‐Chlorsulfopeptiden und Untersuchung ihrer Toxizität
Authors: Scherer Manuel , Bezold Dominik , Gademann Karl
Published: June 2016

Gesundheitsschädliche Algenblüten treten weltweit immer häufiger auf. Daher bedarf es Studien zur Identifikation der verantwortlichen Toxine sowie zu deren Wirkmechanismus, um die Ökosysteme inklusive der betroffenen Menschen und Tiere schützen zu können. In der hier vorgestellten Arbeit wurde das Chlorsulfopeptid Aeruginosin 828A, das für Krebstiere ähnlich toxisch ist wie das bekannte Microcystin‐LR, erstmals synthetisiert. Darüber hinaus wurden drei Kongenere mit verschiedenen Permutationen der Chlorid‐ und Sulfat‐Substituenten hergestellt, mit denen Toxizitätsstudien ohne das Risiko von Kontaminationen durch andere natürliche Toxine durchgeführt werden konnten. In einem Toxizitätsassay mit dem empfindlichen Biberschwanzfeenkrebs (Thamnocephalus platyurus) zeigte sich, dass die Toxizität in Gegenwart der Sulfat‐Gruppe hoch ist, während das Chlorid‐Derivat NMR‐spektroskopischen Untersuchungen zufolge eine andere Konformation einnimmt, was die Protease‐Inhibition beeinflussen könnte.
The Cation–π Interaction in Small‐Molecule Catalysis
Authors: Kennedy C. Rose , Lin Song , Jacobsen Eric N.
Published: June 2016

Catalysis by small molecules (≤1000 Da, 10−9 m) that are capable of binding and activating substrates through attractive, noncovalent interactions has emerged as an important approach in organic and organometallic chemistry. While the canonical noncovalent interactions, including hydrogen bonding, ion pairing, and π stacking, have become mainstays of catalyst design, the cation–π interaction has been comparatively underutilized in this context since its discovery in the 1980s. However, like a hydrogen bond, the cation–π interaction exhibits a typical binding affinity of several kcal mol−1 with substantial directionality. These properties render it attractive as a design element for the development of small‐molecule catalysts, and in recent years, the catalysis community has begun to take advantage of these features, drawing inspiration from pioneering research in molecular recognition and structural biology. This Review surveys the burgeoning application of the cation–π interaction in catalysis.
Investigating the Toxicity of the Aeruginosin Chlorosulfopeptides by Chemical Synthesis
Authors: Scherer Manuel , Bezold Dominik , Gademann Karl
Published: June 2016

Harmful algal blooms are becoming more prevalent all over the world, and identification and mechanism‐of‐action studies of the responsible toxins serve to protect ecosystems, livestock, and humans alike. In this study, the chlorosulfopeptide aeruginosin 828A, which rivals the well‐known toxin microcystin LR in terms of crustacean toxicity, has been synthesized for the first time. Furthermore, three congeners with different permutations of the chloride and sulfate groups were prepared, thereby enabling toxicity studies without the risk of contamination by other natural toxins. Toxicity assays with the sensitive crustacean Thamnocephalus platyurus demonstrated that the introduction of a sulfate group leads to pronounced toxicity, and NMR spectroscopic evidence suggests that the chloride substituent modulates the conformation, which in turn might influence protease inhibition.
Asymmetric Desymmetrization via Metal‐Free C−F Bond Activation: Synthesis of 3,5‐Diaryl‐5‐fluoromethyloxazolidin‐2‐ones with Quaternary Carbon Centers
Authors: Tanaka Junki , Suzuki Satoru , Tokunaga Etsuko , Haufe Günter , Shibata Norio
Published: June 2016

We disclose the first asymmetric activation of a non‐activated aliphatic C−F bond in which a conceptually new desymmetrization of 1,3‐difluorides by silicon‐induced selective C−F bond scission is a key step. The combination of a cinchona alkaloid based chiral ammonium bifluoride catalyst and N,O‐bis(trimethylsilyl)acetoamide (BSA) as the silicon reagent enabled the efficient catalytic cycle of asymmetric Csp3−F bond cleavage under mild conditions with high enantioselectivities. The ortho effect of the aryl group at the prostereogenic center is remarkable. This concept was applied for the asymmetric synthesis of promising agrochemical compounds, 3,5‐diaryl‐5‐fluoromethyloxazolidin‐2‐ones bearing a quaternary carbon center.
Synthesis, Biological, and Computational Evaluation of Substituted 1‐(2‐Methoxyphenyl)‐4‐(1‐phenethylpiperidin‐4‐yl)piperazines and 1‐(2‐Methoxyphenyl)‐4‐[(1‐phenethylpiperidin‐4‐yl)methyl]piperazines as Dopaminergic Ligands
Authors: Penjišević Jelena Z. , Šukalović Vladimir V. , Andrić Deana B. , Roglić Goran M. , Šoškić Vukić , Kostić‐Rajačić Slađana V.
Published: June 2016

Sixteen new 1‐(2‐methoxyphenyl)‐4‐(1‐phenethylpiperidin‐4‐yl)piperazines and 1‐(2‐methoxyphenyl)‐4‐[(1‐phenethylpiperidin‐4‐yl)methyl]piperazines were synthesized to be used as probes for mapping the dopamine D2 receptor (D2DAR) arylpiperazine binding site. All compounds were evaluated for their affinity toward D2DAR in an in vitro competitive displacement assay. The most active one was 1‐(2‐methoxyphenyl)‐4‐{[1‐(3‐nitrophenethyl)piperidin‐4‐yl]methyl}piperazine (25) with an affinity of Ki = 54 nM. Docking analysis was conducted on all herein described compounds, whereas molecular dynamic simulation was performed on ligand 25 to establish its mode of interaction with D2DAR. Two possible docking orientations are proposed; the one with a salt bridge between the piperidine moiety and Asp114 of D2DAR is more stable.
Correlation of Secretory Activity of Neutrophils With Genotype in Patients With Familial Mediterranean Fever
Authors: Gohar Faekah , Orak Banu , Kallinich Tilmann , Jeske Marion , Lieber Mareike , von Bernuth Horst , Giese Arnd , Weissbarth‐Riedel Elisabeth , Haas Johannes‐Peter , Dressler Frank , Holzinger Dirk , Lohse Peter , Neudorf Ulrich , Lainka Elke , Hinze Claas , Masjosthusmann Katja , Kessel Christoph , Weinhage Toni , Foell Dirk , Wittkowski Helmut
Published: June 2016

Objective

Familial Mediterranean fever (FMF) is an autoinflammatory disorder caused by pyrin‐encoding MEFV mutations. Patients present with recurrent but self‐limiting episodes of acute inflammation and often have persistent subclinical inflammation. The pathophysiology is only partially understood, but neutrophil overactivation is a hallmark of the disease. S100A12 is a neutrophil‐derived proinflammatory danger signal that is strongly elevated in active FMF. This study was undertaken to characterize the secretory activity of neutrophils in vitro and investigate the association of S100A12 with disease activity and genotype in patients with FMF.

Methods

Neutrophils from FMF patients carrying the p.M694V mutation (1 compound heterozygous and 5 homozygous) and neutrophils from 4 healthy control subjects were purified and stimulated in vitro. Neutrophil secretion of S100A12, interleukin‐18 (IL‐18), IL‐1β, and caspase 1 was determined. Based on these in vitro analyses, serum concentrations of S100A12, IL‐18, and IL‐1β were also analyzed in 128 clinically and genetically characterized patients with FMF.

Results

In vitro, unstimulated neutrophils from p.M694V‐positive patients spontaneously secreted more S100A12, IL‐18, and caspase 1 compared to neutrophils from healthy controls. Serum concentrations of S100A12 correlated with disease activity and genotype, with the levels being highest in homozygous patients and with compound heterozygotes displaying higher levels than heterozygotes. Compared to individuals negative for the p.M694V mutation, heterozygous, compound heterozygous, or homozygous p.M694V‐positive patients had higher serum levels of S100A12 and IL‐18 during inactive and subclinical disease.

Conclusion

The FMF phenotype is known to be more severe in patients carrying the p.M694V mutation. This report describes 2 molecules secreted by unconventional secretory pathways, S100A12 and IL‐18, whose concentrations correlated with clinical disease activity and genotype in patients with FMF. In this clinically and genetically heterogeneous disease, management of these surrogate markers might help to improve patient care and outcomes.
Suppression of Inflammatory Arthritis by Human Gut‐DerivedPrevotella histicolain Humanized Mice
Authors: Marietta Eric V. , Murray Joseph A. , Luckey David H. , Jeraldo Patricio R. , Lamba Abhinav , Patel Robin , Luthra Harvinder S. , Mangalam Ashutosh , Taneja Veena
Published: June 2016

Objective

The gut microbiome regulates host immune homeostasis. Rheumatoid arthritis (RA) is associated with intestinal dysbiosis. This study was undertaken to test the ability of a human gut‐derived commensal to modulate immune response and treat arthritis in a humanized mouse model.

Methods

We isolated a commensal bacterium,Prevotella histicola,that is native to the human gut and has systemic immune effects when administered enterally. Arthritis‐susceptible HLA–DQ8 mice were immunized with type II collagen and treated withP histicola. Disease incidence, onset, and severity were monitored. Changes in gut epithelial proteins and immune response as well as systemic cellular and humoral immune responses were studied in treated mice.

Results

When treated withP histicolain prophylactic or therapeutic protocols, DQ8 mice exhibited significantly decreased incidence and severity of arthritis compared to controls. The microbial mucosal modulation of arthritis was dependent on regulation by CD103+ dendritic cells and myeloid suppressors (CD11b+Gr‐1+ cells) and by generation of Treg cells (CD4+CD25+FoxP3+) in the gut, resulting in suppression of antigen‐specific Th17 responses and increased transcription of interleukin‐10. Treatment withP histicolaled to reduced intestinal permeability by increasing expression of enzymes that produce antimicrobial peptides as well as tight junction proteins (zonula occludens 1 and occludin). However, the innate immune response via Toll‐like receptor 4 (TLR‐4) and TLR‐9 was not affected in treated mice.

Conclusion

Our results demonstrate that enteral exposure toP histicolasuppresses arthritis via mucosal regulation.P histicolais a unique commensal that can be explored as a novel therapy for RA and may have few or no side effects.
The Autism‐Spectrum Quotient in Siblings of People With Autism
Authors: Ruzich Emily , Allison Carrie , Smith Paula , Ring Howard , Auyeung Bonnie , Baron‐Cohen Simon
Published: June 2016

This study measures the distribution of autistic traits, using the autism‐spectrum quotient (AQ), in siblings of individuals with autism spectrum conditions (ASC). Total AQ scores, along with AQ subscales, were collected from child, adolescent and adult controls, siblings, and volunteers with ASC using one of the three age‐appropriate versions of the instrument: the AQ (adult self‐report), the AQ‐adolescent and AQ‐child (both parent‐reports). We examined the effect of Group (case, sibling and control) and AQ version (adult, adolescent and adult) on total and subscale scores. In addition, we tested for sex differences in all groups and on all versions. We found that in male and female adults, AQ scores in siblings fell between cases and controls (cases > siblings > controls). In children and adolescents, female siblings also scored higher than control females (female cases > female siblings > female controls), but there was no difference between male siblings and controls (male cases > male siblings = male controls). An investigation of subscale scores revealed that male siblings only differed from controls on the “Communication” subscale (male cases > male siblings > male controls), while female siblings differed from controls on all subscales except “Imagination” (female cases > female siblings > female controls). This study confirms the broader autism phenotype in siblings, and reveals this is modulated by sex and AQ version. Autism Res 2017, 10: 289–297. © 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
Risk factors associated with increased prevalence of abdominal aortic aneurysm in women
Authors: Chabok M , Nicolaides A , Aslam M , Farahmandfar M , Humphries K , Kermani N Z , Coltart J , Standfield N
Published: June 2016

Background

Four randomized trials of men aged 65–80 years showed that aneurysm-related mortality was reduced by 40 per cent by ultrasound screening. Screening is considered economically viable when the prevalence of abdominal aortic aneurysm (AAA) is 1·0 per cent or higher. This is not the case for women, in whom the prevalence of AAA is less than 1 per cent. The aim of the present investigation was to determine the prevalence of AAA 3·0 cm or larger in women screened with ultrasound imaging, the risk factors associated with AAA in this population, and whether high-risk groups can be identified with an AAA prevalence of 1 per cent or greater.

Methods

Demographic data and risk factors were collected from the first 50 000 women who attended for private cardiovascular screening in the UK. Tests included ultrasound screening for AAA, ankle : brachial pressure index (ABPI), carotid duplex imaging for carotid atherosclerosis, and electrocardiography for atrial fibrillation.

Results

AAA was detected in 82 of 50 000 women screened; these aneurysms were rare below the age of 66 years (7 of 24 499). In the 66–85-years age group there were 72 AAAs in 25 170 women (0·29 per cent). Univariable analysis demonstrated that a history of stroke/transient ischaemic attack (TIA), hypertension, smoking, atrial fibrillation, ABPI of less than 0·9 and internal carotid artery stenosis of at least 50 per cent were associated with an increased prevalence of AAA (P < 0·001). In multivariable linear logistic regression of risk factors, age 76 years or more, history of stroke/TIA, hypertension and smoking were independent predictors of AAA. This model had an area under the receiver operating characteristic (ROC) curve (AUC) of 0·711 (95 per cent c.i. 0·649 to 0·772) and could identify 2235 women who had 22 AAAs (prevalence 0·98 per cent). By adding ABPI, atrial fibrillation and carotid stenosis, the prediction improved to an AUC of 0·775 (0·724 to 0·826). This model could identify 3701 women who had 58 AAAs (prevalence 1·57 per cent).

Conclusion

This report should stimulate consideration of a targeted AAA screening programme for women aged over 65 years.
Reoperation risk following the first operation for internal herniation in patients with laparoscopic Roux-en-Y gastric bypass
Authors: Danshøj Kristensen S , Naver L , Jess P , Floyd A K
Published: June 2016

Background

Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the most commonly used surgical procedure in the treatment of morbid obesity in Denmark. Internal herniation (IH) and intermittent internal herniation (IIH) are probably the most common late complications in patients with LRYGB. The aim of this study was to investigate a possible increased risk of subsequent operations after an initial IH or IIH event.

Methods

This long-term follow-up study of patients who had surgery for an initial IH or IIH event in 2006–2011, based on the Danish National Patient Registry (NPR), was performed to 2013. During this period, mesenteric defects were not closed routinely during LRYGB.

Results

Data were retrieved from 12 221 patients with LRYGB from the NPR. A total of 383 patients had surgery for an initial IH or IIH event. Some 102 patients (26·6 (95 per cent c.i. 22·5 to 31·3) per cent) had a second operation. Twenty-seven (26·5 (18·9 to 35·8) per cent) of these 102 patients had a third operation, and five (19 (8 to 37) per cent) of the 27 had a fourth operation. Of the 383 patients diagnosed with an initial IH or IIH event, 72 (18·8 per cent) had a second IH/IIH event, 14 (3·7 per cent) had a third event, and three (0·8 per cent) a fourth event requiring surgery.

Conclusion

Patients who have surgery for IH or IIH have a substantial risk of needing further operations.
Successful Fabrication of GaN Epitaxial Layer on Non‐Catalytically‐grown Graphene
Authors: Hwang Sung Won , Choi Suk‐Ho
Published: June 2016

Sapphire is widely used as a substrate for the growth of GaN epitaxial layer (EPI), but has several drawbacks such as high cost, large lattice mismatch, non‐flexibility, and so on. Here, we first employ graphene directly grown on Si or sapphire substrate as a platform for the growth and lift‐off of GaN‐light‐emitting diode (LED) EPI, useful for not only recycling the substrate but also transferring the GaN‐LED EPI to other flexible substrates. Sequential standard processes of nucleation/recrystallization of GaN seeds and deposition of undoped (u‐) GaN/AlN buffer layer were done on graphene/substrate before the growth of GaN‐LED EPI, accompanied by taping and lift‐off of u‐GaN/AlN or GaN‐LED EPI. This approach can overcome the limitations by the catalytic growth and transfer of graphene, and make the oxygen‐plasma treatment of graphene for the growth of GaN EPI unnecessary.
Educating children with autism: Collaboration between parents, teachers, and medical specialists
Authors: Dunn Brittany , Constable Sue , Martins Trish , Cammuso Karen
Published: June 2016

Providing comprehensive care and education services to children and adolescents with autism is a complex process (see Fiske et al., 2014). Typically, the parent is working in collaboration with the educational system, the medical system, and a specialist in neurodevelopment (developmental pediatrician, neurologist, child psychiatrist, or psychologist). These systems each have a distinct role in the child's care. They are often speaking a different “language” from one another, governed by the conventions and (in the case of special education) the laws of their field. At the most vulnerable time of diagnosis, families face the daunting task of negotiating between these professionals and trying to develop comprehensive programming and shared understanding of their child's strengths and needs.
A Practical Guide on the Synthesis of Metal Chelates for Molecular Imaging and Therapy by Means of Click Chemistry
Authors: Notni Johannes , Wester Hans‐Jürgen
Published: June 2016

The copper‐catalyzed cycloaddition of organic azides and alkynes (CuAAC) is one of the most popular reactions for rapid assembly of multifunctional molecular frameworks from commercially available building blocks. It is also attractive for synthesis of conjugates of multidentate chelate ligands (chelators) with molecular targeting vectors, such as peptides or proteins, which serve as precursors for labeling with metal radionuclides or are useful as MRI contrast agents after GdIII complexation. However, applicability of CuAAC for such purposes is complicated by formation of unwanted copper chelates. The alternative use of copper‐free click chemistry, for example, the strain‐promoted alkyne‐azide cycloaddition (SPAAC) or the Diels–Alder reaction of tetrazines and strained alkenes, entails other specific challenges: Introduction of large, isomerically non‐homogeneous and hydrophobic linker groups affects product homogeneity and can severely change pharmacokinetic profiles. Against this background, this review elucidates scope and applicability of both Cu‐catalyzed and Cu‐free alkyne‐azide cycloadditions pertinent to the elaboration of radiometal chelates and MRI contrast agents, with an emphasis on strategies to tackle the problem of copper complexation during CuAAC.
Diazonium Functionalisation of Carbon Nanotubes for Specific Orientation of Multicopper Oxidases: Controlling Electron Entry Points and Oxygen Diffusion to the Enzyme
Authors: Lalaoui Noémie , Holzinger Michael , Le Goff Alan , Cosnier Serge
Published: June 2016

We report the controlled orientation of bilirubin oxidases (BOD) from Myrothecium verrucaria on multiwalled carbon nanotubes (MWCNTs) functionalised by electrografting of 6‐carboxynaphthalenediazonium and 4‐(2‐aminoethyl)benzenediazonium salts. On negatively charged naphthoate‐modified MWCNTs, a high‐potential (0.44 V vs. SCE) oxygen reduction electrocatalysis is observed, occurring via the T1 copper centre. On positively charged ammonium‐modified MWCNTs, a low‐potential (0.15 V) oxygen reduction electrocatalysis is observed, occurring through a partially oxidised state of the T2/T3 trinuclear copper cluster. Finally, chemically modified naphthoate MWCNTs exhibit high bioelectrocatalytic current densities of 3.9 mA cm−2 under air at gas‐diffusion electrode.
Acceptorless Dehydrogenative Oxidation of Secondary Alcohols Catalysed by Cp*IrIII–NHC Complexes
Authors: Gülcemal Süleyman , Gülcemal Derya , Whitehead George F. S. , Xiao Jianliang
Published: June 2016

A series of new IrIII complexes with carbene ligands that contain a range of benzyl wingtip groups have been prepared and fully characterised by NMR spectroscopy, HRMS, elemental analysis and X‐ray diffraction. All the complexes were active in the acceptorless dehydrogenation of alcohol substrates in 2,2,2‐trifluoroethanol to give the corresponding carbonyl compounds. The most active complex bore an electron‐rich carbene ligand; this complex was used to catalyse the highly efficient and chemoselective dehydrogenation of a wide range of secondary alcohols to their respective ketones, with turnover numbers up to 1660. Mechanistic studies suggested that the turnover of the dehydrogenation reaction is limited by the H2‐formation step.
Health Risk Assessment in Calcareous Agricultural Soils Contaminated by Metallic Mining Activity Under Mediterranean Climate
Authors: Béjaoui Imène , Kolsi‐Benzina Naïma , Sappin‐Didier Valérie , Munoz Marguerite
Published: June 2016

The agricultural lands surrounding the ancient mine site of Jebel Ressas (Tunisia) have been contaminated mainly due to the mining waste dumps left without environment protection measures. The metal contamination of agricultural soils and crops was studied to evaluate the local population health risk. The results show the soil Cd and Pb contamination over an area of 180 ha and up to 5 km distance from the dumps. The toxic metals contents in soil exceeded the maximum allowable Canadian limits for agricultural soils, reaching 231 and 20 100 mg kg−1 for cadmium (Cd) and lead (Pb), respectively, but decreasing with the distance from the dumps. Although a low solubility and availability of metals could be expected within the calcareous soils of this area, metals appeared to be absorbed by edible plants (fruits and vegetables). High contents in parsley and mallow were recorded, reaching up to four times the allowable limits (EC 1881/2006) for Cd, and 26 times for Pb. Local population exposure to metals by both soil ingestion and consumption of contaminated plants has been estimated and the health risk has been confirmed for farmlands inhabitants, especially for children. The major source of risk for the local population is dietary. Soil dust contribution to health risk is at the most 3.4% for adults and at the most 13.1% for children.
Design, Synthesis, and Evaluation of 2‐Amino‐6‐nitrobenzothiazole‐Derived Hydrazones as MAO Inhibitors: Role of the Methylene Spacer Group
Authors: Tripathi Rati K. P. , Ayyannan Senthil R.
Published: June 2016

A series of 2‐amino‐6‐nitrobenzothiazole‐derived extended hydrazones were designed, synthesized, and investigated for their ability to inhibit monoamine oxidase A and B (MAO‐A/MAO‐B). The compounds were found to exhibit inhibitory activities in the nanomolar to micromolar range. Some of the compounds showed excellent potency and selectivity against the MAO‐B isoform. N′‐(5‐Chloro‐2‐oxoindolin‐3‐ylidene)‐2‐(6‐nitrobenzothiazol‐2‐ylamino)acetohydrazide (compound 31) showed the highest MAO‐B inhibitory activity (IC50=1.8±0.3 nm, selectivity index [SI]=766.67), whereas compound 6 [N′‐(1‐(4‐bromophenyl)ethylidene)‐2‐(6‐nitrobenzothiazol‐2‐ylamino)acetohydrazide] was found to be the most active MAO‐A inhibitor (IC50=0.42±0.003 μm). Kinetic studies revealed that compounds 6 and 31 exhibit competitive‐type reversible inhibition against both MAO‐A and MAO‐B, respectively. Structure–activity relationship (SAR) studies disclosed several structural aspects significant for potency and the contribution of the methylene spacer toward MAO‐B inhibitory potency, with minimal or no neurotoxicity. Molecular modeling studies yielded a good correlation between experimental and theoretical inhibitory data. Binding pose analysis revealed the significance of cumulative effects of π–π stacking and hydrogen bond interactions for effective stabilization of virtual ligand–protein complexes. Further optimization studies of compound 31, including co‐crystallization of inhibitor–MAO‐B complexes, are essential to develop these compounds as potential therapeutic agents for MAO‐B‐associated neurodegenerative diseases.
Benefit of adjuvant radiotherapy after breast‐conserving therapy among elderly women with T1‐T2N0 estrogen receptor‐negative breast cancer
Authors: Eaton Bree R. , Jiang Renjian , Torres Mylin A. , Kahn Shannon T. , Godette Karen , Lash Timothy L. , Ward Kevin C.
Published: June 2016

BACKGROUND

The purpose of the current study was to evaluate the impact of radiotherapy (RT) among women aged ≥ 70 years with T1‐2N0 estrogen receptor (ER)‐negative breast cancer using Surveillance, Epidemiology, and End Results (SEER)‐Medicare‐linked data.

METHODS

The study included 3432 women, 2850 of whom received and 582 of whom did not receive RT after breast‐conserving surgery. Outcomes were estimated by the cumulative incidence method and compared with the Gray test. The Fine and Gray subdistribution hazard regression models were used to assess the impact of RT and other variables.

RESULTS

Women who received RT were more commonly aged <75 years (42% vs 16%), had T1 tumors (78% vs 65%), ductal carcinoma histology (91% vs 88%), a Charlson‐Deyo Comorbidity Index of 0 (41% vs 25%), and had received chemotherapy (29% vs 12%). The 5‐year cumulative incidence of mastectomy and breast cancer‐specific death for patients who received versus those did not receive adjuvant RT was 4.9% and 8.3% versus 10.8% and 24.1%, respectively (P<.001). On multivariable analysis, the omission of RT was found to be an independent predictor of an increased risk of mastectomy (hazard ratio, 2.33; 95% confidence interval, 1.56‐3.49). Among women aged ≥ 80 years or with T1N0 tumors, the mastectomy incidence with or without receipt of RT was 3.4% vs. 6.9%, and 5.3% vs 7.7%, respectively.

CONCLUSIONS

The use of adjuvant RT after breast‐conserving surgery in older women with T1‐2N0 estrogen receptor‐negative breast cancer is associated with a reduced incidence of future mastectomy and breast cancer death. The magnitude of benefit may be small for women aged ≥80 years or those with T1 tumors. Cancer 2016;122:3059‐3068. © 2016 American Cancer Society.