bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity of inelastic strain during creep of Carrara marble: Microscale strain measurement technique
Authors: Quintanilla‐Terminel Alejandra , Evans Brian
Published: July 2016

We combined the split cylinder technique with microfabrication technology to observe strain heterogeneities that were produced during high‐pressure transient creep of Carrara marble. Samples were patterned with a custom‐designed grid of markers spaced 10 µm apart and containing an embedded coordinate system. The microscale strain measurement (MSSM) technique described here allowed us to analyze the local strain distribution with unprecedented detail over large regions. The description of the strain field is a function of the area over which strain is being computed. The scale at which the strain field can be considered homogeneous can provide insight into the deformation processes taking place. At 400–500°C, when twinning production is prolific, we observe highly strained bands that span several grains. One possible cause for the multigrain bands is the need to relieve strain incompatibilities that result when twins impinge on neighboring grains. At 600–700°C, the strain fields are still quite heterogeneous, and local strain varies substantially within grains and near grain boundaries, but the multigrain slip bands are not present. Deformation is concentrated in much smaller areas within grains and along some grain boundaries. The disappearance of the multigrain slip bands occurs when the deformation conditions allow additional slip systems to be activated. At 600°C, when the total strain is varied from 0.11 to 0.36, the spatial scale of the heterogeneity does not vary, but there are increases in the standard deviation of the distribution of local strains normalized by the total strain; thus, we conclude that the microstructure does not achieve a steady state in this strain interval.
Training Melanoma Detection in Photographs Using the Perceptual Expertise Training Approach
Authors: Xu Buyun , Rourke Liam , Robinson June K. , Tanaka James W.
Published: July 2016

Although a deadly form of skin cancer, melanoma is treatable if detected early. However, current rule‐based training practices in melanoma detection are not effective. We assessed an innovative technique to train melanoma detection using the perceptual expertise principles. Participants in the training group were trained to categorize melanoma and benign lesions to 95% accuracy. Participants in the control group received no training. Prior to testing all participants reviewed the ABCDE rules. Training was evaluated by the pre and post tests using the Melanoma Detection Test where participants categorized images of melanoma and benign lesions. As compared to the control group, the training group showed significant improvement in melanoma detection and became less liberal (i.e., bias toward categorizing a lesion as melanoma), and both improvements maintained a week after the training. These findings indicate that perceptual expertise training is a promising approach to train melanoma detection.Copyright © 2016 John Wiley & Sons, Ltd.
The Impact of Testing on the Formation of Children's and Adults' False Memories
Authors: Brackmann Nathalie , Otgaar Henry , Sauerland Melanie , Howe Mark L.
Published: July 2016

Witnesses are frequently questioned immediately following a crime. The effects of such testing on false recall are inconclusive: Testing may inoculate against subsequent misinformation or enhance false memory formation. We examined whether different types of processing can account for these discrepancies. Drawing from Fuzzy‐trace and Associative‐activation theories, immediate questions that trigger the processing of the global understanding of the event can heighten false memory rates. However, questions that trigger the processing of specific details can inoculate memories against subsequent misinformation. These effects were hypothesized to be more pronounced in children than in adults. Seven/eight‐, 11/12‐, 14/15‐year‐olds, and adults (N = 220) saw a mock‐theft film and were tested immediately with meaning or item‐specific questions. Test results on the succeeding day replicated classic misinformation and testing effects, although our processing hypothesis was not supported. Only adults who received meaning questions benefited from immediate testing and, across all ages, testing led to retrieval‐enhanced suggestibility. © 2016 The Authors. Applied Cognitive Psychology Published by John Wiley & Sons, Ltd.
Metal‐Organic‐Framework‐Based Vaccine Platforms for Enhanced Systemic Immune and Memory Response
Authors: Zhang Yan , Wang Faming , Ju Enguo , Liu Zhen , Chen Zhaowei , Ren Jinsong , Qu Xiaogang
Published: July 2016

Nanoparticulate delivery platforms have shown promising advantages for vaccines in many aspects. However, their application was limited so far by lengthy synthetic protocols, the requirement of specific modification of antigen, and by the low efficiency in inducing antigen‐specific cytotoxic T‐lymphocyte responses. This study demonstrates for the first time the construction of metal‐organic‐framework (MOF) based vaccines by encapsulating ovalbumin (OVA) and attaching the cytosine‐phosphate‐guanine oligodeoxynucleotides (CpG ODNs) in/on zeolitic imidazolate framework‐8 (ZIF‐8) nanoparticles. The pH responsive decomposition feature enables the system to release the protein antigens and CpG ODNs in the same antigen presenting cells more efficiently. More importantly, in addition to the induction of a potent immune memory response, both in vitro and in vivo experiments show that the vaccines can induce strong humoral and cellular immunity. These findings suggest that the MOF‐based vaccine platforms can be used to produce effective vaccines against a range of ailments, which will facilitate the application of MOFs in biomedical areas.
Luminescent Ions in Advanced Composite Materials for Multifunctional Applications
Authors: Bai Gongxun , Tsang Ming‐Kiu , Hao Jianhua
Published: July 2016

Luminescent ions doped materials have been widely applied in many areas, both scientific research and practical fields. Recently, incorporating luminescent ions and advanced materials into versatile and multifunctional systems seems to be a tendency, motivated by the stimulating desires of fundamental studies and technological applications. This feature article provides a general overview of the myriad of luminescent ions‐based advanced composite materials recently investigated. It is demonstrated that the improved or additional properties may be achieved via implementing a strategy of incorporating luminescent ions (lanthanide, transition and main group metal ions) into various types of materials, such as flexible polymers, two‐dimensional atomically thin layers, porous materials, and so on. We outline the design principles, synthesis and processing of various systems joined by luminescent ions doped phosphors. A number of recent works indicate that those novel composite materials allow one to conceive and develop multifunctional applications in a broad area, including optoelectronics, photonics, clean energy, biomedicine, and new types of sensors. Lastly, some challenging issues are discussed and potential directions are suggested for further developing advanced composite materials incorporated with luminescent ions.
Multifunctional Energy Storage and Conversion Devices
Authors: Huang Yan , Zhu Minshen , Huang Yang , Pei Zengxia , Li Hongfei , Wang Zifeng , Xue Qi , Zhi Chunyi
Published: July 2016

Multifunctional energy storage and conversion devices that incorporate novel features and functions in intelligent and interactive modes, represent a radical advance in consumer products, such as wearable electronics, healthcare devices, artificial intelligence, electric vehicles, smart household, and space satellites, etc. Here, smart energy devices are defined to be energy devices that are responsive to changes in configurational integrity, voltage, mechanical deformation, light, and temperature, called self‐healability, electrochromism, shape memory, photodetection, and thermal responsivity. Advisable materials, device designs, and performances are crucial for the development of energy electronics endowed with these smart functions. Integrating these smart functions in energy storage and conversion devices gives rise to great challenges from the viewpoint of both understanding the fundamental mechanisms and practical implementation. Current state‐of‐art examples of these smart multifunctional energy devices, pertinent to materials, fabrication strategies, and performances, are highlighted. In addition, current challenges and potential solutions from materials synthesis to device performances are discussed. Finally, some important directions in this fast developing field are considered to further expand their application.
Broader impacts: international implications and integrative ethical consideration of policy decisions about US chimpanzee research
Authors: Bennett Allyson J. , Panicker Sangeeta
Published: July 2016

Recent decisions and unprecedented evaluative processes about research with chimpanzees (Pan troglodytes) by the US National Institutes of Health (NIH) continue to attract widespread attention by the public, media, and scientific community. Over the past 5 years, actions by the NIH and the United States Fish and Wildlife Services, have significantly truncated valuable scientific research and jeopardized future research. From a global perspective, the decisions have broad consequences for research aimed not only at human health, but also the conservation and welfare of other species. Full consideration of the role that research plays in improving animal welfare in captivity and in the wild, and the impact of the loss of access to chimpanzees for research, remains largely unexamined. At the same time, legal initiatives aimed at protecting chimpanzees by granting them “personhood” status have increasingly raised questions about equity in standards, oversight, and transparency for chimpanzees in other captive settings. Together, the decisions, subsequent actions, and public discussion put the growing need for a more integrative and global approach to decision‐making about the future of captive chimpanzees into sharp relief. In this paper, we outline an expansive framework for ethical consideration to guide dialogue and decisions about animal research, welfare, and equitable treatment of nonhuman animals across settings. Regardless of the setting in which animals live, science plays an indispensable role in informing decisions about individual, species, societal, and environmental health. Thus, the scientific community and broader public need to engage in serious and thoughtful deliberations to weigh the harms and benefits of conducting (or failing to conduct) research that transcends geographic borders and that can guide responsible and informed decisions about the future of chimpanzees.
Das Radikalanion und Dianion von Tetraazapentacen
Authors: Ji Lei , Haehnel Martin , Krummenacher Ivo , Biegger Philipp , Geyer Florian L. , Tverskoy Olena , Schaffroth Manuel , Han Jie , Dreuw Andreas , Marder Todd B. , Bunz Uwe H. F.
Published: July 2016

Das Mono‐ und das Dianion von 6,13‐Bis((triisopropylsilyl)ethinyl)chinoxalino[2,3‐b]phenazin wurden durch Reduktion mit Kaliumanthracenid in THF synthetisiert und anschließend charakterisiert. Sowohl das Radikalanion, 1.−, als auch das Dianion, 12−, konnten isoliert sowie durch optische Methoden und Einkristallstrukturanalyse charakterisiert werden. Lösungen des Radikalanions 1.− sind mehrere Stunden lang luftstabil und wurden durch EPR‐Spektroskopie charakterisiert. Das Dianion 12− ist hochfluoreszierend und photostabil.
Towards a DNA Nanoprocessor: Reusable Tile‐Integrated DNA Circuits
Authors: Gerasimova Yulia V. , Kolpashchikov Dmitry M.
Published: July 2016

Modern electronic microprocessors use semiconductor logic gates organized on a silicon chip to enable efficient inter‐gate communication. Here, arrays of communicating DNA logic gates integrated on a single DNA tile were designed and used to process nucleic acid inputs in a reusable format. Our results lay the foundation for the development of a DNA nanoprocessor, a small and biocompatible device capable of performing complex analyses of DNA and RNA inputs.
Realignment of Nanocrystal Aggregates into Single Crystals as a Result of Inherent Surface Stress
Authors: Liu Zhaoming , Pan Haihua , Zhu Genxing , Li Yaling , Tao Jinhui , Jin Biao , Tang Ruikang
Published: July 2016

Crystallization by particle attachment is widely observed in both natural and synthetic environments. Although this form of nonclassical crystallization is generally described by oriented attachment, random aggregation of building blocks to give single‐crystal products is also observed, but the mechanism of crystallographic realignment is unknown. We herein reveal that random attachment during aggregation‐based growth initially produces a nonoriented growth front. Subsequent evolution of the orientation is driven by the inherent surface stress applied by the disordered surface layer and results in single‐crystal formation by grain‐boundary migration. This mechanism is corroborated by measurements of orientation rate versus external stress, which demonstrated a predictive relationship between the two. These findings advance our understandings about aggregation‐based growth via nanocrystal blocks and suggest an approach to material synthesis that takes advantage of stress‐induced coalignment.
Ungewöhnlich effiziente strukturdirigierte Phosphoreszenz in Silber(I)‐Clustern, realisiert mit Carba‐closo‐dodecaboranylethinyl‐Liganden
Authors: Hailmann Michael , Wolf Natalia , Renner Rebecca , Schäfer Thomas C. , Hupp Benjamin , Steffen Andreas , Finze Maik
Published: July 2016

Ausgehend von {Ag2(12‐C≡C‐closo‐1‐CB11H11)}n und ausgewählten Pyridinliganden wurden photostabile AgI‐Cluster synthetisiert, die, mit einer Ausnahme, eine für AgI‐Verbindungen ungewöhnliche Raumtemperaturphosphoreszenz zeigen. Eine besonders intensive Phosphoreszenz wurde für einen verzerrt pentagonal‐bipyramidalen AgI7‐Cluster mit einer für AgI‐Cluster präzedenzlosen Quantenausbeute von Φ=0.76 beobachtet. Das Lumineszenzverhalten korreliert mit der Struktur des zentralen AgIn‐Motivs, was anhand des Vergleichs der Emissionseigenschaften der Cluster mit unterschiedlicher Anzahl von AgI‐Ionen, unterschiedlicher Ladung und elektronisch unterschiedlichen Pyridinliganden deutlich wird.
Reagent‐Controlled α‐Selective Dehydrative Glycosylation of 2,6‐Dideoxy‐ and 2,3,6‐Trideoxy Sugars
Authors: Nogueira Jason M. , Bylsma Marissa , Bright Danielle K. , Bennett Clay S.
Published: July 2016

We have found that activating either 2,3‐bis(2,3,4‐trimethoxyphenyl)cyclopropenone or 2,3‐bis(2,3,4‐trimethoxyphenyl)cyclopropene‐1‐thione with oxalyl bromide results in the formation of a species that promotes the glycosylation between 2,6‐dideoxy‐sugar hemiacetals and glycosyl acceptors in good yield and high α‐selectivity. Both reactions are mild and tolerate a number of sensitive functional groups including highly acid‐labile 2,3,6‐trideoxy‐sugar linkages.
The Radical Anion and Dianion of Tetraazapentacene
Authors: Ji Lei , Haehnel Martin , Krummenacher Ivo , Biegger Philipp , Geyer Florian L. , Tverskoy Olena , Schaffroth Manuel , Han Jie , Dreuw Andreas , Marder Todd B. , Bunz Uwe H. F.
Published: July 2016

The mono‐ and bis‐reduction of 6,13‐bis((triisopropylsilyl)ethynyl)quinoxalino[2,3‐b]phenazine (1) with potassium anthracenide in THF is reported. Both the radical anion 1.− and the dianion 12− were isolated and characterized by optical and structural (single‐crystal X‐ray diffraction) methods. Solutions of the radical anion 1.− were stable in air for several hours and characterized by EPR spectroscopy. Dianion 12− is highly fluorescent and photostable.
Regioselective Transition‐Metal‐Free Allyl–Allyl Cross‐Couplings
Authors: Ellwart Mario , Makarov Ilya S. , Achrainer Florian , Zipse Hendrik , Knochel Paul
Published: July 2016

Readily prepared allylic zinc halides undergo SN2‐type substitutions with allylic bromides in a 1:1 mixture of THF and DMPU providing 1,5‐dienes regioselectively. The allylic zinc species reacts at the most branched end (γ‐position) of the allylic system furnishing exclusively γ,α′‐allyl–allyl cross‐coupling products. Remarkably, the double bond stereochemistry of the allylic halide is maintained during the cross‐coupling process. Also several functional groups (ester, nitrile) are tolerated. This cross‐coupling of allylic zinc reagents can be extended to propargylic and benzylic halides. DFT calculations show the importance of lithium chloride in this substitution.
Unprecedented Efficient Structure Controlled Phosphorescence of Silver(I) Clusters Stabilized by Carba‐closo‐dodecaboranylethynyl Ligands
Authors: Hailmann Michael , Wolf Natalia , Renner Rebecca , Schäfer Thomas C. , Hupp Benjamin , Steffen Andreas , Finze Maik
Published: July 2016

{Ag2(12‐C≡C‐closo‐1‐CB11H11)}n and selected pyridine ligands have been used for the synthesis of photostable AgI clusters that, with one exception, exhibit for AgI compounds unusual room‐temperature phosphorescence. Extraordinarily intense phosphorescence was observed for a distorted pentagonal bipyramidal AgI7 cluster that shows an unprecedented quantum yield of Φ=0.76 for AgI clusters. The luminescence properties correlate with the structures of the central AgIn motifs as shown by comparison of the emission properties of the clusters with different numbers of AgI ions, different charges, and electronically different pyridine ligands.
Design and Applications of Protein‐Cage‐Based Nanomaterials
Authors: Zhang Yu , Ardejani Maziar S. , Orner Brendan P.
Published: July 2016

Materials science is beginning to focus on biotemplation, and in support of that trend, it is realized that protein cages—proteins that assemble from multiple monomers into architectures with hollow interiors—can instill a number of unique advantages to nanomaterials. In addition, the structural and functional plasticity of many protein‐cage systems permits their engineering for specific applications. In this review, the most commonly used viral and non‐viral protein cages, which exhibit a wide diversity of size, functionality, and chemical and thermal stabilities, are described. Moreover, how they have been exploited for nanomaterial and nanotechnology applications is summarized.
Boundary Control of a Flexible Robotic Manipulator With Output Constraints
Authors: Liu Zhijie , Liu Jinkun
Published: July 2016

In this study, we consider a boundary control problem of a flexible manipulator with input disturbances and output constraints, achieving pre‐set performance attributes on position tracking error and the deflection error at the end of the beam. The dynamics of the system are represented by partial differential equations (PDEs). With the Lyapunov's direct method, a boundary controller with disturbance observer is designed to regulate the angular position and suppress elastic vibration simultaneously. The proposed control scheme allows the errors to converge to an arbitrarily small residual set, with convergence rate larger than a pre‐specified value. Numerical simulations demonstrate the effectiveness of the proposed scheme.
1950 MHz radiofrequency electromagnetic fields do not aggravate memory deficits in 5xFAD mice
Authors: Son Yeonghoon , Jeong Ye Ji , Kwon Jong Hwa , Choi Hyung‐Do , Pack Jeong‐Ki , Kim Nam , Lee Yun‐Sil , Lee Hae‐June
Published: July 2016

The increased use of mobile phones has generated public concern about the impact of radiofrequency electromagnetic fields (RF‐EMF) on health. In the present study, we investigated whether RF‐EMFs induce molecular changes in amyloid precursor protein (APP) processing and amyloid beta (Aβ)‐related memory impairment in the 5xFAD mouse, which is a widely used amyloid animal model. The 5xFAD mice at the age of 1.5 months were assigned to two groups (RF‐EMF‐ and sham‐exposed groups, eight mice per group). The RF‐EMF group was placed in a reverberation chamber and exposed to 1950 MHz electromagnetic fields for 3 months (SAR 5 W/kg, 2 h/day, 5 days/week). The Y‐maze, Morris water maze, and novel object recognition memory test were used to evaluate spatial and non‐spatial memory following 3‐month RF‐EMF exposure. Furthermore, Aβ deposition and APP and carboxyl‐terminal fragment β (CTFβ) levels were evaluated in the hippocampus and cortex of 5xFAD mice, and plasma levels of Aβ peptides were also investigated. In behavioral tests, mice that were exposed to RF‐EMF for 3 months did not exhibit differences in spatial and non‐spatial memory compared to the sham‐exposed group, and no apparent change was evident in locomotor activity. Consistent with behavioral data, RF‐EMF did not alter APP and CTFβ levels or Aβ deposition in the brains of the 5xFAD mice. These findings indicate that 3‐month RF‐EMF exposure did not affect Aβ‐related memory impairment or Aβ accumulation in the 5xFAD Alzheimer's disease model. Bioelectromagnetics. 37:391–399, 2016. © 2016 The Authors Bioelectromagnetics published by Wiley Periodicals, Inc. on behalf of Bioelectromagnetics Society.
Hydro‐aza‐(C59N)fullerenes: Formation Mechanism and Hydrogen Substitution
Authors: Eigler Regina , Heinemann Frank W. , Hirsch Andreas
Published: July 2016

Azafullerenes are as yet the only synthetically available heterofullerenes. Herein, we present plausible reaction pathways towards pentaaryl azafullerenes, focusing on the reactivity of hydro‐azafullerene intermediates and their regiochemistry. The X‐ray structure of a β′‐hydro‐tetraaryl adduct is presented for the first time. The reactivity of dihydro‐azafullerene adducts is demonstrated here through H‐abstraction in mass spectrometric experiments. Moreover, hydride abstraction and subsequent hydroxylation is possible, as well as deprotonation followed by alkylation.
Smart Solution Chemistry to Sn‐Containing Intermetallic Compounds through a Self‐Disproportionation Process
Authors: Zhang Yuelan , Li Liping , Li Qi , Fan Jianming , Zheng Jing , Li Guangshe
Published: July 2016

Developing new methods to synthesize intermetallics is one of the most critical issues for the discovery and application of multifunctional metal materials; however, the synthesis of Sn‐containing intermetallics is challenging. In this work, we demonstrated for the first time that a self‐disproportionation‐induced in situ process produces cavernous Sn−Cu intermetallics (Cu3Sn and Cu6Sn5). The successful synthesis is realized by introducing inorganic metal salts (SnCl2⋅2 H2O) to NaOH aqueous solution to form an intermediate product of reductant (Na2SnO2) and by employing steam pressures that enhance the reduction ability. Distinct from the traditional in situ reduction, the current reduction process avoided the uncontrolled phase composition and excessive use of organic regents. An insight into the mechanism was revealed for the Sn−Cu case. Moreover, this method could be extended to other Sn‐containing materials (Sn−Co, Sn−Ni). All these intermetallics were attempted in the catalytic effect on thermal decompositions of ammonium perchlorate. It is demonstrated that Cu3Sn showed an outstanding catalytic performance. The superior property might be primarily originated from the intrinsic chemical compositions and cavernous morphology as well. We supposed that this smart solution reduction methodology reported here would provide a new recognition for the reduction reaction, and its modified strategy may be applied to the synthesis of other metals, intermetallics as well as some unknown materials.
Dehydrogenative Coupling Reactions with Oxidized Guanidino‐Functionalized Aromatic Compounds: Novel Options for σ‐Bond Activation
Authors: Wild Ute , Federle Stefanie , Wagner Arne , Kaifer Elisabeth , Himmel Hans‐Jörg
Published: July 2016

We present a new option for metal‐free σ‐bond activation, making use of oxidized, guanidino‐functionalized aromatic compounds (GFAs). We demonstrate this new option by the homocoupling reactions of thiols and phosphines. The kinetics and the reaction pathway were studied by a number of experiments (including heterocoupling of thiols and phosphines), supported by quantum‐chemical computations. Reaction of the oxidized GFA with p‐dihydrobenzoquinone to give p‐benzoquinone shows that typical proton‐coupled electron‐transfer reactions are also possible.
Design and Synthesis of 2,2′‐Diindolylmethanes to Selectively Target Certain G‐Quadruplex DNA Structures
Authors: Livendahl Madeleine , Jamroskovic Jan , Ivanova Svetlana , Demirel Peter , Sabouri Nasim , Chorell Erik
Published: July 2016

G‐quadruplex (G4) structures carry vital biological functions, and compounds that selectively target certain G4 structures have both therapeutic potential and value as research tools. Along this line, 2,2′‐diindolylmethanes have been designed and synthesized in this work based on the condensation of 3,6‐ or 3,7‐disubstituted indoles with aldehydes. The developed class of compounds efficiently stabilizes G4 structures without inducing conformational changes in such structures. Furthermore, the 2,2′‐diindolylmethanes target certain G4 structures more efficiently than others and this G4 selectivity can be altered by chemical modifications of the compounds.
Divergent Reactivity of Thioalkynes in Lewis Acid Catalyzed Annulations with Donor–Acceptor Cyclopropanes
Authors: Racine Sophie , Hegedüs Bence , Scopelliti Rosario , Waser Jérôme
Published: July 2016

Efficient methods for the convergent synthesis of (poly)cyclic scaffolds are urgently needed in synthetic and medicinal chemistry. Herein, we describe new annulation reactions of thioalkynes with phthalimide‐substituted donor–acceptor cyclopropanes, which gave access to highly substituted cyclopentenes and polycyclic ring systems. With silyl‐thioalkynes, the Lewis acid catalyzed [3+2] annulation reaction with donor–acceptor cyclopropanes took place to afford 1‐thio‐cyclopenten‐3‐amines. On the other hand, an unprecedented polycyclic compound was formed with alkyl‐thioalkynes through a reaction pathway directly involving the phthalimide group. The two transformations proceeded in good yields and tolerated a large variety of functional groups.
Solution Structure of Turbo‐Hauser Base TMPMgCl⋅LiCl in [D8]THF
Authors: Neufeld Roman , Stalke Dietmar
Published: July 2016

Invited for the cover of this issue are D. Stalke and R. Neufeld from the University of Göttingen. The image symbolizes for the authors′ navigation to the solution structure of the turbo‐Hauser base, TMPMgCl⋅LiCl. Read the full text of the article at 10.1002/chem.201601494.
Association Between Body Mass Index and Age of Presentation With Symptomatic Coronary Artery Disease
Authors: Atique Syed M. , Shadbolt Bruce , Marley Paul , Farshid Ahmad
Published: July 2016

Background

Obesity is increasingly recognized as an important risk factor for coronary artery disease (CAD).

Hypothesis

Patients with increased body mass index (BMI) present at a younger age with symptomatic CAD.

Methods

We analyzed data on 2137 consecutive patients admitted for treatment of CAD proven on angiography from 2010 to 2013, excluding those with prior coronary intervention or bypass surgery.

Results

Mean age was 64.1 ± 12.4 years; 75% were male; 43.6% were overweight (BMI 25–29.9 kg/m2) and 31.6% were obese (BMI ≥30 kg/m2). Patients with BMI ≥25 kg/m2 compared with <25 kg/m2 were more likely to have diabetes (24.5% vs 13.6%), hypertension (56.2% vs 45.5%), and hyperlipidemia (42.4% vs 31.6%; P < 0.0001 for all). On multivariate analysis adjusted for sex and cardiovascular risk factors, patients in higher BMI categories had lower mean age in a linear and stepwise fashion compared with those with normal BMI (P < 0.0001). For example, compared with patients with normal BMI, those with BMI of 35 to 39.9 kg/m2 were on average 9.2 years younger (P < 0.0001). Multivariate analysis examining the interaction between sex and BMI produced similar results for effect of BMI on age of presentation (P = 0.97 for interaction).

Conclusions

After multivariate adjustment, patients with increased BMI presented at an earlier age with symptomatic CAD compared with patients with normal BMI. Primary prevention efforts in those with increased BMI to reduce risk‐factor burden, including evidence‐based treatments for weight reduction, promise to reduce risk or delay onset of CAD.
Fragment Screening of RORγt Using Cocktail Crystallography: Identification of Simultaneous Binding of Multiple Fragments
Authors: Xue Yafeng , Guo Hongwei , Hillertz Per
Published: July 2016

The retinoic‐acid‐related orphan receptor γ t (RORγt), as a master regulator of Th17 cell pathology, has become an attractive target for small‐molecule drug discovery for the treatment of Th17‐cell‐related autoimmune diseases. A crystallographic fragment screening was carried out for RORγt using the ligand binding domain. An overall hit rate of 5.5 % was obtained by screening 384 compounds in 96 cocktails. Five distinct hotspots were identified, and four regions of anchoring polar interactions were observed. In addition, significant induced fit was found for the binding of several fragments. Strikingly, a simultaneous binding of three fragments was revealed which presents interesting features including π–π stacking, multiple hydrogen bonds to the protein, and significant induced fit. Overall, the results offer a complete mapping of the ligand binding pocket and provide valuable inspiration in structure‐based design for RORγt lead generation and optimization. The crystallographic screening also resulted in fragment hits that bind at the surface away from the ligand binding pocket. This surface site is near the plausible dimer interface by analogy with other nuclear receptor systems, which can provide initial hints to explore alternative ways to modulate RORγt through protein–protein interactions.
Randomized trial finds that prostate cancer genetic risk score feedback targets prostate‐specific antigen screening among at‐risk men
Authors: Turner Aubrey R. , Lane Brian R. , Rogers Dan , Lipkus Isaac , Weaver Kathryn , Danhauer Suzanne C. , Zhang Zheng , Hsu Fang‐Chi , Noyes Sabrina L. , Adams Tamara , Toriello Helga , Monroe Thomas , McKanna Trudy , Young Tracey , Rodarmer Ryan , Kahnoski Richard J. , Tourojman Mouafak , Kader A. Karim , Zheng S. Lilly , Baer William , Xu Jianfeng
Published: July 2016

BACKGROUND

Prostate‐specific antigen (PSA) screening may reduce death due to prostate cancer but leads to the overdiagnosis of many cases of indolent cancer. Targeted use of PSA screening may reduce overdiagnosis. Multimarker genomic testing shows promise for risk assessment and could be used to target PSA screening.

METHODS

To test whether counseling based on the family history (FH) and counseling based on a genetic risk score (GRS) plus FH would differentially affect subsequent PSA screening at 3 months (primary outcome), a randomized trial of FH versus GRS plus FH was conducted with 700 whites aged 40 to 49 years without prior PSA screening. Secondary outcomes included anxiety, recall, physician discussion at 3 months, and PSA screening at 3 years. Pictographs versus numeric presentations of genetic risk were also evaluated.

RESULTS

At 3 months, no significant differences were observed in the rates of PSA screening between the FH arm (2.1%) and the GRS‐FH arm (4.5% with GRS‐FH vs. 2.1% with FH: χ2 = 3.13, P = .077); however, PSA screening rates at 3 months significantly increased with given risk in the GRS‐FH arm (P = .013). Similar results were observed for discussions with physicians at 3 months and PSA screening at 3 years. Average anxiety levels decreased after the individual cancer risk was provided (P = .0007), with no differences between groups. Visual presentation by pictographs did not significantly alter comprehension or anxiety.

CONCLUSIONS

This is likely the first randomized trial of multimarker genomic testing to report genomic targeting of cancer screening. This study found little evidence of concern about excess anxiety or overuse/underuse of PSA screening when multimarker genetic risks were provided to patients. Cancer 2016;122:3564–3575. © 2016 American Cancer Society
Chemotherapy for soft tissue sarcoma
Authors: Ratan Ravin , Patel Shreyaskumar R.
Published: July 2016

Soft tissue sarcoma is a term used to describe a heterogeneous group of many rare tumors. Since the initial description of activity of doxorubicin, several additional agents have been brought to bear in the treatment of these diseases. Despite 2 recent drug approvals, doxorubicin and ifosfamide remain the most effective chemotherapy drugs available for the treatment of majority of these tumors. Optimal dosing and administration influence outcomes because of the steep dose‐response curves associated with these agents. The debate endures regarding whether patients who have advanced disease should routinely receive single agents sequentially or in combination. Adjuvant therapy remains similarly controversial, although meta‐analyses do support its use. Contemporary treatment of soft tissue sarcoma routinely incorporates additional lines of treatment that have become available over the last 15 years. Fixed‐dose‐rate gemcitabine with or without docetaxel is a standard second‐line treatment. In keeping with the paradigm shift favoring subset‐specific therapy, several recent approvals are linked with specific sarcoma subtypes. Eribulin has recently been approved on the basis of improved overall survival for patients with adipocytic sarcomas, and trabectedin is now approved in the United States for patients with leiomyosarcoma and liposarcoma. Within the spectrum of targeted therapies, pazopanib is approved for all nonadipocytic sarcomas, and imatinib is approved for dermatofibrosarcoma protuberans. Each of these drugs represents incremental rather than radical progress, although they constitute important and much needed treatment options for patients with these diseases. Cancer 2016;122:2952‐2960. © 2016 American Cancer Society.
National sociodemographic disparities in the treatment of high‐risk prostate cancer: Do academic cancer centers perform better than community cancer centers?
Authors: Mahal Brandon A. , Chen Yu‐Wei , Muralidhar Vinayak , Mahal Amandeep R. , Choueiri Toni K. , Hoffman Karen E. , Hu Jim C. , Sweeney Christopher J. , Yu James B. , Feng Felix Y. , Kim Simon P. , Beard Clair J. , Martin Neil E. , Trinh Quoc‐Dien , Nguyen Paul L.
Published: July 2016

BACKGROUND

Most major cancer organizations seek to reduce sociodemographic disparities in high‐risk cancers partly by increasing access to theoretically high‐quality, academic‐oriented cancer care. The objective of this study was to determine whether academic centers have less sociodemographic treatment disparities than community centers using high‐risk prostate cancer as a test case.

METHODS

The National Cancer Data Base was used to identify 138,019 patients who were diagnosed with nonmetastatic, high‐risk prostate cancer from 2004 to 2012. Multivariable logistic analysis was used to identify independent determinants of definitive therapy. The Gray test and multivariable Cox regression were used to analyze the timing of therapy. All analyses were stratified by academic versus community cancer center.

RESULTS

Compared with white or privately insured patients, black, Hispanic, and uninsured patients with prostate cancer were less likely to receive definitive therapy at both community centers (adjusted odds ratio: 0.60 [95% confidence interval (CI), 0.56‐0.64], 0.69 [95% CI, 0.61‐0.78], and 0.25 [95% CI, 0.22‐0.30], respectively) and academic cancer centers (adjusted odds ratio: 0.50 [95% CI, 0.46‐0.54], 0.56 [95% CI, 0.50‐0.64], and 0.31 [95% CI, 0.28‐0.36], respectively). Among patients who received definitive therapy, black, Hispanic, and uninsured patients were more likely to experience treatment delays at both community centers (≥15, ≥ 10, and ≥19 days, respectively; all Gray P < .001) and academic centers (≥19, ≥ 11, and ≥18 days, respectively); treatment delays were observed among the aforementioned groups even after multivariable Cox regression analysis (P < .001 for all adjusted hazard ratios).

CONCLUSIONS

Nationally, academic cancer centers demonstrate similarly high rates of sociodemographic disparities in cancer treatment patterns as community cancer centers. Making community centers conform to academic center standards may not necessarily reduce treatment disparities. Cancer 2016;122:3371–3377. © 2016 American Cancer Society.
Large‐scale image‐based screening and profiling of cellular phenotypes
Authors: Bougen‐Zhukov Nicola , Loh Sheng Yang , Lee Hwee Kuan , Loo Lit‐Hsin
Published: July 2016

Cellular phenotypes are observable characteristics of cells resulting from the interactions of intrinsic and extrinsic chemical or biochemical factors. Image‐based phenotypic screens under large numbers of basal or perturbed conditions can be used to study the influences of these factors on cellular phenotypes. Hundreds to thousands of phenotypic descriptors can also be quantified from the images of cells under each of these experimental conditions. Therefore, huge amounts of data can be generated, and the analysis of these data has become a major bottleneck in large‐scale phenotypic screens. Here, we review current experimental and computational methods for large‐scale image‐based phenotypic screens. Our focus is on phenotypic profiling, a computational procedure for constructing quantitative and compact representations of cellular phenotypes based on the images collected in these screens. © 2016 International Society for Advancement of Cytometry
Proliferating poplars: the leading edge of landscape change in an Alaskan subalpine chronosequence
Authors: Roland Carl A. , Stehn Sarah E. , Schmidt Joshua , Houseman Brian
Published: July 2016

We remeasured a classic chronosequence study in the subalpine zone of the Alaska Range to evaluate how plant community attributes have changed across a set of different‐aged terraces over a 54‐yr period (1958–2012). Our work focused on whether the tempo and trajectory of successional development described in the original study have changed over this period during which summer temperatures warmed by approximately 2°C. Our work revealed a rapid increase in the distribution, stature, and abundance of balsam poplar trees that was unanticipated in the original successional model alongside evidence that established late‐successional plant communities have changed relatively little over the same time period. The spatial distribution of poplar expansion was both directional and highly variable, with greater expansion occurring in sites that were young surfaces in 1958, or else were disturbed during the intervening period. We present evidence that early successional environments in this region may be particularly susceptible to rapid alteration stimulated by climate warming that has allowed tree establishment and growth in subalpine areas. Sparsely vegetated sites allow for invasion or expansion of some species to be quickly realized because there is less resistance from competition with established vegetation, including mosses that insulate and paludify the soil. We suggest that established vegetation communities may have physical characteristics (such as cold and/or acidic soil profiles) that are inimical to the establishment of balsam poplar and may also be a source of competitive inertia, conferring a measure of resistance to directional changes in the landscape mosaic. However, when an early successional species has traits that allow it to persist and fundamentally alter the vegetation mosaic over time, as is the case with balsam poplar, it may serve as the leading edge of compositional changes with profound consequences. Our results highlight the capacity of a single species to catalyze the changes that may eventually lead to the altering of an entire landscape mosaic.
A Highly Robust Terbium Coordination Polymer as a Multiresponsive Luminescent Sensor for Detecting Pollutant Anions
Authors: Chen Jinlei , Yi Fei‐Yan , Yu Hong , Liu Xu , Han Lei , Pang Guangsheng
Published: July 2016

An extremely stable Tb coordination polymer, TbL2 [HL = 4‐(pyrimidin‐5‐yl)benzoic acid], was synthesized. It exhibits high thermal and chemical stability. TbL2 is a visual multiresponsive luminescent probe that can selectively detect F– among the same main‐group anions as well as various pollutant phosphorus anions.
Dual Role of Acetate in Copper(II) Acetate Catalyzed Dehydrogenation of Chelating Aromatic Secondary Amines: A Kinetic Case Study of Copper‐Catalyzed Oxidation Reactions
Authors: Sreenath Kesavapillai , Yuan Zhao , Macias‐Contreras Miguel , Ramachandran Vasanth , Clark Ronald J. , Zhu Lei
Published: July 2016

Copper(II) acetate is a frequent empirical choice of the copper source in copper(II)‐mediated redox reactions. The effect of the acetate counterion appears crucial but has not been adequately investigated. Herein, we report that copper(II) acetate catalyzes the aerobic dehydrogenation of chelating aromatic secondary amines. The chemoselectivity of acetate and chelating amines in this reaction provides a unique opportunity for a mechanistic study. The progression of this homogeneous reaction is monitored by using electron paramagnetic resonance spectroscopy, UV/Vis absorption spectroscopy, and manometry. The kinetic dependence on the amine substrate, copper(II), and acetate counterion, together with the results of kinetic isotope and substituent effect experiments, suggests that acetate acts both as a bridging ligand of a dinuclear catalytic center for mediating two‐electron transfer steps and as a base in the turnover‐limiting C–H bond‐cleavage step. Upon including 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) as a surrogate base, DBU and acetate act in a complementary manner to enable a rapid, catalytic dehydrogenation reaction of a chelating secondary amine substrate. Finally, the contrasting reactivities between copper(II) acetate (promoting two‐electron transfer) and copper(II) perchlorate (promoting single‐electron transfer) underscores how a counterion could completely alter the mechanistic pathway of a copper‐mediated oxidation reaction.
Indoline‐Based Constrained Peptidomimetic Motifs Obtained via the Joullié–Ugi Reaction of Indolenines
Authors: Golubev Pavel , Bakulina Olga , Dar'in Dmitry , Krasavin Mikhail
Published: July 2016

Sterically demanding indolenines were employed as cyclic imine substrates in the Joullié–Ugi reaction with diverse isocyanides and carboxylic acids resulting in a new type of conformationally constrained indoline‐based peptidomimetic compounds.
Religious identification and interreligious contact in Indonesia and the Philippines: Testing the mediating roles of perceived group threat and social dominance orientation and the moderating role of context
Authors: Kanas Agnieszka , Scheepers Peer , Sterkens Carl
Published: July 2016

This study integrates three theoretical perspectives provided by social identity theory, realistic group conflict theory, and social dominance theory to examine the relationship between religious identification and interreligious contact. It relies on a unique dataset collected among Christian and Muslim students in ethnically and religiously diverse regions of Indonesia and the Philippines, where social cleavages occur along religious lines. Religious identification directly predicts a higher quality of interreligious contact, whereas it indirectly predicts a lower quantity and quality of contact, mediated by higher perception of group threat, and a higher quality of contact, mediated by lower social dominance orientation. Furthermore, these direct and indirect relationships are moderated by religious group membership and relative group size. We conclude that religious identification functions as a ‘double‐edged sword’ predicting both higher quality and lower quantity and quality of interreligious contact through various pathways and with a varying strength depending on intergroup context.
Electrochemical Impedance Spectroscopic Investigation in Detecting 2,4‐dinitrophenylhydrazine Using Catalytic Effect of Copper at Glassy Electrode
Authors: Boumya W. , Hammani H. , Loudiki A. , Achak M. , Bakasse M. , El Mhammedi M. A.
Published: July 2016

This paper reports on the use of electrochemical impedance spectroscopy (EIS) allied to copper (II) for the determination of 2,4‐dinitrophenylhydrazine (DNPH) at glassy carbon electrode (GCE). The experiment measurements were carried out in methanol at a potential of 0.3 V versus Ag/AgCl. The Nyquist plots were modeled with a Randle equivalent circuit, by identifying the charge transfer resistance as the relevant concentration dependent parameter. These measurements show that the impedance spectra of DNPH increased by the formation of non‐electroactive compound produced from specific interaction between DNPH and Cu (II), which will block the electron‐transfer process of the redox probe. Therefore, the proposed methodology offers a detection limit of 4.0×10−8 mol L−1. The proposed methodology was satisfactorily applied to determine DNPH in industrial water samples.
Intramolecular Hydrogen Bonding/Selfprotonation Processes Modulated by the Substituent Effect in Hydroxyl‐substituted Naphthoquinones
Authors: Maldonado Teresita , Martínez‐González Eduardo , Frontana Carlos
Published: July 2016

In this work, an electrochemical and spectroelectrochemical ESR study for a series of hydroxyl substituted 1,4‐naphthoquinones is presented. Results show that the electrochemical behaviour is dependent on the relative positions of these groups within the molecules. For compounds which have hydroxyl groups at the annellated benzene ring, intramolecular hydrogen bonding (a substituent field effect) determines the energy of reduction of the system. When hydroxyl functions are located at the C‐2 or C‐3 positions, a selfprotonation process occurs. The electrogenerated dianion or trianion radicals, derived from deprotonated quinones, show that intramolecular hydrogen bonding has a significant effect both in the spin density distribution and in the energy required for the formation of these radical species. The difference observed in the slope for EpIc vs. log v function for 2,3,5,8‐tetrahydroxy‐1,4‐naphthoquinone suggest that, for this compound, the proton transfer step does not occur as a single, but as a two‐step sequence, where an hydrogen bonded adduct could be present as a stable intermediate. These processes could help to explain the discrepancies observed earlier performing linear free energy relationships these compounds.
On the Analysis of Non‐stationary Impedance Spectra
Authors: Battistel Alberto , Du Guoqing , La Mantia Fabio
Published: July 2016

In this work we study the possibility to analyze the non‐stationary impedance spectra by employing standard equivalent circuits. For this purpose, the dynamic multi‐frequency analysis (DMFA) is introduced and compared with a set of consecutive stationary impedance spectra. In order to prove the hypothesis, the data are obtained by the simulation in the time domain of the electron transfer process between an electrode and a free‐diffusing redox couple in solution. During the simulation, the system is perturbed with a cyclic voltammetry superimposed to a small multisine perturbation (DMFA) or with a series of stationary impedance spectroscopies. Also, a new fitting algorithm, which takes into account the correlation between consecutive spectra, is proposed and tested. Although the Randles circuit can be used to fit both dynamic and stationary impedance spectra, the values of the fitting parameters are different and depend on the direction of the scan and on the rate. This is related to the influence of the diffusion profile on the fitting parameters.