bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface melt dominates Alaska glacier mass balance
Authors: Larsen C. F. , Burgess E. , Arendt A. A. , O'Neel S. , Johnson A. J. , Kienholz C.
Published: June 2015

Mountain glaciers comprise a small and widely distributed fraction of the world's terrestrial ice, yet their rapid losses presently drive a large percentage of the cryosphere's contribution to sea level rise. Regional mass balance assessments are challenging over large glacier populations due to remote and rugged geography, variable response of individual glaciers to climate change, and episodic calving losses from tidewater glaciers. In Alaska, we use airborne altimetry from 116 glaciers to estimate a regional mass balance of −75 ± 11 Gt yr−1 (1994–2013). Our glacier sample is spatially well distributed, yet pervasive variability in mass balances obscures geospatial and climatic relationships. However, for the first time, these data allow the partitioning of regional mass balance by glacier type. We find that tidewater glaciers are losing mass at substantially slower rates than other glaciers in Alaska and collectively contribute to only 6% of the regional mass loss.
Role of Interactivity in Learning from Engineering Animations
Authors: Pedra Agnaldo , Mayer Richard E. , Albertin Alberto Luiz
Published: June 2015

This study examines the pedagogic value of incorporating sophisticated interactivity features into lessons on hand‐held devices. Engineering students (Experiment 1) and non‐engineering college students (Experiment 2) spent 5 min studying an animation showing a six‐step maintenance procedure for a mechanical device called a Power Take‐Off presented on an iPad. In both experiments, students who received high interactivity (i.e., rotation through dragging movements and zoom through pinching movements) reported higher interest but did not show better learning as compared to the low interactivity group (i.e., pause and continue buttons on the touch screen) or no interactivity group. Across two experiments, the interactivity hypothesis was supported in terms of increased interest but not supported in terms of improved learning. Thus, there was not support for the idea that increasing situational interest through high levels of interactivity primes deeper learning processes that produce better learning outcomes. Copyright © 2015 John Wiley & Sons, Ltd.
3D Micromolding of Arrayed Waveguide Gratings on Upconversion Luminescent Layers for Flexible Transparent Displays without Mirrors, Electrodes, and Electric Circuits
Authors: Watanabe Satoshi , Asanuma Takeo , Sasahara Takafumi , Hyodo Hiroshi , Matsumoto Mutsuyoshi , Soga Kohei
Published: June 2015

A new technique for the fabrication of arrayed waveguide gratings on upconversion luminescent layers for flexible transparent displays is reported. Ho3+‐ and Yb3+‐codoped NaYF4 nanoparticles are synthesized by hydrothermal techniques. Transparent films consisting of two transparent polymers on the NaYF4 nanoparticle films exhibit mechanical flexibility and high transparence in visible region. Patterned NaYF4 nanoparticle films are fabricated by calcination‐free micromolding in capillaries. Arrayed waveguide gratings consisting of the two transparent polymers are formed on the patterned NaYF4 nanoparticle films by micromolding in capillaries. Green and red luminescence is observed from the upconversion luminescent layers of the NaYF4 nanoparticle films in the arrayed waveguide gratings under excitation at 980 nm laser light. Arrayed waveguide gratings on the upconversion luminescent layers are fabricated with Er3+‐doped NaYF4 nanoparticles which can convert two photons at 850 and 1500 nm into single photon at 550 nm. These results demonstrate that flexible transparent displays can be fabricated by constructing arrayed waveguide gratings on upconversion luminescent layers, which can operate in nonprojection mode without mirrors, transparent electrodes, and electric circuits.
Massive Bioaccumulation and Self‐Assembly of Phenazine Compounds in Live Cells
Authors: Min Kyoung Ah , Rajeswaran Walajapet G. , Oldenbourg Rudolf , Harris Grant , Keswani Rahul K. , Chiang Mason , Rzeczycki Phillip , Talattof Arjang , Hafeez Mahwish , Horobin Richard W. , Larsen Scott D. , Stringer Kathleen A. , Rosania Gus R.
Published: June 2015

Clofazimine is an orally administered drug that massively bioaccumulates in macrophages, forming membrane‐bound intracellular structures possessing nanoscale supramolecular features. Here, a library of phenazine compounds derived from clofazimine is synthesized and tested for ability to accumulate and form ordered molecular aggregates inside cells. Regardless of chemical structure or physicochemical properties, bioaccumulation is consistently greater in macrophages than in epithelial cells. Microscopically, some self‐assembled structures exhibit a pronounced, diattenuation anisotropy signal, evident by the differential absorption of linearly polarized light, at the peak absorbance wavelength of the phenazine core. The measured anisotropy is well above the background anisotropy of endogenous cellular components, reflecting the self‐assembly of condensed, insoluble complexes of ordered phenazine molecules. Chemical variations introduced at the R‐imino position of the phenazine core lead to idiosyncratic effects on the compounds' bioaccumulation behavior as well as on the morphology and organization of the resulting intracellular structures. Beyond clofazimine, these results demonstrate how the self‐assembly of membrane permeant, orally bioavailable small molecule building blocks can endow cells with unnatural structural elements possessing chemical, physical, and functional characteristics unlike those of other natural cellular components.
Associative Learning with Temporal Contiguity in a Memristive Circuit for Large‐Scale Neuromorphic Networks
Authors: Li Yi , Xu Lei , Zhong Ying‐Peng , Zhou Ya‐Xiong , Zhong Shu‐Jing , Hu Yang‐Zhi , Chua Leon O. , Miao Xiang‐Shui
Published: June 2015

Memristors, acting as artificial synapses, have promised their prospects in neuromorphic systems that imitate the brain's computing paradigm. However, most studies focused on the understanding of the memristive mechanism and how to optimize the synaptic performance, and the implementations of higher‐order cognitive functions are quite limited. Here the experimental demonstration of a representative network level learning function, i.e., associative learning and extinction, in a compact memristive neuromorphic circuit with only one memristor is reported. The association of the conditioned and unconditioned stimulus is established within a temporal window through the spike‐timing‐dependent plasticity rule, whereas the extinction of the formed memory is due to the synaptic depression. The temporal contiguity consists with biological behaviors and reflects nature's cause and effect rule. An efficient methodology of integrating memristors into large‐scale neuromorphic systems for massively parallel computing, such as pattern recognition, is provided herein.
Cation Size Effects on the Electronic and Structural Properties of Solution‐Processed In–X–O Thin Films
Authors: Smith Jeremy , Zeng Li , Khanal Rabi , Stallings Katie , Facchetti Antonio , Medvedeva Julia E. , Bedzyk Michael J. , Marks Tobin J.
Published: June 2015

The nature of charge transport and local structure are investigated in amorphous indium oxide‐based thin films fabricated by spin‐coating. The In–X–O series where X = Sc, Y, or La is investigated to understand the effects of varying both the X cation ionic radius (0.89–1.17 Å) and the film processing temperature (250–300 °C). Larger cations in particular are found to be very effective amorphosizers and enable the study of high mobility (up to 9.7 cm2 V−1 s−1) amorphous oxide semiconductors without complex processing. Electron mobilities as a function of temperature and gate voltage are measured in thin‐film transistors, while X‐ray absorption spectroscopy and ab initio molecular dynamics simulations are used to probe local atomic structure. It is found that trap‐limited conduction and percolation‐type conduction mechanisms convincingly model transport for low‐ and high‐temperature processed films, respectively. Increased cation size leads to increased broadening of the tail states (10–23 meV) and increased percolation barrier heights (24–55 meV) in the two cases. For the first time in the amorphous In–X–O system, such effects can be explained by local structural changes in the films, including decreased In–O and In–M (M = In, X) coordination numbers, increased bond length disorder, and changes in the MO
x
polyhedra interconnectivity.
Functional Pillared Graphene Frameworks for Ultrahigh Volumetric Performance Supercapacitors
Authors: Jiang Lili , Sheng Lizhi , Long Conglai , Wei Tong , Fan Zhuangjun
Published: June 2015

Supercapacitors, also known as electrochemical capacitors, can provide much faster charge–discharge, greater power density, and cyclability than batteries, but they are still limited by lower energy densities (or the amount of energy stored per unit volume). Here, a novel strategy for the synthesis of functional pillared graphene frameworks, in which graphene fragments in‐between graphene sheets, through simple thermal‐treatment of ozone (O3)‐treated graphene oxide at very low temperature of 200 °C is reported. Due to its high packing density, high content of stable oxygen species, and continues ion transport network in‐between graphene sheets, the functional pillared‐graphene framework delivers not only high gravimetric capacitance (353 F g−1 based on the mass of the active material) and ultrahigh volumetric capacitance (400 F cm−3 based on total mass of electrode material) in aqueous electrolyte but also excellent cyclic stability with 104% of its initial capacitance retention after 10 000 cycles. Moreover, the assembled symmetric supercapacitor achieves as high as 27 Wh L−1 of volumetric energy density at a power density of 272 W L−1. This novel strategy holds great promise for future design of high volumetric capacitance supercapacitors.
Soluble Adamantyl‐Substituted Oligothiophenes with Short Fluorescence Decay: An Approach for Ultrafast Optical Signal Processing
Authors: Schlücker Thorben , Dhayalan Vasudevan , Langhals Heinz , Sämann Christoph , Knochel Paul
Published: June 2015

THF‐soluble, adamantyl‐substituted oligothiophenes (n=1–3) were prepared via Negishi cross‐coupling reactions. Thus, the synthesis of 2‐(1‐adamantyl)quaterthiophene was realized by cross‐coupling of 5‐bromo‐2′′‐(1‐adamantyl)terthiophene with 2‐thienylzinc chloride. Treatment of these oligothiophenes with FeCl3 affords the corresponding dimeric compounds, which have pigment properties. In contrast, the mono‐substituted (1‐adamantyl)oligothiophenes (n=1–4) are readily soluble in organic solvents. Particularly the quarter‐oligomer displays remarkable optical properties such as an increased Stokes’ shift in combination with a very fast fluorescence decay of 0.39 ns and a high fluorescence quantum yield. The compound was incorporated in a solid poly(methyl methacrylate) matrix and its optical properties were nearly unaltered. This may allow applications in high‐throughput optical signal processing exceeding the GBit scale.
Patients with chronic rhinosinusitis and simultaneous bronchial asthma suffer from significant extraesophageal reflux
Authors: Zeleník Karol , Matoušek Petr , Formánek Martin , Urban Ondřej , Komínek Pavel
Published: June 2015

Background

The aim of this study was to determine the severity of extraesophageal reflux (EER) in patients with various degrees of chronic rhinosinusitis (CRS), and particularly in patients with simultaneous bronchial asthma.

Methods

Patients with different severity of CRS were invited to participate in the study. Group I consisted of patients with CRS without nasal polyps or bronchial asthma; group II consisted of patients with CRS with nasal polyps but without bronchial asthma; group III consisted of patients with CRS with nasal polyps and bronchial asthma. The age, gender, Reflux Symptom Index, severity of EER evaluated using the Restech system, and number of previous functional endoscopic sinus surgeries (FESSs) were compared between groups.

Results

A total of 90 patients (30 in each group) were recruited for the study. Pathological EER was significantly often present in group III when compared with group I and group II in all parameters analyzed (RYAN score, number of EER episodes, total percentage of time below pH 5.5). Furthermore, patients from group III had undergone more surgeries in the past.

Conclusion

Patients with CRS with nasal polyps and simultaneous bronchial asthma suffer from significant EER. Antireflux therapy can be recommended for these patients. However, the effect has to be confirmed in further studies.
Self‐Immolative Spacers: Kinetic Aspects, Structure–Property Relationships, and Applications
Authors: Alouane Ahmed , Labruère Raphaël , Le Saux Thomas , Schmidt Frédéric , Jullien Ludovic
Published: June 2015

Self‐immolative spacers are covalent assemblies tailored to correlate the cleavage of two chemical bonds after activation of a protective part in a precursor: Upon stimulation, the protective moiety is removed, which generates a cascade of disassembling reactions leading to the temporally sequential release of smaller molecules. Originally introduced to overcome limitations for drug delivery, self‐immolative spacers have gained wide interest in medicinal chemistry, analytical chemistry, and material science. For most applications, the kinetics of the disassembly of the activated self‐immolative spacer governs functional properties. This Review addresses kinetic aspects of self‐immolation. It provides information for selecting a particular self‐immolative motif for a specific demand. Moreover, it should help researchers design kinetic experiments and fully exploit the rich perspectives of self‐immolative spacers.
Energy saving and noise reduction of flow mixing performance intensified by rigid‐flexible combination impeller
Authors: Liu Zuohua , He Haixian , Zhu Jun , Liu Renlong , Tao Changyuan , Wang Yundong
Published: June 2015

During fluid mixing in stirred reactor, energy, which spreads among the fluid with the impeller, is used for fluid rotation and internal transfer. Meanwhile, a part of the energy is consumed by fluid mixing noise. The premises of effective mixing are to improve utilization rate of energy. The energy‐saving and noise reduction behavior of rigid‐flexible combination impeller in fluid mixing were studied by adopting the combination of numerical simulation and experimental analysis. Comparative experiments were carried out to study the noise variation between rigid‐flexible combination impeller and rigid impeller at 210 rpm. The results showed that the energy was mainly concentrated at the tip of rigid impeller (the maximum speed of fluid was 2.85 m/s, while turbulent kinetic energy was 0.32 m2/s2). Meanwhile, the energy at the tip of rigid‐flexible combination impeller was thoroughly dissipated (the maximum speed of fluid was 2.31 m/s, while turbulent kinetic energy was 0.26 m2/s2), which evenly distributed the energy at the flow field, thereby contributing to good mixing performance. The sound pressure level of the rigid‐flexible combination impeller was 7% lower than that of rigid impeller at the same location, whereas the measured value at the surface and the simulated values were identical. Copyright © 2015 Curtin University of Technology and John Wiley & Sons, Ltd.
Discovering hierarchical topic evolution in time‐stamped documents
Authors: Song Jun , Huang Yu , Qi Xiang , Li Yuheng , Li Feng , Fu Kun , Huang Tinglei
Published: June 2015

The objective of this paper is to propose a hierarchical topic evolution model (HTEM) that can organize time‐varying topics in a hierarchy and discover their evolutions with multiple timescales. In the proposed HTEM, topics near the root of the hierarchy are more abstract and also evolve in the longer timescales than those near the leaves. To achieve this goal, the distance‐dependent Chinese restaurant process (ddCRP) is extended to a new nested process that is able to simultaneously model the dependencies among data and the relationship between clusters. The HTEM is proposed based on the new process for time‐stamped documents, in which the timestamp is utilized to measure the dependencies among documents. Moreover, an efficient Gibbs sampler is developed for the proposed HTEM. Our experimental results on two popular real‐world data sets verify that the proposed HTEM can capture coherent topics and discover their hierarchical evolutions. It also outperforms the baseline model in terms of likelihood on held‐out data.
Mendeley readership counts: An investigation of temporal and disciplinary differences
Authors: Thelwall Mike , Sud Pardeep
Published: June 2015

Scientists and managers using citation‐based indicators to help evaluate research cannot evaluate recent articles because of the time needed for citations to accrue. Reading occurs before citing, however, and so it makes sense to count readers rather than citations for recent publications. To assess this, Mendeley readers and citations were obtained for articles from 2004 to late 2014 in five broad categories (agriculture, business, decision science, pharmacy, and the social sciences) and 50 subcategories. In these areas, citation counts tended to increase with every extra year since publication, and readership counts tended to increase faster initially but then stabilize after about 5 years. The correlation between citations and readers was also higher for longer time periods, stabilizing after about 5 years. Although there were substantial differences between broad fields and smaller differences between subfields, the results confirm the value of Mendeley reader counts as early scientific impact indicators.
Interactive constrained dynamics for rigid and deformable objects
Authors: Vezzaro Luca , Zerbato Davide , Fiorini Paolo
Published: June 2015

Following the continuous increase in computational power of consumer hardware, interactive virtual environments have been recently enriched with more and more complex deformable objects. However, many physics engines are still very limited in the way they handle interacting rigid and deformable objects. This paper proposes a constraint‐based approach to real‐time simulation of coupled rigid and deformable objects capable of providing two‐way interactions. Similar techniques have seen widespread usage for either rigid or deformable objects, but not for the simultaneous simulation of both. By extending such approaches, we show not only how interaction is possible but also how it can be performed at real‐time rates. We address contact response and also show how to implement typical constraints to enforce limitations in the degrees of freedom and to enhance the dynamical properties of deformable objects. The method is easily integrated into existing physics engines that use similar constraint solvers and is independent on the kind of deformable object paradigm chosen. The provided simulation results show that the method is fast and effective in handling contacts between rigid and deformable objects and in simulating friction and other kinds of constraints. Copyright © 2015 John Wiley & Sons, Ltd.
Multivariate control charts based on NAS and mid‐infrared spectroscopy for quality control of B5 blends of methyl soybean biodiesel in diesel
Authors: Mitsutake Hery , Guimarães Eloiza , Freitas Helieder C. , Gontijo Lucas C. , Santos Douglas Q. , Borges Neto Waldomiro
Published: June 2015

In this work, mid‐infrared spectroscopy and multivariate control charts based on net analyte signal were applied for quality control of B5 blends of biodiesel/diesel (5% biodiesel/95% diesel). Control charts were constructed using instrumental signal decomposition, generating three charts: the net analyte signal chart for monitoring the analyte of interest (methyl soybean biodiesel); the interference chart, which corresponds to the contribution of all other compounds in the diesel sample (diesel); and the residual chart, which corresponds to non‐systematic variations. Statistical limits were established for each developed chart, using samples inside quality specifications (normal operation conditions). To validate multivariate control charts, new samples were analyzed. The new samples represented samples in‐control and samples out‐of‐control in relation to the content of biodiesel, adulterated biodiesel with severe vegetable oils and adulterated diesel with residual automotive lubricant oil, kerosene, and gasoline. The results obtained show an excellent distinction between the samples inside and out of the quality specifications, with 91% and 100% correctly classified, respectively, which demonstrates that the methodology developed is a viable alternative for quality monitoring of this type of fuel. Copyright © 2015 John Wiley & Sons, Ltd.
Anion‐ and Spacer‐Directed Host–Guest Complexes of Bipyridine with Pyrogallol[4]arene
Authors: Patil Rahul S. , Kumari Harshita , Barnes Charles L. , Atwood Jerry L.
Published: June 2015

New oval‐shaped capsular and bilayer‐type hydrogen‐bonded arrangements of C‐propyl‐ol‐pyrogallol[4]arene (PgC3‐OH) with bipyridine‐type spacer complexes are reported here. These complexes are engineered by virtue of derivatization of C‐alkyl tails of pyrogallol[4]arene and the use of divergent spacer ligands. Complexes of PgC3‐OH, PgC3‐OH with bpy (4,4′‐bipyridine) and PgC3‐OH with bpa (1,2‐bis(4‐pyridyl)acetylene) have bilayer type arrangements; however, the use of hydrogen chloride causes protonation of bpy molecule, which is then entrapped flat within an offset oval‐shaped dimeric hydrogen‐bonded PgC3‐OH nanocapsule. The presence of chloride anion in the crystal lattice controls the geometry of the resultant nanoassembly.
Unexpectedly Simple Synthesis of Benzazoles by tBuONa‐Catalyzed Direct Aerobic Oxidative Cyclocondensation of o‐Thio/Hydroxy/Aminoanilines with Alcohols under Air
Authors: Shi Xinkang , Guo Junmei , Liu Jianping , Ye Mingde , Xu Qing
Published: June 2015

tBuONa‐catalyzed direct aerobic oxidative cyclocondensation reactions of readily available alcohols and o‐thio/hydroxy/aminoanilines under air have been developed and provide an efficient, practical, and green method for the synthesis of benzazoles. Mechanistic studies revealed that o‐substituted anilines promote the initial aerobic alcohol‐oxidation step, which explains the high reactivity and success of this unexpectedly simple and practical cyclocondensation method.
The Electronic Structure of the Al3− Anion: Is it Aromatic?
Authors: Mercero Jose M. , Matito Eduard , Ruipérez Fernando , Infante Ivan , Lopez Xabier , Ugalde Jesus M.
Published: June 2015

Multiconfigurational high‐level electronic structure calculations show that the ${{\rm Al}{{- \hfill \atop 3\hfill}}}$ ring‐like cluster anion has three close low‐lying electronic states of different spin, all of them having strong multiconfigurational character. The aromaticity of the cluster has, therefore, been studied by means of total electron delocalization and normalized multicenter electron delocalization indices evaluated from the multiconfigurational wave functions of each state. The lowest‐lying singlet and triplet states are found to be highly aromatic, whereas the next lowest‐lying state, the quintet state, has much less, though non‐negligible, aromatic character.
ChemInform Abstract: D‐Glucosamine as a Green Ligand for Palladium‐Catalyzed Cross‐Coupling of Aryl and Heteroaryl Halides.
Authors: Jha Abadh Kishor , Shahni Rahul Kumar , Jain Nidhi
Published: June 2015

D‐glucosamine is found to be an efficient green replacement for phosphine ligands in the palladium‐catalyzed Heck coupling of aryl and heteroaryl halides.
ChemInform Abstract: Asymmetric N‐Heterocyclic Carbene Catalyzed Annulation of 2‐Alkenylbenzothiazoles with α‐Chloro Aldehydes.
Authors: Song Xiaoxiao , Ni Qijian , Zhu Chen , Raabe Gerhard , Enders Dieter
Published: June 2015

The NHC‐catalyzed 1‐azadiene Diels—Alder reactions give efficient access to optically active benzothiazolopyridinone derivatives.
ChemInform Abstract: Synthesis of Spiro Compounds as Medicinal Agents; New Opportunities for Drug Design and Discovery. Part I: A Review
Authors: Molvi Khurshid I. , Haque Navedul , Awen Bahlul Z. S. , Zameeruddin Mohammad
Published: June 2015

Review: 109 refs.
Numerical methods and software tools for simulation, design, and resonant mode analysis of radio frequency birdcage coils used in MRI
Authors: Gurler Necip , Ider Yusuf Ziya
Published: June 2015

Design of magnetic resonance imaging (MRI) radiofrequency (RF) coils using lumped circuit modeling based techniques begins to fail at high frequencies, and therefore more accurate models based on the electromagnetic field calculations must be used. Field calculations are also necessary to understand the interactions between the RF field and the subject inside the coil. Furthermore, observing the resonance behavior of the coil and the fields at the resonance frequencies have importance for design and analysis. In this study, finite element method (FEM) based methods have been proposed for accurate time‐harmonic electromagnetic simulations, estimation of the tuning capacitors on the rungs or end rings, and the resonant mode analysis of the birdcage coils. Capacitance estimation was achieved by maximizing the magnitude of the port impedance at the desired frequency while simultaneously minimizing the variance of RF magnetic field in the region of interest. In order for the proposed methods to be conveniently applicable, two software tools, resonant mode and frequency domain analyzer (RM‐FDA) and Optimum Capacitance Finder (OptiCF), were developed. Simulation results for the validation and verification of the software tools are provided for different cases including human head simulations. Additionally, two handmade birdcage coils (low‐pass and high‐pass) were built and resonance mode measurements were made. Results of the software tools are compared with the measurement results as well as with the results of the lumped circuit modeling based method. It has been shown that the proposed software tools can be used for accurate simulation and design of birdcage coils. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 45B: 13–32, 2015
The importance of assessing priorities of reproductive health concerns among adolescent and young adult patients with cancer
Authors: Murphy Devin , Klosky James L. , Reed Damon R. , Termuhlen Amanda M. , Shannon Susan V. , Quinn Gwendolyn P.
Published: June 2015

Visions for the future are a normal developmental process for adolescents and young adults (AYAs) with and without cancer, and these visions often include expectations of sexual and romantic relationships. AYA cancer survivors indicate reproductive health is an issue of great importance and more attention is needed in the health care setting throughout the cancer experience, beginning at diagnosis. Various practice guidelines are predominately focused on fertility; are intended to influence survivorship care plans; and do not encompass the broad scope of reproductive health that includes romantic partnering, friendships, body image, sexuality, sexual identity, fertility, contraception, and more. Although interventions to reduce reproductive health‐related sequelae from treatment are best approached as an evolving process, practitioners are not certain of the priorities of these various reproductive health content areas. Strategies incongruent with the reproductive health priorities of AYAs will likely thwart adequate follow‐up care and foster feelings of isolation from the treatment team. Research is needed to identify these priorities and ensure discussions of diverse content areas. This review explored various domains of reproductive health and emphasized how understanding the priorities of the AYA cancer cohort will guide future models of care. Cancer 2015;121:2529–2536. © 2015 American Cancer Society.
Pharmacokinetic and Pharmacodynamic Comparison of Once‐Daily Efavirenz (400 mg vs. 600 mg) in Treatment‐Naïve HIV‐Infected Patients: Results of the ENCORE1 Study
Authors: Dickinson L , Amin J , Else L , Boffito M , Egan D , Owen A , Khoo S , Back D , Orrell C , Clarke A , Losso M , Phanuphak P , Carey D , Cooper DA , Emery S ,   R Puls, on behalf of the ENCORE1 Study Group
Published: June 2015

Daily efavirenz 400 mg (EFV400) was virologically noninferior to 600 mg (EFV600) at 48 weeks in treatment‐naïve patients. We evaluated EFV400 and EFV600 pharmacokinetics (NONMEM v. 7.2), assessing patient demographics and genetic polymorphisms (CYP2B6, CYP2A6, CYP3A4, NR1I3) as covariates and explored relationships with efficacy (plasma HIV‐RNA (pVL) <200 copies/mL) and safety outcomes at 48 weeks in 606 randomized ENCORE1 patients (female = 32%, African = 37%, Asian = 33%; EFV400 = 311, EFV600 = 295). CYP2B6 516G>T/983T>C/CYP2A6*9B/*17 and weight were associated with efavirenz CL/F. Exposure was significantly lower for EFV400 (geometric mean ratio, GMR; 90% confidence interval, CI: 0.73 (0.68–0.78)) but 97% (EFV400) and 98% (EFV600) of evaluable pVL was <200 copies/mL at 48 weeks (P = 0.802). Four of 20 patients with mid‐dose concentrations <1.0 mg/L had pVL ≥200 copies/mL (EFV400 = 1; EFV600 = 3). Efavirenz exposure was similar between those with and without efavirenz‐related side effects (GMR; 90% CI: 0.95 (0.88–1.02)). HIV suppression was comparable between doses despite significantly lower EFV400 exposure. Comprehensive evaluation of efavirenz pharmacokinetics/pharmacodynamics revealed important limitations in the accepted threshold concentration.
Early clinical evaluation of the intranasal TLR7 agonist GSK2245035: Use of translational biomarkers to guide dosing and confirm target engagement
Authors: Tsitoura D , Ambery C , Price M , Powley W , Garthside S , Biggadike K , Quint D
Published: June 2015

Modulation of the airways' immune milieu is a key therapeutic goal for remission from respiratory allergies. To explore this hypothesis, GSK2245035, a selective Toll‐like receptor 7 (TLR7) agonist with preferential Type‐1 interferon (IFN)‐stimulating properties, was developed for intranasal application. Doses for clinical assessment were extrapolated from translational biomarker studies in primates. Randomized, double‐blind, placebo‐controlled trials in healthy volunteers and patients with allergic rhinitis demonstrated that intranasal GSK2245035 doses <100 ng were tolerated and did not cause nasal inflammation. Higher doses were not tested due to considerable cytokine release syndrome‐related symptoms observed at 100 ng. Clear target engagement, reflected by local and peripheral increase of IFN‐gamma‐inducible protein‐10, was observed at 20 ng, indicating IFN‐stimulated immune changes at tolerated doses. Repeat intranasal administration at weekly intervals did not tolerize or amplify the pharmacological response. Intranasal GSK2245035 has an acceptable safety profile at doses that induce local TLR7‐mediated immune responses.
A switch‐utilization‐improved switched‐inductor switched‐capacitor converter with adapting stage number
Authors: Chang Yuen‐Haw , Chen Yu‐Jhang
Published: June 2015

A novel closed‐loop switched‐inductor switched‐capacitor converter (SISCC) is proposed by using the pulse‐width‐modulation (PWM) compensation for the step‐up DC–DC conversion/regulation, and together by combining the adaptive‐stage‐number (ASN), control for the higher switch utilization and wider supply voltage range. The power part of SISCC is composed of two cascaded sub‐circuits, including (i) a serial‐parallel switched‐capacitor circuit withncpumping capacitors and (ii) a switched‐inductor booster withmcresonant capacitors, so as to obtain the high step‐up gain of (nc + 1) × mc /(1 − D) at most, whereDis the duty cycle of PWM adopted to enhance output regulation as well as robustness to source/loading variation. Besides, the ASN control is presented with adapting the stage numbern(n = 0, 1, 2, …, nc) of pumping capacitors to obtain a flexible gain of (n + 1) × mc /(1 − D), and further in order to make the SISCC operating at a properly small duty cycle for improving switch utilization and/or supply voltage range. Some theoretical analysis and control design include formulation, steady‐state analysis, ASN‐based conversion ratio, efficiency, output ripple, stability, inductance and capacitance selection, and control design. Finally, the performance of this scheme is verified experimentally on an ASN‐based SISCC prototype, and all results are illustrated to show the efficacy of this scheme. Copyright © 2015 John Wiley & Sons, Ltd.
The mouse gene expression database: New features and how to use them effectively
Authors: Finger Jacqueline H. , Smith Constance M. , Hayamizu Terry F. , McCright Ingeborg J. , Xu Jingxia , Eppig Janan T. , Kadin James A. , Richardson Joel E. , Ringwald Martin
Published: June 2015

The Gene Expression Database (GXD) is an extensive and freely available community resource of mouse developmental expression data. GXD curates and integrates expression data from the literature, via electronic data submissions, and by collaborations with large‐scale projects. As an integral component of the Mouse Genome Informatics Resource, GXD combines expression data with genetic, functional, phenotypic, and disease‐related data, and provides tools for the research community to search for and analyze expression data in this larger context. Recent enhancements include: an interactive browser to navigate the mouse developmental anatomy and find expression data for specific anatomical structures; the capability to search for expression data of genes located in specific genomic regions, supporting the identification of disease candidate genes; a summary displaying all the expression images that meet specified search criteria; interactive matrix views that provide overviews of spatio‐temporal expression patterns (Tissue × Stage Matrix) and enable the comparison of expression patterns between genes (Tissue × Gene Matrix); data zoom and filter utilities to iteratively refine summary displays and data sets; and gene‐based links to expression data from other model organisms, such as chicken, Xenopus, and zebrafish, fostering comparative expression analysis for species that are highly relevant for developmental research. genesis 53:510–522, 2015. © 2015 Wiley Periodicals, Inc.
Radial glial cell‐specific ablation in the adult Zebrafish brain
Authors: Shimizu Yuki , Ito Yoko , Tanaka Hideomi , Ohshima Toshio
Published: June 2015

The zebrafish brain can continue to produce new neurons in widespread neurogenic brain regions throughout life. In contrast, neurogenesis in the adult mammalian brain is restricted to the subventricular zone (SVZ) and dentate gyrus (DG). In neurogenic regions in the adult brain, radial glial cells (RGCs) are considered to function as neural stem cells (NSCs). We generated a Tg(gfap:Gal4FF) transgenic zebrafish line, which enabled us to express specific genes in RGCs. To study the function of RGCs in neurogenesis in the adult zebrafish brain, we also generated a Tg(gfap: Gal4FF; UAS:nfsB‐mcherry) transgenic zebrafish line, which allowed us to induce cell death exclusively within RGCs upon addition of metronidazole (Mtz) to the media. RGCs expressing nitroreductase were specifically ablated by the Mtz treatment, decreasing the number of proliferative RGCs. Using the Tg(gfap:Gal4FF; UAS:nfsB‐mcherry) transgenic zebrafish line, we found that RGCs were specifically ablated in the adult zebrafish telencephalon. The Tg(gfap:Gal4FF) line could be useful to study the function of RGCs. genesis 53:431–439, 2015. © 2015 Wiley Periodicals, Inc.
IL‐15 dependent induction of IL‐18 secretion as a feedback mechanism controlling human MAIT‐cell effector functions
Authors: Sattler Arne , Dang‐Heine Chantip , Reinke Petra , Babel Nina
Published: June 2015

Mucosal‐associated invariant T (MAIT) cells are characterized by an invariant TCRVα7.2 chain recognizing microbial vitamin B metabolites presented by the MHC‐Ib molecule MR1. They are mainly detectable in the CD8+ and CD8−CD4− “double negative” T‐cell compartments of mammals and exhibit both Th1‐ and Th17‐associated features. As MAIT cells show a tissue‐homing phenotype and operate at mucosal surfaces with myriads of pathogenic encounters, we wondered how IL‐15, a multifaceted cytokine being part of the intestinal mucosal barrier, impacts on their functions. We demonstrate that in the absence of TCR cross‐linking, human MAIT cells secrete IFN‐γ, increase perforin expression and switch on granzyme B production in response to IL‐15. As this mechanism was dependent on the presence of CD14+ cells and sensitive to IL‐18 blockade, we identified IL‐15 induced IL‐18 production by monocytes as an inflammatory, STAT5‐dependent feedback mechanism predominantly activating the MAIT‐cell population. IL‐15 equally affects TCR‐mediated MAIT‐cell functions since it dramatically amplifies bacteria‐induced IFN‐γ secretion, granzyme production, and cytolytic activity at early time points, an effect being most pronounced under suboptimal TCR stimulation conditions. Our data reveal a new quality of IL‐15 as player in an inflammatory cytokine network impacting on multiple MAIT‐cell functions.
HIV–TB coinfection impairs CD8+ T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses
Authors: Suarez Guadalupe V. , Angerami Matías T. , Vecchione María B. , Laufer Natalia , Turk Gabriela , Ruiz Maria J. , Mesch Viviana , Fabre Bibiana , Maidana Patricia , Ameri Diego , Cahn Pedro , Sued Omar , Salomón Horacio , Bottasso Oscar A. , Quiroga María F.
Published: June 2015

Tuberculosis (TB) is the leading cause of death among HIV‐positive patients. The decreasing frequencies of terminal effector (TTE) CD8+T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb). We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV–TB patients. Here, we aimed to study Mtb‐specific cytotoxicity, IFN‐γ secretion, memory status of CD8+T cells, and their modulation by DHEA during HIV–TB coinfection. CD8+T cells from HIV–TB patients showed a more differentiated phenotype with diminished naïve and higher effector memory and TTE T‐cell frequencies compared to healthy donors both in total and Mtb‐specific CD8+T cells. Notably, CD8+T cells from HIV–TB patients displayed higher Terminal Effector (TTE) CD45RAdim proportions with lower CD45RA expression levels, suggesting a not fully differentiated phenotype. Also, PD‐1 expression levels on CD8+T cells from HIV–TB patients increased although restricted to the CD27+ population. Interestingly, DHEA plasma levels positively correlated with TTE in CD8+T cells and in vitro DHEA treatment enhanced Mtb‐specific cytotoxic responses and terminal differentiation in CD8+T cells from HIV–TB patients. Our data suggest that HIV–TB coinfection promotes a deficient CD8+ T‐cell differentiation, whereas DHEA may contribute to improving antitubercular immunity by enhancing CD8+T‐cell functions during HIV–TB coinfection.
Electrochemically Exfoliated Black Phosphorus Nanosheets – Prospective Field Emitters
Authors: Erande Manisha B. , Suryawanshi Sachin R. , More Mahendra A. , Late Dattatray J.
Published: June 2015

Herein we report field emission (FE) investigations on an electrochemically exfoliated few‐layered black phosphorus nanosheet emitter at a base pressure of approximately 1 × 10–8 mbar. The turn‐on electric field required to draw an emission current density of approximately 10 μA/cm2 is found to be about 4.2 V/μm. Furthermore, few‐layered black phosphorus nanosheet emitters deliver an emission current density of about 170 μA/cm2 at an applied field of about 7.5 V/μm. The emission current vs. time plot measured at preset current values of about 5 μA shows emission current fluctuations within ±10 % of the average value, indicating the highly stable nature of the black phosphorus field emitter. Thus, the 2D black phosphorus nanosheets synthesized using the simple electrochemical exfoliation method can be utilized for micro/nanoelectronics and flat panel FE display applications.
Enantioselective Synthesis of Quaternary Carbon Stereogenic Centers through the Primary Amine‐Catalyzed Michael Addition Reaction of α‐Substituted Cyclic Ketones at High Pressure
Authors: Horinouchi Ryo , Kamei Kouhei , Watanabe Riki , Hieda Nobushige , Tatsumi Naoki , Nakano Keiji , Ichikawa Yoshiyasu , Kotsuki Hiyoshizo
Published: June 2015

The enantioselective Michael addition reaction of α‐substituted cyclic ketones with acrylates was efficiently promoted by a primary amine chiral catalyst under high‐pressure conditions (1.0 GPa) in tetrahydrofuran. This method was highly successful for the construction of an all‐carbon‐substituted quaternary‐carbon stereogenic center at the α‐position of cyclic ketones in high enantiomeric excess, and could be conveniently applied to the formal synthesis of (+)‐aspidospermidine.
Synthesis and Energetic Properties of 4‐Diazo‐2,6‐dinitrophenol and 6‐Diazo‐3‐hydroxy‐2,4‐dinitrophenol
Authors: Klapötke Thomas M. , Preimesser Andreas , Stierstorfer Jörg
Published: June 2015

4‐Amino‐3,5‐dinitroaniline (3) was synthesized by fluorine/amine exchange of 4‐fluoro‐3,5‐dinitroaniline in ethanol. 4‐Diazo‐2,6‐dinitrophenol (Iso‐DDNP, 4) was obtained after nitration in HNO3 (100 %) and acetic anhydrid. 4‐Amino‐2,3,5‐trinitrophenol (7) was obtained by nitration of N‐(4‐acetoxyphenyl)acetamide and deprotection of the amine. Further nitration resulted in 6‐diazo‐3‐hydroxy‐2,4‐dinitrophenol (8). The thermal stability and sensitivity of 4 and 8 toward impact and friction was compared to commercially used DDNP (2‐diazo‐4,6‐dinitrophenol). All target compounds were characterized by single‐crystal X‐ray diffraction, NMR and elemental analysis and DSC. The sensitivities were determined by BAM methods (drophammer and friction tester). The heats of formation were calculated by using CBS‐4M electronic enthalpies and the atomization method. Various detonation parameters such as detonation velocity and pressure were computed by using the EXPLO5 computer code V6.01.
Asymmetric Formal [3+2] Cycloaddition Reaction of Succinaldehyde and Nitroalkene Catalyzed by Diphenylprolinol Silyl Ether
Authors: Umemiya Shigenobu , Hayashi Yujiro
Published: June 2015

The enantioselective domino Michael/Henry reaction of nitroalkenes with succinaldehyde was found to proceed efficiently upon using diphenylprolinol silyl ether as the organocatalyst. The reaction affords cis‐disubstituted nitropentenes with excellent diastereoselectivities and enantioselectivities after treatment of the Michael product with Ac2O and pyridine.
Bank erosion in agricultural drainage networks: new challenges from structure‐from‐motion photogrammetry for post‐event analysis
Authors: Prosdocimi Massimo , Calligaro Simone , Sofia Giulia , Dalla Fontana Giancarlo , Tarolli Paolo
Published: June 2015

Drainage channels are an integral part of agricultural landscapes, and their impact on catchment hydrology is strongly recognized. In cultivated and urbanized floodplains, channels have always played a key role in flood protection, land reclamation, and irrigation. Bank erosion is a critical issue in channels. Neglecting this process, especially during flood events, can result in underestimation of the risk in flood‐prone areas.

The main aim of this work is to consider a low‐cost methodology for the analysis of bank erosion in agricultural drainage networks, and in particular for the estimation of the volumes of eroded and deposited material. A case study located in the Veneto floodplain was selected. The research is based on high‐resolution topographic data obtained by an emerging low‐cost photogrammetric method (structure‐from‐motion or SfM), and results are compared to terrestrial laser scanning (TLS) data. For the SfM analysis, extensive photosets were obtained using two standalone reflex digital cameras and an iPhone5® built‐in camera. Three digital elevation models (DEMs) were extracted at the resolution of 0.1 m using SfM and were compared with the ones derived by TLS. Using the different DEMs, the eroded areas were then identified using a feature extraction technique based on the topographic parameter Roughness Index (RI). DEMs derived from SfM were effective for both detecting erosion areas and estimating quantitatively the deposition and erosion volumes. Our results underlined how smartphones with high‐resolution built‐in cameras can be competitive instruments for obtaining suitable data for topography analysis and Earth surface monitoring. This methodology could be potentially very useful for farmers and/or technicians for post‐event field surveys to support flood risk management. Copyright © 2015 John Wiley & Sons, Ltd.
Convergent and invariant object representations for sight, sound, and touch
Authors: Man Kingson , Damasio Antonio , Meyer Kaspar , Kaplan Jonas T.
Published: June 2015

We continuously perceive objects in the world through multiple sensory channels. In this study, we investigated the convergence of information from different sensory streams within the cerebral cortex. We presented volunteers with three common objects via three different modalities—sight, sound, and touch—and used multivariate pattern analysis of functional magnetic resonance imaging data to map the cortical regions containing information about the identity of the objects. We could reliably predict which of the three stimuli a subject had seen, heard, or touched from the pattern of neural activity in the corresponding early sensory cortices. Intramodal classification was also successful in large portions of the cerebral cortex beyond the primary areas, with multiple regions showing convergence of information from two or all three modalities. Using crossmodal classification, we also searched for brain regions that would represent objects in a similar fashion across different modalities of presentation. We trained a classifier to distinguish objects presented in one modality and then tested it on the same objects presented in a different modality. We detected audiovisual invariance in the right temporo‐occipital junction, audiotactile invariance in the left postcentral gyrus and parietal operculum, and visuotactile invariance in the right postcentral and supramarginal gyri. Our maps of multisensory convergence and crossmodal generalization reveal the underlying organization of the association cortices, and may be related to the neural basis for mental concepts. Hum Brain Mapp 36:3629–3640, 2015. © 2015 Wiley Periodicals, Inc.
Emotional context facilitates cortical prediction error responses
Authors: Vogel Bob O. , Shen Christina , Neuhaus Andres H.
Published: June 2015

In the predictive coding framework, mismatch negativity (MMN) is regarded a correlate of the prediction error that occurs when top–down predictions conflict with bottom–up sensory inputs. Expression‐related MMN is a relatively novel construct thought to reflect a prediction error specific to emotional processing, which, however, has not yet been tested directly. Our paradigm includes both neutral and emotional deviants, thereby allowing for investigating whether expression‐related MMN is emotion‐specific or unspecifically arises from violations of a given sequence. Twenty healthy participants completed a visual sequence oddball task where they were presented with (1) sequence deviants, (2) emotional sequence deviants, and (3) emotional deviants. Mismatch components were assessed at ventral occipitotemporal scalp sites and analyzed regarding their amplitudes, spatiotemporal profiles, and neuronal sources. Expression‐related MMN could be clearly separated from its neutral counterpart in all investigated aspects. Specifically, expression‐related MMN showed enhanced amplitude, shorter latency, and different neuronal sources. Our results, therefore, provide converging evidence for a quantitative specificity of expression‐related MMN and seems to provide an opportunity to study prediction error during preattentive emotional processing. Our neurophysiological evidence ultimately suggests that a basic cognitive operator, the prediction error, is enhanced at the cortical level by processing of emotionally salient stimuli. Hum Brain Mapp 36:3641–3652, 2015. © 2015 Wiley Periodicals, Inc.