bluuebunny/crossref_metadata_2025 huggingface dataset:
A Fully GPU-Based Ray-Driven Backprojector via a Ray-Culling Scheme with Voxel-Level Parallelization for Cone-Beam CT Reconstruction
Authors: Park Hyeong-Gyu , Shin Yeong-Gil , Lee Ho
Published: April 2014

A ray-driven backprojector is based on ray-tracing, which computes the length of the intersection between the ray paths and each voxel to be reconstructed. To reduce the computational burden caused by these exhaustive intersection tests, we propose a fully graphics processing unit (GPU)-based ray-driven backprojector in conjunction with a ray-culling scheme that enables straightforward parallelization without compromising the high computing performance of a GPU. The purpose of the ray-culling scheme is to reduce the number of ray-voxel intersection tests by excluding rays irrelevant to a specific voxel computation. This rejection step is based on an axis-aligned bounding box (AABB) enclosing a region of voxel projection, where eight vertices of each voxel are projected onto the detector plane. The range of the rectangular-shaped AABB is determined by min/max operations on the coordinates in the region. Using the indices of pixels inside the AABB, the rays passing through the voxel can be identified and the voxel is weighted as the length of intersection between the voxel and the ray. This procedure makes it possible to reflect voxel-level parallelization, allowing an independent calculation at each voxel, which is feasible for a GPU implementation. To eliminate redundant calculations during ray-culling, a shared-memory optimization is applied to exploit the GPU memory hierarchy. In experimental results using real measurement data with phantoms, the proposed GPU-based ray-culling scheme reconstructed a volume of resolution 28032803176 in 77 seconds from 680 projections of resolution 10243768 , which is 26 times and 7.5 times faster than standard CPU-based and GPU-based ray-driven backprojectors, respectively. Qualitative and quantitative analyses showed that the ray-driven backprojector provides high-quality reconstruction images when compared with those generated by the Feldkamp-Davis-Kress algorithm using a pixel-driven backprojector, with an average of 2.5 times higher contrast-to-noise ratio, 1.04 times higher universal quality index, and 1.39 times higher normalized mutual information.
The Technique, Resources and Costs of Stereotactic Body Radiotherapy of Prostate Cancer
Authors: Sharieff Waseem , Greenspoon Jeffrey N. , Dayes Ian , Chow Tom , Wright James , Lukka Himu
Published: April 2014

Robotic system has been used for stereotactic body radiotherapy (SBRT) of prostate cancer. Arc-based and fixed-gantry systems are used for hypofractionated regimens (10-20 ractions) and the standard regimen (39 fractions); they may also be used to deliver SBRT. Studies are currently underway to compare efficacy and safety of these systems and regimens. Thus, we describe the technique and required resources for the provision of robotic SBRT in relation to the standard regimen and other systems to guide investment decisions. Using administrative data of resource volumes and unit prices, we computed the cost per patient, cost per cure and cost per quality adjusted life year (QALY) of four regimens (5, 12, 20 and 39 fractions) and three delivery systems (robotic, arc-based and fixed-gantry) from a payer’s perspective. We performed sensitivity analyses to examine the effects of daily hours of operation and in-room treatment delivery times on cost per patient. In addition, we estimated the budget impact when a robotic system is preferred over an arc-based or fixed-gantry system. Costs of SBRT were $6333/patient (robotic), $4368/patient (arc-based) and $4443/patient (fixed-gantry). When daily hours of operation were varied, the cost of robotic SBRT varied from $9324/patient (2 hours daily) to $5250/patient (10 hours daily). This was comparable to the costs of 39 fraction standard regimen which were $5935/patient (arc-based) and $7992/ patient (fixed-gantry). In settings of moderate to high patient volume, robotic SBRT is cost effective compared to the standard regimen. If SBRT can be delivered with equivalent efficacy and safety, the arc-based system would be the most cost effective system.
Solar cycle variation of the electron density in the topside ionosphere at local nighttime observed by DEMETER during 2006–2008
Authors: Zhang Xuemin , Qian Jiadong , Shen Xuhui
Published: April 2014

The solar cycle variations of electron density (Ne) in the topside ionosphere are presented by observations around local time 22:30 from Detection of Electro‐Magnetic Emissions Transmitted from Earthquake Regions (DEMETER) satellite during 2006–2008 in the low solar activity, in which the revisited orbits are selected to construct Ne time sequences at different points. The results show that electron density (Ne) reduced 50–100% since 2006 to 2008 at equatorial area and middle latitudes, with much bigger maximal Ne in 2006 but even no yearly peak in 2007 and 2008 around 30° latitude. The seasonal asymmetry is revealed by the yearly maxima of Ne in December over Southern Hemisphere always being larger than those in June over Northern Hemisphere. Furthermore, the equinoctial asymmetry is found around the magnetic equator and high northern latitudes under the low solar activity, and the latter one has not been revealed in other research. Ne from IRI2012 is close to the actual observation by DEMETER in 2008, even better than those in 2006 and 2007, indicating the great improvement of this empirical ionospheric model in this extremely low solar minimum. After comparison with the fitted results by indices of F10.7 and EUV combined with the first five periods in Ne, EUV is a little better to describe the variations in Ne during this solar minimum. By discussing the relationship among nighttime Ne and molecules in upper atmosphere, the [O/N2] density ratio is the key factor at high latitude, while [O] density plays a certain role to electron density around the equator.
Magnetic clouds and origins in STEREO era
Authors: Yan Li , Luhmann J. G. , Lynch B. J. , Kilpua E. K. J.
Published: April 2014

When a coronal mass ejection (CME) encounters the Earth, the Earth's electromagnetic environment is disturbed, especially when it is a magnetic cloud (MC) with enhanced, steady, and long‐lasting southward field. The speed and the magnetic field of an MC are the two important properties for its geoeffectiveness. The correspondence between a CME and its resulting MC is not straightforward, partly due to the CME velocity and the complications during propagation through corona and the solar wind. From 2007 to 2012, we have three observing points at 1 AU near the ecliptic plane (ACE and STEREO A and B). We search for MC events encountered at one of the three observers and study the statistics independently and in comparison. We found that the annual number of MCs at each receiver varies significantly and the temporal variation at each receiver does not always follow the solar activity level. The speed and the magnetic field strength of the MCs do vary with the solar activity level. The polarity of MC magnetic field at ACE and STEREO also shows large fluctuations. We have also identified the CME and solar activity sources for the L1 MC events. STEREO SECCHI images served critical roles in the determination of the CMEs both in solar quiet times and active times. We found that halo CMEs are not necessarily good indicators for receiving MCs. Further studies of CME initial velocity and the propagation through the heliosphere are needed in order to improve our space weather forecasting capability.
First results using TWINS‐derived ion temperature boundary conditions in CRCM
Authors: Elfritz J. G. , Keesee A. M. , Buzulukova N. , Fok M. ‐C. , Scime E. E.
Published: April 2014

We have integrated dynamic, spatiotemporally resolved ion temperature boundary conditions into the Comprehensive Ring Current Model (CRCM), which are based on 2‐D equatorial maps derived from the Two Wide‐Angle Imaging Neutral‐Atom Spectrometers (TWINS) energetic neutral atom (ENA) data. The high‐speed stream‐driven event on 22 July 2009 is simulated and compared against an identical simulation using a statistically derived boundary condition model. ENA‐derived temperatures allow users to include event‐specific observations associated with a dynamic plasma sheet. This method also provides temperatures in the important region between geosynchronous orbit and the plasma sheet, a region which existing empirical models exclude. We find that the spatial and energy distributions of ring current flux and pressure have sensitive dependence on boundary conditions during this event. The coupling of boundary conditions to the time history of the convection field strength also plays an important role by throttling the influence of the boundary plasma on the inner magnetosphere. Simulated moments and spectra from our simulations are compared with remotely imaged ion temperatures from TWINS and also in situ energy spectra and temperature moments from Time History of Events and Macroscale Interactions during Substorms‐D. Storm time dusk‐dawn asymmetries consistent with observational data, such as Zhang et al. (2006), are reproduced well when CRCM is provided with the event‐specific boundary model. A hot localized structure observed by TWINS at geosynchronous midnight during a strong northward interplanetary magnetic field interval is also reproduced with this boundary model, whereas the empirical boundary model fails to yield this feature.
Oblique reflections in the Mars Express MARSIS data set: Stable density structures in the Martian ionosphere
Authors: J. Andrews D. , André M. , Opgenoorth H. J , Edberg N. J. T. , Diéval C. , Duru F. , Gurnett D. A. , Morgan D. , Witasse O.
Published: April 2014

The Mars Advanced Radar for Subsurface and Ionospheric Sounding (MARSIS) onboard the European Space Agency's Mars Express (MEX) spacecraft routinely detects evidence of localized plasma density structures in the Martian dayside ionosphere. Such structures, likely taking the form of spatially extended elevations in the plasma density at a given altitude, give rise to oblique reflections in the Active Ionospheric Sounder data. These structures are likely related to the highly varied Martian crustal magnetic field. In this study we use the polar orbit of MEX to investigate the repeatability of the ionospheric structures producing these anomalous reflections, examining data taken in sequences of multiple orbits which pass over the same regions of the Martian surface under similar solar illuminations, within intervals lasting tens of days. Presenting three such examples, or case studies, we show for the first time that these oblique reflections are often incredibly stable, indicating that the underlying ionospheric structures are reliably reformed in the same locations and with qualitatively similar parameters. The visibility, or lack thereof, of a given oblique reflection on a single orbit can generally be attributed to variations in the crustal field within the ionosphere along the spacecraft trajectory. We show that, within these examples, oblique reflections are generally detected whenever the spacecraft passes over regions of intense near‐radial crustal magnetic fields (i.e., with a “cusp‐like” configuration). The apparent stability of these structures is an important feature that must be accounted for in models of their origin.
Traveltime delay and initial phase reversal of distant tsunamis coupled with the self‐gravitating elastic Earth
Authors: Watada Shingo , Kusumoto Satoshi , Satake Kenji
Published: April 2014

Systematic tsunami traveltime delays of up to 15 min relative to the numerically simulated long waves from the 2010 Chilean and 2011 Tohoku‐Oki earthquakes were widely observed at deep ocean tsunamimeters. Enigmatic small negative phases appearing before the main peak were commonly found only at the trans‐oceanic locations. The frequency dependence of the measured tsunami phase velocities shows reverse dispersions at long periods, i.e., the tsunami speed becomes slower at periods beyond 1000 s. This is consistent with the phase velocities of a tsunami mode coupled with a self‐gravitating elastic Earth, suggesting that the effects of compression and dilatation of seawater, elastic tsunami loadings on a solid Earth, and the geopotential variations associated with the motion of mass during tsunami propagation are responsible for the traveltime delays and the initial negative phases. Simple 1‐D tsunami propagation tests confirm that the reverse dispersion creates a small negative phase that precedes the main peak at large distances. A new method to simulate tsunami waveforms on real ocean bathymetry that takes into account seawater compressibility, the elasticity of the Earth, and geopotential perturbations has been developed by applying a phase correction to the simulated long waves. The simulated waveforms, in which phase corrections are applied for the dispersion effects, accurately reproduce the observed waveforms, including a small initial negative phase that appears at distant locations. The traveltime difference between the observed and simulated waveforms has been decreased to less than 5 min and the waveform difference between them remarkably diminishes.
How important is intensified evaporation for Mediterranean precipitation extremes?
Authors: Winschall Andreas , Sodemann Harald , Pfahl Stephan , Wernli Heini
Published: April 2014

The moisture sources for heavy precipitation events in the northwestern Mediterranean are investigated with a Lagrangian moisture source diagnostic, which is based on the analysis of moisture changes during 6 h time intervals along backward trajectories, originating from the location of the heavy precipitation events. We consider the 50 strongest events in each season in the region 0–15°E, 42–46°N during the years 1989–2009. The results of the moisture source diagnostic indicate that during precipitation extremes the Mediterranean Sea surface is only one of several source regions in all seasons, and typically matched by moisture from the North Atlantic in autumn and winter and land evapotranspiration in summer. The event‐to‐event variability is large. Individual events can be dominated by land evapotranspiration, moisture transport from the North Atlantic, or an export of moisture from the tropics. The time of maximum moisture uptake varies between a few hours to more than a week before the precipitation event. The results from the moisture source analysis are used for investigating whether intense surface evaporation occurs prior to heavy precipitation. Surface evaporation anomalies at the moisture sources are positive over the North Atlantic and the European and African land surface, whereas no signal is present over the Mediterranean. Therefore, for the Mediterranean moisture contribution, convergence from the background moisture reservoir is essential, whereas for the remote sources anomalously intense surface evaporation is required to foster the moisture supply for Mediterranean heavy precipitation events.
β1‐adrenergic receptor activation enhances memory in Alzheimer's disease model
Authors: Coutellier Laurence , Ardestani Pooneh Memar , Shamloo Mehrdad
Published: April 2014

Objective

Deficits in social recognition and learning of social cues are major symptoms of neurodegenerative disorders such as Alzheimer's disease (AD). Here, we studied the role of β1‐noradrenergic signaling in cognitive function to determine whether it could be used as a potential therapeutic target for AD.

Methods

Using pharmacological, biochemical, and behavioral tools, we assessed social recognition and the β1‐adrenergic receptor (ADR) and its downstream protein kinase A (PKA)/phospho‐cAMP response element‐binding protein (pCREB) signaling cascade in the medial amygdala (MeA) in Thy1‐hAPPLond/Swe+(APP) mouse model of AD.

Results

Our results demonstrated that APP mice display a significant social recognition deficit which is dependent on the β1‐adrenergic system. Moreover, betaxolol, a selective β1‐ADR antagonist, impaired social but not object/odor learning in C57Bl/6 mice. Our results identifies activation of the PKA/pCREB downstream of β1‐ADR in MeA as responsible signaling cascade for learning of social cues in MeA. Finally, we found that xamoterol, a selective β1‐ADR partial agonist, rescued the social recognition deficit of APP mice by increasing nuclear pCREB.

Interpretation

Our data indicate that activation of β1‐ADR in MeA is essential for learning of social cues, and that an impairment of this cascade in AD may contribute to pathogenesis and cognitive deficits. Therefore, selective activation of β1‐ADR may be used as a therapeutic approach to rescue memory deficits in AD. Further safety and translational studies will be needed to ensure the safety of this approach.
A New In Situ Microscopy Approach to Study the Degradation and Failure Mechanisms of Time‐Dependent Dielectric Breakdown: Set‐Up and Opportunities
Authors: Liao Zhongquan , Gall Martin , Yeap Kong Boon , Sander Christoph , Aubel Oliver , Mühle Uwe , Gluch Jürgen , Niese Sven , Standke Yvonne , Rosenkranz Rüdiger , Löffler Markus , Vogel Norman , Beyer Armand , Engelmann Hans‐Jürgen , Guttmann Peter , Schneider Gerd , Zschech Ehrenfried
Published: April 2014

The time dependent dielectric breakdown (TDDB) in copper/ultra‐low‐k on‐chip interconnect stacks of integrated circuits has become one of the most critical reliability concerns in recent years. In this paper, a novel experimental in situ microscopy approach using transmission X‐ray microscopy (TXM) and scanning transmission electron microscopy (STEM) is proposed to study TDDB degradation and failure mechanisms. It combines electrical testing and imaging techniques. Low‐dose bright field (BF) STEM inserting a small condenser aperture is chosen to reduce the beam damage of the dielectric material, while the electron spectroscopic imaging technique is used for the chemical analysis to detect the migration path of Cu atoms. This new experimental approach will contribute to an improved understanding of the TDDB effect.
Bioreducible Carboxymethyl Dextran Nanoparticles for Tumor‐Targeted Drug Delivery
Authors: Thambi Thavasyappan , You Dong Gil , Han Hwa Seung , Deepagan V. G. , Jeon Sang Min , Suh Yung Doug , Choi Ki Young , Kim Kwangmeyung , Kwon Ick Chan , Yi Gi‐Ra , Lee Jun Young , Lee Doo Sung , Park Jae Hyung
Published: April 2014

Bioreducible carboxymethyl dextran (CMD) derivatives are synthesized by the chemical modification of CMD with lithocholic acid (LCA) through a disulfide linkage. The hydrophobic nature of LCA allows the conjugates (CMD‐SS‐LCAs) to form self‐assembled nanoparticles in aqueous conditions. Depending on the degree of LCA substitution, the particle diameters range from 163 to 242 nm. Doxorubicin (DOX), chosen as a model anticancer drug, is effectively encapsulated into the nanoparticles with high loading efficiency (>70%). In vitro optical imaging tests reveal that the fluorescence signal of DOX quenched in the bioreducible nanoparticles is highly recovered in the presence of glutathione (GSH), a tripeptide capable of reducing disulfide bonds in the intracellular compartments. Bioreducible nanoparticles rapidly release DOX when they are incubated with 10 mm GSH, whereas the drug release is greatly retarded in physiological buffer (pH 7.4). DOX‐loaded bioreducible nanoparticles exhibit higher toxicity to SCC7 cancer cells than DOX‐loaded nanoparticles without the disulfide bond. Confocal laser scanning microscopy observation demonstrate that bioreducible nanoparticles can effectively deliver DOX into the nuclei of SCC7 cells. In vivo biodistribution study indicates that Cy5.5‐labeled CMD‐SS‐LCAs selectively accumulate at tumor sites after systemic administration into tumor‐bearing mice. Notably, DOX‐loaded bioreducible nanoparticles exhibit higher antitumor efficacy than reduction‐insensitive control nanoparticles. Overall, it is evident that bioreducible CMD‐SS‐LCA nanoparticles are useful as a drug carrier for cancer therapy.
Health in post‐Black Death London (1350–1538): Age patterns of periosteal new bone formation in a post‐epidemic population
Authors: DeWitte Sharon N.
Published: April 2014

Previous research has shown that the Black Death targeted older adults and individuals who had been previously exposed to physiological stressors. This project investigates whether this selectivity of the Black Death, combined with post‐epidemic rising standards of living, led to significant improvements in patterns of skeletal stress markers, and by inference in health, among survivors and their descendants. Patterns of periosteal lesions (which have been previously shown, using hazard analysis, to be associated with elevated risks of mortality in medieval London) are compared between samples from pre‐Black Death (c. 1,000–1,300,n = 464) and post‐Black Death (c. 1,350–1,538,n = 133) London cemeteries. To avoid the assumptions that stress markers alone provide a direct measure of health and that a change in frequencies of the stress marker by itself indicates changes in health, this study assesses age‐patterns of the stress marker to obtain a more nuanced understanding of the population‐level effects of an epidemic disease. Age‐at‐death in these samples is estimated using transition analysis, which provides point estimates of age even for the oldest adults in these samples and thus allows for an examination of physiological stress across the lifespan. The frequency of lesions is significantly higher in the post‐Black Death sample, which, at face value, might indicate a general decline in health. However, a significant positive association between age and periosteal lesions, as well as a significantly higher number of older adults in the post‐Black Death sample more likely suggests improvements in health following the epidemic. Am J Phys Anthropol 155:260–267, 2014. © 2014 Wiley Periodicals, Inc.
Examining short‐term nutritional status among BaAka foragers in transitional economies
Authors: Remis Melissa J. , Jost Robinson Carolyn A.
Published: April 2014

Foragers in transitioning economies are at an increased risk of negative health outcomes as they undergo changes in subsistence patterns and diet. Here, we provide anthropometric data and examine the nutrition and health of adult BaAka foragers in relationship to declining wildlife and economic change in the Dzanga Sangha Protected Areas (APDS), Central African Republic. From June to August 2012, we collected biological data and dietary recall surveys from individuals in Mossapoula (MS) and Yandoumbé (YDBE) villages using standard anthropometric techniques and a single capillary blood finger prick. In our analysis, we identified variation in anthropometric measurements and hemoglobin levels by village (MS = 66, YDBE = 75) and gender (64 men, 77 women). Immigration, increased gun hunting and wildlife trades have reduced forager reliance on forest resources. These changes are evidenced in the marginal health of contemporary BaAka foragers of APDS. Although anthropometric measures of nutritional status do not significantly differ between communities, hemoglobin data highlight inequities in access to forest products between villages with different proximity to community hunting zones. Further, poor dietary diversity and low frequency of purchased foods in the diet indicate that the transition to a market economy has not been fully realized and diets are impoverished. Economic changes appear to have had the most impact at MS village, where forest use is most restricted and consumption of meat and forest products was reduced. This work highlights the nutritional and health needs of foragers in rapidly transitioning economies; especially those impacted by conservation management and zoning policies. Am J Phys Anthropol 154:365–375, 2014. © 2014 Wiley Periodicals, Inc.
Dehydrochlorination of poly(vinyl chloride) modified with titanium dioxide/poly(ethylene oxide) based paint photocatalysts
Authors: Miyazaki Kensuke , Sato Hiroaki , Kikuchi Shinpei , Nakatani Hisayuki
Published: April 2014

The dehydrochlorination of poly(vinyl chloride) (PVC) film samples modified with titanium dioxide (TiO2)/poly(ethylene oxide) (PEO) based paint photocatalysts [the addition of methyl linoleate (ML) or methyl oleate (MO)] was performed. After 24 h of UV photoirradiation, the sample with TiO2/PEO showed that there existed a structure with the longest polyene length, whereas that with TiO2/PEO/ML contained the most polyene structures. The chloroform‐soluble fraction of the sample with TiO2/PEO contained a poly(vinyl alcohol) (PVA) structure instead of a polyene one and showed a novel method of PVA production via PVC photodegradation. The molecular weight curve of the fraction shifted slightly to a lower molecular weight compared to that without the photocatalyst; this showed that slight polymer chain scission occurred. The 1H‐NMR and 13C‐NMR spectra showed that the content of PVA units was about 20%, and the PVA sequence was blocky. The fraction of the sample with TiO2/PEO/ML contained the highest methyl group content; this showed that the branch degree was highest as was the polyene content. These highest contents were due to the existence of the grafted ML. Pyrolysis gas chromatography/mass spectroscopy measurements suggested that there existed more polyene and graft units in the chloroform‐insoluble fractions of the samples with TiO2/PEO, TiO2/PEO/ML, and TiO2/PEO/MO, respectively. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40760.
Preparation of PLLA/PDLA stereocomplexes using a novel initiator based on Mg(II) and Ti(IV) alkoxides
Authors: Silvino Alexandre Carneiro , Corrêa Priscila Santos , Dias Marcos Lopes
Published: April 2014

Herein we describe the obtention of polylactide stereocomplexes using a novel initiator system comprising Mg(II) and Ti(IV) centers. The stereocomplexes were successfully prepared using two different routes: by PDLA and PLLA co‐precipitation from chloroform solutions and two‐step diblock copolymerization. For the PDLA/PLLA mixing procedure, individual homochiral polymers were prepared in solution at different monomer/initiator ratios; whereas, the PLA stereoblock was prepared employing one‐pot sequential polymerization of both chiral monomers. The products analyzed by WAXD showed the characteristic stereocrystal reflections while the high melting temperatures found in the DSC runs confirmed the formation of PLA stereocomplexes in both cases. Surprisingly, one of the stereocomplexes showed a second endothermic event at 250.1°C and to our knowledge this is the highest melting temperature reported for PLA stereocomplexes till date. These results point to the discovery of an effective initiator based on low toxicity metals for the preparation of biodegradable materials with interesting thermal properties. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40771.
Thermodynamic and kinetic aspects of defectivity in directed self‐assembly of cylinder‐forming diblock copolymers in laterally confining thin channels
Authors: Kim Bongkeun , Laachi Nabil , Delaney Kris T. , Carilli Michael , Kramer Edward J. , Fredrickson Glenn H.
Published: April 2014

We use self‐consistent field theory to calculate the energy of defect formation in cylinder‐forming diblock copolymers in laterally confining thin channels. We focus on two isolated defects, dislocations and disclinations and explore a wide range of polymer and channel characteristics. Our findings suggest appropriate conditions for the design of optimized graphoepitaxial processes, where defects are limited to very low concentrations. Using the string method, we also investigate the energy barriers and kinetic pathways of the transition from defective to perfect states. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40790.
Morphology controlled synthesis of polyaniline nanostructures using swollen liquid crystal templates
Authors: Dutt Sunil , Siril Prem Felix
Published: April 2014

Preparation of zero‐dimensional and one‐dimensional nanostructures of polyaniline (PANI) were achieved by using swollen liquid crystals (SLCs) as ‘soft' templates. The monomer (aniline) was first entrapped in SLCs by replacing the oil phase (cyclohexane) with a mixture of aniline and cyclohexane. Zero‐dimensional nanostructures of PANI were obtained by thorough mixing of APS with the mesophases. One‐dimensional nanostructures were prepared by allowing slow diffusion of APS through the mesophase. PANI nanostructures were extracted from the mesophase and were characterized by UV‐visible spectroscopy, FTIR spectroscopy, powder X‐ray diffraction, atomic force microscopy, scanning electron microscopy (SEM), and conductivity measurements. A plausible mechanism for the formation of the nanostructures has been proposed. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2014,131, 40800.
FUNCTIONAL CHARACTERIZATION OF AN ANTENNAL ESTERASE FROM THE NOCTUID MOTH, Spodoptera exigua
Authors: He Peng , Zhang Jin , Li Zhao‐Qun , Zhang Ya‐Nan , Yang Ke , Dong Shuang‐Lin , He Peng
Published: April 2014

Odorant‐degrading esterases (ODEs) act in the fast deactivation of ester pheromone components and plant volatiles in insects. However, only few ODEs have been characterised to date. In this study, six full‐length putative ODE genes (designated SexiCXE4, 5, 17, 18, 20, and 31) were cloned from the male antennae of Spodoptera exigua. The deduced amino acid sequences possessed typical characteristics of a carboxylesterase (CXE) and shared high identities with reported insect CXEs. The tissue and temporal expression patterns were investigated by quantitative real time PCR. Although all six SexiCXEs are expressed in antennae of both sexes, SexiCXE4, 17 and 20 are antennae‐enriched; while SexiCXE5 and SexiCXE18 are dominantly expressed in wings, and SexiCXE31 is mainly expressed in proboscises, heads and legs. With the highly biased expression in antennae and proboscises, SexiCXE4 was selected for further functional assay. The recombinant SexiCXE4 were expressed in High‐five cells and purified by a Ni2+ affinity column. SexiCXE4 has much higher enzyme activity against plant volatiles (Z)‐3‐hexenyl acetate and hexyl acetate than to the sex pheromone components, suggesting that it may function mostly in the degradation of the plant volatiles.
Cell‐Penetrable Lysine Dendrimers for Anti‐Cancer Drug Delivery: Synthesis and Preliminary Biological Evaluation
Authors: Zhao Jing , Zhou Rui , Fu Xiaoyu , Ren Wen , Ma Lifang , Li Ran , Zhao Yi , Guo Li
Published: April 2014

Improving the cell penetration and enhancing the cell selectivity of drugs have been approved for overcoming the major drawbacks of chemotherapeutic agents: the toxicity to normal cells and the drug resistance in tumors. In this paper, lysine dendrimers (G1–G3) were chosen as novel cell‐penetrating carriers for anti‐cancer drugs based on the internalization mechanism of cell‐penetrating peptides and the characteristics of dendritic peptides. After labeling with fluorescein isothiocyanate (FITC), the cell‐penetrable capacity of lysine dendrimers was certified by flow cytometric analysis. In a preliminary biological evaluation, the conjugates of lysine dendrimers and 5‐fluorouracil showed the expected advantages: stable drug release, low toxicity to normal cells, and moderate inhibition of tumor cells. These results imply that cell‐penetrable lysine dendrimers could be potential carriers in drug delivery of anti‐cancer medicine.
Intraarticular Sprifermin (Recombinant Human Fibroblast Growth Factor 18) in Knee Osteoarthritis: A Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Lohmander L. Stefan , Hellot Scarlett , Dreher Don , Krantz Eduard F. W. , Kruger Dawie S. , Guermazi Ali , Eckstein Felix
Published: April 2014

Objective

To evaluate the efficacy and safety of intraarticular sprifermin (recombinant human fibroblast growth factor 18) in the treatment of symptomatic knee osteoarthritis (OA).

Methods

The study was a randomized, double‐blind, placebo‐controlled, proof‐of‐concept trial. Intraarticular sprifermin was evaluated at doses of 10 μg, 30 μg, and 100 μg. The primary efficacy end point was change in central medial femorotibial compartment cartilage thickness at 6 months and 12 months as determined using quantitative magnetic resonance imaging (qMRI). The primary safety end points were nature, incidence, and severity of local and systemic treatment‐emergent adverse events (AEs) and acute inflammatory reactions, as well as results of laboratory assessments. Secondary end points included changes in total and compartment femorotibial cartilage thickness and volume as assessed by qMRI, changes in joint space width (JSW) seen on radiographs, and pain scores on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

Results

One hundred ninety‐two patients were randomized and evaluated for safety, 180 completed the trial, and 168 were evaluated for the primary efficacy end point. We found no statistically significant dose response in change in central medial femorotibial compartment cartilage thickness. Sprifermin was associated with statistically significant, dose‐dependent reductions in loss of total and lateral femorotibial cartilage thickness and volume and in JSW narrowing in the lateral femorotibial compartment. All groups had improved WOMAC pain scores, with statistically significantly less improvement at 12 months in patients receiving the 100‐μg dose of sprifermin as compared with those receiving placebo. There was no significant difference in serious AEs, treatment‐emergent AEs, or acute inflammatory reactions between sprifermin and placebo groups.

Conclusion

No statistically significant relationship between treatment group and reduction in central medial femorotibial compartment cartilage thickness was observed; however, prespecified structural secondary end points showed statistically significant dose‐dependent reductions after sprifermin treatment. Sprifermin was not associated with any local or systemic safety concerns.
Local Monin–Obukhov similarity in heterogeneous terrain
Authors: Figueroa‐Espinoza Bernardo , Salles Paulo
Published: April 2014

Experimental results concerning turbulence in a coastal zone are presented. The presence of internal boundary layers and advection in complex terrain precludes the use of Monin–Obukhov similarity theory (MOST) to estimate effective values of the turbulent transport (of momentum and heat) parameters. However, the use of local Monin–Obukhov similarity is less restrictive: if an analogy is made between the stability integrated functions for horizontally homogeneous terrain and a corresponding term in complex terrain, effective values of the Obukhov and roughness lengths can be obtained using sonic anemometry.
Hepatic microsomal UDP‐glucuronosyltransferase (UGT) activities in the microminipig
Authors: Higashi Eriko , Ando Akihiro , Iwano Shunsuke , Murayama Norie , Yamazaki Hiroshi , Miyamoto Yohei
Published: April 2014

The microminipig, a small minipig, was bred as a novel experimental animal for nonclinical pharmacology/toxicology studies by Fuji Micra Inc. (Shizuoka, Japan). Species differences in drug metabolism between humans and the microminipig need to be elucidated in more detail in order to discuss the results of nonclinical studies. Glucuronidation catalysed by UDP‐glucuronosyltransferase (UGT) is an important pathway in the metabolism of a wide variety of compounds. The aim of the present study was to identify the characteristics of hepatic UGT activity in the microminipig and compare them with those in humans and other experimental animals. This study examined in vitro UGT activities using liver microsomes from microminipigs (8 months old and 1 day old), humans, mice, rats, dogs, monkeys and minipigs. The glucuronides of estradiol, imipramine, serotonin, propofol, 3′‐azido‐3′‐deoxythymidine (AZT) and morphine, selective substrates of human UGT1A1, 1A4, 1A6, 1A9 and 2B7 (AZT and morphine), respectively, were measured using LC‐MS/MS. Estradiol‐3‐glucuronidation activity was higher in the microminipig than in humans and the other animals. High levels of estradiol‐3‐glucuronidation were observed in the microsomes of 1‐day‐old microminipigs. Imipramine‐N‐glucuronidation, a distinctive conjugation by human UGT1A4, was catalysed by microminipig liver microsomes, but not by dog liver microsomes. Although AZT‐glucuronidation activity was low in the microminipig compared with humans, morphine‐3‐glucuronidation activity in the microminipig was higher than that in humans. The UGT activities in the microminipig were similar to those in the minipig. The results of the present study have provided useful information for selecting an appropriate animal model for nonclinical studies. Copyright © 2014 John Wiley & Sons, Ltd.
Logrank‐type tests with presmoothing
Authors: Jácome M. Amalia , López‐de‐Ullibarri Ignacio
Published: April 2014

The logrank test is the most popular choice for testing the equality of two survival distributions with time‐to‐event data. It is based on the comparison of the Nelson–Aalen estimates of the corresponding cumulative hazard functions. The improvements of the logrank test in the literature have been accomplished using weighted logrank tests, with the weight chosen appropriately to maximize power. Notwithstanding, power also depends on the efficiency of the estimation of the cumulative hazard function. The presmoothed estimator has been shown to be more efficient than the Nelson–Aalen estimator under some general assumptions. We introduce a new logrank‐type test that, instead of the Nelson–Aalen estimator, is based on its presmoothed counterpart. An extensive simulation study has been conducted to compare the performance of this new test with the classical one. This study shows that the new test has the proper size under the null hypothesis, while improving the power over a wide range of alternatives. The new test is illustrated with several real data examples.
What about sparsity when data are curves?
Authors: Ferraty Frédéric
Published: April 2014

This is a discussion around the paper “Overview of object oriented data analysis” by J. Steve Marron and Andrés M. Alonso.
Avoiding antibody aggregation during processing: Establishing hold times
Authors: Joshi Varsha , Shivach Tarun , Kumar Vijesh , Yadav Nitin , Rathore Anurag
Published: April 2014

Aggregation of biotech products used therapeutically, such as antibodies, can contribute to potential immunogenicity of the product. Charge‐based heterogeneities may also impact the safety and/or efficacy of a therapeutic. In this study, an approach based on empirical modeling and least squares regression is suggested for establishing hold times for process intermediates during production of monoclonal antibody (Mab) therapeutics. Two immunoglobulins were analyzed with respect to aggregation and charge heterogeneity in buffer conditions that are typically used during downstream processing of Mab products. Size exclusion chromatography, ion exchange chromatography (IEC), and circular dichroism were used. We found that aggregation primarily occurs at pH 3 (buffers used in affinity chromatography) and is higher in citrate buffer compared to acetate and glycine buffers. Aggregation is minimal in buffers used in anion exchange chromatography (Tris–HCl buffer at pH 7.2 and 8) and in cation exchange chromatography (citrate buffer at pH 6, acetate buffer at pH 6, and phosphate buffer at pH 6.5 and 7.5). The behavior is opposite in the case of charged heterogeneities (basic and acidic variants) as measured by IEC. The product is more susceptible to degradation at high pH than at low pH. The data presented here demonstrate that product stability can be a significant issue within the routinely used manufacturing conditions. We suggest that the approach presented needs to be adopted by all manufacturers to ensure product stability during processing.
Influence of PEG length on conformational and binding properties of CCK peptides exposed by supramolecular aggregates
Authors: Accardo Antonella , Ringhieri Paola , Palumbo Rosanna , Morelli Giancarlo
Published: April 2014

Five novel peptide amphiphiles (PAs), with common formula (C18)2‐PEGx‐CCK8 in which the CCK8 peptide and the (C18)2‐hydrophobic moiety are spaced by polyethylene linkers of different length (PEG moieties with molecular weights of 700, 1000, 1500, 2000, and 3000 Daltons) are described. They act as potential target‐selective nanocarriers towards tumor cells overexpressing cholecistokynin receptors. PAs self‐assemble in supramolecular aggregates, with hydrodynamic radius ranging between 63 and 104 nm, as indicated by DLS measurements. Fluorescence studies suggested that, irrespective from the PEG length, the tryptophan residue located at the center of the CCK8 sequence is completely surrounded by water molecules at high mobility. This result indicates a potential capability of all formulated nanovectors to recognize the overexpressed CCK‐2 receptors. CD data suggest that CCK8 peptide, in most of PAs in their aggregate form, adopts a conformation allowing the interaction with the receptor. Anyway, biological data obtained by flow cytometry analysis indicate that the five PAs have a different binding ability towards the CCK‐2 receptors, with higher binding properties shown by PA containing PEG with MW of 2000 Dalton. Therefore, PEG2000 can be considered as the best spacer in the formulation of nanovectors based on CCK8 peptide amphiphiles. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 304–312, 2014.
SCAI expert consensus statement for femoral‐popliteal arterial intervention appropriate use
Authors: Klein Andrew J. , Pinto Duane S. , Gray Bruce H. , Jaff Michael R. , White Christopher J. , Drachman Douglas E.
Published: April 2014

Successful endovascular intervention for femoral‐popliteal (FP) arterial disease provides relief of claudication and offers limb‐salvage in cases of critical limb ischemia. Technologies and operator technique have evolved to the point where we may now provide effective endovascular therapy for a spectrum of lesions, patients, and clinical scenarios. Endovascular treatment of this segment offers a significant alternative to surgical revascularization, and may confer improved safety for a wide range of patients, not solely those deemed high surgical risk. Although endovascular therapy of the FP segment has historically been hampered by high rates of restenosis, emerging technologies including drug‐eluting stents, drug‐coated balloons, and perhaps bio‐absorbable stent platforms, provide future hope for more durable patency in complex disease. By combining lessons learned from clinical trials, international trends in clinical practice, and insights regarding emerging technologies, we may appropriately tailor our application of endovascular therapy to provide optimal care to our patients. This document was developed to guide physicians in the clinical decision‐making related to the contemporary application of endovascular intervention among patients with FP arterial disease. © 2014 Wiley Periodicals, Inc.
Characterizing multivariate calibration tradeoffs (bias, variance, selectivity, and sensitivity) to select model tuning parameters
Authors: Kalivas John H. , Palmer Jon
Published: April 2014

Common methods used to form multivariate calibration models are partial least squares, principal component regression, and ridge regression. There are many aspects to forming a calibration model. The focus in this paper is determining “good” values of respective meta‐parameters (tuning parameters). In most situations, some form of cross‐validation and the resultant root mean square error of cross‐validation (RMSECV) values are evaluated. The RMSECV values can be thought of as a prediction accuracy (bias) measure and does not isolate variance information. The methods of partial least squares, principal component regression, and ridge regression (and others) are biased regression methods, and hence, there is a bias/variance tradeoff that should be considered in determining tuning parameter values. Presented in this paper are new combinations of model accuracy and fit that can be plotted with a model variance indicator for selecting appropriate tuning parameter values. For the spectroscopic and industrial data sets evaluated, these new combinations appear to remove ambiguities that can occur in RMSECV plots. Essentially, the user's preference for the degree of balance between bias and variance ultimately decides the tuning parameter selection and the underlying tradeoff between model selectivity and sensitivity. From the analysis of the selectivity/sensitivity tradeoff, a new definition of model selectivity is proposed that is able to discern when or when not a model vector deviates from the target orthogonal net analyte signal model vector as the well as the degree of deviation. A new merit is also proposed that simultaneously evaluates model selectivity and sensitivity. Copyright © 2013 John Wiley & Sons, Ltd.
ChemInform Abstract: Preparation, Electronic Structure and Luminescence Properties of Ce3+‐Activated CaZnOS under UV and X‐Ray Excitation.
Authors: Zhang Zhi‐Jun , Feng Ang , Sun Xin‐Yuan , Guo Kai , Man Zhen‐Yong , Zhao Jing‐Tai
Published: April 2014

Ca1‐2xCexLixZnOS samples (0 ≤ x ≤ 0.15) are prepared by a solid‐state reaction of CaO, ZnS, Li2CO3, and CeO2 (5% H2/N2 reducing atmosphere, Mo crucible, 950—1050 °C, 48 h).
ChemInform Abstract: Crystal Growth, Nonlinear Frequency‐Doubling and Spectral Characteristic of Nd:Ca9La(VO4)7 Crystal.
Authors: Zhuang Naifeng , Liu Xiaofeng , Xu Qianrui , Chen Xin , Zhao Bin , Hu Xiaolin , Chen Jianzhong
Published: April 2014

Pure and Nd‐doped Ca9La(VO4)7 crystals with various Nd3+ levels (3.2, 18.9, 31.4, and 32 at.%) are grown by the Czochralski method at 1430 °C from powders prepared by solid state reaction of a stoichiometric mixture of CaCO3, V2O5, La2O3, and Nd2O3 (alumina crucible, 1000 °C, 8 h).
ChemInform Abstract: High‐Temperature Thermoelectric Properties of the Solid—Solution Zintl Phase Eu11Cd6Sb12‐xAsx (x < 3).
Authors: Kazem Nasrin , Xie Weiwei , Ohno Saneyuki , Zevalkink Alexandra , Miller Gordon J. , Snyder G. Jeffrey , Kauzlarich Susan M.
Published: April 2014

Single crystals of the title compounds are prepared from the elements in a Sn flux (alumina crucibles, 950 °C, 96 h) and characterized by powder and single crystal XRD, transport properties measurements, and TB‐LMTO‐ASA electronic structure calculations.
ChemInform Abstract: Electronic Structure and Electrical Properties of Ba2LaTaO6.
Authors: Kumari Premlata , Dutta Alo , Shannigrahi Santiranjan , Prasad S. , Sinha T. P.
Published: April 2014

Ba2LaTaO6 is prepared by solid state reaction of a stoichiometric mixture of BaCO3, La2O3, and Ta2O5 (1350 °C, 6 h).
ChemInform Abstract: Magnetic and Magnetocaloric Properties of Equiatomic Alloys RAl (R: Ho and Er).
Authors: Yang L. H. , Zhang H. , Hu F. X. , Sun J. R. , Pan L. Q. , Shen B. G.
Published: April 2014

HoAl and ErAl intermetallics are prepared by melting of the elements under Ar followed by annealing (1173 K, 30 d) and quenching in liquid N2.
ChemInform Abstract: A New Cesium Pentaborate with New B10O19 Building Blocks.
Authors: Jiao Anqing , Yu Hongwei , Wu Hongping , Pan Shilie , Zhang Xingwen
Published: April 2014

Single crystals of a new polymorph of CsB5O8 are grown from a mixture of Cs2CO3, H3BO3, and MoO3 in a molar ratio of 1:4:2 (Pt crucible, 650 °C, 20 h; controlled cooling).
ChemInform Abstract: Enantioselective Protonation of Alkenyl Trifluoroacetates Catalyzed by Chiral Tin Methoxide.
Authors: Yanagisawa Akira , Sugita Takuya , Yoshida Kazuhiro
Published: April 2014

Optically active ketones containing a tertiary stereogenic center at the α‐position are obtained by catalytic enantioselective protonation of alkenyl trifluoroacetates.
ChemInform Abstract: Imine Hydrogenation by Alkylaluminum Catalysts.
Authors: Hatnean Jillian A. , Thomson Jordan W. , Chase Preston A. , Stephan Douglas W.
Published: April 2014

iBu2AlH as well as iBu3Al are shown to be efficient hydrogenation catalyst for a variety of imines (I) (15 examples).