bluuebunny/crossref_metadata_2025 huggingface dataset:
Influences of the interplanetary magnetic field clock angle and cone angle on the field‐aligned currents in the magnetotail
Authors: Cheng Z. W. , Shi J. K. , Dunlop M. , Liu Z. X.
Published: October 2013

The influences of the interplanetary magnetic field (IMF) cone angle θ and clock angle ϕ on the field‐aligned currents (FACs) at the plasma sheet boundary layers (PSBLs) have been investigated using Cluster Data. The FAC occurrence increases monotonically with IMF cone angle and has two peaks at −90° and +110° clock angle, respectively. The peak at +110° is distinctly larger than that at −90°. Overall, there are more FACs between 0° < ϕ < 180°, indicating that FACs occurrence is closely associated with duskward IMF. More FACs occur when 90° < |ϕ| < 180°, implying that FAC is closely associated with southward IMF. The large FAC densities occur when 60° < |ϕ| < 120°. The density also has two peaks and the peak at +90° clock angle (duskward IMF) is larger than that at −90° (dawnward IMF). These results indicate that the IMF influence on the FACs is from all IMF components and not only from a single component.
Unprecedented recent summer warmth in Arctic Canada
Authors: Miller Gifford H. , Lehman Scott J. , Refsnider Kurt A. , Southon John R. , Zhong Yafang
Published: October 2013

Arctic air temperatures have increased in recent decades, along with documented reductions in sea ice, glacier size, and snow cover. However, the extent to which recent Arctic warming has been anomalous with respect to long‐term natural climate variability remains uncertain. Here we use 145 radiocarbon dates on rooted tundra plants revealed by receding cold‐based ice caps in the eastern Canadian Arctic to show that 5000 years of regional summertime cooling has been reversed, with average summer temperatures of the last ~100 years now higher than during any century in more than 44,000 years, including the peak warmth of the early Holocene when high‐latitude summer insolation was 9% greater than present. Reconstructed changes in snowline elevation suggest that summers cooled ~2.7°C over the past 5000 years, approximately twice the response predicted by Coupled Model Intercomparison Project Phase 5 climate models. Our results indicate that anthropogenic increases in greenhouse gases have led to unprecedented regional warmth.
Magnetic flux pileup and plasma depletion in Mercury's subsolar magnetosheath
Authors: Gershman Daniel J. , Slavin James A. , Raines Jim M. , Zurbuchen Thomas H. , Anderson Brian J. , Korth Haje , Baker Daniel N. , Solomon Sean C.
Published: October 2013

Measurements from the Fast Imaging Plasma Spectrometer (FIPS) and Magnetometer (MAG) on the MErcury Surface, Space ENvironment, GEochemistry, and Ranging spacecraft during 40 orbits about Mercury are used to characterize the plasma depletion layer just exterior to the planet's dayside magnetopause. A plasma depletion layer forms at Mercury as a result of piled‐up magnetic flux that is draped around the magnetosphere. The low average upstream Alfvénic Mach number (MA ~3–5) in the solar wind at Mercury often results in large‐scale plasma depletion in the magnetosheath between the subsolar magnetopause and the bow shock. Flux pileup is observed to occur downstream under both quasi‐perpendicular and quasi‐parallel shock geometries for all orientations of the interplanetary magnetic field (IMF). Furthermore, little to no plasma depletion is seen during some periods with stable northward IMF. The consistently low value of plasma β, the ratio of plasma pressure to magnetic pressure, at the magnetopause associated with the low average upstream MA is believed to be the cause for the high average reconnection rate at Mercury, reported to be nearly 3 times that observed at Earth. Finally, a characteristic depletion length outward from the subsolar magnetopause of ~300 km is found for Mercury. This value scales among planetary bodies as the average standoff distance of the magnetopause.
Impact of tropospheric tides on the nitric oxide 5.3 μm infrared cooling of the low‐latitude thermosphere during solar minimum conditions
Authors: Oberheide J. , Mlynczak M. G. , Mosso C. N. , Schroeder B. M. , Funke B. , Maute A.
Published: October 2013

This paper explores the impact of diurnal tides that begin near the surface as heat is released by evaporation and condensation on Earth's upper atmosphere natural thermostat: the nitric oxide (NO) infrared cooling of the thermosphere at 5.3 μm. Equatorial NO volume emission rate measurements from 100 to 180 km made by Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) on TIMED during the solar minimum year 2008 are analyzed on two important nonmigrating tides, the DE2 and DE3 components. DE3 (DE2) amplitudes maximize around 125 km altitude and, depending on season, are on the order of 0.18 (0.16) nW/m3. This represents a substantial modulation of the mean NO emission that maximizes in the same altitude range with a value of about 0.8 nW/m3. Tropospheric tides are therefore important not only for the dynamics and electrodynamics of the ionosphere‐thermosphere system but also for modulating the thermospheric energy budget. Supporting photochemical tidal modeling indicates that the main tidal coupling mechanism is the temperature dependence of the collisional excitation of the NO (ν=1) vibrational state. However, the response to vertical tidal advection is also important. It is in‐phase with the response to temperature and contributes as much as 50% to the NO tides at and above the emission maximum. Neutral density tidal variations contribute about 25% but with a 9 h phase offset resulting in a net damping. These results imply that NO 5.3 μm emissions are a suitable proxy for studying tidal dynamics in the thermosphere where no global temperature measurements are available.
A simple model for spatial disaggregation of evaporative fraction: Comparative study with thermal sharpened land surface temperature data over India
Authors: Eswar R. , Sekhar M. , Bhattacharya B. K.
Published: October 2013

Evaporative fraction (EF) is a measure of the amount of available energy at the earth surface that is partitioned into latent heat flux. The currently operational thermal sensors like the Moderate Resolution Imaging Spectroradiometer (MODIS) on satellite platforms provide data only at 1000 m, which constraints the spatial resolution of EF estimates. A simple model (disaggregation of evaporative fraction (DEFrac)) based on the observed relationship between EF and the normalized difference vegetation index is proposed to spatially disaggregate EF. The DEFrac model was tested with EF estimated from the triangle method using 113 clear sky data sets from the MODIS sensor aboard Terra and Aqua satellites. Validation was done using the data at four micrometeorological tower sites across varied agro‐climatic zones possessing different land cover conditions in India using Bowen ratio energy balance method. The root‐mean‐square error (RMSE) of EF estimated at 1000 m resolution using the triangle method was 0.09 for all the four sites put together. The RMSE of DEFrac disaggregated EF was 0.09 for 250 m resolution. Two models of input disaggregation were also tried with thermal data sharpened using two thermal sharpening models DisTrad and TsHARP. The RMSE of disaggregated EF was 0.14 for both the input disaggregation models for 250 m resolution. Moreover, spatial analysis of disaggregation was performed using Landsat‐7 (Enhanced Thematic Mapper) ETM + data over four grids in India for contrasted seasons. It was observed that the DEFrac model performed better than the input disaggregation models under cropped conditions while they were marginally similar under non‐cropped conditions.
Neural networks to predict exosphere temperature corrections
Authors: Choury Anna , Bruinsma Sean , Schaeffer Philippe
Published: October 2013

Precise orbit prediction requires a forecast of the atmospheric drag force with a high degree of accuracy. Artificial neural networks are universal approximators derived from artificial intelligence and are widely used for prediction. This paper presents a method of artificial neural networking for prediction of the thermosphere density by forecasting exospheric temperature, which will be used by the semiempirical thermosphere Drag Temperature Model (DTM) currently developed. Artificial neural network has shown to be an effective and robust forecasting model for temperature prediction. The proposed model can be used for any mission from which temperature can be deduced accurately, i.e., it does not require specific training. Although the primary goal of the study was to create a model for 1 day ahead forecast, the proposed architecture has been generalized to 2 and 3 days prediction as well. The impact of artificial neural network predictions has been quantified for the low‐orbiting satellite Gravity Field and Steady‐State Ocean Circulation Explorer in 2011, and an order of magnitude smaller orbit errors were found when compared with orbits propagated using the thermosphere model DTM2009.
Differentiation of Hepatocytes from Pluripotent Stem Cells
Authors: Mallanna Sunil K. , Duncan Stephen A.
Published: October 2013

Differentiation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells into hepatocyte‐like cells provides a platform to study the molecular basis of human hepatocyte differentiation, to develop cell culture models of liver disease, and to potentially provide hepatocytes for treatment of end‐stage liver disease. Additionally, hepatocyte‐like cells generated from human pluripotent stem cells could serve as platforms for drug discovery, determination of pharmaceutical‐induced hepatotoxicity, and evaluation of idiosyncratic drug‐drug interactions. Here, we describe a step‐wise protocol previously developed in our laboratory that facilitates the highly efficient and reproducible differentiation of human pluripotent stem cells into hepatocyte‐like cells. Our protocol uses defined culture conditions and closely recapitulates key developmental events that are found to occur during hepatogenesis. Curr. Protoc. Stem Cell Biol. 26:1G.4.1‐1G.4.13. © 2013 by John Wiley & Sons, Inc.
25th Anniversary Article: The Evolution of Electronic Skin (E‐Skin): A Brief History, Design Considerations, and Recent Progress
Authors: Hammock Mallory L. , Chortos Alex , Tee Benjamin C.‐K. , Tok Jeffrey B.‐H. , Bao Zhenan
Published: October 2013

Human skin is a remarkable organ. It consists of an integrated, stretchable network of sensors that relay information about tactile and thermal stimuli to the brain, allowing us to maneuver within our environment safely and effectively. Interest in large‐area networks of electronic devices inspired by human skin is motivated by the promise of creating autonomous intelligent robots and biomimetic prosthetics, among other applications. The development of electronic networks comprised of flexible, stretchable, and robust devices that are compatible with large‐area implementation and integrated with multiple functionalities is a testament to the progress in developing an electronic skin (e‐skin) akin to human skin. E‐skins are already capable of providing augmented performance over their organic counterpart, both in superior spatial resolution and thermal sensitivity. They could be further improved through the incorporation of additional functionalities (e.g., chemical and biological sensing) and desired properties (e.g., biodegradability and self‐powering). Continued rapid progress in this area is promising for the development of a fully integrated e‐skin in the near future.
Profound Methyl Effects in Drug Discovery and a Call for New CH Methylation Reactions
Authors: Schönherr Heike , Cernak Tim
Published: October 2013

The methyl group is one of the most commonly occurring carbon fragments in small‐molecule drugs. This simplest alkyl fragment appears in more than 67 % of the top‐selling drugs of 2011 and can modulate both the biological and physical properties of a molecule. This Review focuses on so‐called magic methyl effects on binding potency, where the seemingly mundane change of CH to CMe improves the IC50 value of a drug candidate more than 100‐fold. This discussion is followed by a survey of recent advances in synthetic chemistry that allow the direct methylation of C(sp2)H and C(sp3)H bonds. It is our hope that the relevance of the meager methyl group to drug discovery as presented herein will inspire reports on new CH methylation reactions.
A fundamental analysis of dynamics of waste biodegradation in aerobic processes
Authors: Ajbar AbdelHamid , AlZeghayer Youssef
Published: October 2013

This paper studies the static and dynamic behavior of a biological wastewater treatment process consisting of an aerobic bioreactor and a settler. The process is described by a three‐variable model that takes explicitly into account the mass balance of oxygen. The analysis is carried out for the general case where the biomass specific growth rate is assumed to depend arbitrarily on substrate, biomass, and oxygen. The biomass yield coefficient is also assumed to depend arbitrarily on the substrate. General conditions describing the behavior of the model are derived. The general analysis is applied to an experimentally validated model where the specific growth rate depends on substrate and oxygen following a multiplicative Monod form. Practical diagrams are constructed that delineate the effect of various operating parameters on the performance of the biodegradation. The model is also studied for the case of a variable yield coefficient. The analysis shows the existence of a periodic behavior for some range of model parameters. The results of the paper allowed a useful understanding of the dynamics of the aerobic biodegradation including the effect of operating parameters, the specific growth rate, and the biomass yield coefficient on the existence of instabilities in the process. © 2013 Curtin University of Technology and John Wiley & Sons, Ltd.
Microbial polysaccharide‐based membranes: Current and future applications
Authors: Freitas Filomena , Alves Vítor D. , Reis Maria A. , Crespo João G. , Coelhoso Isabel M.
Published: October 2013

Microbial polysaccharides are characterized by high molecular structure variability which translates into a wide range of different properties offering interesting opportunities for application in many different areas, including membrane‐based products and processes. Due to their new or improved properties, microbial polysaccharides can replace plant, algae, and animal products, either in their traditional or in new applications. The main constraint to their wider use is the production costs that are still higher than that of other natural and synthetic polymers. The current applications of microbial polysaccharide membranes in medical, food, and industrial processes are outlined. The limitations still faced by these membranes and the requirements for obtaining innovative products and processes are also addressed. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 40047.
Improvement in Social Deficits in Autism Spectrum Disorders Using a Theatre‐Based, Peer‐Mediated Intervention
Authors: Corbett Blythe A. , Swain Deanna M. , Coke Catherine , Simon David , Newsom Cassandra , Houchins‐Juarez Nea , Jenson Ashley , Wang Lily , Song Yanna
Published: October 2013

Social Emotional NeuroScience Endocrinology Theatre is a novel intervention program aimed at improving reciprocal social interaction in youth with autism spectrum disorder (ASD) using behavioral strategies and theatrical techniques in a peer‐mediated model. Previous research using a 3‐month model showed improvement in face perception, social interaction, and reductions in stress. The current study assessed a 2‐week summer camp model. Typically developing peers were trained and paired with ASD youth (8–17 years). Social perception and interaction skills were measured before and after treatment using neuropsychological and parental measures. Behavioral coding by reliable, independent raters was conducted within the treatment context (theatre) and outside the setting (playground). Salivary cortisol levels to assess physiological arousal were measured across contexts (home, theatre, and playground). A pretest–posttest design for within‐group comparisons was used, and prespecified pairwise comparisons were achieved using a nonparametric Wilcoxon signed‐rank test. Significant differences were observed in face processing, social awareness, and social cognition (P < 0.05). Duration of interaction with familiar peers increased significantly over the course of treatment (P < 0.05), while engagement with novel peers outside the treatment setting remained stable. Cortisol levels rose on the first day of camp compared with home values yet declined by the end of treatment and further reduced during posttreatment play with peers. Results corroborate previous findings that the peer‐mediated theatre program contributes to improvement in core social deficits in ASD using a short‐term, summer camp treatment model. Future studies will explore treatment length and peer familiarity to optimize and generalize gains. Autism Res 2014,7: 4–16. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Genetic Effects on Cerebellar Structure Across Mouse Models of Autism Using a Magnetic Resonance Imaging Atlas
Authors: Steadman Patrick E. , Ellegood Jacob , Szulc Kamila U. , Turnbull Daniel H. , Joyner Alexandra L. , Henkelman R. Mark , Lerch Jason P.
Published: October 2013

Magnetic resonance imaging (MRI) of autism populations is confounded by the inherent heterogeneity in the individuals' genetics and environment, two factors difficult to control for. Imaging genetic animal models that recapitulate a mutation associated with autism quantify the impact of genetics on brain morphology and mitigate the confounding factors in human studies. Here, we used MRI to image three genetic mouse models with single mutations implicated in autism: Neuroligin‐3 R451C knock‐in, Methyl‐CpG binding protein‐2 (MECP2) 308‐truncation and integrin β3 homozygous knockout. This study identified the morphological differences specific to the cerebellum, a structure repeatedly linked to autism in human neuroimaging and postmortem studies. To accomplish a comparative analysis, a segmented cerebellum template was created and used to segment each study image. This template delineated 39 different cerebellar structures. For Neuroligin‐3 R451C male mutants, the gray (effect size (ES) = 1.94, FDR q = 0.03) and white (ES = 1.84, q = 0.037) matter of crus II lobule and the gray matter of the paraflocculus (ES = 1.45, q = 0.045) were larger in volume. The MECP2 mutant mice had cerebellar volume changes that increased in scope depending on the genotype: hemizygous males to homozygous females. The integrin β3 mutant mouse had a drastically smaller cerebellum than controls with 28 out of 39 cerebellar structures smaller. These imaging results are discussed in relation to repetitive behaviors, sociability, and learning in the context of autism. This work further illuminates the cerebellum's role in autism. Autism Res 2014, 7: 124–137. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Population‐based meta‐analysis of furosemide pharmacokinetics
Authors: Van Wart Scott A. , Shoaf Susan E. , Mallikaarjun Suresh , Mager Donald E.
Published: October 2013

Furosemide is a loop diuretic frequently used to treat fluid overload conditions such as hepatic cirrhosis and congestive heart failure (CHF). A population‐based meta‐analysis approach in NONMEM® was used to develop a PK model characterizing the time‐course of furosemide in plasma and excretion into the urine for healthy subjects and fluid overload patients. Furosemide PK data from healthy subjects receiving 80 mg of oral furosemide were supplemented with additional individual and aggregate plasma concentration and urinary excretion versus time data from the literature after intravenous (i.v.) or oral furosemide administration (10–500 mg) to healthy subjects or fluid overload patients. A three‐compartment model with zero‐order input following i.v. administration (or first‐order absorption using a Weibull function after oral administration) and first‐order elimination best described furosemide PK. A covariate analysis identified creatinine clearance (CLCR) as a statistically significant predictor of renal clearance (CLR), with a population mean CLR of 4.67, 3.11, 1.95 and 1.17 l/h for a subject with normal renal function (CLCR = 120 ml/min) or mild (CLCR = 80 ml/min), moderate (CLCR = 50 ml/min) or severe (CLCR = 30 ml/min) renal impairment. Oral bioavailability was 59.1% and non‐renal clearance was 2.02 l/h. A PC‐VPC and other model diagnostics demonstrated that the population PK model can reasonably predict the rate of urinary furosemide excretion over time using dosing history and commonly available demographic data, allowing for convenient assessment of PK‐PD relationships for furosemide when given alone or in combination with other agents used to treat fluid overload conditions. Copyright © 2013 John Wiley & Sons, Ltd.
The Use and Acceptance of Other Scientifically Relevant Information (OSRI) in the U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program
Authors: Bishop Patricia L. , Willett Catherine E.
Published: October 2013

The U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program (EDSP) currently relies on an initial screening battery (Tier 1) consisting of five in vitro and six in vivo assays to evaluate a chemical's potential to interact with the endocrine system. Chemical companies may request test waivers based on Other Scientifically Relevant Information (OSRI) that is functionally equivalent to data gathered in the screening battery or that provides information on a potential endocrine effect. Respondents for 47 of the first 67 chemicals evaluated in the EDSP submitted OSRI in lieu of some or all Tier 1 tests, seeking 412 waivers, of which EPA granted only 93. For 20 of the 47 chemicals, EPA denied all OSRI and required the entire Tier 1 battery. Often, the OSRI accepted was either identical to data generated by the Tier 1 assay or indicated a positive result. Although identified as potential sources of OSRI in EPA guidance, Part 158 guideline studies for pesticide registration were seldom accepted by EPA. The 93 waivers reduced animal use by at least 3325 animals. We estimate 27,731 animals were used in the actual Tier 1 tests, with additional animals being used in preparation for testing. Even with EPA's shift toward applying 21st‐century toxicology tools to screening of endocrine disruptors in the future, acceptance of OSRI will remain a primary means for avoiding duplicative testing and reducing use of animals in the EDSP. Therefore, it is essential that EPA develop a consistent and transparent basis for accepting OSRI.
Nucleus of the solitary tract in the C57BL/6J mouse: Subnuclear parcellation, chorda tympani nerve projections, and brainstem connections
Authors: Ganchrow Donald , Ganchrow Judith R. , Cicchini Vanessa , Bartel Dianna L. , Kaufman Daniel , Girard David , Whitehead Mark C.
Published: October 2013

The nucleus of the solitary tract (NST) processes gustatory and related somatosensory information rostrally and general viscerosensory information caudally. To compare its connections with those of other rodents, this study in the C57BL/6J mouse provides a subnuclear cytoarchitectonic parcellation (Nissl stain) of the NST into rostral, intermediate, and caudal divisions. Subnuclei are further characterized by NADPH staining and P2X2 immunoreactivity (IR). Cholera toxin subunit B (CTb) labeling revealed those NST subnuclei receiving chorda tympani nerve (CT) afferents, those connecting with the parabrachial nucleus (PBN) and reticular formation (RF), and those interconnecting NST subnuclei. CT terminals are densest in the rostral central (RC) and medial (M) subnuclei; less dense in the rostral lateral (RL) subnucleus; and sparse in the ventral (V), ventral lateral (VL), and central lateral (CL) subnuclei. CTb injection into the PBN retrogradely labels cells in the aforementioned subnuclei; RC and M providing the largest source of PBN projection neurons. Pontine efferent axons terminate mainly in V and rostral medial (RM) subnuclei. CTb injection into the medullary RF labels cells and axonal endings predominantly in V at rostral and intermediate NST levels. Small CTb injections within the NST label extensive projections from the rostral division to caudal subnuclei. Projections from the caudal division primarily interconnect subnuclei confined to the caudal division of the NST; they also connect with the area postrema. P2X2‐IR identifies probable vagal nerve terminals in the central (Ce) subnucleus in the intermediate/caudal NST. Ce also shows intense NADPH staining and does not project to the PBN. J. Comp. Neurol. 522:1565–1596, 2014. © 2013 Wiley Periodicals, Inc.
Paramagnetic Relaxation of Long‐Lived Coherences in Solution NMR
Authors: Singh Maninder , Srinivas Chinthalapalli , Deb Mayukh , Kurur Narayanan D.
Published: October 2013

Long‐lived coherences (LLCs) are known to have lifetimes much longer than transverse magnetization or single quantum coherences (SQCs). The effect of paramagnetic ions on the relaxation of LLCs is not known. This is particularly important, as LLCs have potential applications in various fields like analytical NMR, in vivo NMR and MR imaging methods. We study here the behaviour of LLCs in the presence of paramagnetic relaxation agents. The stepwise increase in the concentration of the metal ion is followed by measuring various relaxation rates. The effect of paramagnetic ions is analysed in terms of the external random field’s contribution to the relaxation of two coupled protons in 2,3,6‐trichlorobenzaldehyde. The LLCs relax faster than ordinary SQCs in the presence of paramagnetic ions of varying character. This is explained on the basis of an increase in the contribution of the external random field to relaxation due to a paramagnetic relaxation mechanism. Comparison is also made with ordinary Zeeman relaxation rates like R1, R2, R1ρ and also with rate of relaxation of long‐lived states RLLS which are known to be less sensitive to paramagnetically induced relaxation. Also, the extent of correlation of random fields at two proton sites is studied and is found to be strongly correlated with each other. The obtained correlation constant is found to be independent of the nature of added paramagnetic impurities.
Exploring Pathways for Activation of Carbon Monoxide by Palladium Iminophosphines
Authors: Kuganathan Navaratnarajah , Veal Edward , Green Malcolm L. H. , Green Jennifer C. , Pascu Sofia I.
Published: October 2013

DFT calculations on palladium(II) methyl complexes incorporating P/N ligands demonstrate that CO activation in the presence of competing ligands, such as CH3CN or C2H4, occurs through an associative mechanism involving CO/ligand exchange, followed by migratory insertion of CO into the PdMe bond. Recent investigations into the PdII coordination of CO and C2H4 and their subsequent insertion into the PdMe bonds of complexes of the type [PdMe(iminophosphine)(NCMe)]+ are reported.
Applications of 2‐C‐Formyl‐Glycals in Organic Synthesis
Authors: Ramesh Namakkal G.
Published: October 2013

The chemistry of 2‐C‐formyl‐glycals has witnessed tremendous growth over the last two decades. Functionalized compounds derived from 2‐C‐formyl‐glycals have found applications in organic synthesis, carbohydrate chemistry, medicinal chemistry, supramolecular chemistry, and materials chemistry. These advancements can be mainly attributed to the availability of a very simple and general procedure for the direct formylation of glycals by using the Vilsmeier–Haack reaction. The highly conjugated α,β‐unsaturated carbonyl functional group present in 2‐C‐formyl‐glycals provides opportunities for synthetic elaboration, which can lead to a variety of natural and unnatural compounds for varied applications. This review summarizes the recent developments in the synthesis and applications of these versatile chiral intermediates.
Effective delivery of large genes to the retina by dual AAV vectors
Authors: Trapani Ivana , Colella Pasqualina , Sommella Andrea , Iodice Carolina , Cesi Giulia , de Simone Sonia , Marrocco Elena , Rossi Settimio , Giunti Massimo , Palfi Arpad , Farrar Gwyneth J , Polishchuk Roman , Auricchio Alberto
Published: October 2013

Retinal gene therapy with adeno‐associated viral (AAV) vectors is safe and effective in humans. However, AAV's limited cargo capacity prevents its application to therapies of inherited retinal diseases due to mutations of genes over 5 kb, like Stargardt's disease (STGD) and Usher syndrome type IB (USH1B). Previous methods based on ‘forced’ packaging of large genes into AAV capsids may not be easily translated to the clinic due to the generation of genomes of heterogeneous size which raise safety concerns. Taking advantage of AAV's ability to concatemerize, we generated dual AAV vectors which reconstitute a large gene by either splicing (trans‐splicing), homologous recombination (overlapping), or a combination of the two (hybrid). We found that dual trans‐splicing and hybrid vectors transduce efficiently mouse and pig photoreceptors to levels that, albeit lower than those achieved with a single AAV, resulted in significant improvement of the retinal phenotype of mouse models of STGD and USH1B. Thus, dual AAV trans‐splicing or hybrid vectors are an attractive strategy for gene therapy of retinal diseases that require delivery of large genes.
Comparative study on nutrient composition, phytochemical, and functional characteristics of raw, germinated, and fermented Moringa oleifera seed flour
Authors: Ijarotimi Oluwole S. , Adeoti Oluwole A. , Ariyo Oluwaseun
Published: October 2013

Moringa oleifera seeds were processed as raw M. oleifera (RMO), germinated M. oleifera (GMO), and fermented M. oleifera (FMO), and were evaluated for proximate, minerals, amino acids, fatty acids, phytochemicals/antinutrients, and functional properties. Protein content of GMO (23.69 ± 0.11 g/100 g) was higher than FMO (21.15 ± 0.08 g/100 g) and that of RMO (18.86 ± 0.09 g/100 g) (P < 0.05), respectively. Energy value of FMO (465.32 ± 0.48 kcal) was higher than GMO (438.62 ± 0.12 kcal) and that of RMO (409.04 ± 1.61 kcal), respectively. Mineral contents in GMO were significantly higher in iron, sodium, potassium, magnesium, and copper, while FMO were higher in calcium, phosphorus, and magnesium, and both were significantly lower than those in RMO (P < 0.05). Total essential amino acids (TEAAs) in FMO (31.07 mg/g crude protein) were higher than in GMO (26.52 mg/g crude protein), and were higher than that in RMO (23.56 mg/g crude protein). Linoleic acid (58.79 ± 0.02–62.05 ± 0.01 g/100 g) and behenic acid (0.13 ± 0.00–0.20 ± 0.06 g/100 g) were the predominant and least fatty acids, respectively. Phytochemical/antinutrient compositions in FMO samples were significantly lower than GMO, and both were significantly lower when compared with RMO samples (P < 0.05). The bulk density (pack and loose), foaming capacity, swelling capacity, and water absorption capacity (WAC) of FMO were significantly higher than those of GMO, and there was no significant difference between GMO and RMO samples. The study established that fermentation processing methods increased the protein content, essential amino acid, and polyunsaturated fatty acid profiles, and reduced antinutrient compositions of M. oleifera seed than germination processing techniques; hence, fermentation techniques should be encouraged in processing moringa seeds in food processing.
Retrieval study at 623 human mesh explants made of polypropylene – impact of mesh class and indication for mesh removal on tissue reaction
Authors: Klosterhalfen B. , Klinge U.
Published: October 2013

Textile meshes frequently are implanted in the abdominal wall to reinforce a hernia repair. However, revisions for mesh associated complications confirm that these devices are not completely free of risk. Explanted devices offer an opportunity to define the impact of mesh structure on tissue response. This retrieval study analyses the tissue reaction to 623 polypropylene mesh samples (170 class 1 with large pores, and 453 class 2 with small pores) explanted for pain, infection, or recurrence. Histopathological assessment included morphometry of inflammatory infiltrate (IF) and connective tissue (CT), and of collagen 1/3 ratio. Half of the meshes were removed after more than 23 month. Despite large inter‐individual differences removal for infection showed more IF than for pain or recurrence with significant correlation of IF with CT. Class 1 meshes with large pores showed less IF, CT, fistula formation, calcification, and bridging than class 2 meshes with small pores. Meshes removed for recurrence showed a lowered collagen 1/3 ratio in 70%. Large pore class 1 meshes showed an improved tissue response and may be considered as favorable to prevent inflammatory side effects. The presence of lowered collagen 1/3 ratio in most of the samples with recurrences stresses the relevance of an intact healing process. Late manifestation of complications demands long‐lasting follow‐up. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 101B: 1393–1399, 2013.
Biocompatibility and preclinical feasibility tests of a temperature‐sensitive hydrogel for the purpose of surgical wound pain control and cartilage repair
Authors: Seol Dongrim , Magnetta Michael J. , Ramakrishnan Prem S. , Kurriger Gail L. , Choe Hyeonghun , Jang Keewoong , Martin James A. , Lim Tae‐Hong
Published: October 2013

We recently introduced a novel pluronic F127 and hyaluronic acid‐based hydrogel (HG) designed to deliver a broad range of therapeutics. The reverse‐thermal responsive HG exhibits physical properties that seem to be ideal for the local delivery of drug‐ and cell‐based therapies to specific anatomic sites through percutaneous injection. However, questions related to the HG's safety and efficacy must first be addressed. To address these issues, we performed standard in vitro cytotoxicity and drug release tests and in vivo biocompatibility tests in a rat model. In addition, we determined whether the HG was an effective stem cell carrier in a rat cartilage defect model. We found that the HG showed viability and biocompatibility levels similar to those reported for F127 or hyaluronic acid alone. In vitro drug release studies with bupivacaine, a drug used clinically for local pain relief, revealed that after an initial burst bupivacaine was released continuously for 10 days. Stem cells loaded in the HG were retained in situ and stimulated cartilage regeneration in experimental defects. Taken as a whole, these findings support further efforts to develop the HG as a versatile system for the delivery of a wide range of therapeutic agents in humans. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 101B: 1508–1515, 2013.
Multi‐level quantum monte Carlo wave functions for complex reactions: The decomposition of α‐hydroxy‐dimethylnitrosamine
Authors: Fracchia Francesco , Filippi Claudia , Amovilli Claudio
Published: October 2013

We present here several novel features of our recently proposed Jastrow linear generalized valence bond (J‐LGVB) wave functions, which allow a consistently accurate description of complex potential energy surfaces (PES) of medium‐large systems within quantum Monte Carlo (QMC). In particular, we develop a multilevel scheme to treat different regions of the molecule at different levels of the theory. As prototypical study case, we investigate the decomposition of α‐hydroxy‐dimethylnitrosamine, a carcinogenic metabolite of dimethylnitrosamine (NDMA), through a two‐step mechanism of isomerization followed by a retro‐ene reaction. We compute a reliable reaction path with the quadratic configuration interaction method and employ QMC for the calculation of the electronic energies. We show that the use of multideterminantal wave functions is very important to correctly describe the critical points of this PES within QMC, and that our multilevel J‐LGVB approach is an effective tool to significantly reduce the cost of QMC calculations without loss of accuracy. As regards the complex PES of α‐hydroxy‐dimethylnitrosamine, the accurate energies computed with our approach allows us to confirm the validity of the two‐step reaction mechanism of decomposition originally proposed within density functional theory, but with some important differences in the barrier heights of the individual steps. © 2013 Wiley Periodicals, Inc.
Randomized, placebo‐controlled study to assess the impact on QT/QTc interval of supratherapeutic doses of ceftazidime–avibactam or ceftaroline fosamil–avibactam
Authors: Das Shampa , Armstrong Jon , Mathews David , Li Jianguo , Edeki Timi
Published: October 2013

Potential effects of supratherapeutic doses of intravenous (IV) ceftazidime–avibactam and ceftaroline fosamil–avibactam on cardiac repolarization were assessed in a thorough QT/QTc study. This was a double‐blind, randomized, placebo‐controlled, four‐period crossover Phase I study (NCT01290900) in healthy males (n = 51). Subjects received, in randomized order and separated by ≥3 days washout: single doses of IV ceftaroline fosamil 1,500 mg with avibactam 2,000 mg; IV ceftazidime 3,000 mg with avibactam 2,000 mg; oral moxifloxacin 400 mg (open‐label positive control); and IV placebo (saline). Least square mean and two‐sided 90% confidence intervals (CI) for change from baseline in Fridericia‐corrected QT interval (ΔQTcF) for active treatments versus placebo were estimated at 10 time points over 24 hours. The upper bound of the two‐sided 90% CI for placebo‐corrected ΔQTcF did not exceed 10 milliseconds at any time point over 24 hours for ceftaroline fosamil–avibactam or ceftazidime–avibactam. The lower bound of the two‐sided 90% CI for the difference between moxifloxacin and placebo in ΔQTcF over 1–4 hours was >5 milliseconds, confirming assay sensitivity. Pharmacokinetics results confirmed achievement of supratherapeutic plasma concentrations. No safety concerns were raised. In conclusion, supratherapeutic doses of ceftaroline fosamil–avibactam or ceftazidime–avibactam were not associated with QT/QTc prolongation in this study population.
Prenatal diagnosis of robinow syndrome: A case report
Authors: Castro Simon , Peraza Efren , Barraza Astrid , Zapata Marco
Published: October 2013

Robinow syndrome, also known as fetal face syndrome, is a rare genetically heterogeneous condition characterized mainly by mesomelic limb shortening, facial malformations, and genital abnormalities. This report describes the sonographic findings in a case of autosomal‐dominant Robinow syndrome diagnosed at 23.1 weeks' gestation, in a patient with no history of affected relatives. Here we describe the sonographic characteristics of this syndrome from the diagnosis until birth. The prenatal and postnatal findings, the differential diagnosis, and the prognosis of patients with this syndrome are discussed. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound, 42:297–300, 2014
Ultrasound‐guided thrombin injection in the treatment of iatrogenic arterial pseudoaneurysms: Single‐center experience
Authors: Kleczynski Paweł , Rakowski Tomasz , Dziewierz Artur , Jakala Jacek , Dudek Dariusz
Published: October 2013

The aim of this study was to assess the safety and efficacy of ultrasound‐guided percutaneous thrombin injection for the treatment of postcatheterization arterial pseudoaneurysms. We evaluated retrospectively 82 consecutive subjects treated with percutaneous ultrasound‐guided thrombin injection of postcatheterization femoral (n = 79), brachial (n = 2), and radial (n = 1) pseudoaneurysms from January 2006 to April 2012. Pseudoaneurysm size, thrombin dose, and therapy outcome were documented. All pseudoaneurysm sacs were thrombosed with a single injection. The overall primary success rate (complete sac thrombosis) was 92.7%. A 30‐day Doppler ultrasound follow‐up showed a 100% procedural success. There were no complications. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound 42:24–26, 2014
A Complementary Synthetic Approach to Fluorazone
Authors: Calvert Matthew B. , Sperry Jonathan
Published: October 2013

Pyrrole undergoes a regioselective zinc‐mediated acylation with 2‐bromobenzoyl chloride followed by a Cu‐catalyzed N‐arylation under microwave irradiation, delivering the important heteroaromatic of fluorazone.
Core/Shell Polymer Particles by Semibatch Combined Suspension/Emulsion Polymerizations for Enzyme Immobilization
Authors: Besteti Marina D. , Cunha Aline G. , Freire Denise M. G. , Pinto José Carlos
Published: October 2013

Semibatch combined suspension–emulsion polymerizations are performed for production of polymer supports to be used for immobilization of lipase B from Candida antarctica (CALB), using styrene, methyl methacrylate, and cardanol as monomers. It is shown that the obtained polymer particles present the characteristic core–shell particle structure, with specific areas and average pore sizes that are comparable to values presented by Accurel MP 1000. It is also shown that the produced particles can be used successfully for immobilization of CALB, leading to immobilization efficiencies and enzyme activities that are better than the ones obtained with Accurel MP 1000.
Radical Thiol‐yne Chemistry on Diphenylacetylene: Selective and Quantitative Addition Enabling the Synthesis of Hyperbranched Poly(vinyl sulfide)s
Authors: Pötzsch Robert , Komber Hartmut , Stahl Brian C. , Hawker Craig J. , Voit Brigitte I.
Published: October 2013

A powerful variation of traditional radical thiol‐yne reaction with diphenylacetylene (DPA)‐based starting materials leading to the quantitative and selective formation of the corresponding vinyl sulfides is reported. A variety of different thiols are shown to undergo reaction with DPA and the influence of their structure on reactivity is studied. The results obtained from the model reactions are then used to guide the efficient synthesis of hyperbranched poly(vinyl sulfide) (hb‐PVS) systems by employing a dithiol and a trialkyne in an A2 + B3 approach. The polymers obtained show excellent solubility in common organic solvents and exhibit high refractive indices (e.g., 1.70 at 589 nm). The combined ease of processability and potential for cross‐linking make these materials very interesting for applications, such as coatings for optical devices. The selective mono‐addition thiol‐yne reaction on DPA serves not only as a synthetic method for the preparation of PVS but could also be applied to the general modification of acetylene‐containing materials.

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Reproducibility of phase rotation STEAM at 3T: Focus on glutathione
Authors: Wijtenburg S. Andrea , Gaston Frank E. , Spieker Elena A. , Korenic Stephanie A. , Kochunov Peter , Hong L. Elliot , Rowland Laura M.
Published: October 2013

Purpose

The purpose of this study was to determine the reproducibility of a very short echo time (TE) phase rotation stimulated echo acquisition mode (STEAM) sequence at 3T with a focus on the detection of glutathione.

Methods

Ten healthy subjects were scanned on two separate visits. Spectra were acquired from voxels placed in the anterior and posterior cingulates. Reproducibility was assessed using mean coefficients of variation (CVs) and mean absolute differences (ADs), and reliability was assessed using standard error of measurement (SEM) and intraclass correlations (ICCs). Phantoms containing glutathione and metabolites with overlapping resonances were scanned to test the validity of glutathione quantification.

Results

Excellent reproducibility as illustrated by CVs ≤8.3% and ADs ≤11.6% for both regions was obtained for glutathione and other commonly reported metabolites. Reproducibility measures for γ‐aminobutyric acid and glutamine were good overall with CVs ranging from 6.4%–10.5% and ADs ranging from 8.6%–15.5% for both regions. Glutathione absolute and relative reliability were very good (SEMs ≤9.9%) and fair (ICCs = 0.42–0.51), respectively. Phantom studies demonstrated the ability to accurately detect glutathione from other metabolites with overlapping resonances with great precision (R2 = 0.99).

Conclusion

A very short TE phase rotation STEAM sequence proved reproducible for metabolites difficult to quantify but important for the study of psychiatric and neurological illness. Magn Reson Med 72:603–609, 2014. © 2013 Wiley Periodicals, Inc.
Navigator artifact reduction in three‐dimensional late gadolinium enhancement imaging of the atria
Authors: Keegan Jennifer , Drivas Peter , Firmin David N.
Published: October 2013

Purpose

Navigator‐gated three‐dimensional (3D) late gadolinium enhancement (LGE) imaging demonstrates scarring following ablation of atrial fibrillation. An artifact originating from the slice‐selective navigator‐restore pulse is frequently present in the right pulmonary veins (PVs), obscuring the walls and making quantification of enhancement difficult. We describe a simple sequence modification to greatly reduce or remove this artifact.

Methods

A navigator‐gated inversion‐prepared gradient echo sequence was modified so that the slice‐selective navigator‐restore pulse was delayed in time from the nonselective preparation (NAV‐restore‐delayed). Both NAV‐restore‐delayed and conventional 3D LGE acquisitions were performed in 11 patients and the results compared.

Results

One patient was excluded due to severe respiratory motion artifact in both NAV‐restore‐delayed and conventional acquisitions. Moderate to severe artifact was present in 9 of the remaining 10 patients using the conventional sequence and was considerably reduced when using the NAV‐restore‐delayed sequence (ostial PV to blood pool ratio, 1.7 ± 0.5 versus 1.1 ± 0.2, respectively [P < 0.0001]; qualitative artifact scores, 2.8 ± 1.1 versus 1.2 ± 0.4, respectively [P < 0.001]). While navigator signal‐to‐noise ratio was reduced with the NAV‐restore‐delayed sequence, respiratory motion compensation was unaffected.

Conclusions

Shifting the navigator‐restore pulse significantly reduces or eliminates navigator artifact. This simple modification improves the quality of 3D LGE imaging and potentially aids late enhancement quantification in the atria. Magn Reson Med 72:779–785, 2014. © 2013 Wiley Periodicals, Inc.