bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of point mutations and large intragenic deletions in Fanconi anemia using next‐generation sequencing technology
Authors: Nicchia Elena , Greco Chiara , De Rocco Daniela , Pecile Vanna , D'Eustacchio Angela , Cappelli Enrico , Corti Paola , Marra Nicoletta , Ramenghi Ugo , Pillon Marta , Farruggia Piero , Dufour Carlo , Pallavicini Alberto , Torelli Lucio , Savoia Anna
Published: July 2015

Fanconi anemia (FA) is a rare bone marrow failure disorder characterized by clinical and genetic heterogeneity with at least 17 genes involved, which make molecular diagnosis complex and time‐consuming. Since next‐generation sequencing technologies could greatly improve the genetic testing in FA, we sequenced DNA samples with known and unknown mutant alleles using the Ion PGM™ system (IPGM). The molecular target of 74.2 kb in size covered 96% of the FA‐coding exons and their flanking regions. Quality control testing revealed high coverage. Comparing the IPGM and Sanger sequencing output of FANCA, FANCC, and FANCG we found no false‐positive and a few false‐negative variants, which led to high sensitivity (95.58%) and specificity (100%) at least for these two most frequently mutated genes. The analysis also identified novel mutant alleles, including those in rare complementation groups FANCF and FANCL. Moreover, quantitative evaluation allowed us to characterize large intragenic deletions of FANCA and FANCD2, suggesting that IPGM is suitable for identification of not only point mutations but also copy number variations.
Chimeric groin free flaps: Design and clinical application
Authors: Chao Wai‐Nang , Wang Po‐Hui , Chen Bing‐Ren , Chen Shiuan‐Chih
Published: July 2015

Background

Reconstruction of composite extremity defects or through‐and‐through oral defects remains challenging for surgeons. Chimeric flaps are ideal for repairing these lesions. In this article, we report the design of various chimeric groin free flaps for the reconstruction of both complex oral and extremity defects in 18 patients.

Methods

Between 2010 and 2014, 18 patients with composite tissue defect or two defects in the extremities or head and neck region, underwent reconstruction with cutaneous–cutaneous, musculo‐cutaneous, or osteo‐cutaneous chimeric groin free flaps. The size and pedicles length of the chimeric groin flaps based on the superficial circumflex iliac artery (SCIA) were tailored to the lesions. Patient‐reported post‐operative outcomes at the out‐patient department were evaluated.

Results

The types of chimeric groin free flaps included cutaneous–cutaneous (n = 12), musculo‐cutaneous (n = 1), and osteo‐cutaneous (n = 5) flaps. Three to four SCIA branches (mean: 3.33) could be used for flap design. The cutaneous flap size ranged from 1.5 cm × 6 cm to 11 cm × 30 cm, and the bone flap size ranged from 1 cm × 1.5 cm to 2.5 cm × 6 cm. All flaps survived, and no significant complications developed at recipient or donor sites. Functional recovery after reconstruction was satisfactory in most patients after a mean of 17.27 months (ranging 2–42 months) of follow‐up.

Conclusion

The innovative flap technique presented herein has advantages including greater reliability, as well as the ability to tailor the dimensions and flap paddles to specific lesions and reconstruct two defects or one composite defect using only one (chimeric) flap. © 2015 Wiley Periodicals, Inc. Microsurgery 36:206–215, 2016.
Flow‐through omental flap to free anterolateral thigh flap for complex chest wall reconstruction: Case report and review of the literature
Authors: Luan Anna , Galvez Michael G. , Lee Gordon K.
Published: July 2015

Despite the options currently available for chest wall reconstruction, patients with complex composite defects may still pose a significant challenge for the reconstructive surgeon when only using conventional methods. In particular, prior radiotherapy and/or large en bloc resection may leave inadequate regional flaps and recipient vessels for free tissue transfer. Here, we describe a case in which we reconstruct a 14 cm × 18 cm complex chest wall defect, secondary to tumor resection and infected sternum debridement, with a pedicled flow‐through omental flap to a 14 cm × 22 cm free anterolateral thigh flap using the omental gastroepiploic vessels as recipient vessels. Reconstruction was successful with excellent flap viability, and no complications at recipient or donor sites. We review the literature on complex chest wall reconstruction and introduce this valuable option of utilizing a pedicled omental flap as a flow‐through flap to a free flap for patients without viable recipient vessels or local flaps. © 2015 Wiley Periodicals, Inc. Microsurgery 36:70–76, 2016.
Volume of interest‐based fourier transform method for calculation of static magnetic field maps from susceptibility distributions
Authors: Dewal Rahul P. , Yang Qing X.
Published: July 2015

Purpose

Calculation of static magnetic field (B0) inhomogeneity maps of high‐resolution susceptibility models by means of convolution with dipole kernels often encounters limitations in computer memory (RAM) for large input data matrices. In many applications, only a small portion of the full volume of the computer model is a volume of interest (VOI) or a susceptibility perturbation source. This work presents a VOI‐based method to significantly reduce the computer memory usage for such applications.

Theory and Methods

The VOI‐based method is presented and compared with the conventional method for calculation of the B0 field in the brain and heart of a human body model in terms of calculation speed, memory requirement, and calculation error relative to the full model results.

Results

Use of the VOI‐based method significantly reduced memory usage in the human body model calculations over the conventional method without loss of accuracy and with comparable calculation speed.

Conclusion

The proposed method can be valuable for rapid calculation of B0 distributions on standard computer hardware for applications such as subject‐specific B0 field calculations derived from anatomic scans. Magn Reson Med 75:2473–2480, 2016. © 2015 Wiley Periodicals, Inc.
Analysis of mcDESPOT‐ and CPMG‐derived parameter estimates for two‐component nonexchanging systems
Authors: Bouhrara Mustapha , Reiter David A. , Celik Hasan , Fishbein Kenneth W. , Kijowski Richard , Spencer Richard G.
Published: July 2015

Purpose

To compare the reliability and stability of the multicomponent‐driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) and Carl‐Purcell‐Meiboom‐Gill (CPMG) approaches to parameter estimation.

Methods

The stability and reliability of mcDESPOT and CPMG‐derived parameter estimates were compared through examination of energy surfaces, evaluation of model sloppiness, and Monte Carlo simulations. Comparisons were performed on an equal time basis and assuming a two‐component system. Parameter estimation bias, reflecting accuracy, and dispersion, reflecting precision, were derived for a range of signal‐to‐noise ratios (SNRs) and relaxation parameters.

Results

The energy surfaces for parameters incorporated into the mcDESPOT signal model exhibit flatness, a complex structure of local minima, and instability to noise to a much greater extent than the corresponding surfaces for CPMG. Although both mcDESPOT and CPMG performed well at high SNR, the CPMG approach yielded parameter estimates of considerably greater accuracy and precision at lower SNR.

Conclusion

mcDESPOT and CPMG both permit high‐quality parameter estimates under SNR that are clinically achievable under many circumstances, depending upon available hardware and resolution and acquisition time constraints. At moderate to high SNR, the mcDESPOT approach incorporating two‐step phase increments can yield accurate parameter estimates while providing values for longitudinal relaxation times that are not available through CPMG. However, at low SNR, the CPMG approach is more stable and provides superior parameter estimates. Magn Reson Med 75:2406–2420, 2016. © 2015 Wiley Periodicals, Inc.
Parallel transmission pulse design with explicit control for the specific absorption rate in the presence of radiofrequency errors
Authors: Martin Adrian , Schiavi Emanuele , Eryaman Yigitcan , Herraiz Joaquin L. , Gagoski Borjan , Adalsteinsson Elfar , Wald Lawrence L. , Guerin Bastien
Published: July 2015

Purpose

A new framework for the design of parallel transmit (pTx) pulses is presented introducing constraints for local and global specific absorption rate (SAR) in the presence of errors in the radiofrequency (RF) transmit chain.

Methods

The first step is the design of a pTx RF pulse with explicit constraints for global and local SAR. Then, the worst possible SAR associated with that pulse due to RF transmission errors (“worst‐case SAR”) is calculated. Finally, this information is used to re‐calculate the pulse with lower SAR constraints, iterating this procedure until its worst‐case SAR is within safety limits.

Results

Analysis of an actual pTx RF transmit chain revealed amplitude errors as high as 8% (20%) and phase errors above 3° (15°) for spokes (spiral) pulses. Simulations show that using the proposed framework, pulses can be designed with controlled “worst‐case SAR” in the presence of errors of this magnitude at minor cost of the excitation profile quality.

Conclusion

Our worst‐case SAR‐constrained pTx design strategy yields pulses with local and global SAR within the safety limits even in the presence of RF transmission errors. This strategy is a natural way to incorporate SAR safety factors in the design of pTx pulses. Magn Reson Med 75:2493–2504, 2016. © 2015 Wiley Periodicals, Inc.
Reverse retrospective motion correction
Authors: Zahneisen Benjamin , Keating Brian , Singh Aditya , Herbst Michael , Ernst Thomas
Published: July 2015

Purpose

One potential barrier for using prospective motion correction (PMC) in the clinic is the unpredictable nature of a scan because of the direct interference with the imaging sequence. We demonstrate that a second set of “de‐corrected” images can be reconstructed from a scan with PMC that show how images would have appeared without PMC enabled.

Theory and Methods

For three‐dimensional scans, the effects of PMC can be undone by performing a retrospective reconstruction based on the inverse of the transformation matrix used for real time gradient feedback. Retrospective reconstruction is performed using a generalized SENSE approach with continuous head motion monitored using a single‐marker optical camera system.

Results

Reverse retrospective reconstruction is demonstrated for phantom and in vivo scans using an magnetization‐prepared rapid gradient echo (MPRAGE) sequence including parallel and Partial Fourier acceleration.

Conclusion

Reverse retrospective reconstruction can almost perfectly undo the effects of prospective feedback, and thereby provide a second image data set with the effects of motion correction removed. In case of correct feedback, one can directly compare the quality of the corrected with that of the uncorrected scan. Additionally, because erroneous feedback during PMC may introduce artifacts, it is possible to eliminate artifacts in a corrupted scan by reversing the false gradient updates. Magn Reson Med 75:2341–2349, 2016. © 2015 Wiley Periodicals, Inc.
Effects of moderate‐ and high‐intensity chronic exercise on brain‐derived neurotrophic factor expression in fast and slow muscles
Authors: Jiménez‐Maldonado Alberto , Cerna‐Cortés Joel , Castro‐Rodríguez Elena M. , Montero Sergio A. , Muñiz Jesús , Rodríguez‐Hernández Alejandrina , Lemus Mónica , De Álvarez‐Buylla Elena Roces
Published: July 2015

Introduction: Brain‐derived neurotrophic factor (BDNF) protein expression is sensitive to cellular activity. In the sedentary state, BDNF expression is affected by the muscle phenotype. Methods: Eighteen Wistar rats were divided into the following 3 groups: sedentary (S); moderate‐intensity training (MIT); and high‐intensity training (HIT). The training protocol lasted 8 weeks. Forty‐eight hours after training, total RNA and protein levels in the soleus and plantaris muscles were obtained. Results: In the plantaris, the BDNF protein level was lower in the HIT than in the S group (P < 0.05). A similar effect was found in the soleus (without significant difference). In the soleus, higher Bdnf mRNA levels were found in the HIT group (P < 0.001 vs. S and MIT groups). In the plantaris muscle, similar Bdnf mRNA levels were found in all groups. Conclusions: These results indicate that high‐intensity chronic exercise reduces BDNF protein level in fast muscles and increases Bdnf mRNA levels in slow muscles. Muscle Nerve 53: 446–451, 2016
Temporal pattern of stimulation modulates reflex bladder activation by pudendal nerve stimulation
Authors: McGee Meredith J. , Grill Warren M.
Published: July 2015

Aims

Reflex bladder activation and inhibition by electrical stimulation of pudendal nerve (PN) afferents is a promising approach to restore control of bladder function in persons with lower urinary tract dysfunction caused by disease or injury. The objective of this work was to determine whether bladder activation evoked by pudendal afferent stimulation was dependent on the temporal pattern of stimulation, and whether specific temporal patterns of stimulation produced larger bladder contractions than constant frequency stimulation.

Methods

The mean and maximum contraction pressures evoked by different temporal patterns of stimulation of the dorsal genital branch of the pudendal nerve were measured under isovolumetric conditions in α‐chloralose anesthetized cats. A computational model of the spinal neural network mediating the pudendo‐vesical reflex was used to understand the mechanisms of different bladder responses to patterned stimulation.

Results

The pattern of stimulation significantly affected the magnitude of evoked bladder contractions; several temporal patterns were as effective as regular stimulation, but no pattern evoked larger bladder contractions. Random patterns and patterns with pauses, burst‐like activity, or high frequency components evoked significantly smaller bladder contractions, supporting the use of regular frequency stimulation in the development of neural prosthetic approaches for bladder control.

Conclusions

These results reveal that the bladder response to pudendal afferent stimulation is dependent on the pattern, as well as the frequency, of stimulation. The computational model revealed that the effects of patterned pudendal afferent stimulation were determined by the dynamic properties of excitatory and inhibitory interneurons in the lumbosacral spinal cord. Neurourol. Urodynam. 35:882–887, 2016. © 2015 Wiley Periodicals, Inc.
Systems composed of two types of nonidentical and dependent components
Authors: Eryilmaz Serkan
Published: July 2015

A coherent system of order n that consists two different types of dependent components is considered. The lifetimes of the components in each group are assumed to follow an exchangeable joint distribution, and the two random vectors, which represent the lifetimes of the components in each group are also assumed to be dependent. Under this particular form of dependence, all components are assumed to be dependent but they are categorized with respect to their reliability functions. Mixture representation is obtained for the survival function of the system's lifetime. Mixture representations are also obtained for the series and parallel systems consisting of disjoint modules such that all components of Type I are involved in one module (subsystem) and all components of Type II are placed in the other module. The theoretical results are illustrated with examples. © 2015 Wiley Periodicals, Inc. Naval Research Logistics 62: 388–394, 2015
Virtual element methods for parabolic problems on polygonal meshes
Authors: Vacca Giuseppe , Beirão da Veiga Lourenco
Published: July 2015

The virtual element method (VEM) is a recent technology that can make use of very general polygonal/polyhedral meshes without the need to integrate complex nonpolynomial functions on the elements and preserving an optimal order of convergence. In this article, we develop for the first time, the VEM for parabolic problems on polygonal meshes, considering time‐dependent diffusion as our model problem. After presenting the scheme, we develop a theoretical analysis and show the practical behavior of the proposed method through a large array of numerical tests. © 2015 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 31: 2110–2134, 2015
Building entrepreneurial universities in a specific culture—barriers and opportunities
Authors: Bhayani Ali
Published: July 2015

Globally universities are facing an increasingly dynamic environment, and many have responded through becoming more entrepreneurial. European and US universities have adopted new governance structures, diversified their funding, changed their organisational structures and adopted an entrepreneurial culture to drive more innovative behaviour. Using multiple case studies, based on semi‐structured interviews, the barriers and opportunities for entrepreneurialism in five UAE universities are identified. UAE universities possess inherent qualities necessary for entrepreneurialism, including steerage, concern for economic surplus plus their performance driven environment allows quick response to the dynamic external environment; however, there are certain areas that require further development such as developing a culture of innovation, incentivising Universities to take risks as well as gaining appropriate support from the State. Based on the results of this work a change agenda has been chartered to further support and develop entrepreneurial universities in the Middle Eastern environment.

Copyright © 2015 John Wiley & Sons, Ltd.
High‐performance filaments by melt spinning low viscosity nylon 6 using horizontal isothermal bath process
Authors: Najafi Mesbah , Avci Huseyin , Kotek Richard
Published: July 2015

Several techniques and treatments have been developed for the production of high‐performance nylon‐6 fibers. The inherent problems of low productivity, high production cost, and high energy consumption, complexity of chemical reaction, mass transfer, and waste recovery systems make most of them inappropriate for industrial application. Horizontal isothermal bath (hIB) is an alternative ecofriendly simple treatment that can be used during melt spinning process for production of technical textile fibers. The efficacy of hIB in improving the mechanical properties of multifilament nylon‐6 yarn is studied in this research. The results showed that such treatment can increase the molecular orientation of the amorphous and crystalline functions up to 0.54 and 0.983, respectively, and raised both the amorphous isotropy and fiber birefringence by 67 and 45%, respectively. Hot drawing of the yarn at a very low draw ratio of 1.38, increased the tenacity and modulus up to 10 and 43.9 g/den, respectively, and decreased the elongation to 27%. POLYM. ENG. SCI., 55:2457–2464, 2015. © 2015 Society of Plastics Engineers
Post‐translational modifications of the cardiac proteome in diabetes and heart failure
Authors: Wende Adam R.
Published: July 2015

Cardiovascular complications are the leading cause of death in diabetic patients. Decades of research has focused on altered gene expression, altered cellular signaling, and altered metabolism. This work has led to better understanding of disease progression and treatments aimed at reversing or stopping this deadly process. However, one of the pieces needed to complete the puzzle and bridge the gap between altered gene expression and changes in signaling/metabolism is the proteome and its host of modifications. Defining the mechanisms of regulation includes examining protein levels, localization, and activity of the functional component of cellular machinery. Excess or misutilization of nutrients in obesity and diabetes may lead to PTMs contributing to cardiovascular disease progression. PTMs link regulation of metabolic changes in the healthy and diseased heart with regulation of gene expression itself (e.g. epigenetics), protein enzymatic activity (e.g. mitochondrial oxidative capacity), and function (e.g. contractile machinery). Although a number of PTMs are involved in each of these pathways, we will highlight the role of the serine and threonine O‐linked addition of β‐N‐acetyl‐glucosamine or O‐GlcNAcylation. This nexus of nutrient supply, utilization, and storage allows for the modification and translation of mitochondrial function to many other aspects of the cell.
Restricted mobility of side chains on concave surfaces of solenoid proteins may impart heightened potential for intermolecular interactions
Authors: Ramya L. , Gautham N. , Chaloin Laurent , Kajava Andrey V.
Published: July 2015

Significant progress has been made in the determination of the protein structures with their number today passing over a hundred thousand structures. The next challenge is the understanding and prediction of protein–protein and protein–ligand interactions. In this work we address this problem by analyzing curved solenoid proteins. Many of these proteins are considered as “hub molecules” for their high potential to interact with many different molecules and to be a scaffold for multisubunit protein machineries. Our analysis of these structures through molecular dynamics simulations reveals that the mobility of the side‐chains on the concave surfaces of the solenoids is lower than on the convex ones. This result provides an explanation to the observed preferential binding of the ligands, including small and flexible ligands, to the concave surface of the curved solenoid proteins. The relationship between the landscapes and dynamic properties of the protein surfaces can be further generalized to the other types of protein structures and eventually used in the computer algorithms, allowing prediction of protein–ligand interactions by analysis of protein surfaces. Proteins 2015; 83:1654–1664. © 2015 Wiley Periodicals, Inc.
Solution NMR and molecular dynamics reveal a persistent alpha helix within the dynamic region of PsbQ from photosystem II of higher plants
Authors: Rathner Petr , Rathner Adriana , Horničáková Michaela , Wohlschlager Christian , Chandra Kousik , Kohoutová Jaroslava , Ettrich Rüdiger , Wimmer Reinhard , Müller Norbert
Published: July 2015

The extrinsic proteins of photosystem II of higher plants and green algae PsbO, PsbP, PsbQ, and PsbR are essential for stable oxygen production in the oxygen evolving center. In the available X‐ray crystallographic structure of higher plant PsbQ residues S14‐Y33 are missing. Building on the backbone NMR assignment of PsbQ, which includes this “missing link”, we report the extended resonance assignment including side chain atoms. Based on nuclear Overhauser effect spectra a high resolution solution structure of PsbQ with a backbone RMSD of 0.81 Å was obtained from torsion angle dynamics. Within the N‐terminal residues 1–45 the solution structure deviates significantly from the X‐ray crystallographic one, while the four‐helix bundle core found previously is confirmed. A short α‐helix is observed in the solution structure at the location where a β‐strand had been proposed in the earlier crystallographic study. NMR relaxation data and unrestrained molecular dynamics simulations corroborate that the N‐terminal region behaves as a flexible tail with a persistent short local helical secondary structure, while no indications of forming a β‐strand are found. Proteins 2015; 83:1677–1686. © 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.
Processes leading to heavy precipitation associated with two Mediterranean cyclones observed during the HyMeX SOP1
Authors: Flaounas Emmanouil , Lagouvardos Konstantinos , Kotroni Vassiliki , Claud Chantal , Delanoë Julien , Flamant Cyrille , Madonna Erica , Wernli Heini
Published: July 2015

Two deep cyclones occurred in the Mediterranean between 25 and 31 October 2012, during the first Special Observation Period (SOP1) of the Hydrological cycle in the Mediterranean Experiment (HyMeX). Both cyclones were associated with extreme rainfall covering a large part of the western Mediterranean Sea, where 24 h accumulated precipitation measurements exceeded 150 mm. We combine complementary observations from airborne radar and lidar systems, ZEUS lightning detection network and meteorological surface stations along with satellite diagnostics on deep convection, for a detailed microphysics and (thermo‐)dynamical analysis of the two extreme rainfall cases. In addition, we use operational analysis data from the European Centre for Medium‐range Weather Forecasts (ECMWF) for analysing the synoptic conditions and diagnosing strongly ascending air masses in the vicinity of the cyclones, so‐called warm conveyor belts (WCBs). The analysis revealed the different physical characteristics of the two cyclones responsible for the extreme rainfalls. Both cyclones were associated with a WCB and a comma cloud, but deep convection, intense lightning and very cold cloud tops occurred only for the first case while the second cyclone was mostly associated with stratiform rainfall, a strong WCB, and only a few embedded cells of deep convection.
The forecast skill horizon
Authors: Buizza Roberto , Leutbecher Martin
Published: July 2015

Numerical weather prediction has seen, in the past 25 years, a shift from a ‘deterministic’ approach, based on single numerical integrations, to a probabilistic one, with ensembles of numerical integrations used to estimate the probability distribution function of forecast states. This shift to a probabilistic approach enabled a better extraction of predictive signals at longer lead times and provided a meaningful framework for extending the forecast length beyond 10 days. In this work, the limit of predictive skill is assessed for ECMWF monthly ensemble forecasts at different spatial and temporal scales. The forecast skill horizon is defined as the lead time when the ensemble ceases to be more skilful than a climatological distribution, using a continuous ranked probability score as metric. Results based on 32‐day ensemble forecasts indicate that the forecast skill horizon is sensitive to the spatial and temporal scale of the predicted phenomena, to the variable considered and the area analysed. On average over 1 year of forecasts, the forecast skill horizon for instantaneous, grid‐point fields is between 16 and 23 days, while it is considerably longer for time‐ and spatial‐average fields. Forecast skill horizons longer than the 2 weeks that were thought to be the limit are now achievable thanks to major advances in numerical weather prediction. More specifically, they are possible because forecasts are now framed in probabilistic terms, with a probability distribution estimated using ensembles generated using forecast models that include more components (e.g. a dynamical ocean and ocean waves) and more faithfully represent processes. Moreover, the forecasts start from more accurate initial conditions constructed using better data‐assimilation methods and more observational data.
Improved accuracy and precision in δ15NAIR measurements of explosives, urea, and inorganic nitrates by elemental analyzer/isotope ratio mass spectrometry using thermal decomposition
Authors: Lott Michael J. , Howa John D. , Chesson Lesley A. , Ehleringer James R.
Published: July 2015

Rationale

Elemental analyzer systems generate N2 and CO2 for elemental composition and isotope ratio measurements. As quantitative conversion of nitrogen in some materials (i.e., nitrate salts and nitro‐organic compounds) is difficult, this study tests a recently published method – thermal decomposition without the addition of O2 – for the analysis of these materials.

Methods

Elemental analyzer/isotope ratio mass spectrometry (EA/IRMS) was used to compare the traditional combustion method (CM) and the thermal decomposition method (TDM), where additional O2 is eliminated from the reaction. The comparisons used organic and inorganic materials with oxidized and/or reduced nitrogen and included ureas, nitrate salts, ammonium sulfate, nitro esters, and nitramines. Previous TDM applications were limited to nitrate salts and ammonium sulfate. The measurement precision and accuracy were compared to determine the effectiveness of converting materials containing different fractions of oxidized nitrogen into N2.

Results

The δ13CVPDB values were not meaningfully different when measured via CM or TDM, allowing for the analysis of multiple elements in one sample. For materials containing oxidized nitrogen, 15N measurements made using thermal decomposition were more precise than those made using combustion. The precision was similar between the methods for materials containing reduced nitrogen. The %N values were closer to theoretical when measured by TDM than by CM. The δ15NAIR values of purchased nitrate salts and ureas were nearer to the known values when analyzed using thermal decomposition than using combustion.

Conclusions

The thermal decomposition method addresses insufficient recovery of nitrogen during elemental analysis in a variety of organic and inorganic materials. Its implementation requires relatively few changes to the elemental analyzer. Using TDM, it is possible to directly calibrate certain organic materials to international nitrate isotope reference materials without off‐line preparation. Copyright © 2015 John Wiley & Sons, Ltd.
Gas‐phase fragmentation of deprotonated tryptophan and its clusters [Trpn–H]– induced by different activation methods
Authors: Feketeová Linda , Khairallah George N. , O'Hair Richard A. J. , Nielsen Steen Brøndsted
Published: July 2015

Rationale

Non‐covalent amino acid clusters are the subject of intense research in diverse areas including peptide bond formation studies or the determination of proton affinities or methylating abilities of amino acids. However, most of the research has focused on positive ions and little is known about anionic clusters.

Methods

Fragmentation reactions of deprotonated tryptophan (Trp), [Trp−H]− and Trp singly deprotonated non‐covalently bound clusters [Trpn−H]−, n = 2, 3, 4, were investigated using low‐energy collision‐induced dissociation (CID) with He atoms, high‐energy CID with Na atoms, and electron‐induced dissociation (EID) with 20–35 eV electrons. Fragmentation of the monomeric Trp anion, where all labile hydrogens were exchanged for deuterium [d4‐Trp−D]−, was investigated using low‐energy CID and EID, in order to shed light on the dissociation mechanisms.

Results

The main fragmentation channel for Trp cluster anions, [Trpn−H]−, n >1, is the loss of the neutral monomer. The fragmentation of the deprotonated Trp monomer induced by electrons resembles the fragmentation induced by high‐energy collisions through electronic excitation of the parent. However, the excitation must precede in a different way, shown through only monomer loss from larger clusters, n >1, in case of EID, but intracluster chemistry in the case of high‐energy CID.

Conclusions

The anion of the indole ring C8H6N− has been identified in the product ion spectra of [Trpn−H]− using all activation methods, thus providing a diagnostic marker ion. No evidence was found for formation of peptide bonds as a route to prebiotic peptides in the fragmentation reactions of these singly deprotonated Trp cluster ions. Copyright © 2015 John Wiley & Sons, Ltd.
The Africa Center for Biostatistical Excellence: a proposal for enhancing biostatistics capacity for sub‐Saharan Africa
Authors: Machekano Rhoderick , Young Taryn , Rusakaniko Simbarashe , Musonda Patrick , Sartorius Ben , Todd Jim , Fegan Greg , Thabane Lehana , Chikte Usuf
Published: July 2015

Sub‐Saharan Africa has a shortage of well‐trained biomedical research methodologists, in particular, biostatisticians. In July 2014, a group of biostatisticians and researchers from the region attended a brainstorming workshop to identify ways in which to reduce the deficit in this critical skill. The workshop recognized that recommendations from previous workshops on building biostatistics capacity in sub‐Saharan Africa had not been implemented. The discussions culminated with a proposal to setup an Africa Center for Biostatistical Excellence, a collaborative effort across academic and researcher institutions within the region, as a vehicle for promoting biostatistics capacity building through specialized academic masters programs as well as regular workshops targeting researchers. Copyright © 2015 John Wiley & Sons, Ltd.
Intranuclear Actin Regulates Osteogenesis
Authors: Sen Buer , Xie Zhihui , Uzer Gunes , Thompson William R. , Styner Maya , Wu Xin , Rubin Janet
Published: July 2015

Depolymerization of the actin cytoskeleton induces nuclear trafficking of regulatory proteins and global effects on gene transcription. We here show that in mesenchymal stem cells (MSCs), cytochalasin D treatment causes rapid cofilin-/importin-9-dependent transfer of G-actin into the nucleus. The continued presence of intranuclear actin, which forms rod-like structures that stain with phalloidin, is associated with induction of robust expression of the osteogenic genes osterix and osteocalcin in a Runx2-dependent manner, and leads to acquisition of osteogenic phenotype. Adipogenic differentiation also occurs, but to a lesser degree. Intranuclear actin leads to nuclear export of Yes-associated protein (YAP); maintenance of nuclear YAP inhibits Runx2 initiation of osteogenesis. Injection of cytochalasin into the tibial marrow space of live mice results in abundant bone formation within the space of 1 week. In sum, increased intranuclear actin forces MSC into osteogenic lineage through controlling Runx2 activity; this process may be useful for clinical objectives of forming bone. Stem Cells  2015;33:3065–3076
Quick and easy preparation method for decoction of Kampo formula inspired by the method of boiling powdered crude drugs in the Song period of China
Authors: Fueki Tsukasa , Makino Toshiaki , Matsuoka Takanori , Beppu Masashi , Sunaga Takao , Tanaka Koichiro , Nagamine Koichi , Namiki Takao
Published: July 2015

Aim

For the purpose of reducing both the consumption of crude drug resources and patient burden in preparing the decoctions, we developed a new preparation method for the decoctions of Kampo formula: immersion of powdered crude drugs in hot water (IPCD method), inspired by a method of decoction that was widely used in the Song period of China.

Methods

Ephedra herb (terrestrial stem of Ephedra sinica), scutellaria root (root of Scutellaria baicalensis), and Kampo formulas that contain several crude drugs including ephedra herb and scutellaria root were powdered, and then immersed in hot water to extract the ingredients. The residue was filtered out using a commercially available tea server. The contents of marker compounds in the decoctions were measured.

Results

Using the IPCD method, the amounts of marker compounds from ephedra herb and scutellaria root transferred to hot water exceeded by 1.3–1.4‐fold that obtained by the standard method of decocting the same amounts of cut crude drugs for >30 min. The amount of transferred marker compounds reached a plateau within 4 min after the beginning of immersion, suggesting that only 4 min of immersion is sufficient for the IPCD method. The sludge residue of powdered crude drug produced by immersion could be easily filtered with a commercially available tea server.

Conclusion

Using this method, the same or greater amounts of marker compounds were transferred in the decoctions in a much shorter time with lower consumption of crude drugs than with the usual decoction method.
Modulation of cytokines and chemokines expression by NAC in cadmium chloride treated human lung cells
Authors: Odewumi Caroline O. , Latinwo Lekan M. , Ruden Michael L. , Badisa Veera L. D. , Fils‐Aime Sheila , Badisa Ramesh B.
Published: July 2015

Cadmium (Cd), is one of the most hazardous metals found in the environment. Cd exposure through inhalation has been linked to various diseases in lungs. It was shown that Cd induces proinflammatory cytokines through oxidative stress mechanism. In this report, we studied the immunomodulatory effect of a well known antioxidant, N‐acetylcysteine (NAC) on cadmium chloride (CdCl2) treated human lung A549 cells through human cytokine array 6. The lung cells were treated with 0 or 75 µM CdCl2 alone, 2.5 mM NAC alone, or co‐treated with 2.5 mM NAC and 75 µM CdCl2 for 24 h. The viability of cells was measured by crystal violet dye. The array results were validated by human IL‐1alpha enzyme‐ linked immunosorbent assay (ELISA) kit. The viability of the 75 µM CdCl2 alone treated cells was decreased to 44.5%, while the viability of the co‐treated cells with 2.5 mM NAC was increased to 84.1% in comparison with untreated cells. In the cell lysate of CdCl2 alone treated cells, 19 and 8 cytokines were up and down‐regulated, while in the medium 15 and 3 cytokines were up and downregulated in comparison with the untreated cells. In the co‐treated cells, all these cytokines expression was modulated by the NAC treatment. The IL‐1α ELISA result showed the same pattern of cytokine expression as the cytokine array. This study clearly showed the modulatory effect of NAC on cytokines and chemokines expression in CdCl2‐treated cells and suggests the use of NAC as protective agent against cadmium toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1612–1619, 2016.
Percutaneous minimally invasive fetoscopic surgery for spina bifida aperta. Part III: neurosurgical intervention in the first postnatal year
Authors: Graf K. , Kohl T. , Neubauer B. A. , Dey F. , Faas D. , Wanis F. A. , Reinges M. H. T. , Uhl E. , Kolodziej M. A.
Published: July 2015

Objective

To evaluate the need for postnatal neurosurgical intervention after fetoscopic patch coverage of spina bifida aperta (SBA).

Methods

This was a retrospective analysis of a cohort of 71 fetuses which underwent minimally invasive fetoscopic patch coverage of SBA between 21 + 0 and 29 + 1 weeks of gestation. Postnatal neurosurgical procedures were classified into two types: re‐coverage of the SBA within the first 3 months following birth, and shunt placement as treatment of associated hydrocephalus within the first year.

Results

Location of the SBA was lumbosacral in 59 cases, lumbar in seven, thoracic in three and sacral in two. In total, 20/71 (28%) patients underwent early postnatal neurosurgical intervention by means of re‐coverage of the SBA. This was performed because of cerebrospinal fluid leakage in seven (35%), adhesions with functional deterioration in three (15%), incomplete coverage in five (25%) and skin defect in five (25%) cases. Ventriculoperitoneal shunt placement within 1 year was required in 32 (45%) cases and was preceded by ventriculostomy in two. Three (4%) infants needed Chiari decompression surgery in the first 12 months following birth, because of syringomyelia or gait disturbance.

Conclusions

Fetoscopic patch coverage of SBA may require postnatal re‐coverage in some cases. In most cases, conservative wound treatment shows good results, without requiring neurosurgical intervention. The low 1‐year‐shunt rate is comparable to data of the Management of Myelomeningocele Study and lower compared with published data of patients with postnatal only coverage of SBA. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Evaluation of right ventricular function in fetal hypoplastic left heart syndrome by color tissue Doppler imaging
Authors: Graupner O. , Enzensberger C. , Wieg L. , Willruth A. , Steinhard J. , Gembruch U. , Doelle A. , Bahlmann F. , Kawecki A. , Degenhardt J. , Wolter A. , Herrmann J. , Axt‐Fliedner R. ,   on behalf of the Fetal Cardiac Imaging Research Group Germany
Published: July 2015

Objective

Postnatal outcome of fetuses with hypoplastic left heart syndrome (HLHS) is determined mainly by right ventricular function. Our study examines whether there are differences in right ventricular function during gestation of fetuses with HLHS compared with healthy fetuses.

Methods

A prospective study was conducted including 20 fetuses with HLHS and 20 gestational age‐matched controls. Peak systolic and diastolic right ventricular free wall velocities were assessed using color tissue Doppler imaging (c‐TDI). Subsequently, isovolumic time intervals, ejection time (ET′), E′/A′ ratio and tissue Doppler‐derived myocardial performance index (MPI′) were calculated. Possible changes to c‐TDI indices during the course of pregnancy in both the HLHS group and the control group were investigated.

Results

Examination of right ventricular function revealed significantly lower E′ velocities (13.6 vs 21.0 cm/s; P = 0.017) and E′/A′ ratios (0.55 vs 0.76; P = 0.012) and prolonged isovolumic contraction time (ICT′) (57.0 vs 45.7 ms; P = 0.008) in the HLHS group compared with healthy fetuses. Furthermore, isovolumic relaxation time and MPI′ increased significantly with gestational age in HLHS fetuses but not in controls. Values for systolic and diastolic peak velocities (E′, A′, S′), ET′ and ICT′ did not change significantly during gestation in either group.

Conclusion

Right ventricular function in HLHS is altered as early as in fetal life, well before palliative surgery is performed. Future research should provide further insight into ventricular remodeling during gestation in cases of HLHS. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Design space exploration of gyrocopter‐type airborne wind turbines
Authors: Rancourt David , Bolduc‐Teasdale François , Bouchard Etienne Demers , Anderson Michael J. , Mavris Dimitri N.
Published: July 2015

This paper presents a multidisciplinary framework for the design and analysis of gyrocopter‐type airborne wind turbines. In this concept, four rotary wings provide lift to a flying vehicle, and excess power is extracted using gearboxes and generators before being transferred to the ground through electrical conductors embedded in a structural tether. A physical breakdown of the system was performed, and five models were constructed: wind model, rotor aerodynamics, structural mass, electrical system, and tether (structures and aerodynamics). A stochastic optimizer in the framework enforces interdisciplinary compatibility and maximizes electrical power transmitted to the ground under various operating conditions. The framework is then used to explore the design space of this advanced concept in numerous flight conditions. The effect of implementing new technologies was also studied in order to evaluate their effect on the overall performance of the system. It is shown through a 1.3MW design that a gyrocopter‐type airborne generator could provide more power than a ground‐based wind turbine for a given blade radius, although only a fraction of the available wind power can be harvested using off‐the‐shelf technologies and components. The work presented in this study demonstrates the challenges of designing a high altitude wind generator and shows that performance is affected by complex interactions between each subsystem. Copyright © 2015 John Wiley & Sons, Ltd.
Thermal expansion of polycrystalline gallium nitride: an X‐ray diffraction study
Authors: Minikayev R. , Paszkowicz W. , Piszora P. , Knapp M. , Bähtz C. , Podsiadło S.
Published: July 2015

Gallium nitride is studied at ambient and nonambient temperatures by powder X‐ray diffraction followed by Rietveld refinement of the structure. The structure is reported for the ambient temperature on the basis of laboratory data. The diffraction data collected using a synchrotron beam serve for derivation of the lattice parameter and thermal expansion dependencies on temperature. The variation of unit‐cell size on temperature was studied in detail in a broad range 11 K < T < 1073 K. The obtained dependencies of a, c and V and thermal expansion coefficients are smooth, and the results are consistent with previously collected data. The c/a ratio shows an almost linear decreasing trend with rising temperature. The magnitude of thermal expansion obtained in the described experiments is similar to a recently reported theoretical one. Copyright © 2015 John Wiley & Sons, Ltd.
A crossover study comparing gabapentin and fluoxetine for the treatment of vasomotor symptoms among postmenopausal women
Authors: Rahmanian Mojgan , Mohseni Arash , Ghorbani Raheb
Published: July 2015

Objective

To compare the effectiveness of fluoxetine and gabapentin for treatment of vasomotor symptoms (VMS) after the menopause.

Methods

Between March 2011 and March 2012, a randomized crossover study was performed at a center in Semnan, Iran, among postmenopausal women aged 45–57 years with hot flashes (≥ 2 per day for previous 4 months) for which they had received no previous treatment. Participants were divided into two groups with consecutive numbers assigned in order of recruitment. In the first treatment round (4 weeks), group A received 20 mg/day fluoxetine and group B received 300 mg/day gabapentin. After a 2‐week washout period, group A received gabapentin and group B received fluoxetine in a second round (4 weeks). Information about VMS was obtained with the Greene Climacteric Scale questionnaire. Participants and all investigators except one were masked to group assignment.

Results

Data for 79 participants (39 in group A, 40 in group B) were analyzed. In both treatment rounds, gabapentin caused greater reductions in the severity of hot flashes than did fluoxetine (P < 0.001 for both). After the first round of treatment, those who had received gabapentin reported greater reductions in the severity of night sweats (P < 0.001).

Conclusion

Gabapentin at a dose of 300 mg/day is more effective for treatment of VMS among postmenopausal women than is 20 mg/day fluoxetine.

Iranian Registry of Clinical Trials: IRCT2014092711019N3.
Effect of prenatal betamethasone on fetal, uteroplacental, and maternal blood flow velocity in pregnancies complicated by fetal growth restriction
Authors: Niroomanesh Shirin , Shojaei Kobra , Moghadam Sahar F. , Mohammadi Noshin , Rahimi Zahra , RezaeiKeyhanaei Khadija
Published: July 2015

Objective

To assess Doppler flow velocity in fetal, uteroplacental, and maternal arteries before and after betamethasone therapy among singleton pregnancies complicated by fetal growth restriction (FGR).

Methods

A prospective, longitudinal, multicenter study was conducted at three university‐affiliated hospitals in Tehran, Iran, between January 1 and November 30, 2013. The inclusion criteria were FGR, a gestational age of 24–34 weeks, no fetal anomalies, and no previous betamethasone therapy. Doppler blood flow was measured in uterine, umbilical, and middle cerebral arteries before treatment, and 24 hours and 5 days after completion of betamethasone therapy (two 12‐mg doses at a 24‐hour interval).

Results

Overall, 40 women were enrolled. Doppler blood flow through the uterine and umbilical arteries showed significant but transient changes across the three timepoints (P < 0.001), whereas the middle cerebral artery showed no changes.

Conclusion

Prenatal betamethasone led to transient improvements in blood flow in the uterine and umbilical arteries among pregnancies affected by FGR.