bluuebunny/crossref_metadata_2025 huggingface dataset:
Time‐dependent scattering of generalized plane waves by a wedge
Authors: Komech A.I. , Merzon A.E. , Méndez J.E. De la Paz
Published: January 2015

We obtain explicit formulas for the scattering of plane waves with arbitrary profile by a wedge under Dirichlet, Neumann and Dirichlet‐Neumann boundary conditions. The diffracted wave is given by a convolution of the profile function with a suitable kernel corresponding to the boundary conditions. We prove the existence and uniqueness of solutions in appropriate classes of distributions and establish the Sommerfeld type representation for the diffracted wave.

As an application, we establish (i) stability of long‐time asymptotic local perturbations of the profile functions and (ii) the limiting amplitude principle in the case of a harmonic incident wave. Copyright © 2015 John Wiley & Sons, Ltd.
Damage processes in thermoviscoelastic materials with damage‐dependent thermal expansion coefficients
Authors: Heinemann Christian , Rocca Elisabetta
Published: January 2015

In this paper, we prove existence of global in time weak solutions for a highly nonlinear PDE system arising in the context of damage phenomena in thermoviscoelastic materials. The main novelty of the present contribution with respect to the ones already present in the literature consists in the possibility of taking into account a damage‐dependent thermal expansion coefficient. This term implies the presence of nonlinear coupling terms in the PDE system, which make the analysis more challenging. Copyright © 2015 John Wiley & Sons, Ltd.
Dietary apigenin reduces LPS‐induced expression of miR‐155 restoring immune balance during inflammation
Authors: Arango Daniel , Diosa‐Toro Mayra , Rojas‐Hernandez Laura S. , Cooperstone Jessica L. , Schwartz Steven J. , Mo Xiaokui , Jiang Jinmai , Schmittgen Thomas D. , Doseff Andrea I.
Published: January 2015

Scope

High incidence of inflammatory diseases afflicts the increasing aging‐population infringing a great health burden. Dietary flavonoids, including the flavone apigenin, are emerging as important anti‐inflammatory nutraceuticals due to their health benefits, lack of adverse effects and reduced costs. MicroRNAs (miRs) play a central role in inflammation by regulating gene expression, yet how dietary ingredients affect miRs is poorly understood. The aim of this study was to identify miRs involved in the anti‐inflammatory activity of apigenin and apigenin‐rich diets and determine their immune regulatory mechanisms in macrophages and in vivo.

Methods and results

A high‐throughput quantitative reverse transcriptase PCR screen of 312 miRs in macrophages revealed that apigenin reduced LPS‐induced miR‐155 expression. Analyses of miR‐155 precursor and primary transcript indicated that apigenin regulated miR‐155 transcriptionally. Apigenin‐reduced expression of miR‐155 led to the increase of anti‐inflammatory regulators forkhead box O3a and smooth‐muscle‐actin and MAD‐related protein 2 in LPS‐treated macrophages. In vivo, apigenin or a celery‐based apigenin‐rich diet reduced LPS‐induced expression of miR‐155 and decreased tumor necrosis factor α in lungs from LPS‐treated mice.

Conclusion

These results demonstrate that apigenin and apigenin‐rich diets exert effective anti‐inflammatory activity in vivo by reducing LPS‐induced expression of miR‐155, thereby restoring immune balance.
NMR metabolomics for soil analysis provide complementary, orthogonal data to MIR and traditional soil chemistry approaches – a land use study
Authors: Rochfort Simone , Ezernieks Vilnis , Mele Pauline , Kitching Matt
Published: January 2015

The present study was designed to analyse soils by different methodologies to determine the range of traits that could be investigated for the study of environmental soil samples. Proton nuclear magnetic resonance spectroscopy (1H NMR) was employed for metametabolomic analysis of soils from agricultural systems (managed) or from soils in a native state (remnant). The metabolomic methodologies employed (grinding and extraction with sonication) are capable of breaking up cell walls and so enabled characterisation of both extracellular and intracellular components of soil. Diffuse mid‐infrared spectroscopy (MIR) data was obtained for the same sample sets, and in addition, elemental composition was determined by conventional laboratory chemical testing methods. Also investigated was the antibiotic activity of the soil extracts. Resilient or suppressive soils are valued in the agricultural setting as they convey disease resistance (against bacterial and fungal pathogens) to crop plants. In order to test if any such biological activity could be detected in the soils, the extracts were tested against the bacteria Bacillus subtilis. Several extracts showed strong growth inhibition against the bacteria with the most active clustered together in principle component analysis (PCA) of the metabolomic data. The study showed that the NMR metabolomic approach corresponds more accurately to land use and biochemical properties potentially associated with suppression, while MIR data correlated well to inorganic chemical analysis. Thus, the study demonstrates the utility in combining these spectroscopic methods for soil analysis. Copyright © 2015 John Wiley & Sons, Ltd.
129Xe and 131Xe nuclear magnetic dipole moments from gas phase NMR spectra
Authors: Makulski Włodzimierz
Published: January 2015

3He, 129Xe and 131Xe NMR measurements of resonance frequencies in the magnetic field B0 = 11.7586 T in different gas phase mixtures have been reported. Precise radiofrequency values were extrapolated to the zero gas pressure limit. These results combined with new quantum chemical values of helium and xenon nuclear magnetic shielding constants were used to determine new accurate nuclear magnetic moments of 129Xe and 131Xe in terms of that of the 3He nucleus. They are as follows: μ(129Xe) = −0.7779607(158)μN and μ(131Xe) = +0.6918451(70)μN. By this means, the new ‘helium method’ for estimations of nuclear dipole moments was successfully tested. Gas phase NMR spectra demonstrate the weak intermolecular interactions observed on the 3He and 129Xe and 131Xe shielding in the gaseous mixtures with Xe, CO2 and SF6. Copyright © 2015 John Wiley & Sons, Ltd.
Water dynamics in different biochar fractions
Authors: Conte Pellegrino , Nestle Nikolaus
Published: January 2015

Biochar is a carbonaceous porous material deliberately applied to soil to improve its fertility. The mechanisms through which biochar acts on fertility are still poorly understood. The effect of biochar texture size on water dynamics was investigated here in order to provide information to address future research on nutrient mobility towards plant roots as biochar is applied as soil amendment. A poplar biochar has been stainless steel fractionated in three different textured fractions (1.0–2.0 mm, 0.3–1.0 mm and <0.3 mm, respectively). Water‐saturated fractions were analyzed by fast field cycling (FFC) NMR relaxometry. Results proved that 3D exchange between bound and bulk water predominantly occurred in the coarsest fraction. However, as porosity decreased, water motion was mainly associated to a restricted 2D diffusion among the surface‐site pores and the bulk‐site ones. The X‐ray μ‐CT imaging analyses on the dry fractions revealed the lowest surface/volume ratio for the coarsest fraction, thereby corroborating the 3D water exchange mechanism hypothesized by FFC NMR relaxometry. However, multi‐micrometer porosity was evidenced in all the samples. The latter finding suggested that the 3D exchange mechanism cannot even be neglected in the finest fraction as previously excluded only on the basis of NMR relaxometry results. X‐ray μ‐CT imaging showed heterogeneous distribution of inorganic materials inside all the fractions. The mineral components may contribute to the water relaxation mechanisms by FFC NMR relaxometry. Further studies are needed to understand the role of the inorganic particles on water dynamics. Copyright © 2015 John Wiley & Sons, Ltd.
Natural abundant 17O NMR in a 1.5‐T Halbach magnet
Authors: Sørensen Morten K. , Bakharev Oleg N. , Jensen Ole , Nielsen Niels Chr.
Published: January 2015

We present mobile, low‐field 17O NMR as a means for monitoring oxygen in liquids. Whereas oxygen is one of the most important elements, oxygen NMR is limited by a poor sensitivity related to low natural abundance and gyro‐magnetic ratio of the NMR active 17O isotope. Here, we demonstrate 17O NMR detection at a Larmor frequency of 8.74 MHz in a 1.5‐T Halbach neodymium magnet with a home‐built digital NMR instrument suitable for large‐scale production and in‐line monitoring applications. The proposed 17O NMR sensor may be applied for direct, noninvasive measurements of water content in, for example, oil, manure, or food in automated quality or process control. Copyright © 2015 John Wiley & Sons, Ltd.
PROMISE: Parallel‐imaging and compressed‐sensing reconstruction of multicontrast imaging using SharablE information
Authors: Gong Enhao , Huang Feng , Ying Kui , Wu Wenchuan , Wang Shi , Yuan Chun
Published: January 2015

Purpose

A typical clinical MR examination includes multiple scans to acquire images with different contrasts for complementary diagnostic information. The multicontrast scheme requires long scanning time. The combination of partially parallel imaging and compressed sensing (CS‐PPI) has been used to reconstruct accelerated scans. However, there are several unsolved problems in existing methods. The target of this work is to improve existing CS‐PPI methods for multicontrast imaging, especially for two‐dimensional imaging.

Theory and Methods

If the same field of view is scanned in multicontrast imaging, there is significant amount of sharable information. It is proposed in this study to use manifold sharable information among multicontrast images to enhance CS‐PPI in a sequential way. Coil sensitivity information and structure based adaptive regularization, which were extracted from previously reconstructed images, were applied to enhance the following reconstructions. The proposed method is called Parallel‐imaging and compressed‐sensing Reconstruction Of Multicontrast Imaging using SharablE information (PROMISE).

Results

Using L1‐SPIRiT as a CS‐PPI example, results on multicontrast brain and carotid scans demonstrated that lower error level and better detail preservation can be achieved by exploiting manifold sharable information. Besides, the privilege of PROMISE still exists while there is interscan motion.

Conclusion

Using the sharable information among multicontrast images can enhance CS‐PPI with tolerance to motions. Magn Reson Med 73:523–535, 2015. © 2014 Wiley Periodicals, Inc.
Whole‐body magnetic resonance imaging evaluation of facioscapulohumeral muscular dystrophy
Authors: Leung Doris G. , Carrino John A. , Wagner Kathryn R. , Jacobs Michael A.
Published: January 2015

Introduction: Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary disorder that causes progressive muscle wasting. Increasing knowledge of the pathophysiology of FSHD has stimulated interest in developing biomarkers of disease severity. Methods: Two groups of MRI scans were analyzed: whole‐body scans from 13 subjects with FSHD; and upper and lower extremity scans from 34 subjects with FSHD who participated in the MYO‐029 clinical trial. Muscles were scored for fat infiltration and edema‐like changes. Fat infiltration scores were compared with muscle strength and function. Results: The analysis revealed a distinctive pattern of both frequent muscle involvement and frequent sparing in FSHD. Averaged fat infiltration scores for muscle groups in the legs correlated with quantitative muscle strength and 10‐meter walk times. Conclusions: Advances in MRI technology allow for acquisition of rapid, high‐quality, whole‐body imaging in diffuse muscle disease. This technique offers a promising disease biomarker in FSHD and other muscle diseases. Muscle Nerve 52: 512–520, 2015
Effects of gender and hand dominance on size of the lower trapezius muscle
Authors: Uthaikhup Sureeporn , Wannaprom Nipaporn , Kummaung Panuwat
Published: January 2015

Introduction: The influence of gender and hand dominance on the size of the lower trapezius muscle has not been studied. We aimed to identify the effects of gender and hand dominance on thickness of this muscle. Methods: Thirty healthy subjects (15 men and 15 women) were recruited for the study. The thickness of the lower trapezius muscles was measured bilaterally at the level of T8 at rest and with contraction at 130° of shoulder abduction using ultrasound imaging. Results: Men had significantly greater thickness of the lower trapezius muscle than women, both at rest and with contraction (P < 0.01). Greater lower trapezius muscle thickness was found on the dominant side compared with the non‐dominant side (P < 0.05). Conclusion: Gender and side dominance differences should be controlled for when investigating lower trapezius muscle thickness. Muscle Nerve 52: 576–579, 2015
Quantitative and qualitative adaptations of muscle fibers to glucocorticoids
Authors: Minetto Marco Alessandro , Qaisar Rizwan , Agoni Valentina , Motta Giovanna , Longa Emanuela , Miotti Danilo , Pellegrino Maria Antonietta , Bottinelli Roberto
Published: January 2015

Introduction: The aim of this study was to understand the effects of short‐term glucocorticoid administration in healthy subjects. Methods: Five healthy men received dexamethasone (8 mg/day) for 7 days. Vastus lateralis muscle biopsy and knee extension torque measurement were performed before and after administration. A large number of individual muscle fibers were dissected from the biopsy samples (pre‐administration: n = 165, post‐administration: n = 177). Results: Maximal knee extension torque increased after administration (∼13%), whereas both type 1 and type 2A fibers had decreased cross‐sectional area (type 1: ∼11%, type 2A: ∼17%), myosin loss (type 1: ∼18%, type 2A: ∼32%), and loss of specific force (type 1: ∼24%, type 2A: ∼33%), which were preferential for fast fibers. Conclusion: Short‐term dexamethasone administration in healthy subjects elicits quantitative and qualitative adaptations of muscle fibers that precede (and may predict) the clinical appearance of myopathy in glucocorticoid‐treated subjects. Muscle Nerve 52: 631–639, 2015
Hybrid time integration and coupled solution methods for nonlinear finite element analysis of partially saturated deformable porous media at small strain
Authors: Kim Jaehong , Wang Wei , Regueiro Richard A.
Published: January 2015

The goal of the paper is to determine the most efficient, yet accurate and stable, finite element nonlinear solution method for analysis of partially saturated deformable porous media at small strain. This involves a comparison between fully implicit, semi‐implicit, and explicit time integration schemes, with monolithically coupled and staggered‐coupled nonlinear solution methods and the hybrid combination thereof. The pore air pressure pa is assumed atmospheric, that is, pa=0 at reference pressure. The solid skeleton is assumed to be pressure‐sensitive nonlinear isotropic elastic. Coupled partially saturated ‘consolidation’ in the presence of surface infiltration and traction is simulated for a simple one‐dimensional uniaxial strain example and a more complicated plane strain slope example with gravity loading. Three mixed plane strain quadrilateral elements are considered: (i) Q4P4; (ii) stabilized Q4P4S; and (iii) Q9P4; “Q” refers to the number of solid skeleton displacement nodes, and “P” refers to the number of pore fluid pressure nodes. The verification of the implementation against an analytical solution for partially saturated pore water flow (no solid skeleton deformation) and comparison between the three time integration schemes (fully implicit, semi‐implicit, and explicit) are presented. It is observed that one of the staggered‐coupled semi‐implicit schemes (SIS(b)), combined with the fully implicit monolithically coupled scheme to resolve sharp transients, is the most efficient computationally. Copyright © 2015 John Wiley & Sons, Ltd.
Maintenance and flight scheduling of low observable aircraft
Authors: Cho Philip , Farias Vivek , Kessler John , Levi Retsef , Magnanti Thomas , Zarybnisky Eric
Published: January 2015

In this article, we focus on relatively new maintenance and operational scheduling challenges that are faced by the United States Air Force concerning low‐observable (LO) or stealth aircraft. The LO capabilities of an aircraft degrade stochastically as it flies, making it difficult to make maintenance scheduling decisions. Maintainers can address these damages, but must decide, which aircraft should be put into maintenance, and for how long. Using data obtained from an active duty Air Force F‐22 wing and interviews with Air Force maintainers and program specialists, we model this problem as a generalization of the well‐known restless multiarmed bandit superprocess. Specifically, we use an extension of the traditional model to allow for actions that require varying lengths of time, and generate two separate index policies from a single model; one for maintenance actions and one for the flying action. These index policies allow maintenance schedulers to intuitively, quickly, and effectively rank a fleet of aircraft based on each aircraft's LO status and decide, which aircraft should enter into LO maintenance and for how long, and which aircraft should be used to satisfy daily sortie requirements. Finally, we present extensive data‐driven, detailed simulation results, where we compare the performance of the index policies against policies currently used by the Air Force, as well as some other possible more naive heuristics. The results indicate that the index policies significantly outperform existing policies in terms of fully mission capable (FMC) rates. In particular, the experiments highlight the importance of coordinated maintenance and flying decisions. © 2015 Wiley Periodicals, Inc. 62:60–80, 2015
Specific absorption rate in neonates undergoing magnetic resonance procedures at 1.5 T and 3 T
Authors: Malik Shaihan J. , Beqiri Arian , Price Anthony N. , Teixeira Jose Nuno , Hand Jeffrey W. , Hajnal Joseph V.
Published: January 2015

MRI is finding increased clinical use in neonatal populations; the extent to which electromagnetic models used for quantification of specific absorption rate (SAR) by commercial MRI scanners accurately reflect this alternative scenario is unclear. This study investigates how SAR predictions relating to adults can be related to neonates under differing conditions when imaged using 1.5 T and 3 T MRI scanners. Electromagnetic simulations were produced in neonatal subjects of different sizes and positions within a generic MRI body transmit device operating at both 64 MHz and 128 MHz, corresponding to 1.5 T and 3 T MRI scanners, respectively. An adult model was also simulated, as was a spherical salt‐water phantom, which was also used in a calorimetry experiment. The SAR in neonatal subjects was found to be less than that experienced in an adult in all scenarios; however, the overestimation factor was variable. For example a 3 T body scan resulting in local 10 g SAR of 10.1 W kg−1 in an adult would deposit 2.6 W kg−1 in a neonate: an approximately fourfold difference. The SAR experienced by neonatal subjects undergoing MRI is lower than that in adults in equivalent situations. If the safety of such procedures is assessed using adult‐appropriate models then the result is a conservative estimate. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.
A model‐based reconstruction for undersampled radial spin‐echo DTI with variational penalties on the diffusion tensor
Authors: Knoll Florian , Raya José G. , Halloran Rafael O. , Baete Steven , Sigmund Eric , Bammer Roland , Block Tobias , Otazo Ricardo , Sodickson Daniel K.
Published: January 2015

Radial spin‐echo diffusion imaging allows motion‐robust imaging of tissues with very low T2 values like articular cartilage with high spatial resolution and signal‐to‐noise ratio (SNR). However, in vivo measurements are challenging, due to the significantly slower data acquisition speed of spin‐echo sequences and the less efficient k‐space coverage of radial sampling, which raises the demand for accelerated protocols by means of undersampling. This work introduces a new reconstruction approach for undersampled diffusion‐tensor imaging (DTI). A model‐based reconstruction implicitly exploits redundancies in the diffusion‐weighted images by reducing the number of unknowns in the optimization problem and compressed sensing is performed directly in the target quantitative domain by imposing a total variation (TV) constraint on the elements of the diffusion tensor. Experiments were performed for an anisotropic phantom and the knee and brain of healthy volunteers (three and two volunteers, respectively). Evaluation of the new approach was conducted by comparing the results with reconstructions performed with gridding, combined parallel imaging and compressed sensing and a recently proposed model‐based approach. The experiments demonstrated improvements in terms of reduction of noise and streaking artifacts in the quantitative parameter maps, as well as a reduction of angular dispersion of the primary eigenvector when using the proposed method, without introducing systematic errors into the maps. This may enable an essential reduction of the acquisition time in radial spin‐echo diffusion‐tensor imaging without degrading parameter quantification and/or SNR. Copyright © 2015 John Wiley & Sons, Ltd.
Bridge or buffer: two ideas of effective corporate governance and public engagement
Authors: Kim Soojin , Kim Jeong‐Nam
Published: January 2015

This study identifies organizational factors that influence corporatate governance and formulation of public relations strategies for public enagement. This study explores intertwined relationships between public relations strategies and organizational factors. A total of 22 qualitative interviews were conducted with a diverse pool of communication consultants. Results show that the two public relations strategies, bridging and buffering, are frequently observed and linked with key factors such as size, organizational culture, environment specificity, and strategic orientation. Implications for future public relations and corporate governance research are discussed. Copyright © 2015 John Wiley & Sons, Ltd.
Prospective cardiac MRI for the analysis of biventricular function in children undergoing cancer treatments
Authors: de Ville de Goyet Maëlle , Brichard Benedicte , Robert Annie , Renard Laurette , Veyckemans Francis , Vanhoutte Laetitia , Moniotte Stephane
Published: January 2015

Background

Cardiotoxicity is one of the most serious long‐term complications in childhood cancer survivors. Measurement of the left ventricular ejection and shortening fraction remains the most common screening tool for cardiac systolic dysfunction. However, M‐mode echocardiography can be viewed as a crude approach as refined strategies are now available. The aim of this prospective study was to determine the role of cardiac MRI in the detection of subclinical left or right ventricular dysfunction as well as the prevalence of myocardial scaring in patients undergoing cancer treatments.

Procedure

Eighty‐one children were enrolled in a pre‐chemotherapy and then in a yearly protocol including a: (i) clinical evaluation; (ii) laboratory evaluation; (iii) electrocardiogram; (iv) echocardiogram; and (v) a cardiac magnetic resonance imaging (cMRI).

Results

Early left ventricular systolic dysfunction was only detected in two patients. The entire cohort presented a significant increase of the left atrial volume as measured by cMRI. This finding correlated with the total cumulative dose of anthracyclines (r = 0.34; P < 0.05) and the mean left ventricular radiation dose (r = 0.86; P < 0.05). We also observed a mild increase of myocardial scaring, similarly correlated to the radiation dose (r = 0.85; P < 0.05).

Conclusions

Screening tools for late‐onset cardiomyopathy secondary to cancer treatment are lacking. Our findings support the use of cMRI for the evaluation of the left atrial volume, as an early marker of diastolic dysfunction, and myocardial delayed enhancement, as a marker of myocardial fibrosis and scaring. Longer follow‐up and larger studies are still needed to better define the role of cMRI in the evaluation of childhood cancer survivors. Pediatr Blood Cancer 2015;62:867–874. © 2015 Wiley Periodicals, Inc.
Functional nature of a novel mutant CYLD observed in pediatric lymphoblastic B‐cell leukemia
Authors: Arora Mansi , Kaul Deepak , Varma Neelam
Published: January 2015

The Deubiquitinating enzyme, Cylindromatosis (CYLD), has been established as a crucial regulator of B‐cells. The present study was addressed to identify the nature of CYLD‐dependent RNomics in patients of pediatric age group with B‐ALL. The study revealed the presence of a novel mutant CYLD of 55 kDa in these patients. The mutant CYLD displayed its ability to restrict the cells in G2 phase of cell cycle, down‐regulate PLK‐1 and block the nuclear translocation of BCL3. Based upon these results, we propose that this mutant CYLD has the capacity to act as a differential marker characteristic of B‐cell lymphoblastic leukemia. Pediatr Blood Cancer 2015;62:1066–1069. © 2015 Wiley Periodicals, Inc.
Studies on the molecular mechanisms of seed germination
Authors: Han Chao , Yang Pingfang
Published: January 2015

Seed germination that begins with imbibition and ends with radicle emergence is the first step for plant growth. Successful germination is not only crucial for seedling establishment but also important for crop yield. After being dispersed from mother plant, seed undergoes continuous desiccation in ecosystem and selects proper environment to trigger germination. Owing to the contribution of transcriptomic, proteomic, and molecular biological studies, molecular aspect of seed germination is elucidated well inArabidopsis. Recently, more and more proteomic and genetic studies concerning cereal seed germination were performed on rice (Oryza sativa) and barley (Hordeum vulgare), which possess completely different seed structure and domestication background withArabidopsis. In this review, both the common features and the distinct mechanisms of seed germination are compared among different plant species includingArabidopsis, rice, and maize. These features include morphological changes, cell and its related structure recovery, metabolic activation, hormone behavior, and transcription and translation activation. This review will provide more comprehensive insights into the molecular mechanisms of seed germination.
Lysine conjugation properties in human IgGs studied by integrating high‐resolution native mass spectrometry and bottom‐up proteomics
Authors: Gautier Violette , Boumeester Anja J. , Lössl Philip , Heck Albert J. R.
Published: January 2015

Antibody–drug conjugates (ADCs) are a novel class of biopharmaceuticals several of which are now being investigated in clinical studies. In ADCs, potent cytotoxic drugs are coupled via a linker to reactive residues in IgG monoclonal antibodies. Linkage to lysine residues in the IgGs, using N‐hydroxysuccinimide ester based chemistry, is one of the possible options. To control drug load and specificity, proper knowledge is required about which lysine residues are most accessible and reactive. Here, we combine native MS and bottom‐up proteomics to monitor the overall drug load and site‐specific lysine reactivity, using N‐hydroxysuccinimide‐based tandem mass tags. High‐resolution Orbitrap native MS enables us to monitor and quantify, due to the achieved baseline resolution, the sequential incorporation of up to 69 tandem mass tag molecules into human IgGs. Complementary, bottom‐up proteomics facilitates the identification of some very reactive “hot‐spot” conjugation sites. However, we also identify lysine residues that are highly resistant to chemical labeling. Our integrated approach gives insight into the conjugation properties of IgGs at both the intact protein and residue levels, providing fundamental information for controlling drug load and specificity in lysine‐linked ADCs.
Capillary zone electrophoresis on‐line coupled to mass spectrometry: A perspective application for clinical proteomics
Authors: Pejchinovski Martin , Hrnjez Dajana , Ramirez‐Torres Adela , Bitsika Vasiliki , Mermelekas George , Vlahou Antonia , Zürbig Petra , Mischak Harald , Metzger Jochen , Koeck Thomas
Published: January 2015

Clinical proteomics, a rapidly growing field, intends to use specific diagnostic proteomic/peptidomic markers for initial diagnosis or prognosis of the progression of various diseases. Analyses of disease‐associated markers in defined biological samples can provide valuable molecular diagnostic information for these diseases. This approach relies on sensitive and highly standardized modern analytical techniques. In the recent years, one of these technologies, CZE online coupled to MS (CZE‐MS), has been increasingly used for the detection of peptide biomarkers (<20 kDa) in body fluids such as urine. This review presents the most relevant urinary proteomic studies addressing the application of CZE‐MS in clinically relevant biomarker research between the years 2006 and 2014.
Western blotting revisited: Critical perusal of underappreciated technical issues
Authors: Gorr Thomas A. , Vogel Johannes
Published: January 2015

The most commonly used semiquantitative analysis of protein expression still employs protein separation by denaturing SDS‐PAGE with subsequent Western blotting and quantification of the resulting ODs of bands visualized with specific antibodies. However, many questions regarding this procedure are usually ignored, although still in need of answering: Does isolation or separation procedure harm the integrity or affect modifications (e.g., phosphorylation) of the protein of interest? Does denaturation reduce binding of antibodies used for detection? Should denaturation be performed or should a native gel be run? How can artificial degradations or aggregations be distinguished from biological relevant ones? If the antibody detects multiple bands (which is not uncommon), which one(s) should be taken into account for quantification and why? Which loading control protein should be chosen and is it really “housekeeping” and how can this be verified? Is the image acquisition system linear and does it come with a sufficient dynamic range? How to account and control for background staining? This article is intended to address these questions and raise the readers awareness to possible Western blot alternatives in the attempt of minimizing possible pitfalls that might loom anywhere from protein isolation to acquisition of final quantitative data.
Expression profile analysis of microRNAs in prostate cancer by next‐generation sequencing
Authors: Song Chunjiao , Chen Huan , Wang Tingzhang , Zhang Weiguang , Ru Guomei , Lang Juan
Published: January 2015

BACKGROUND

Prostate cancer (PCa) is the second leading cause of tumor mortality among males in western societies. In China, the diagnostic and fatality rate of PCa is increasing yearly.

METHODS

To characterize underlying molecular mechanisms, the microRNA (miRNA) profile of high‐grade PCa, low‐grade PCa, and benign prostate hyperplasia (BPH) were compared using high‐throughput Illumina sequencing and quantitative real‐time PCR (qRT‐PCR) methods. Moreover, a variety of biological information softwares and databases were applied to predict the target genes of miRNA, molecular functions, and signal pathways.

RESULTS

Eighteen miRNAs were differentially expressed (fold change ≥2, P < 0.05), of which thirteen were upregulated and five were downregulated by sequencing. This was confirmed by qRT‐PCR in more clinical tissue samples. In the tumors, miRNAs (miR‐125b‐5p, miR‐126‐5p, miR‐151a‐5p, miR‐221‐3p, and miR‐222‐3p) were significantly upregulated with downregulation of miR‐486‐5p. In addition, 13 novel miRNAs were identified from three prostate tissue libraries, with 12 of them assayed in 21 human normal tissues by qRT‐PCR. Multiple databases indicated target genes for these differentially expressed miRNAs. Function annotation of target genes indicated that most of them tend to target genes involved in signal transduction and cell communication, especially cancer‐related PI3K‐Akt and p53 signaling pathway.

CONCLUSIONS

The small RNA transcriptomes obtained in this study uncovers six differentially expressed miRNAs and 12 novel miRNAs, and provides a better understanding of the expression and function of miRNAs in the development of PCa and reveals several miRNAs in PCa that may have biomarker and therapeutic potentials. Prostate 75: 500–516, 2015. © 2015 Wiley Periodicals, Inc.
Reduced alphabet for protein folding prediction
Authors: Huang Jitao T. , Wang Titi , Huang Shanran R. , Li Xin
Published: January 2015

What are the key building blocks that would have been needed to construct complex protein folds? This is an important issue for understanding protein folding mechanism and guiding de novo protein design. Twenty naturally occurring amino acids and eight secondary structures consist of a 28‐letter alphabet to determine folding kinetics and mechanism. Here we predict folding kinetic rates of proteins from many reduced alphabets. We find that a reduced alphabet of 10 letters achieves good correlation with folding rates, close to the one achieved by full 28‐letter alphabet. Many other reduced alphabets are not significantly correlated to folding rates. The finding suggests that not all amino acids and secondary structures are equally important for protein folding. The foldable sequence of a protein could be designed using at least 10 folding units, which can either promote or inhibit protein folding. Reducing alphabet cardinality without losing key folding kinetic information opens the door to potentially faster machine learning and data mining applications in protein structure prediction, sequence alignment and protein design. Proteins 2015; 83:631–639. © 2015 Wiley Periodicals, Inc.
Hierarchical domain‐motion analysis of conformational changes in sarcoplasmic reticulum Ca2+‐ATPase
Authors: Kobayashi Chigusa , Koike Ryotaro , Ota Motonori , Sugita Yuji
Published: January 2015

Sarco(endo)plasmic reticulum Ca2+‐ATPase transports two Ca2+ per ATP‐hydrolyzed across biological membranes against a large concentration gradient by undergoing large conformational changes. Structural studies with X‐ray crystallography revealed functional roles of coupled motions between the cytoplasmic domains and the transmembrane helices in individual reaction steps. Here, we employed “Motion Tree (MT),” a tree diagram that describes a conformational change between two structures, and applied it to representative Ca2+‐ATPase structures. MT provides information of coupled rigid‐body motions of the ATPase in individual reaction steps. Fourteen rigid structural units, “common rigid domains (CRDs)” are identified from seven MTs throughout the whole enzymatic reaction cycle. CRDs likely act as not only the structural units, but also the functional units. Some of the functional importance has been newly revealed by the analysis. Stability of each CRD is examined on the morphing trajectories that cover seven conformational transitions. We confirmed that the large conformational changes are realized by the motions only in the flexible regions that connect CRDs. The Ca2+‐ATPase efficiently utilizes its intrinsic flexibility and rigidity to response different switches like ligand binding/dissociation or ATP hydrolysis. The analysis detects functional motions without extensive biological knowledge of experts, suggesting its general applicability to domain movements in other membrane proteins to deepen the understanding of protein structure and function. Proteins 2015; 83:746–756. © 2015 Wiley Periodicals, Inc.
Contactless electroreflectance spectroscopy of ZnO/ZnMgO quantum wells: Optical transitions and Fabry–Perot features
Authors: Wełna M. , Kudrawiec R. , Misiewicz J. , Yano M. , Koike K. , Sasa S.
Published: January 2015

Contactless electroreflectance (CER) spectroscopy was applied to study optical transitions in ZnO/ZnMgO quantum wells (QWs) of various widths and barrier contents (Mg = 10, 20, and 30%) grown on sapphire substrates with a Zn0.9Mg0.1O or ZnO buffer layer. Spectral features related to absorption in ZnO QW region and ZnMgO barrier were clearly observed in CER spectra. The spectral position of these features correlates very well with photoluminescence peaks related to emission from ZnO QW and ZnMgO barrier. Besides CER resonances, which are associated with optical transitions, some spectral features related to the Fabry–Perot (F–P) interference effect were clearly observed for these samples. They appear for these structures due to a strong contrast of refractive index between the sapphire and Zn(Mg)O layers and they are observed in the region of transparency for Zn(Mg)O epilayers. For some samples the F–P related signal is quite strong and interferes with CER resonances related to QW transitions. However the two contributions (i.e., CER signal related to optical transitions and the Fabry–Perot effect) can be recognized when the proper analysis of CER spectra is performed. This analysis is presented and discussed in this paper.
Analysis of diagnostic climate model cloud parametrizations using large‐eddy simulations
Authors: Rosch J. , Heus T. , Brueck M. , Salzmann M. , Mülmenstädt J. , Schlemmer L. , Quaas J.
Published: January 2015

Current climate models often predict fractional cloud cover on the basis of a diagnostic probability density function (PDF) describing the subgrid‐scale variability of the total water specific humidity, qt, favouring schemes with limited complexity. Standard shapes are uniform or triangular PDFs, the widths of which are assumed to scale with the grid‐box mean qt or the grid‐box mean saturation specific humidity, qs. In this study, the qt variability is analysed from large‐eddy simulations for two stratocumulus, two shallow cumulus, and one deep convective cases. We find that, in most cases, triangles are a better approximation to the simulated PDFs than uniform distributions. In 2 of the 24 slices examined, the actual distributions were so strongly skewed that the simple symmetric shapes could not capture the PDF at all. The distribution width for either shape scales acceptably well with both the mean values of qt and qs, the former being a slightly better choice. The qt variance is underestimated by the fitted PDFs, but overestimated by the existing parametrizations. While the cloud fraction is in general relatively well diagnosed from fitted or parametrized uniform or triangular PDFs, it fails to capture cases with small partial cloudiness, and in 10–30% of the cases misdiagnoses clouds in clear skies or vice versa. The results suggest choosing a parametrization with a triangular shape, where the distribution width would scale with the grid‐box mean qt using a scaling factor of 0.076. However, this is subject to the caveat that the reference simulations examined here were partly for rather small domains and driven by idealised boundary conditions.
Process, Policy, and Implementation of Pool‐Wide Drawdowns on the Upper Mississippi River: A Promising Approach for Ecological Restoration of Large Impounded Rivers
Authors: Kenow K. P. , Benjamin G. L. , Schlagenhaft T. W. , Nissen R. A. , Stefanski M. , Wege G. J. , Jutila S. A. , Newton T. J.
Published: January 2015

The Upper Mississippi River (UMR) has been developed and subsequently managed for commercial navigation by the U.S. Army Corps of Engineers (USACE). The navigation pools created by a series of lock and dams initially provided a complex of aquatic habitats that supported a variety of fish and wildlife. However, biological productivity declined as the pools aged. The River Resources Forum, an advisory body to the St. Paul District of the USACE, established a multiagency Water Level Management Task Force (WLMTF) to evaluate the potential of water level management to improve ecological function and restore the distribution and abundance of fish and wildlife habitat. The WLMTF identified several water level management options and concluded that summer growing season drawdowns at the pool scale offered the greatest potential to provide habitat benefits over a large area. Here we summarize the process followed to plan and implement pool‐wide drawdowns on the UMR, including involvement of stakeholders in decision making, addressing requirements to modify reservoir operating plans, development and evaluation of drawdown alternatives, pool selection, establishment of a monitoring plan, interagency coordination, and a public information campaign. Three pool‐wide drawdowns were implemented within the St. Paul District and deemed successful in providing ecological benefits without adversely affecting commercial navigation and recreational use of the pools. Insights are provided based on more than 17 years of experience in planning and implementing drawdowns on the UMR. Copyright © 2015 John Wiley & Sons, Ltd.
Re‐operating the Three Gorges Reservoir for Environmental Flows: A Preliminary Assessment of Trade‐offs
Authors: Rheinheimer D. E. , Liu P. , Guo S.
Published: January 2015

The Three Gorges Reservoir (TGR), located on the Yangtze River in China, is operated for hydropower, flood control and navigation, with minimal environmental releases. This study explored the potential trade‐offs between better environmental releases from the TGR and hydropower generation using three performance indicators. Spearman's rank correlation coefficient between unimpaired flows and regulated flows was used as an indicator of environmental performance (eco rho). Energy generation as a fraction of capacity (energy fraction) and power reliability were used as hydropower performance indicators. We first assessed TGR performance without and with basic instream flow requirements (IFRs). We then imposed an IFR consisting of a minimum release of fraction k of inflow and maximum release of 1/k of inflow and assessed the sensitivity of reservoir performance to different fixed k values. Finally, we allowed k to vary within the year in a genetic algorithm to estimate the Pareto optimal trade‐offs between performance indicators. In all cases, flood and navigation rules were prioritized over environmental and hydropower. With a fixed k of 1.0, eco rho increased from 0.865 to nearly 1.0 (completely natural). Energy fraction reduced from 43.5 to 39.3%, or about 9.5%, and power reliability decreased from 97.0 to 59.2%. The Pareto optimal trade‐off surface not only showed similar results but also indicated that energy fraction and environmental performance can both be increased together, up to a point, but at a cost of reliability. This study helps understand the potential costs of re‐operating the TGR. Limitations and potential future directions are discussed. Copyright © 2015 John Wiley & Sons, Ltd.
Anionic Lipid, pH‐Sensitive Liposome‐Gold Nanoparticle Hybrids for Gene Delivery – Quantitative Research of the Mechanism
Authors: Du Baoji , Tian Li , Gu Xiaoxiao , Li Dan , Wang Erkang , Wang Jin
Published: January 2015

Gene therapy is a potential method for treating a large range of diseases. Gene vectors are widely used in gene therapy for promoting the gene delivery efficiency to the target cells. Here, gold nanoparticles (AuNPs) coated with dimethyldioctadecylammonium bromide (DODAB)/dioleoylphosphatidylethanolamine (DOPE) are synthesized using a facile method for a new gene vector (DODAB/DOPE‐AuNPs), which possess 3‐ and 1.5‐fold higher transfection efficiency than those of DODAB‐AuNPs and a commercial transfection agent, respectively. Meanwhile, it is nontoxic with concentrations required for effective gene delivery. Imaging and quantification studies of cellular uptake reveal that DOPE increases gene copies in cells, which may be attributed to the smaller size of AuNPs/DNA complexes. The dissociation efficiency of DNA from the endocytic pathway is quantified by incubating with different buffers and investigated directly in the cells. The results suggest that DOPE increases the internalization of AuNPs/DNA complexes and promotes DNA release from early endosomes for the vector is sensitive to the anionic lipid membrane and the decreasing pH along the endocytic pathway. The new vector contains the potential to be the new alternative as gene delivery vector for biomedical applications.
Nano‐to‐Microdesign of Marimo‐Like Carbon Nanotubes Supported Frameworks via In‐spaced Polymerization for High Performance Silicon Lithium Ion Battery Anodes
Authors: Huang Yao‐Hui , Bao Qi , Chen Bing‐Hong , Duh Jenq‐Gong
Published: January 2015

Silicon (Si) has been perceived as a promising anode material for lithium‐ion batteries for decades due to its superior theoretical capacity, environmental benignity, and earth abundance. To accommodate the drastic volume expansion during lithiation, which is the primary drawback leading to poor cycling life, a novel structural design via fabricating the Marimo‐like carbon nanotubes frameworks with silicon nanoparticle (SiNP) filling in internal space has been developed. This facile fabrication procedure involves an in‐spaced polymerization process through ex situ polymerization, using pyrrole monomers with a soft organic template in which well‐dispersed SiNPs are present. Carbonization post‐treatment is then performed to construct rigid conductive networks. The thus‐fabricated 3D Marimo‐like hybrid structure exhibits a remarkably improved electrochemical performance compared with that of the simple ball‐milling method, which mainly originates from their structural advantages, including the built‐in buffer spaces and the robust line‐to‐line contact mode between the components. The state‐of‐the‐art structure exhibits an optimal high‐rate capability (422 mAh g−1 at a current rate of 2 A g−1) and long cycling stability (916 mAh g−1 for 200th cycles at a current rate of 0.2 A g−1) and achieves the requirements for industrial production with the facile and cost‐effective synthetic approach.
An investigation of statistical software testing
Authors: Thévenod‐Fosse P , Waeselynck H
Published: January 2015

Software validation embodies two notions: fault removal and fault forecasting. Statistical testing involves exercising a piece of software by supplying it with input values that are randomly selected according to a defined probability distribution on its input domain. It can be used as a practical tool for revealing faults in a fault removal phase, and for assessing software dependability in a fault forecasting phase. In both of these, its efficiency is linked to the adequacy of the input probability distribution with respect to the test experiment goal. In this paper a mixed validation strategy combining deterministic and random test data is defined, and the theoretical and experimental work performed to support the strategy is reported. The quoted results relate to the unit testing of four real programs from the nuclear field. They confirm the high fault revealing power of statistical structural testing. Two main directions for further investigation of statistical testing are indicated by the reported work. These are described and solutions to the associated problems are outlined.
Validating software measures
Authors: Fenton Norman , Kitchenham Barbara
Published: January 2015

There are two distinct notions of validation for software measures. On the one hand there is the informal notion that a measure is only valid if it is useful and practical. Although this view of validation is important, it is almost impossible to test. On the other hand there is a formal notion of validation of measures and it is this view which is addressed here. By considering software measures in the context of measurement theory, and by considering a classification of software entities into products, processes and resources the paper describes what the authors believe are the necessary (but not sufficient) activities required for validation, and show how far this deviates from the ‘accepted’ view of validation.