bluuebunny/crossref_metadata_2025 huggingface dataset:
Flow and shape reconstructions from remote measurements
Authors: Zia Qazi Muhammad Zaigham , Potthast Roland W.E.
Published: December 2012

We develop a point source method (PSM) to obtain flow field reconstructions from remote measurements. The PSM belongs to the class of decomposition methods in inverse scattering because it solves the nonlinear and ill‐posed inverse shape reconstruction problem by a decomposition into a linear ill‐posed problem and a nonlinear well‐posed problem. As a model problem, we investigate the reconstruction of the flow field of two‐dimensional stationary Oseen equation,
urn:x-wiley:1704214:media:mma2670:mma2670-math-0001 which is obtained by linearizing the Navier–Stokes equation with kinematic viscosity μ > 0 around the constant velocity u0. In contrast to acoustics or electromagnetics, the use of the PSM in fluid dynamics leads to a number of challenges in terms of the analysis and the proper setup of the scheme, in particular, because the null‐spaces of the integral operators under consideration are no longer trivial and the fundamental solution is not symmetric in its spatial coordinate. We provide a suitable formulation of the method and prove convergence of flow reconstructions by the PSM. For the realization of the reconstruction when the inclusions are not known, we employ domain sampling. We will demonstrate the feasibility of the method for reconstructing one or several objects by numerical examples. Copyright © 2012 John Wiley & Sons, Ltd.
Microarray and pathway analysis highlight Nrf2/ARE‐mediated expression profiling by polyphenolic myricetin
Authors: Qin Si , Chen Jihua , Tanigawa Shunsuke , Hou De‐Xing
Published: December 2012

Scope

Myricetin is a dietary flavonol and widely distributed in many edible plants. It has been reported to have many bioactivities and considered as a promising chemopreventive compound. The present study aimed to investigate the influences of myricetin on gene expressions in genome‐wide and underlying mechanisms.

Methods and results

Among total 44K gene probes, myricetin treatment upregulated the signals of 143 gene probes (0.33% of total probes) and downregulated signals of 476 gene probes (1.08% of total probes) by greater than or equal to twofold in HepG2 cells. The network pathway analysis revealed that nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2)‐mediated antioxidant response element (ARE) activation is involved in myricetin‐induced genes expressions. Molecular data revealed that myricetin activated Nrf2‐ARE pathway by inhibiting Nrf2 ubiquitination and protein turnover, stimulating Nrf2 expression and kelch‐like erythroid cell‐derived protein with CNC homology (ECH)‐associated protein 1 modification. All of these events finally increased nuclear Nrf2 accumulation and ARE‐binding activity to enhance ARE‐mediated genes expressions. Additionally, treatment with Nrf2 small interfering RNA attenuated the myricetin‐induced ARE activity and gene expression.

Conclusion

An Nrf2‐mediated ARE activation is involved in myricetin‐induced expression profiling in hepatic cells.
In vivo magnetic resonance spectroscopy detection of combined glutamate‐glutamine in healthy upper cervical cord at 3 T
Authors: Solanky Bhavana S , Abdel‐Aziz Khaled , Yiannakas Marios C , Berry Alaine M , Ciccarelli Olga , Wheeler‐Kingshott Claudia AM
Published: December 2012

The possibility of quantifying the superimposed signal of glutamate and glutamine (Glx) and its components by 1 H magnetic resonance spectroscopy (MRS) in the spinal cord is an exciting challenge with important clinical applications in neurological conditions. The spinal cord is a particularly difficult region of interest due to its small volume, magnetic field inhomogeneities and physiological motion. In this study, we investigated for the first time the feasibility of obtaining quantitative measurements of Glx in healthy cervical spinal cord by 1 H MRS at 3 T.

The aim of this study was to compare two commercially available MRS sequences by spectral simulations and in vivo. A short echo time (TE) point resolved spectroscopy (PRESS) with TE = 30 ms and a stimulated echo acquisition mode (STEAM) with TE = 11 ms and mixing time (TM) = 17 ms were compared for reliability of Glx fit. Data allowed us to determine sample size estimates for future clinical studies for the first time.

Results showed that PRESS provided a reliable fit for Glx in all cases (Cramér Rao lower bounds < 20%) whereas no reliable Glx fits were achieved using STEAM. Neither protocol provided reliable Glu quantification. The power calculations showed that a minimum sample size of 17 subjects per group was needed to detect Glx changes of > 20% using the PRESS sequence. This study proposed a clinically feasible MRS method for Glx detection in the human cervical cord in vivo including sample sizes needed for conclusive clinical studies. Copyright © 2012 John Wiley & Sons, Ltd.
Qualitative and quantitative ultrashort‐TE MRI of cortical bone
Authors: Du Jiang , Bydder Graeme M.
Published: December 2012

Osteoporosis causes over 1.5 million fractures per year, costing about $15 billion annually in the USA. Current guidelines utilize bone mineral density (BMD) to assess fracture risk; however, BMD alone only accounts for 30–50% of fractures. The other two major components of bone, organic matrix and water, contribute significantly to bone mechanical properties, but cannot be assessed with conventional imaging techniques in spite of the fact that they make up about 57% of cortical bone by volume. Conventional clinical MRI usually detects signals from water in tissues without difficulty, but cannot detect the water bound to the organic matrix, or the free water in the microscopic pores of the Haversian and the lacunar‐canalicular system of cortical bone, because of their very short apparent transverse relaxation times (T2*). In recent years, a new class of sequences, ultrashort‐TE (UTE) sequences, with nominal TEs of less than 100 µs, which are much shorter than the TEs available with conventional sequences, have received increasing interest. These sequences can detect water signals from within cortical bone and provide an opportunity to study disease of this tissue in a new way. This review summarizes the recent developments in qualitative UTE imaging (techniques and contrast mechanisms to produce bone images with high contrast) and quantitative UTE imaging (techniques to quantify the MR properties, including T1, T2* and the magnetization transfer ratio, and tissue properties, including bone perfusion, as well as total, bound and free water content) of cortical bone in vitro and in vivo. The limitations of the current techniques for clinical applications and future directions are also discussed. Copyright © 2012 John Wiley & Sons, Ltd.
NetCube: a comprehensive network traffic analysis model based on multidimensional OLAP data cube
Authors: Park Daihee , Yu Jaehak , Park Jun‐Sang , Kim Myung‐Sup
Published: December 2012

Network traffic monitoring and analysis are essential for effective network operation and resource management. In particular, multidimensional analysis for long‐term traffic data is necessary for comprehensive understanding of the traffic trend and effective quality‐of‐service provision considering the extremely dynamic behavior of the current Internet, where various types of traffic occur from high‐speed network links and greatly increasing number of applications. However, only limited analysis results are provided, as the existing network traffic analysis tools and systems are developed and deployed focusing on their own specialized analysis purposes. Consequently, it is difficult to understand the network comprehensively and deeply, which increases the necessity for multilateral analysis of long‐term traffic data. In this paper, we propose a novel traffic analysis model for large volumes of Internet traffic accumulated over a long period of time. The NetCube, the proposed network traffic analysis model using online analytical processing (OLAP) on a multidimensional data cube, provides an easy and fast way to construct a multidimensional traffic analysis system for comprehensive and detailed analysis of long‐term traffic data by utilizing simple OLAP operations and powerful data‐mining techniques on various abstraction levels of traffic data to complete the analysis purpose. We validate the feasibility and applicability of the proposed NetCube traffic analysis model by implementing a traffic analysis system and applying it to our campus network. Copyright © 2012 John Wiley & Sons, Ltd.
An adaptive scheme for a class of interpolatory model reduction methods for frequency response problems
Authors: Hetmaniuk Ulrich , Tezaur Radek , Farhat Charbel
Published: December 2012

Frequency sweep problems arise in many structural dynamic, acoustic, and structural acoustic applications. In each case, they incur the evaluation of a frequency response function for a typically large number of frequencies. Because each function evaluation requires the solution of an often large‐scale system of equations, frequency sweep problems are computationally intensive. Interpolatory model order reduction is a powerful tool for reducing their cost. However, the performance of this tool depends on the location and number of the interpolation frequency points. It also depends on the number of consecutive frequency derivatives of the response function that are matched at each frequency point. So far, these two choices have been made in the literature in a heuristic manner. In contrast, this paper proposes an automatic adaptive strategy based on monitoring the Euclidean norm of the relative residual associated with the function to be evaluated over the frequency band of interest. More specifically, the number of interpolation points and the number of matched frequency derivatives are adaptively increased until the global Euclidean norm of the relative residual is reduced below a user‐specified tolerance. The robustness, accuracy, and computational efficiency of this adaptive strategy are highlighted with the solution of several frequency sweep problems associated with large‐scale structural dynamic, acoustic, and structural acoustic finite element models. Copyright © 2012 John Wiley & Sons, Ltd.
Uncertainty‐based robust aerodynamic optimization of rotor blades
Authors: Wang Xiaodong , Hirsch Charles , Liu Zhiyi , Kang Shun , Lacor Chris
Published: December 2012

The aerodynamic performance of a compressor is highly sensitive to uncertain working conditions. This paper presents an efficient robust aerodynamic optimization method on the basis of nondeterministic computational fluid dynamic (CFD) simulation and multi‐objective genetic algorithm (MOGA). A nonintrusive polynomial chaos method is used in conjunction with an existing well‐verified CFD module to quantify the uncertainty propagation in the flow field. This method is validated by comparing with a Monte Carlo method through full 3D CFD simulations on an axial compressor (National Aeronautics and Space Administration rotor 37). On the basis of the validation, the nondeterministic CFD is coupled with a surrogate‐based MOGA to search for the Pareto front. A practical engineering application is implemented to the robust aerodynamic optimization of rotor 37 under random outlet static pressure. Two curve angles and two sweep angles at tip and hub are used as design variables. Convergence analysis shows that the surrogate‐based MOGA can obtain the Pareto front properly. Significant improvements of both mean and variance of the efficiency are achieved by the robust optimization. The comparison of the robust optimization results with that of the initial design, and a deterministic optimization demonstrate that the proposed method can be applied to turbomachinery successfully. Copyright © 2012 John Wiley & Sons, Ltd.
Thermal degradation and flammability behavior of polypropylene/clay/carbon nanotube composite systems
Authors: Hapuarachchi Tharindu Dhanushka , Peijs Ton , Bilotti Emiliano
Published: December 2012

This paper reports on the testing and development of a polypropylene (PP) nanocomposite systems with improved flame retardancy. The work utilizes the unique properties of sepiolite nanoclay (Sep) in combination with carbon nanotubes (CNTs) in order to develop an optimized ternary nanocomposite system. Thermogravimetric analysis (TGA) showed significant improvements to the residual char towards the later stages of the thermal ramp. The pyrolysis combustion flow calorimeter (PCFC) was employed to screen the various PP composites with respect to their potential flammability performance. The heat release capacity, which is an indicator of a materials fire hazard, did not show any reduction with the addition of nanofillers using the apparatus standard testing procedure. However, this changed by switching to a lower burn within the PCFC's furnace; this diverted oxygen to the pyrolysing sample. Using the results gained from TGA and the PCFC, the optimized ternary nanocomposite system (10 wt.% Sep + 2 wt.% CNT) was compounded on a larger scale and tested in the cone calorimeter. This showed a significant reduction of 82% in peak heat release rate in comparison to unfilled PP. Comparisons were also made between the testing of these samples in the PCFC and cone calorimeter. The main objectives were to develop a flame‐retardant PP nanocomposite ternary system as well as assessing the PCFC with traditional techniques. Copyright © 2012 John Wiley & Sons, Ltd.
C‐glucosidic Ellagitannins from Lythri herba (European Pharmacopoeia): Chromatographic Profile and Structure Determination
Authors: Piwowarski Jakub P. , Kiss Anna K.
Published: December 2012

Introduction

Lythri herba, a pharmacopoeial plant material (European Pharmacopoea), is obtained from flowering parts of purple loosestrife (Lythrum salicaria L.). Although extracts from this plant material have been proven to possess some interesting biological activities and its pharmacopoeial standardisation is based on total tannin content determination, the phytochemical characterisation of this main group of compounds has not yet been fully conducted.

Objective

To isolate ellagitannins from Lythri herba, determine their structures and develop chromatographic methods for their qualitative analysis.

Results

Five C‐glucosidic ellagitannins – monomeric‐ vescalagin and castalagin together with new dimeric structures – salicarinins A–C, composed of vescalagin and stachyurin, vescalagin and casuarinin, castalagin and casuarinin units connected via formation of valoneoyl group, were isolated using column chromatography and preparative HPLC. Structures were determined according to 1H and 13C‐NMR (one‐ and two‐dimensional), electrospray ionisation–time of flight (ESI–TOF), electrospray ionisation‐ion trap (ESI‐MSn) and circular dichroism (CD) spectra, together with acidic hydrolysis products analysis. HPTLC on RP‐18 modified plates and HPLC–DAD–MSn on RP‐18 column methods were developed for separation of the five main ellagitannins. Copyright © 2012 John Wiley & Sons, Ltd.
Contextualized Project Management Practice: A Cluster Analysis of Practices and Best Practices
Authors: Besner Claude , Hobbs Brian
Published: December 2012

The specificity of project management in different contexts and industries is recognized, but little empirical research encompasses a sufficiently broad range of contexts and project types to precisely identify these specificities. This article adopts such a wide perspective based on a large sample of data from an ongoing empirical investigation of project management practice. Contextual archetypes are identified (i.e., clusters of experienced practitioners that share similar organizational and project contexts). Archetypes of contextualized practice are then investigated through the study of the extent of use of empirically identified toolsets in each cluster. The results empirically confirm some well-known assumptions about practice but also sharpen the knowledge and understanding of practice in real complex multidimensional contexts. A new concept of “performing-maturity” emerged from the data. This concept sheds light on the entangled imbrications of maturity, competence, and success. Practices are regressed against performing-maturity to reveal best contextualized practices.
A Bayesian Approach to Improve Estimate at Completion in Earned Value Management
Authors: Caron Franco , Ruggeri Fabrizio , Merli Alessandro
Published: December 2012

Forecasting represents a core project management process. Estimates at completion in terms of cost and schedule provide essential data and advice to the project team in order to lead and control the project and implement suitable corrective measures. In order to improve the forecasting process, a Bayesian model has been developed within the earned value management framework aiming to calculate a confidence interval for the estimates of both cost and schedule at the completion of the project. The model is based on the integration of data records and qualitative knowledge provided by experts. The model has been tested in an oil and gas project.
Potentiating Effect of the Flavonolignan (‐)‐Hydnocarpin in Combination with Vincristine in a Sensitive and P‐gp‐Expressing Acute Lymphoblastic Leukemia Cell Line
Authors: Bueno Pérez Lynette , Pan Li , Sass Ellen , Gupta Sneha V. , Lehman Amy , Kinghorn A. Douglas , Lucas David M.
Published: December 2012

The potentiating action of the flavonolignan, (‐)‐hydnocarpin, in combination with vincristine was evaluated in the 697 acute lymphoblastic leukemia cell line and a P‐gp‐expressing variant, 697‐R. Vincristine at 3 nM caused nearly complete growth inhibition in 697 cells versus a 17% growth inhibition in 697‐R cells. When combined with (‐)‐hydnocarpin at concentrations of 10 and 5 μM, vincristine‐mediated growth inhibition in the 697‐R cells increased significantly over the sum of the individual agents to 72% (p ≤ 0.0001) and 41% (p = 0.0256), respectively. Vincristine at 1.5 nM (66% growth inhibition) and 0.75 nM (39% growth inhibition) combined with (‐)‐hydnocarpin at 10 μM (42% growth inhibition) in the 697 cells caused a significant increase in growth inhibition to 83% (p = 0.03) and to 61% (p < 0.0001), respectively, when compared to vincristine treatment as a single agent. To investigate the mechanism for the vincristine re‐sensitization caused by (‐)‐hydnocarpin, the P‐gp inhibitory effect of (‐)‐hydnocarpin was evaluated. Copyright © 2012 John Wiley & Sons, Ltd.
Simulation of the Decontamination Efficiency of PET Recycling Processes based on Solid‐state Polycondensation
Authors: Welle Frank
Published: December 2012

The recollection rates for postconsumer poly(ethylene terephthalate) (PET) bottles and the recycling capacities are increasing year by year. The postconsumer PET bottles were recycled either to fibres or to new packaging applications. For packaging applications, the so‐called super‐clean recycling technologies are applied to decontaminate the postconsumer PET pellets. Most of these processes are based on solid‐state polycondensation processes. Because experimental determination of the cleaning efficiency is a time‐consuming and expensive procedure, it would be useful to predict the cleaning efficiencies, e.g. for process development and optimization. Within this study, the decontamination kinetics of a PET super‐clean recycling process based on solid‐state polycondensation was determined. From the decontamination kinetics, the diffusion coefficients were calculated. By use of the diffusion coefficients, the decontamination kinetics was simulated using migration modelling approaches for spherical pellets. The result of this study shows that the decontamination of PET pellets in solid‐state polycondensation processes follows Fickian laws. The diffusion coefficients of the investigated migrants are not influenced by vacuum or inert gas process conditions. The diffusion equations used in commercially available software packages for migration calculation can be used for the simulation of the decontamination efficiencies of PET recycling processes. Copyright © 2012 John Wiley & Sons, Ltd.
Memory and other properties of multiple test procedures generated by entangled graphs
Authors: Maurer Willi , Bretz Frank
Published: December 2012

Methods for addressing multiplicity in clinical trials have attracted much attention during the past 20 years. They include the investigation of new classes of multiple test procedures, such as fixed sequence, fallback and gatekeeping procedures. More recently, sequentially rejective graphical test procedures have been introduced to construct and visualize complex multiple test strategies. These methods propagate the local significance level of a rejected null hypothesis to not‐yet rejected hypotheses. In the graph defining the test procedure, hypotheses together with their local significance levels are represented by weighted vertices and the propagation rule by weighted directed edges. An algorithm provides the rules for updating the local significance levels and the transition weights after rejecting an individual hypothesis. These graphical procedures have no memory in the sense that the origin of the propagated significance level is ignored in subsequent iterations. However, in some clinical trial applications, memory is desirable to reflect the underlying dependence structure of the study objectives. In such cases, it would allow the further propagation of significance levels to be dependent on their origin and thus reflect the grouped parent–descendant structures of the hypotheses. We will give examples of such situations and show how to induce memory and other properties by convex combination of several individual graphs. The resulting entangled graphs provide an intuitive way to represent the underlying relative importance relationships between the hypotheses, are as easy to perform as the original individual graphs, remain sequentially rejective and control the familywise error rate in the strong sense. Copyright © 2012 John Wiley & Sons, Ltd.
An improved quadratic inference function for parameter estimation in the analysis of correlated data
Authors: Westgate Philip M. , Braun Thomas M.
Published: December 2012

Generalized estimating equations (GEE) are commonly employed for the analysis of correlated data. However, the quadratic inference function (QIF) method is increasing in popularity because of its multiple theoretical advantages over GEE. We base our focus on the fact that the QIF method is more efficient than GEE when the working covariance structure for the data is misspecified. It has been shown that because of the use of an empirical weighting covariance matrix inside its estimating equations, the QIF method's realized estimation performance can potentially be inferior to GEE's when the number of independent clusters is not large. We therefore propose an alternative weighting matrix for the QIF, which asymptotically is an optimally weighted combination of the empirical covariance matrix and its model‐based version, which is derived by minimizing its expected quadratic loss. Use of the proposed weighting matrix maintains the large‐sample advantages the QIF approach has over GEE and, as shown via simulation, improves small‐sample parameter estimation. We also illustrated the proposed method in the analysis of a longitudinal study. Copyright © 2012 John Wiley & Sons, Ltd.
A PRC2-Dependent Repressive Role of PRDM14 in Human Embryonic Stem Cells and Induced Pluripotent Stem Cell Reprogramming
Authors: Chan Yun-Shen , Göke Jonathan , Lu Xinyi , Venkatesan Nandini , Feng Bo , Su I-Hsin , Ng Huck-Hui
Published: December 2012

PRDM14 is an important determinant of the human embryonic stem cell (ESC) identity and works in concert with the core ESC regulators to activate pluripotency-associated genes. PRDM14 has been previously reported to exhibit repressive activity in mouse ESCs and primordial germ cells; and while PRDM14 has been implicated to suppress differentiation genes in human ESCs, the exact mechanism of this repressive activity remains unknown. In this study, we provide evidence that PRDM14 is a direct repressor of developmental genes in human ESCs. PRDM14 binds to silenced genes in human ESCs and its global binding profile is enriched for the repressive trimethylation of histone H3 lysine 27 (H3K27me3) modification. Further investigation reveals that PRDM14 interacts directly with the chromatin regulator polycomb repressive complex 2 (PRC2) and PRC2 binding is detected at PRDM14-bound loci in human ESCs. Depletion of PRDM14 reduces PRC2 binding at these loci and the concomitant reduction of H3K27me3 modification. Using reporter assays, we demonstrate that gene loci bound by PRDM14 exhibit repressive activity that is dependent on both PRDM14 and PRC2. In reprogramming human fibroblasts into induced pluripotent stem cells (iPSCs), ectopically expressed PRDM14 can repress these developmental genes in fibroblasts. In addition, we show that PRDM14 recruits PRC2 to repress a key mesenchymal gene ZEB1, which enhances mesenchymal-to-epithelial transition in the initiation event of iPSC reprogramming. In summary, our study reveals a repressive role of PRDM14 in the maintenance and induction of pluripotency and identifies PRDM14 as a new regulator of PRC2.
Chronic methamphetamine exposure produces a delayed, long‐lasting memory deficit
Authors: North Ashley , Swant Jarod , Salvatore Michael F. , Gamble‐george Joyonna , Prins Petra , Butler Brittany , Mittal Mukul K. , Heltsley Rebecca , Clark John T. , Khoshbouei Habibeh
Published: December 2012

Methamphetamine (METH) is a highly addictive and neurotoxic psychostimulant. Its use in humans is often associated with neurocognitive impairment. Whether this is due to long‐term deficits in short‐term memory and/or hippocampal plasticity remains unclear. Recently, we reported that METH increases baseline synaptic transmission and reduces LTP in an ex vivo preparation of the hippocampal CA1 region from young mice. In the current study, we tested the hypothesis that a repeated neurotoxic regimen of METH exposure in adolescent mice decreases hippocampal synaptic plasticity and produces a deficit in short‐term memory. Contrary to our prediction, there was no change in the hippocampal plasticity or short‐term memory when measured after 14 days of METH exposure. However, we found that at 7, 14, and 21 days of drug abstinence, METH‐exposed mice exhibited a deficit in spatial memory, which was accompanied by a decrease in hippocampal plasticity. Our results support the interpretation that the deleterious cognitive consequences of neurotoxic levels of METH exposure may manifest and persist after drug abstinence. Therefore, therapeutic strategies should consider short‐term as well as long‐term consequences of methamphetamine exposure. Synapse 67:245–257, 2013. © 2012 Wiley Periodicals, Inc.
State-Space Analysis of Working Memory in Schizophrenia: An FBIRN Study
Authors: Janoos Firdaus , Brown Gregory , Mórocz Istvan Á. , Wells William M.
Published: December 2012

The neural correlates of working memory (WM) in schizophrenia (SZ) have been extensively studied using the multisite fMRI data acquired by the Functional Biomedical Informatics Research Network (fBIRN) consortium. Although univariate and multivariate analysis methods have been variously employed to localize brain responses under differing task conditions, important hypotheses regarding the representation of mental processes in the spatio-temporal patterns of neural recruitment and the differential organization of these mental processes in patients versus controls have not been addressed in this context. This paper uses a multivariate state-space model (SSM) to analyze the differential representation and organization of mental processes of controls and patients performing the Sternberg Item Recognition Paradigm (SIRP) WM task. The SSM is able to not only predict the mental state of the subject from the data, but also yield estimates of the spatial distribution and temporal ordering of neural activity, along with estimates of the hemodynamic response. The dynamical Bayesian modeling approach used in this study was able to find significant differences between the predictability and organization of the working memory processes of SZ patients versus healthy subjects. Prediction of some stimulus types from imaging data in the SZ group was significantly lower than controls, reflecting a greater level of disorganization/heterogeneity of their mental processes. Moreover, the changes in accuracy of predicting the mental state of the subject with respect to parametric modulations, such as memory load and task duration, may have important implications on the neurocognitive models for WM processes in both SZ and healthy adults. Additionally, the SSM was used to compare the spatio-temporal patterns of mental activity across subjects, in a holistic fashion and to derive a low-dimensional representation space for the SIRP task, in which subjects were found to cluster according to their diagnosis.
An Introduction to Normalization and Calibration Methods in Functional MRI
Authors: Liu Thomas T. , Glover Gary H. , Mueller Bryon A. , Greve Douglas N. , Brown Gregory G.
Published: December 2012

In functional magnetic resonance imaging (fMRI), the blood oxygenation level dependent (BOLD) signal is often interpreted as a measure of neural activity. However, because the BOLD signal reflects the complex interplay of neural, vascular, and metabolic processes, such an interpretation is not always valid. There is growing evidence that changes in the baseline neurovascular state can result in significant modulations of the BOLD signal that are independent of changes in neural activity. This paper introduces some of the normalization and calibration methods that have been proposed for making the BOLD signal a more accurate reflection of underlying brain activity for human fMRI studies.
Multiobjective Blockmodeling for Social Network Analysis
Authors: Brusco Michael , Doreian Patrick , Steinley Douglas , Satornino Cinthia B.
Published: December 2012

To date, most methods for direct blockmodeling of social network data have focused on the optimization of a single objective function. However, there are a variety of social network applications where it is advantageous to consider two or more objectives simultaneously. These applications can broadly be placed into two categories: (1) simultaneous optimization of multiple criteria for fitting a blockmodel based on a single network matrix and (2) simultaneous optimization of multiple criteria for fitting a blockmodel based on two or more network matrices, where the matrices being fit can take the form of multiple indicators for an underlying relationship, or multiple matrices for a set of objects measured at two or more different points in time. A multiobjective tabu search procedure is proposed for estimating the set of Pareto efficient blockmodels. This procedure is used in three examples that demonstrate possible applications of the multiobjective blockmodeling paradigm.
Statin Treatment Improves Plasma Lipid Levels but not HDL Subclass Distribution in Patients Undergoing Percutaneous Coronary Intervention
Authors: Tian Li , Chen Yucheng , Li Chuanwei , Zeng Zhi , Xu Yanhua , Long Shiyin , Fu Mingde
Published: December 2012

Despite the established efficacy of statin therapy, the risk of cardiovascular events remains high in many patients. We examined high‐density lipoprotein (HDL) subclass distribution profiles among statin‐treated coronary heart disease (CHD) patients undergoing percutaneous coronary intervention (PCI). Plasma HDL subclasses were measured in 85 patients with established CHD and quantified by two‐dimensional gel electrophoresis and immunoblotting. In CHD patients with statin treatment, the mean value of total cholesterol (TC) reached the desirable level and the triacylglycerol level (TAG) was borderline high. Moreover, low density lipoprotein cholesterol (LDL‐C), high density lipoprotein cholesterol (HDL‐C), apolipoproteinA‐I, and apolipoproteinB‐100 levels in these patients resembled those in normolipidemic healthy subjects. The HDL subclass did not show a normal distribution and was characterized by the lower large‐sized HDL2b contents and higher contents of small‐sized preβ1‐HDL in CHD patients, compared to those in normolipidemic control subjects. Multiple stepwise regression analysis revealed that the severity of coronary stenosis, determined by the Gensini Score, was significantly and independently predicted by HDL2b and HDL3b. Statin therapy was effective in modifying plasma lipids levels, but not adequate as a monotherapy to normalize the HDL subclass distribution phenotype of patients with CHD undergoing PCI. The HDL subclass distribution may aid in risk stratification, especially in patients with CHD and therapeutic LDL‐C and HDL‐C levels.
Lipoxygenase Products in the Urine Correlate with Renal Function and Body Temperature but not with Acute Transplant Rejection
Authors: Reinhold Stephan W. , Scherl Thomas , Stölcker Benjamin , Bergler Tobias , Hoffmann Ute , Weingart Christian , Banas Miriam C. , Kollins Dmitrij , Kammerl Martin C. , Krüger Bernd , Kaess Bernhard , Krämer Bernhard K. , Banas Bernhard
Published: December 2012

Acute transplant rejection is the leading cause of graft loss in the first months after kidney transplantation. Lipoxygenase products mediate pro‐ and anti‐inflammatory actions and thus we aimed to correlate the histological reports of renal transplant biopsies with urinary lipoxygenase products concentrations to evaluate their role as a diagnostic marker. This study included a total of 34 kidney transplant recipients: 17 with an acute transplant rejection and 17 controls. LTE4, LTB4, 12‐HETE and 15‐HETE concentrations were measured by enzyme immunoassay. Urinary lipoxygenase product concentrations were not significantly changed during an acute allograft rejection. Nevertheless, LTB4 concentrations correlated significantly with the body temperature (P ≤ 0.05) 3 months after transplantation, and 12‐ and 15‐HETE concentrations correlated significantly with renal function (P ≤ 0.05) 2 weeks after transplantation. In conclusion, our data show a correlation for LTB4 with the body temperature 3 months after transplantation and urinary 12‐ and 15‐HETE concentrations correlate positively with elevated serum creatinine concentrations but do not predict acute allograft rejection.
Comparative Effects of Sandalwood Seed Oil on Fatty Acid Profiles and Inflammatory Factors in Rats
Authors: Li Guipu , Singh Anish , Liu Yandi , Sunderland Bruce , Li Duo
Published: December 2012

The aim of the present study was to investigate the effect of sandalwood seed oil on fatty acid (FA) profiles and inflammatory factors in rats. Fifty male Sprague–Dawley rats were randomly divided into five different dietary groups: 10 % soybean oil (SO), 10 % olive oil (OO), 10 % safflower oil (SFO), 10 % linseed oil (LSO) and 8 % sandalwood seed oil blended with 2 % SO (SWSO) for 8 weeks. The SWSO group had a higher total n‐3 polyunsaturated fatty acids (PUFA) levels but lower n‐6:n‐3 PUFA ratios in both adipose tissue and liver than those in the SO, OO and SFO groups (p < 0.05). Although the SWSO group had a much lower 18:3n‐3 level (4.51 %) in their dietary lipids than the LSO group (58.88 %), the levels of docosahexaenoic acid (DHA: 22:6n‐3) in liver lipids and phospholipids of the SWSO group (7.52 and 11.77 %) were comparable to those of the LSO group (7.07 and 13.16 %). Ximenynic acid, a predominant acetylenic FA in sandalwood seed oil, was found to be highly incorporated into adipose tissue (13.73 %), but relatively lower in liver (0.51 %) in the SWSO group. The levels of prostaglandin F2α, prostaglandin E2, thromboxane B2, leukotriene B4, tumor necrosis factor‐α and interleukin‐1β in both liver and plasma were positively correlated with the n‐6:n‐3 ratios, suggesting that increased n‐6 PUFA appear to increase the formation of pro‐inflammatory cytokines, whereas n‐3 PUFA exhibit anti‐inflammatory activity. The present results suggest that sandalwood seed oil could increase tissue levels of n‐3 PUFA, DHA and reduce the n‐6:n‐3 ratio, and may increase the anti‐inflammatory activity in rats.
Are You Really Happy? Children’s Understanding of Real vs. Pretend Emotions
Authors: Sidera Francesc , Amadó Anna , Serrat Elisabet
Published: December 2012

This paper studies children’s capacity to understand that the emotions displayed in pretend play contexts do not necessarily correspond to internal emotions, and that pretend emotions may create false beliefs in an observer. A new approach is taken by asking children about pretend emotions in terms of pretence-reality instead of appearance-reality. A total of 37 four-year-olds and 33 six-year-olds were asked to participate in tasks where they had to pretend an emotion or where they were told stories in which the protagonists pretended an emotion. In each task children were asked: a) if the pretend emotion was real or just pretended and b) if an observer would think that the emotional expression was real or just pretended. Results showed that four-year-olds are capable of understanding that pretend emotions are not necessarily real. Overall, six-year-olds performed better than younger children. Furthermore, both age groups showed difficulty in understanding that pretend emotions might unintentionally mislead an observer. Results are discussed in relation to previous research on children’s ability to understand pretend play and the emotional appearance-reality distinction.
Scrum adoption and architectural extensions in developing new service applications of large financial IT systems
Authors: Ihme Tuomas
Published: December 2012

The use of modern agile software development methods in large organisations requires tailoring agile development to the organisations’ needs. This study concentrated on studying integrating software product line and agile application development in the context of large and complex financial IT systems. The study was conducted by interviewing a wide representation from the case organisation’s personnel developing in-house software for the company’s own use. The results indicate that the guidelines of the Scrum method for agile project management are valid also for the studied company type. However, each project in the studied company should acknowledge the constraints set by other projects and the complex technical infrastructure, data security issues and system portfolio in the organisation’s product line platform. In order to promote re-use and avoid risks, means and mechanisms are needed to coordinate and synchronise multiple projects and their releases on business level, the project’s compatibility with its constraints on system architecture level and the direction of software architecture on project team level.
The Autonomic Nervous System Questionnaire and the Brief Patient Health Questionnaire as screening instruments for panic disorder in Finnish primary care
Authors: Tilli V. , Suominen K. , Karlsson H.
Published: December 2012

Purpose

As panic disorder often remains unrecognized in the health care system, some screening methods have been developed to enhance its recognition. The aim of this study was to test and compare the Autonomic Nervous System Questionnaire (ANS) and the Brief Patient Health Questionnaire (BPHQ) in primary care.

Subjects and methods

A total sample of 211 primary care outpatients was studied. The Structured Clinical Interview for DSM-IV was the criterion standard for the presence of panic disorder. Indices of diagnostic utility for both screening methods were calculated and compared.

Results

The AUC (area under the ROC curve) was 0.885 for the ANS and 0.877 for the BPHQ. At the optimal cut-off level, the ANS had the sensitivity of 0.88 and specificity of 0.77; the BPHQ had the sensitivity of 0.79 and the specificity of 0.87. There was not any statistically significant difference between the screens.

Conclusions

Both screening methods can be recommended both for clinical practice and research use. In busy primary care practice, the BPHQ may be more useful, as it can be used together with the depression module of the BPHQ.
Psychoeducation and cognitive-behavioral therapy for patients with refractory bipolar disorder: A 5-year controlled clinical trial
Authors: González Isasi A. , Echeburúa E. , Limiñana J.M. , González-Pinto A.
Published: December 2012

Objective:

The aim of this research, which represents an additional and longer follow-up to a previous trial, was to evaluate a 5-year follow-up study of a combined treatment (pharmacological + psychoeducational and cognitive-behavioral therapy) as compared with a standard pharmacological treatment in patients with refractory bipolar disorder.

Method:

Forty patients were randomly assigned to either an Experimental group–under combined treatment — or a Control group — under pharmacological treatment. Data were analyzed by analysis of variance (ANOVA), with repeated measures at different evaluation time points.

Results:

Between-group differences were significant at all evaluation time points after treatment. Experimental group had less hospitalization events than Control group in the 12-month evaluation (P = 0.015). The Experimental group showed lower depression and anxiety in the 6-month (P = 0.006; P = 0.019), 12-month (P = 0.001; P < 0.001) and 5-year (P < 0.001, P < 0.001) evaluation time points. Significant differences emerged in mania and misadjustment already in the post-treatment evaluation (P = 0.009; P < 0.001) and were sustained throughout the study (6-month: P = 0.006, P < 0.001; 12-month: P < 0.001, P < 0.001; 5-year: P = 0.004, P < 0.001). After 5-year follow-up, 88.9% of patients in the Control group and 20% of patients in the Experimental group showed persistent affective symptoms and/or difficulties in social-occupational functioning.

Conclusions:

A combined therapy is long-term effective for patients with refractory bipolar disorder. Suggestions for future research are commented.
Excessive checking for non-anxiogenic stimuli in obsessive-compulsive disorder
Authors: Clair A.-H. , N’Diaye K. , Baroukh T. , Pochon J.-B. , Morgiève M. , Hantouche E. , Falissard B. , Pelissolo A. , Mallet L.
Published: December 2012

Background

Repetitive checking in obsessive-compulsive disorder (OCD) would serve to relieve obsession-related anxiety and/or to compensate memory deficit, but experimental literature on this subject is inconsistent. The main objective is to test the influence of obsession-related anxiety and memory on repetitive checking in OCD.

Methods

Twenty-three OCD checkers, 17 OCD non-checkers and 41 controls performed a delayed-matching-to-sample task with an unrestricted checking option. Some stimuli were obsession-related in order to measure the influence of anxiety on checking. A version of the task without checking possibility was used to assess memory abilities.

Results

OCD checkers had similar memory performances but checked more than the other groups when presented with non-anxiogenic stimuli. Level of anxiety associated to the stimulus did not influence the number of checks.

Conclusions

Increased checking in OCD checkers, being independent of memory abilities and primary obsession-related anxiety, would, therefore, be closer to an automated behaviour than a coping strategy.
Shining a light on posterior cortical atrophy
Authors: Crutch Sebastian J. , Schott Jonathan M. , Rabinovici Gil D. , Boeve Bradley F. , Cappa Stefano F. , Dickerson Bradford C. , Dubois Bruno , Graff‐Radford Neill R. , Krolak‐Salmon Pierre , Lehmann Manja , Mendez Mario F. , Pijnenburg Yolande , Ryan Natalie S. , Scheltens Philip , Shakespeare Tim , Tang‐Wai David F. , van der Flier Wiesje M. , Bain Lisa , Carrillo Maria C. , Fox Nick C.
Published: December 2012

Posterior cortical atrophy (PCA) is a clinicoradiologic syndrome characterized by progressive decline in visual processing skills, relatively intact memory and language in the early stages, and atrophy of posterior brain regions. Misdiagnosis of PCA is common, owing not only to its relative rarity and unusual and variable presentation, but also because patients frequently first seek the opinion of an ophthalmologist, who may note normal eye examinations by their usual tests but may not appreciate cortical brain dysfunction. Seeking to raise awareness of the disease, stimulate research, and promote collaboration, a multidisciplinary group of PCA research clinicians formed an international working party, which had its first face‐to‐face meeting on July 13, 2012 in Vancouver, Canada, prior to the Alzheimer's Association International Conference.
Targeted tumor therapy by epidermal growth factor appended toxin and purified saponin: An evaluation of toxicity and therapeutic potential in syngeneic tumor bearing mice
Authors: Thakur Mayank , Mergel Katharina , Weng Alexander , von Mallinckrodt Benedicta , Gilabert-Oriol Roger , Dürkop Horst , Melzig Matthias F. , Fuchs Hendrik
Published: December 2012

Targeted toxin‐based therapeutics are hindered by poor intracellular uptake, limited stability and non‐specific immune stimulation. To address these problems, ligand‐targeted toxins in combination with low dose saponin mixtures have been adapted and tested in vivo in the past, however, undefined saponin raw mixtures are not suitable for use in clinical development. In the present work we therefore used a targeted toxin (Sap3‐EGF, i.e. saporin fused to epidermal growth factor) in combination with a structurally defined isolated saponin m/z 1861 (SO‐1861). In vitro evaluation confirmed a 6900‐fold enhancement in the cytotoxic efficacy of Sap3‐EGF against TSA‐EGFR target cells. The required dose of the targeted toxin was appreciably reduced and there was a highly synergistic effect observed. An ex vivo hemolysis assay showed no or very less hemolysis up to 10 μg/mL of SO‐1861. In the acute toxicity studies SO‐1861 was found to be non‐toxic up to a dose of 100 μg/treatment. The enzymes aspartate aminotransferase, alanine aminotransferase, and glutamate dehydrogenase did not show any statistically significant liver damage, which was further confirmed by histological examination. Additionally, creatinine was also similar to the control group thus ruling out damage to kidney. In vivo studies in a syngeneic BALB/c tumor model characterized by EGFR overexpression were done by applying 30 μg SO‐1861 and 0.1 μg Sap3‐EGF per treatment. A more than 90% reduction (p < 0.05) in the average tumor volume was observed by this combined therapy.
Point-contact Andreev reflection spectroscopy of a magnetic superconductor Dy0.6Y0.4Rh3.85Ru0.15B4
Authors: Rybaltchenko L. F. , Khristenko E. V. , Ishchenko L. A. , Terekhov A. V. , Zolochevskii I. V. , Salenkova T. V. , Khlybov E. P. , Zaleski A. J.
Published: December 2012

The Andreev reflection spectra dI/dV(V) of the magnetic superconductor Dy0.6Y0.4Rh3.85Ru0.15B4 have been investigated. Pronounced stimulation of superconductivity by an external magnetic field has been observed for the first time. The effect showed up as enhancement of the gap structure (and hence the gap itself) in the spectra and its shift towards higher voltages with an increasing field. In the intermediate fields the structure also behaved strangely: instead of the usual smooth decrease with an increasing field, the gap features dropped abruptly near the critical point Hc2. Of interest is also the abnormally high relative gap value 2Δ/kBTc ≈ 4 (as compared to conventional singlet superconductors) which was found for some contacts from a comparison of experimental spectra and the modified Blonder–Tinkham–Klapwijk theory. We attribute the features revealed in the point-contact spectroscopic investigations of Dy0.6Y0.4Rh3.85Ru0.15B4 in a magnetic field to the triplet-type Cooper pairing in the compound because only in this case one can expect the stimulation of superconductivity in the stationary magnetic fields up to ∼0.7Hc2.