bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship of health behaviors with sleep and fatigue in transplant caregivers
Authors: Ross A. , Yang L. , Klagholz S. D. , Wehrlen L. , Bevans M. F.
Published: July 2015

Objective

The burden and psychological impact of providing care to a loved one with cancer is significant and associated with a number of problems including sleep disturbance and fatigue. While engaging in healthy behaviors such as proper nutrition, exercise, and stress reduction may improve sleep and fatigue, few studies have focused on this relationship. The objective of this study is to examine the relationship of health behaviors with sleep quality and fatigue in transplant caregivers.

Methods

Data were analyzed from a cross‐sectional survey of 78 caregivers of patients undergoing allogeneic hematopoietic stem cell transplantation. Measures included: Health‐Promoting Lifestyle Profile II (HPLP‐II), Brief Symptom Inventory (Distress), Caregiver Reaction Assessment (Caregiver Burden), Pittsburgh Sleep Quality Index, and the Multidimensional Fatigue Symptom Inventory Short‐Form.

Results

Controlling for age, gender, BMI, burden and distress, health behaviors predicted sleep quality (B = −0.408, p = 0.021) and fatigue (B = −0.966, p < 0.001). Stress management (B = −0.450, p = 0.001), nutrition (B = −0.249, p = 0.048), and interpersonal relationships (B = −0.319, p = 0.049) were the HPLP‐II subscales that significantly predicted sleep quality; nearly every HPLP‐II subscale predicted fatigue.

Conclusions

Despite the burden and distress associated with caregiving, engaging in healthy behaviors may help to improve sleep and fatigue in transplant caregivers. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Factitious disorder (Munchausen's syndrome) in oncology: case report and literature review
Authors: Baig Muhammad R. , Levin Tomer T. , Lichtenthal Wendy G. , Boland Patrick J. , Breitbart William S.
Published: July 2015

Background

Factitious disorder is where patients repeatedly seek medical care for feigned illnesses in the absence of obvious external rewards; ‘Munchausen's syndrome’ is the historical name for this disorder.

Method

We report on a case that was presented to a tertiary oncology center as a suspected rare bone cancer.

Results and Conclusions

Psychosocial clinicians working in oncology settings should be aware of the complexities of diagnosing factitious disorder in cancer settings where empathy is prominent and suspicion unusual. Moreover, comorbidity can cloud the diagnosis (in this case substance abuse), and, even when accurately diagnosed, there are no evidence‐based management approaches to offer to the patient. What seems to linger most after the patient is discharged, usually in a huff, are strong counter‐transference feelings and substantial medical bills. Copyright © 2015 John Wiley & Sons, Ltd.
Deposition of ZnO Nanocrystals on Fe3O4 Nanocubes and Their Special Luminescent and Magnetic Properties
Authors: Chen Yi , Chen Longyi , Chen Longyan , Zhang Jin
Published: July 2015

With increasing miniaturization, it is extremely important to maintain the magnetization stability at small scale. Herein, more efforts and interests focus on the interface of magnetic core and semiconductor shell to obtain desired magnetic and/or luminescent properties. Here, Fe3O4 nanocubes are synthesized via a thermal decomposition followed by coating ZnO nanocrystals. To create a large interface, large Fe3O4 nanocubes with 78 ± 3 nm average side‐length are synthesized through adjusting the ratio of iron precursor to stabilizer. The average diameter of the particular ZnO nanostructures coated on the nanocubic Fe3O4 is around 10 ± 2 nm. In addition to the photoluminescent properties of the ZnO‐coated nanostructures, core‐shell Fe3O4@ZnO nanostructures demonstrate enhanced UV absorption at 360 nm, which has a 20 nm blueshift compared to bulk ZnO. The superparamagnetic properties of Fe3O4@ZnO core–shell hybrid nanocrystals at room temperature are dominated by the ferromagnetic properties when the temperature is lower than the Blocking temperature, 235.7 K. The observed exchange bias and temperature‐dependent magnetization can result from the interfacial interphase between ZnO and Fe3O4. The anisotropy contributed by the interfacial interphase allows the nanostructures to maintain stable magnetization in miniaturized devices.
Synthesis of Manganese Oxide Microspheres by Ultrasonic Spray Pyrolysis and Their Application as Supercapacitors
Authors: Zhang Yinan , Huff Laura A. , Gewirth Andrew A. , Suslick Kenneth S.
Published: July 2015

Manganese oxide (MnO2) microspheres are prepared using an ultrasonic spray pyrolysis (USP) process. A mixed solution of potassium permanganate and hydrochloric acid is nebulized into microsized droplets, which are then carried by air flow through a furnace tube. Each microdroplet serves as one microreactor and produces one microsphere. Upon heating, KMnO4 is decomposed into MnO2 microspheres; this synthetic process can easily be scaled up. Characterization of the MnO2 microspheres by scanning electron microscopy, transmission electron microscopy, powder X‐ray diffraction, Raman spectroscopy, and X‐ray photoelectron spectra is described. Different morphologies of MnO2 microspheres can be controlled by tuning the precursor concentrations (and ratios) and furnace temperatures. Microspheres synthesized at 150 °C give amorphous MnO2 while synthesis at 500 °C yields crystalline α‐MnO2. The electrochemical properties investigated by cyclic voltammetry give specific capacitance as high as 320 F g−1, demonstrating promising properties as supercapacitors. In addition, these microspheres can be directly sprayed on conductive substrates, such as carbon fiber paper, and may have useful applications as a supercapacitor electrode coating. The supercapacitive properties of MnO2 microspheres at higher charge and discharge rates can be improved by increasing the surface area coverage or coating them with a thin layer of conductive polymer.
Oleylamine‐Assisted Phase‐Selective Synthesis of Cu2−xS Nanocrystals and the Mechanism of Phase Control
Authors: Fu Wenping , Liu Lige , Yang Gaoling , Deng Luogen , Zou Bingsuo , Ruan Weidong , Zhong Haizheng
Published: July 2015

Environmentally friendly Cu2−x
S compounds exist in many different mixed phases in nature, while their nanoscale counterparts can be pure phase with interesting localized surface plasmon resonance properties. Because of the complexity of composition and phase, controllable synthesis of Cu2−x
S nanocrystals becomes an important scientific issue in colloidal chemistry. In this work, a hot‐injection method is developed to synthesize Cu2−x
S nanocrystals by injecting a sulfur precursor into a copper precursor using oleylamine and octadecene as solvents. By varying the reaction parameters (temperature, volume ratio of oleylamine/octadecene, molar ratio of Cu/S in the precursors), hexagonal CuS, monoclinic Cu1.75S, and rhombohedral Cu1.8S, nanocrystals can be selectively synthesized, providing a platform to illustrate the mechanism of crystal phase control. The crystal phase control of Cu2−x
S nanocrystals is oleylamine‐determined by controlling the molar ratio of Cu/S in the reaction precursors as well as the ratio of Cu2−x
S clusters/Cu+ in the subsequent reaction. More importantly, temperature plays an important role in varying the molar ratio of Cu/S and Cu2−x
S clusters/Cu+ in the reaction system, which significantly influences the crystal phase of the resulting Cu2−x
S nanocrystals. The understanding into crystal control provides a guideline to realize reproducible phase‐selective synthesis and obtain well‐defined high‐quality materials with precise control.
A new method for detection of tumor driver‐dependent changes of protein sialylation in a colon cancer cell line reveals nectin‐3 as TGFBR2 target
Authors: Lee Jennifer , Warnken Uwe , Schnölzer Martina , Gebert Johannes , Kopitz Jürgen
Published: July 2015

Protein‐linked glycans play key roles in cell differentiation, cell–cell interactions, cell growth, adhesion and immune response. Aberrant glycosylation is a characteristic feature of tumor cells and is involved in tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. It can serve as cancer biomarker and treatment target. To enable comprehensive screening for the impact of tumor driving mutations in colorectal cancer cells we present a method for specific analysis of tumor driver‐induced glycome changes. The strategy is based on a combination of three technologies, that is recombinase‐mediated cassette exchange (RMCE), Click‐It chemistry and mass spectrometry. The new method is exemplified by the analysis of the impact of inactivating mutations of the TGF‐ß‐receptor type II (TGFBR2) on sialic acid incorporation into protein‐linked glycans of the colon cancer cell line HCT116. Overall, 70 proteins were found to show de novo sialic acid incorporation exclusively upon TGFBR2 expression whereas 7 proteins lost sialylation upon TGFBR2 reconstitution. Validation of detected candidate glycoproteins is demonstrated with the cell surface glycoprotein nectin‐3 known to be involved in metastasis, invasion and prognosis of various cancers. Altogether, our new approach can help to systematically puzzle out the influence of tumor‐specific mutations in a major signaling pathway, as exemplified by the TGFBR2 tumor suppressor, on the tumor glycome. It facilitates the identification of glycan‐based tumor markers that could be used for diagnostic and therapeutic applications. In principle the outlined strategy can be adapted to any cancer cell line, tumor driver mutation and several glycan‐building blocks.
Cofactor‐induced reversible folding of Flavodoxin‐4 from Lactobacillus acidophilus
Authors: Dutta Samit Kumar , Serrano Pedro , Geralt Michael , Axelrod Herbert L. , Xu Qingping , Lesley Scott A. , Godzik Adam , Deacon Ashley M. , Elsliger Marc‐André , Wilson Ian A. , Wüthrich Kurt
Published: July 2015

Flavodoxins in combination with the flavin mononucleotide (FMN) cofactor play important roles for electron transport in prokaryotes. Here, novel insights into the FMN‐binding mechanism to flavodoxins‐4 were obtained from the NMR structures of the apo‐protein from Lactobacillus acidophilus (YP_193882.1) and comparison of its complex with FMN. Extensive reversible conformational changes were observed upon FMN binding and release. The NMR structure of the FMN complex is in agreement with the crystal structure (PDB ID: 3EDO) and exhibits the characteristic flavodoxin fold, with a central five‐stranded parallel β–sheet and five α‐helices forming an α/β‐sandwich architecture. The structure differs from other flavoproteins in that helix α2 is oriented perpendicular to the β‐sheet and covers the FMN‐binding site. This helix reversibly unfolds upon removal of the FMN ligand, which represents a unique structural rearrangement among flavodoxins.
Effective protein model structure refinement by loop modeling and overall relaxation
Authors: Lee Gyu Rie , Heo Lim , Seok Chaok
Published: July 2015

Protein structures predicted by state‐of‐the‐art template‐based methods may still have errors when the template proteins are not similar enough to the target protein. Overall target structure may deviate from the template structures owing to differences in sequences. Structural information for some local regions such as loops may not be available when there are sequence insertions or deletions. Those structural aspects that originate from deviations from templates can be dealt with by ab initio structure refinement methods to further improve model accuracy. In the CASP11 refinement experiment, we tested three different refinement methods that utilize overall structure relaxation, loop modeling, and quality assessment of multiple initial structures. From this experiment, we conclude that the overall relaxation method can consistently improve model quality. Loop modeling is the most useful when the initial model structure is high quality, with GDT‐HA >60. The method that used multiple initial structures further refined the already refined models; the minor improvements with this method raise the issue of problem with the current energy function. Future research directions are also discussed. Proteins 2016; 84(Suppl 1):293–301. © 2015 Wiley Periodicals, Inc.
Fungicides affect Japanese beetle Popillia japonica (Coleoptera: Scarabaeidae) egg hatch, larval survival and detoxification enzymes
Authors: Obear Glen R , Adesanya Adekunle W , Liesch Patrick J , Williamson R Chris , Held David W
Published: July 2015

BACKGROUND

Larvae of the Japanese beetle, Popillia japonica (Coleoptera: Scarabaeidae), have a patchy distribution in soils, which complicates detection and management of this insect pest. Managed turf systems are frequently under pest pressure from fungal pathogens, necessitating frequent fungicide applications. It is possible that certain turfgrass fungicides may have lethal or sublethal adverse effects on eggs and larvae of P. japonica that inhabit managed turf systems. In this study, eggs and first‐, second‐ and third‐instar larvae were treated with the fungicides chlorothalonil and propiconazole, and survival was compared with that of untreated controls as well as positive controls treated with the insecticide trichlorfon.

RESULTS

Chlorothalonil reduced survival of first‐instar larvae treated directly and hatched from treated eggs. Propiconazole delayed egg hatch, reduced the proportion of eggs that successfully hatched and reduced survival of first‐instar larvae treated directly and hatched from treated eggs. Sublethal doses of the fungicides lowered the activities of certain detoxification enzymes in third‐instar grubs.

CONCLUSIONS

Fungicide applications to turfgrass that coincide with oviposition and egg hatch of white grubs may have sublethal effects. This work is applicable both to high‐maintenance turfgrass such as golf courses, where applications of pesticides are more frequent, and to home lawn services, where mixtures of multiple pesticides are commonly used. © 2015 Society of Chemical Industry
Dominance of Cry1F resistance in Spodoptera frugiperda (Lepidoptera: Noctuidae) on TC1507Bt maize in Brazil
Authors: Farias Juliano R , Andow David A , Horikoshi Renato J , Sorgatto Rodrigo J , Santos Antonio C dos , Omoto Celso
Published: July 2015

BACKGROUND

Dominance of resistance has been one of the major parameters affecting the rate of evolution of resistance to Bt crops. High dose is the capacity of Bt crops to kill heterozygous insects and has been an essential component of the most successful strategy to manage resistance to these crops. Experiments were conducted to evaluate directly and indirectly whether the TC1507 event is high dose to Spodoptera frugiperda (JE Smith).

RESULTS

About 8% of heterozygote neonate larvae were able to survive, complete larval development and emerge as normal adults on TC1507 leaves, while susceptible larvae could not survive for 5 days. The estimated dominance of resistance was 0.15 ± 0.09 and significantly higher than zero; therefore, the resistance to Cry1F expressed in TC1507 was not completely recessive. A 25‐fold dilution of TC1507 maize leaf tissue in an artificial diet was able to cause a maximum mortality of only 37%, with growth inhibition of 82% at 7 days after larval infestation.

CONCLUSION

Resistance to Cry1F in TC1507 maize is incompletely recessive in S. frugiperda. TC1507 maize is not high dose for S. frugiperda. Additional or alternative resistance management strategies, such as the replacement of single‐trait Bt maize with pyramided Bt maize, which produces multiple proteins targeting the same insect pests, should be implemented wherever this technology is in use and S. frugiperda is the major pest. © 2015 Society of Chemical Industry
Dislocation density reduction in multicrystalline silicon via cyclic annealing
Authors: Choi Kwangmin , Castellanos Sergio , Powell Douglas Michael , Buonassisi Tonio , Choi Hyunjoo
Published: July 2015

Manufacturing processes to reduce dislocation densities in multicrystalline silicon (mc‐Si) solar cells could reduce the cost of photovoltaics by increasing cell efficiency with minimum additional process complexity. The present work investigates how cyclically varying temperature (stress) in mc‐Si blocks can lead to dislocation‐density reduction. Cyclic annealing is found to be more effective at activating immobile dislocations than isothermal annealing. Once immobile dislocations are activated, however, they are hypothesized to impede density reduction of mobile dislocations by accelerating multiplication of overall dislocations. Thus, a combined process of thermal cycling and isothermal annealing is found to provide a maximum dislocation density reduction of ∼70%, with 12 h of static annealing followed by 12 h of cyclic annealing.

Dislocation etch‐pit images of as‐grown control and mc‐Si sample after 12 h cyclic annealing followed by 12 h static annealing.
Grain boundary networks in nanocrystalline alloys from atom probe tomography quantization and autocorrelation mapping
Authors: Chen Ying , Schuh Christopher A.
Published: July 2015

A local spatial autocorrelation‐based modeling method is developed to reconstruct nanoscale grain structures in nanocrystalline materials from atom probe tomography (APT) data, which provide atomic positions and species, with minimal noise. Using a nanocrystalline alloy with an average grain size of 16 nm as a model material, we reconstruct the three‐dimensional grain boundary network by carrying out two series of APT data quantization using ellipsoidal binning, the first probing the anisotropy in the apparent local atomic density and the second quantifying the local spatial autocorrelation. This approach enables automatic and efficient quantification and visualization of grain structure in a large volume and at the finest nanoscale grain sizes, and provides a means for correlating local chemistry with grain boundaries or triple junctions in nanocrystalline materials.

Nanoscale grain boundary networks are reconstructed from atom probe tomography data, which provide atomic positions and species for a fraction of atoms within a nanocrystalline material with an average grain size of 16 nm, using a quantization and local spatial autocorrelation‐based approach.
Differential Inhibition of T Lymphocyte Proliferation and Cytokine Synthesis by [6]‐Gingerol, [8]‐Gingerol, and [10]‐Gingerol
Authors: Bernard Megan , Furlong Suzanne J. , Power Coombs Melanie R. , Hoskin David W.
Published: July 2015

[6]‐Gingerol, [8]‐gingerol, and [10]‐gingerol are pungent components of fresh ginger, extracts of which inhibit various components of the inflammatory response. Because little is known regarding the effect of gingerols with different unbranched alkyl side chain lengths on the activation and effector function of T lymphocytes, we compared the effects of [6]‐gingerol, [8]‐gingerol, and [10]‐gingerol on murine T lymphocyte proliferation, expression of CD25 and CD69 activation markers, cytokine synthesis, and interleukin (IL)‐2 receptor signaling. All three gingerols inhibited DNA synthesis by T lymphocytes, as well as interferon‐γ synthesis. In contrast, only [8]‐gingerol and [10]‐gingerol inhibited CD25 and CD69 expression, and IL‐2 synthesis. None of the gingerols affected IL‐4 synthesis. Exogenous IL‐2 enhanced T lymphocyte proliferation in the presence of [6]‐gingerol but did not significantly increase T lymphocyte proliferation in the presence of [8]‐gingerol or [10]‐gingerol. In line with this finding, [8]‐gingerol and [10]‐gingerol impaired IL‐2‐induced proliferation of CTLL‐2 cells, but constitutive CD25 expression was unaffected, indicating inhibition of IL‐2 receptor signaling. In general, [10]‐gingerol and [8]‐gingerol were more potent inhibitors of T lymphocytes than [6]‐gingerol. Suppression of T lymphocyte responses by gingerols suggests that these phytochemicals may be beneficial in chronic inflammatory conditions associated with excessive or inappropriate T lymphocyte activation. Copyright © 2015 John Wiley & Sons, Ltd.
Mechanisms initiating heavy precipitation over Italy during HyMeX Special Observation Period 1: a numerical case study using two mesoscale models
Authors: Barthlott Christian , Davolio Silvio
Published: July 2015

This study focuses on the initiation of deep convection during a heavy precipitation episode, which occurred during the first Special Observation Period (SOP 1) of the Hydrological cycle in the Mediterranean Experiment (HyMeX). In the course of 14 and 15 October 2012 (Intensive Observation Period 13), intense convective events affected southern France, Corsica and several regions of Italy. Numerical simulations are performed with two state‐of‐the‐art numerical weather prediction models (COSMO and MOLOCH), driven by the same initial and boundary data and operated on an identical domain. With this set‐up, the sensitivity of the model results to horizontal grid spacing and terrain elevation is assessed. Furthermore, model outputs are compared with observations from rain‐gauges, radars and radiosondes made during the campaign. Although the higher resolution runs show a higher correlation with observed precipitation, the influence of model grid spacing on total precipitation amount or timing is rather weak. Since the overall performance of both mesoscale models is fairly good, they are used together to investigate the physical processes characterizing IOP 13. In particular, the differences in the location and timing of convection between the simulations are used to identify and explore those processes that need to be well represented in order to reproduce the mechanisms initiating heavy precipitation in the Mediterranean region adequately.
Handling Uncertainties in Fault Tree Analysis by a Hybrid Probabilistic–Possibilistic Framework
Authors: Wang Dong , Zhang Yan , Jia Xiang , Jiang Ping , Guo Bo
Published: July 2015

Fault tree analysis is a method largely used in probabilistic risk assessment. Uncertainties should be properly handled in fault tree analyses to support a robust decision making. While many sources of uncertainties are considered, dependence uncertainties are not much explored. Such uncertainties can be labeled as ‘epistemic’ because of the way dependence is modeled. In practice, despite probability theory, alternative mathematical structures, including possibility theory and fuzzy set theory, for the representation of epistemic uncertainty can be used. In this article, a fuzzy β factor is considered to represent the failure dependence uncertainties among basic events. The relationship between β factor and system failure probability is analyzed to support the use of a hybrid probabilistic–possibilistic approach. As a result, a complete hybrid probabilistic–possibilistic framework is constructed. A case study of a high integrity pressure protection system is discussed. The results show that the proposed method provides decision makers a more accurate understanding of the system under analysis when failure dependencies are involved. Copyright © 2015 John Wiley & Sons, Ltd.
Optimization of Pultrusion Process Parameters via Design of Experiments and Response Surface
Authors: Faria Neto Antonio , Fernando Branco Costa Antonio
Published: July 2015

Experimental designs were implemented to investigate the effects of mold temperature and pulling speed on the tensile strength of cylindrical cables produced by pultrusion. A two‐level factorial design with a central point revealed that the linear model is not applicable for describing the influence of the process parameters on the tensile strength. Additional experiments were performed to investigate the contribution of quadratic terms. A three‐level factorial design revealed that only the linear and the quadratic‐linear interactions can be discarded from the complete quadratic model. In the investigated range of the parameters, the tensile strength always increases with the mold temperature and decreases with the pulling speed. Thus, cables produced at the highest temperature and the lowest speed are the most resistant. Compared with the mold temperature, the pulling speed has a minor influence on the tensile strength. Based on these findings, during periods of higher demand, the pulling speed can be increased without significant loss in tensile strength. For the cases where the tensile strength is critical, the rise in speed can be compensated by a mild increase in temperature. This way, the gain in quality, translated into cables with better resistance, highly compensates for the additional energy consumption. Copyright © 2015 John Wiley & Sons, Ltd.
Earth observation as a tool for tracking progress towards the Aichi Biodiversity Targets
Authors: O'Connor Brian , Secades Cristina , Penner Johannes , Sonnenschein Ruth , Skidmore Andrew , Burgess Neil D. , Hutton Jon M.
Published: July 2015

Biodiversity is continuing to decline. This crisis has been recognised by the Convention on Biological Diversity (CBD), whose members have set ambitious targets to avert ongoing declines in the state of biodiversity by 2020. These so called “Aichi Biodiversity Targets” (ABTs) are organized around five strategic goals, with indicators showing the level of progress made towards each target. Currently, measurements of many ABT indicators are not available. The Essential Biodiversity Variable (EBV) framework, developed by the Group on Earth Observations Biodiversity Observation Network (GEO BON), attempts to form a coherent and harmonised set of observations of biodiversity. In this paper, we explore the potential role of Earth Observation (EO) as a tool to support biodiversity monitoring against the ABT and EBV frameworks. We show that EO‐based measurements are adequate for assessing progress towards 11 out of 20 ABTs. In addition, 14 of the 22 candidate EBVs have a fully or partly remotely‐sensed component and can be considered as Remote Sensing Essential Biodiversity Variables (RS‐EBVs). Those with a partial EO component require further in‐situ data and/or modelling effort to complete the EBV. While the status of biodiversity can be assessed with both fully and partly measured RS‐EBVs, assessing trends is more challenging, particularly for partly measured RS‐EBVs, as coincident time series of EO and supporting data are lacking. A synthetic pathway for developing generic biodiversity indicators using RS‐EBVs is proposed.
Answering the Questions of Whether and When Learning Occurs: Using Discrete‐Time Survival Analysis to Investigate the Ways in Which College Chemistry Students’ Ideas About Structure–Property Relationships Evolve
Authors: UNDERWOOD SONIA M. , REYES‐GASTELUM DAVID , COOPER MELANIE M.
Published: July 2015

Longitudinal studies can provide significant insights into how students develop competence in a topic or subject area over time. However, there are many barriers, such as retention of students in the study and the complexity of data analysis, that make these studies rare. Here, we present how a statistical framework, discrete‐time survival analysis, can help overcome these barriers to longitudinal assessment studies using data from our research on students’ understanding of structure–property relationships in chemistry. In the study presented, we administered the Implicit Information from Lewis Structures Instrument (IILSI)—an instrument designed to elicit from students what information can be predicted using a Lewis structure—to three cohorts of students at five time points over a two‐year period, throughout their general chemistry and organic chemistry courses, to determine the ways in which student ideas about structure–property relationships evolved. Using survival analysis, we were able to identify both whether and when learning occurred over the two‐year period. The single model also allowed us to construct trajectories to determine the ways in which students developed the ideas that underlie structure–property relationships in chemistry.
Adaptive sample size modification in clinical trials: start small then ask for more?
Authors: Jennison Christopher , Turnbull Bruce W.
Published: July 2015

We consider sample size re‐estimation in a clinical trial, in particular when there is a significant delay before the measurement of patient response. Mehta and Pocock have proposed methods in which sample size is increased when interim results fall in a ‘promising zone’ where it is deemed worthwhile to increase conditional power by adding more subjects. Our analysis reveals potential pitfalls in applying this approach. Mehta and Pocock use results of Chen, DeMets and Lan to identify when increasing sample size, but applying a conventional level α significance test at the end of the trial does not inflate the type I error rate: we have found the greatest gains in power per additional observation are liable to lie outside the region defined by this method. Mehta and Pocock increase sample size to achieve a particular conditional power, calculated under the current estimate of treatment effect: this leads to high increases in sample size for a small range of interim outcomes, whereas we have found it more efficient to make moderate increases in sample size over a wider range of cases. If the aforementioned pitfalls are avoided, we believe the broad framework proposed by Mehta and Pocock is valuable for clinical trial design. Working in this framework, we propose sample size rules that apply explicitly the principle of adding observations when they are most beneficial. The resulting trial designs are closely related to efficient group sequential tests for a delayed response proposed by Hampson and Jennison. Copyright © 2015 John Wiley & Sons, Ltd.
Nonparametric meta‐analysis for diagnostic accuracy studies
Authors: Zapf Antonia , Hoyer Annika , Kramer Katharina , Kuss Oliver
Published: July 2015

Summarizing the information of many studies using a meta‐analysis becomes more and more important, also in the field of diagnostic studies. The special challenge in meta‐analysis of diagnostic accuracy studies is that in general sensitivity and specificity are co‐primary endpoints. Across the studies both endpoints are correlated, and this correlation has to be considered in the analysis. The standard approach for such a meta‐analysis is the bivariate logistic random effects model. An alternative approach is to use marginal beta‐binomial distributions for the true positives and the true negatives, linked by copula distributions. In this article, we propose a new, nonparametric approach of analysis, which has greater flexibility with respect to the correlation structure, and always converges. In a simulation study, it becomes apparent that the empirical coverage of all three approaches is in general below the nominal level. Regarding bias, empirical coverage, and mean squared error the nonparametric model is often superior to the standard model, and comparable with the copula model. The three approaches are also applied to two example meta‐analyses. Copyright © 2015 John Wiley & Sons, Ltd.
Ultrasmall Nanoplatforms as Calcium‐Responsive Contrast Agents for Magnetic Resonance Imaging
Authors: Moussaron Albert , Vibhute Sandip , Bianchi Andrea , Gündüz Serhat , Kotb Shady , Sancey Lucie , Motto‐Ros Vincent , Rizzitelli Silvia , Crémillieux Yannick , Lux Francois , Logothetis Nikos K. , Tillement Olivier , Angelovski Goran
Published: July 2015

The preparation of ultrasmall and rigid platforms (USRPs) that are covalently coupled to macrocycle‐based, calcium‐responsive/smart contrast agents (SCAs), and the initial in vitro and in vivo validation of the resulting nanosized probes (SCA‐USRPs) by means of magnetic resonance imaging (MRI) is reported. The synthetic procedure is robust, allowing preparation of the SCA‐USRPs on a multigram scale. The resulting platforms display the desired MRI activity—i.e., longitudinal relaxivity increases almost twice at 7 T magnetic field strength upon saturation with Ca2+. Cell viability is probed with the MTT assay using HEK‐293 cells, which show good tolerance for lower contrast agent concentrations over longer periods of time. On intravenous administration of SCA‐USRPs in living mice, MRI studies indicate their rapid accumulation in the renal pelvis and parenchyma. Importantly, the MRI signal increases in both kidney compartments when CaCl2is also administrated. Laser‐induced breakdown spectroscopy experiments confirm accumulation of SCA‐USRPs in the renal cortex. To the best of our knowledge, these are the first studies which demonstrate calcium‐sensitive MRI signal changes in vivo. Continuing contrast agent and MRI protocol optimizations should lead to wider application of these responsive probes and development of superior functional methods for monitoring calcium‐dependent physiological and pathological processes in a dynamic manner.
Microfluidic Design of Magnetoresponsive Photonic Microcylinders with Multicompartments
Authors: Sim Jae Young , Lee Gun Ho , Kim Shin‐Hyun
Published: July 2015

Colloidal photonic structures have been designed to have granular format to use them for paint pigments, encoded carriers, and display pixels. However, conventional approaches only provide spherical or discoid shapes, restricting their applications. Cylindrical granules with fan‐shaped compartments in the cross section are appealing for microcarriers with abundant optical codes and active display pigments for color switching. In this work, a stratified laminar flow of concentrated silica particles is employed, formed in a cylindrical microchannel, to produce cylindrical photonic microparticles with multiple compartments. To accomplish this, a microfluidic device is designed to have one cylindrical main channel connected with four branch channels. Four different photocurable suspensions are independently injected through the branches to form quarter‐cylindrically compartmentalized streams in the main channel. Local ultraviolet irradiation on the main channel polymerizes the suspension, thereby forming cylindrical microparticles with four compartments. In each compartment, silica particles form ordered array which develops particle size–dependent structural color. Therefore, different colors can be incorporated into single microcylinder by employing different sizes of silica particles. Moreover, one of the compartments can be rendered to be magnetoresponsive by embedding aligned magnetic particles, which enables the remote control of microcylinder orientation and therefore the switching of structural colors.
Establishing an Evolutionary Learning Laboratory for Improving the Quality of Life of Vietnamese Women in Small‐scale Agriculture: Part I—The Current Situation
Authors: Ha Tuan M. , Bosch Ockie J. H. , Nguyen Nam C.
Published: July 2015

The study was carried out in Haiphong, a typical lowland area of the Red River Delta of Northern Vietnam. The main objective of this research was to analyse the current conditions under which women smallholders are operating (Part I), in order to serve as a basis to identify major challenges and potential intervention strategies to reduce labour hardship and improve their quality of life (Part II). Both qualitative and quantitative data collection methods were employed to gain an in‐depth understanding of the current conditions. It was found that issues associated with the target group were multi‐dimensional, requiring multi‐stakeholder related interventions. These varied from interrelated problems such as a lack of capital and production devices to market constraints, production capability and gender‐biased domestic chores and production tasks. A comprehensive and informed approach is therefore required that focuses on (i) coordinated planning and multi‐stakeholder cooperation; (ii) enhanced transparency and accountability; and (iii) utilization and mobilization of available resources. Although the suggested solutions are legitimate as based on the traditional approach of context and problem analyses, it is clearly insufficient to understand the systemic interplays among different issues and to address the real issues and root causes of the difficulties the women are facing. Copyright © 2015 John Wiley & Sons, Ltd.
Modelling and Simulation of the Melting Process in Electric Arc Furnaces—Influence of Numerical Solution Methods
Authors: Meier Thomas , Logar Vito , Echterhof Thomas , Škrjanc Igor , Pfeifer Herbert
Published: July 2015

Increasing demands on the steel market are leading to introduction of many technological innovations regarding the electric arc furnaces (EAFs). The area with significant potential is also advanced computer support, based on mathematical models estimating the process values which are not continuously measured, such as chemical compositions and temperatures of the steel, slag and gas. To achieve optimal process control using EAF models, two crucial characteristics of the later are required, i.e. sufficient accuracy and calculation speed, both affected by selection of the modelling approach and ordinary differential equation (ODE) solving method. The aim of this paper is to investigate the estimation accuracy and calculation speed of an EAF model, evaluated by three solving methods, i.e. fixed step Euler, variable step Runge‐Kutta and Backward Differentiation Formula (BDF). The results are showing that the selection of the ODE solver has an enormous effect on simulation outcome. All three methods proved to be appropriate to obtain the estimated process values; however, achieving a desired level of precision leads to significant deviations in computational speeds. Thus, when aiming for optimal model based EAF control, proper selection of the ODE solver is as important as the modelling approach, but too often neglected.
Molecular Mechanisms Mediating Retinal Reactive Gliosis Following Bone Marrow Mesenchymal Stem Cell Transplantation
Authors: Tassoni Alessia , Gutteridge Alex , Barber Amanda C. , Osborne Andrew , Martin Keith R.
Published: July 2015

A variety of diseases lead to degeneration of retinal ganglion cells (RGCs) and their axons within the optic nerve resulting in loss of visual function. Although current therapies may delay RGC loss, they do not restore visual function or completely halt disease progression. Regenerative medicine has recently focused on stem cell therapy for both neuroprotective and regenerative purposes. However, significant problems remain to be addressed, such as the long-term impact of reactive gliosis occurring in the host retina in response to transplanted stem cells. The aim of this work was to investigate retinal glial responses to intravitreally transplanted bone marrow mesenchymal stem cells (BM-MSCs) to help identify factors able to modulate graft-induced reactive gliosis. We found in vivo that intravitreal BM-MSC transplantation is associated with gliosis-mediated retinal folding, upregulation of intermediate filaments, and recruitment of macrophages. These responses were accompanied by significant JAK/STAT3 and MAPK (ERK1/2 and JNK) cascade activation in retinal Muller glia. Lipocalin-2 (Lcn-2) was identified as a potential new indicator of graft-induced reactive gliosis. Pharmacological inhibition of STAT3 in BM-MSC cocultured retinal explants successfully reduced glial fibrillary acidic protein expression in retinal Muller glia and increased BM-MSC retinal engraftment. Inhibition of stem cell-induced reactive gliosis is critical for successful transplantation-based strategies for neuroprotection, replacement, and regeneration of the optic nerve. Stem Cells  2015;33:3006–3016
G‐protein‐coupled inward rectifier potassium channels involved in corticostriatal presynaptic modulation
Authors: Meneses David , Mateos Verónica , Islas Gustavo , Barral Jaime
Published: July 2015

Presynaptic modulation has been associated mainly with calcium channels but recent data suggests that inward rectifier potassium channels (KIR) also play a role. In this work we set to characterize the role of presynaptic KIR channels in corticostriatal synaptic transmission. We elicited synaptic potentials in striatum by stimulating cortical areas and then determined the synaptic responses of corticostriatal synapsis by using paired pulse ratio (PPR) in the presence and absence of several potassium channel blockers. Unspecific potassium channels blockers Ba2+ and Cs+ reduced the PPR, suggesting that these channels are presynaptically located. Further pharmacological characterization showed that application of tertiapin‐Q, a specific KIR3 channel family blocker, also induced a reduction of PPR, suggesting that KIR3 channels are present at corticostriatal terminals. In contrast, exposure to Lq2, a specific KIR1.1 inward rectifier potassium channel, did not induce any change in PPR suggesting the absence of these channels in the presynaptic corticostriatal terminals. Our results indicate that KIR3 channels are functionally expressed at the corticostriatal synapses, since blockage of these channels result in PPR decrease. Our results also help to explain how synaptic activity may become sensitive to extracellular signals mediated by G‐protein coupled receptors. A vast repertoire of receptors may influence neurotransmitter release in an indirect manner through regulation of KIR3 channels. Synapse 69:446–452, 2015. 2015 Wiley Periodicals, Inc.
Inhibition of PDE2A, but not PDE9A, modulates presynaptic short‐term plasticity measured by paired‐pulse facilitation in the CA1 region of the hippocampus
Authors: Fernández‐Fernández Diego , Rosenbrock Holger , Kroker Katja S.
Published: July 2015

Phosphodiesterase (PDE) inhibitors are currently considered promising therapeutic targets for treatment of cognitive impairment in diseases such as Schizophrenia and Alzheimer's disease. Inhibitors of PDE2A and PDE9A have emerged as potential candidates shown to improve synaptic plasticity and memory function in animals. However, the functional relevance of their putative different localization in the neuron is not understood. Thus, this study aims at elucidating potential presynaptic effects of PDE2A inhibition in comparison to the inhibition of PDE9A. For this purpose, we used paired‐pulse facilitation (PPF), a model of short‐term synaptic plasticity related to presynaptic function. First, we performed a series of experiments to validate the model in acute rat hippocampal slices using several reference substances including calcium channel blockers, glutamatergic receptor antagonists, and GPCR agonists. Second, we analysed the effect of PDE2A and PDE9A inhibition and their role regulating the influence that the second messengers cAMP and cGMP exert on basal transmission. Our results show that the interplay between the adenylyl cyclase activator forskolin, the soluble guanylyl cyclase activator BAY 41‐8543 and the PDE2A inhibitor PF‐999 reveals a primarily presynaptic mechanism of action of PDE2A inhibition. On the contrary, inhibition of PDE9A did not alter PPF under similar conditions. In conclusion, these data provide new evidence supporting a role of PDE2A modulating short‐term synaptic plasticity. Moreover, this function of PDE2A is suggested to rely on an active modulation of the cAMP hydrolysis as a response to changes in cGMP levels at the presynaptic level. Synapse 69:484–496, 2015. © 2015 Wiley Periodicals, Inc.
Recent Advances in the Base‐Induced Sommelet–Hauser Rearrangement of Amino Acid Derived Ammonium Ylides
Authors: Tayama Eiji
Published: July 2015

The Sommelet–Hauser rearrangement ofN‐benzylic ammonium ylides generated from ammonium salts is an interesting and useful transformation that enables one to convert a readily accessible C–N bond into a new C–C bond to an aromatic ring. The rearrangement was discovered by Sommelet in 1937, studied in detail by Hauser, and applied to organic synthesis by Sato until 1999. Further studies have not advanced because several competitive side reactions and structural limitations of the products severely limit the substrate scope and synthetic applications. In this Personal Account, a history of the research in problem solving and recent advances in the base‐induced Sommelet–Hauser rearrangement are described. This synthetic method developed by my group provides efficient access to various types of α‐aryl‐α‐amino acid and α‐aryl‐β‐amino acid derivatives.
The Magic of Wondering
Authors: Coiro Julie
Published: July 2015

The ability to ask questions is essential to learning, reasoning, and understanding. This column introduces a sequence of activities that incorporate the use of digital images and online texts into intentional opportunities for even the youngest learners to work with their teachers and classmates as they wonder, anticipate, explore, and think deeply about things that matter to them.
Radiostability of cefoselis sulfate in the solid state
Authors: Garbacki Piotr , Zalewski Przemysław , Skibiński Robert , Kozak Maciej , Ratajczak Magdalena , Lewandowska Kornelia , Bednarski Waldemar , Podborska Agnieszka , Mizera Mikołaj , Jelińska Anna , Cielecka‐Piontek Judyta
Published: July 2015

The possibility of applying radiation sterilization to cefoselis sulfate was investigated. The lack of changes in the chemical structure of cefoselis sulfate irradiated with a dose of 25 kGy, required to attain sterility, was confirmed by ultraviolet, Fourier transform infrared, Raman, differential scanning calorimetry, scanning electron microscopy, X‐ray diffraction and chromatographic methods. Electron paramagnetic resonance studies showed that radiation has created some radical defects that concentration was no more than over a dozen parts per million. The antibacterial activity of cefoselis sulfate was unaltered for Gram‐positive bacteria but changed for Gram‐negative strains, as shown by microbiological tests. Copyright © 2015 John Wiley & Sons, Ltd.
Rietveld refinement of the structure of copper indium diselenide
Authors: Paszkowicz Wojciech , Bacewicz Rajmund , Wojciechowski Tomasz
Published: July 2015

Structure refinement for copper indium diselenide, CuInSe2, based on powder diffraction data is reported. The studied sample was prepared by grinding a single crystal grown using the vertical Bridgman–Stockbarger method. The diffraction data were collected using a high‐resolution powder diffractometer. Rietveld refinement for CuInSe2 provides the following lattice parameters values for the chalcopyrite‐type unit cell: a = 5.78277(9) Å, c = 11.6211(2) Å. The Se fractional coordinate is xSe = 0.2285(2) and the calculated density is 5.748(2) g/cm3. These structural data are briefly discussed on the basis of the earlier reported data. Copyright © 2015 John Wiley & Sons, Ltd.