bluuebunny/crossref_metadata_2025 huggingface dataset:
Intersubject variability and induced gamma in the visual cortex: DCM with empirical Bayes and neural fields
Authors: Pinotsis Dimitris A. , Perry Gavin , Litvak Vladimir , Singh Krish D. , Friston Karl J.
Published: September 2016

This article describes the first application of a generic (empirical) Bayesian analysis of between‐subject effects in the dynamic causal modeling (DCM) of electrophysiological (MEG) data. It shows that (i) non‐invasive (MEG) data can be used to characterize subject‐specific differences in cortical microcircuitry and (ii) presents a validation of DCM with neural fields that exploits intersubject variability in gamma oscillations. We find that intersubject variability in visually induced gamma responses reflects changes in the excitation‐inhibition balance in a canonical cortical circuit. Crucially, this variability can be explained by subject‐specific differences in intrinsic connections to and from inhibitory interneurons that form a pyramidal‐interneuron gamma network. Our approach uses Bayesian model reduction to evaluate the evidence for (large sets of) nested models—and optimize the corresponding connectivity estimates at the within and between‐subject level. We also consider Bayesian cross‐validation to obtain predictive estimates for gamma‐response phenotypes, using a leave‐one‐out procedure. Hum Brain Mapp 37:4597–4614, 2016. © The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Promising in vivo efficacy of the BET bromodomain inhibitor OTX015/MK‐8628 in malignant pleural mesothelioma xenografts
Authors: Vázquez Ramiro , Licandro Simonetta Andrea , Astorgues‐Xerri Lucile , Lettera Emanuele , Panini Nicolò , Romano Michela , Erba Eugenio , Ubezio Paolo , Bello Ezia , Libener Roberta , Orecchia Sara , Grosso Federica , Riveiro María Eugenia , Cvitkovic Esteban , Bekradda Mohamed , D'Incalci Maurizio , Frapolli Roberta
Published: September 2016

It has recently been reported that a large proportion of human malignant pleural mesothelioma (MPM) cell lines and patient tissue samples present high expression of the c‐MYC oncogene. This gene drives several tumorigenic processes and is overexpressed in many cancers. Although c‐MYC is a strategic target to restrain cancer processes, no drugs acting as c‐MYC inhibitors are available. The novel thienotriazolodiazepine small‐molecule bromodomain inhibitor OTX015/MK‐8628 has shown potent antiproliferative activity accompanied by c‐MYC downregulation in several tumor types. This study was designed to evaluate the growth inhibitory effect of OTX015 on patient‐derived MPM473, MPM487 and MPM60 mesothelioma cell lines and its antitumor activity in three patient‐derived xenograft models, MPM473, MPM487 and MPM484, comparing it with cisplatin, gemcitabine and pemetrexed, three agents which are currently used to treat MPM in the clinic. OTX015 caused a significant delay in cell growth both in vitro and in vivo. It was the most effective drug in MPM473 xenografts and showed a similar level of activity as the most efficient treatment in the other two MPM models (gemcitabine in MPM487 and cisplatin in MPM484). In vitro studies showed that OTX015 downregulated c‐MYC protein levels in both MPM473 and MPM487 cell lines. Our findings represent the first evidence of promising therapeutic activity of OTX015 in mesothelioma.
EZH2 coupled with HOTAIR to silence MicroRNA‐34a by the induction of heterochromatin formation in human pancreatic ductal adenocarcinoma
Authors: Li Chi‐Han , Xiao Zhangang , Tong Joanna Hung–Man , To Ka‐Fai , Fang Xiangdong , Cheng Alfred SL , Chen Yangchao
Published: September 2016

MicroRNA‐34a (miR‐34a) is frequently downregulated in pancreatic ductal adenocarcinoma (PDAC) cells, however, the silencing mechanism remains unclear. Enhancer of zeste homolog 2 (EZH2) is overexpressed in PDAC, and our previous miRNA profiling showed that inhibition of EZH2 in PDAC cells led to the re‐expression of a group of tumor suppressor miRNAs including miR‐34a. Here, we studied the effect of ectopic EZH2 expression to the silencing of miR‐34a, and identified HOTAIR as an interacting partner to induce heterochromatin formation during miR‐34a repression. We identified EZH2 as a major player in silencing miR‐34a. Inhibition of EZH2 upregulated miR‐34a expression in PDAC cells, while EZH2 overexpression in human pancreatic ductal epithelial (HPDE) cells repressed miR‐34a expression and decreased the miR‐34a promoter activity. We then showed that HOTAIR played a critical role in EZH2‐mediated repression of miR‐34a, as knockdown of HOTAIR attenuated the miR‐34a inhibition effect in EZH2‐overexpressing HPDE cells. HOTAIR physically interacted with miR‐34a promoter, and the EZH2‐interacting region located at 5′ HOTAIR RNA was essential in repressing miR‐34a and promoting cell proliferation. More importantly, we showed that the interaction between EZH2 and HOTAIR underlay the silencing of miR‐34a through induction of heterochromatin formation. We first showed that manipulation of EZH2 level interfered the occupancy of heterochromatin markers H3K9me2, heterochromatin associated protein 1α and 1γ in PDAC cells. In turn, we showed that knockdown of HOTAIR reduced the occupancy of EZH2 at miR‐34a promoter. The identification of HOTAIR‐guided miR‐34a silencing opened a new avenue in miR‐34a‐oriented therapy against PDAC.
Pharmacokinetics of 14C‐ortho‐phenylphenol following intravenous administration in pigs
Authors: Nixon Emma , Brooks James D. , Routh Patricia A. , Chittenden Jason T. , Baynes Ronald E.
Published: September 2016

Workers in the USA are exposed to industrial formulations, which may be toxic. These formulations often contain preservatives or biocides such as ortho‐phenylphenol (OPP). There are limited data describing OPP following intravenous administration to assess truly the clearance of this chemical in humans and other species. In vivo experiments were conducted in pigs to determine related pharmacokinetic parameters. 14C‐OPP was administered as an intravenous bolus dose. Blood, feces, urine and tissue samples were collected for analysis by liquid scintillation. Data were analyzed using non‐compartmental and compartmental pharmacokinetic model approaches. These data fitted a three‐compartment model and showed that the half‐life of 14C‐OPP following the intravenous bolus in pigs was 46.26 ± 10.01 h. The kidneys play a crucial role in clearance of 14C‐OPP with a large percentage of the dose being found in the urine (70.3 ± 6.9% dose). Comparisons with other species suggest that 14C‐OPP clearance in pigs (2.48 ml h–1 kg–1) is less than that in humans (18.87 ml h–1 kg–1) and rats (35.51 ml h–1 kg–1). Copyright © 2016 John Wiley & Sons, Ltd.
Chitosan/poly‐octanoic acid 2‐thiophen‐3‐yl‐ethyl ester blends as a scaffold to maintain myoblasts regeneration potential in vitro
Authors: Padilla Cristina , Ramos Andrea , González Natalia , Isaacs Mauricio , Zacconi Flavia , Olguín Hugo C. , Valenzuela Loreto M.
Published: September 2016

Satellite cells are a small cell population that function as muscle‐specific adult stem cells. When muscle damage occurs, these cells are able to activate, proliferate, and ultimately fuse with each other in order to form new myofibers or fuse with existing ones. For tissue engineering applications, obtaining a sufficient number of myoblasts prior transplantation that maintains their regenerative capacity is critical. This can be obtained by in vitro expansion of autologous satellite cells. However, once plated, the self‐renewal and regenerative capacity of myoblasts is rapidly lost, obtaining low yields per biopsy. For this purpose, we evaluated in vitro culture of the murine myoblast cell line C2C12 and mouse primary myoblasts with chitosan and chitosan/poly‐octanoic acid 2‐thiophen‐3‐yl‐ethyl ester blends (poly(OTE)). The films of chitosan/poly(OTE) blends were heterogeneous and slightly rougher than chitosan and poly(OTE) films. Poly(OTE) presence improved myoblast adhesion in both cell types and prevented complete differentiation, but maintaining their differentiation potential in vitro. We identified that the polymer blend chitosan/poly(OTE) could be a suitable substrate to culture satellite cells/myoblasts in vitro preventing differentiation prior transplantation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 118–130, 2017.
Healing Humiliation: From Reaction to Creative Action
Authors: Hartling Linda M. , Lindner Evelin G.
Published: September 2016

In the midst of global crises, feelings of humiliation are intensified (Lindner,; Moïsi,). Counselors are often on the front lines of suffering during turbulent times. This article explores how the dynamics of humiliation are coming to the forefront of concern around the globe. Applying a relational framework, the authors examine the impact of humiliation, offering a case example that illustrates how counselors can lead their clients out of destructive reactions into creative action.
Using Relational‐Cultural Theory in LGBTQQ Counseling: Addressing Heterosexism and Enhancing Relational Competencies
Authors: Singh Anneliese A. , Moss Lauren
Published: September 2016

The authors describe the use of a relational‐cultural theory (RCT) lens (Miller, ) in counseling practice with lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQQ) clients. A review of LGBTQQ counseling and RCT literature is discussed. A case vignette of a counselor applying RCT tenets to work with a LGBTQQ client is described. Implications for using RCT as a counseling theoretical framework with LGBTQQ clients are reviewed.
Relational‐Cultural Theory: Fostering the Growth of a Paradigm Through Empirical Research
Authors: Lenz A. Stephen
Published: September 2016

This study identified empirical literature supporting relational‐cultural theory (RCT) for explaining experiences of individuals, assessing theoretical constructs, and providing an effective treatment option. A systematic review of available literature revealed that (a) RCT was a useful framework for understanding client experiences, (b) there is considerable support for the psychometric validation of RCT constructs, and (c) support for RCT interventions is currently limited. Limitations of studies reviewed, recommendations for future research, and implications for counselors are provided.
The Identity Development of Urban Minority Young Men in Single‐Mother Households
Authors: Vargas Angela P. , Park‐Taylor Jennie , Harris Abigail M. , Ponterotto Joseph G.
Published: September 2016

This phenomenological study explored the gender and career identity development of 13 urban minority young men, with an emphasis on the potential impact of father absence and single‐mother parenting. Six themes were identified: (a) emotional intelligence and maternal appreciation and internalization, (b) consequent assumption of a parentified role, (c) nontraditional perception of masculinity, (d) experienced paternal void, (e) resilience, and (f) the limitations and aspirations in career pathways. Implications for practice and research are discussed.
Synthesis and evaluation of an 18F‐labeled derivative of F3 for targeting surface‐expressed nucleolin in cancer and tumor endothelial cells
Authors: Lam Phoebe Y.H. , Hillyar Christopher R.T. , Able Sarah , Vallis Katherine A.
Published: September 2016

The surface overexpression of nucleolin provides an anchor for the specific attachment of biomolecules to cancer and angiogenic endothelial cells. The peptide F3 is a high‐affinity ligand of the nucleolin receptor (NR) that has been investigated as a carrier to deliver biologically active molecules to tumors for both therapeutic and imaging applications. A site‐specific PEGylated F3 derivative was radiolabeled with [18F]Al‐F. The binding affinity and cellular distribution of the compound was assessed in tumor (H2N) and tumor endothelial (2H‐11) cells. Specific uptake via the NR was demonstrated by the siRNA knockdown of nucleolin in both cell lines. The partition and the plasma stability of the compound were assessed at 37°C. The enzyme‐mediated site‐specific modification of F3 to give NODA‐PEG‐F3 (NP‐F3) was achieved. Radiolabeling with [18F]Al‐F gave 18F‐NP‐F3. 18F‐NP‐F3 demonstrated high affinity for cancer and tumor endothelial cells. The siRNA knockdown of nucleolin resulted in a binding affinity reduction of 50% to 60%, confirming cell surface binding via the NR. NP‐F3 was stable in serum for 2 h. 18F‐NP‐F3 is reported as the first 18F‐labeled F3 derivative. It was obtained in a site‐specific, high‐yield, and efficient manner and binds to surface NR in the low nanomolar range, suggesting it has potential as a tumor and angiogenesis tracer.
Effects of Piper cubeba L. essential oil on methicillin‐resistant Staphylococcus aureus: an AFM and TEM study
Authors: Alharbi Naiyf S. , Khaled Jamal M. , Alzaharni Khalid E. , Mothana Ramzi A. , Alsaid Mansour S. , Alhoshan Mansour , Dass Lawrence Arockiasamy , Kadaikunnan Shine , Alobaidi Ahmed S.
Published: September 2016

The increasing prevalence of antibiotic‐resistant bacteria is creating a real challenge for health care systems worldwide, making the development of novel antibiotics a necessity. In addition to the development of new antibiotics, there is an urgent need for in‐depth characterization of the mechanisms of bacterial resistance toward new drugs. Here, we used essential oils extracted in our laboratory from Piper cubeba against methicillin‐resistant Staphylococcus aureus ATCC 43300, one of the most prominent antibiotic‐resistant bacteria. Effects of the essential oils extracted from P cubeba on bacteria were mainly evaluated using 2 powerful microscopy techniques: atomic force microscopy and transmission electron microscopy. High‐resolution atomic force microscopy images of the cells were obtained close to their native environment by immobilizing the cells on porous Polyether sulfone membranes, which were prepared in our laboratory with a wide range and distribution of pore sizes and depth. Inhibition zones (mm) and minimum inhibitory concentrations were determined. Two different concentrations of the oil were used to treat the cells: 50 μg/mL minimum inhibitory concentration and 25 μg/mL. The 50 μg/mL oil solution caused severe damage to the bacterial cells at microscopic levels while the 25 μg/mL solution showed no effects compared to the control. However, at nanoscopic levels, the 25 μg/mL oil solution caused significant changes in the cell wall, which could potentially impair bacterial activities. These results were also confirmed by transmission electron microscopy micrographs. Our results indicate that the extract has a good biological activity against methicillin‐ and oxacillin‐resistant S aureus and that it acts on the cell wall and plasma (cytoplasmic) membrane.
Assessing distribution‐based climate model bias correction methods over an alpine domain: added value and limitations
Authors: Ivanov Martin A. , Kotlarski Sven
Published: September 2016

Climate impact assessment and decision making in the light of projected future climate change require accurate and robust climate scenarios at the local scale. The latter are targeted by statistical bias correction (BC) and downscaling of climate model output. A nowadays well‐established technique is quantile mapping (QM). Here, we apply several different implementations of empirical QM, a parametric (and computationally more expensive) QM method for daily precipitation, and a mean‐BC to an ensemble of regional climate scenarios over the topographically structured terrain of Switzerland. The performance of these methods in the current climate and their long‐term stability are analysed with respect to distributional and temporal statistics as well as climate impact indices for daily temperature and precipitation. We select an optimal QM implementation, study its effect on the inter‐variable consistency, and compare its climate change signal (CCS) to that of a delta‐change (DC) method. The results demonstrate that QM effectively reduces raw model biases. The most important improvements are corrected magnitudes and, for precipitation, also wet‐day frequencies. The quantile‐dependent bias removal is superior to the mean‐BC with respect to distribution‐tail statistics. Temporal statistics and climate impact indices are also improved. There is no performance benefit from the parametric QM method. The selected empirical QM implementation substantially improves the joint temperature–precipitation distribution and maintains the temperature–precipitation cross‐correlation function as represented by raw climate model data. The CCS analysis reveals the superiority of QM over the DC method with respect to distribution‐tail characteristics and temporal statistics. This work reveals empirical QM as a reliable and stable method for BC and downscaling from state‐of‐the‐art regional climate models to local weather stations over alpine terrain, confirming and expanding previous studies.
Surveillance and molecular typing of Cronobacter spp. in commercial powdered infant formula and follow‐up formula from 2011 to 2013 in Shandong Province, China
Authors: Zhang Huaning , Hou Peibin , Lv Hui , Chen Yuzhen , Li Xinpeng , Ren Yanyan , Wang Mei , Tan Hailian , Bi Zhenwang
Published: September 2016

BACKGROUND

Infection with Cronobacter spp. leads to neonatal meningitis, necrotizing enterocolitis and bacteremia. Cronobacter spp. are reported to comprise an important pathogen contaminating powdered infant formula (PIF) and follow‐up formula (FUF), although little is known about the contamination level of Cronobacter spp. in PIFs and FUFs in China.

RESULTS

In total, 1032 samples were collected between 2011 and 2013. Forty‐two samples were positive, including 1.6% in PIFs and 6.5% in FUFs. The strains were susceptible to most antibiotics except for cefoxitin. Pulsed‐field gel electrophoresis after XbaI digestion produced a total of 36 banding patterns. The 38 strains were found in 27 sequence types (STs), of which nine types (ST454 to ST462) had not been reported in other countries. The clinically relevant strains obtained from the 38 isolates in the present study comprised three ST3, two ST4, two ST8 and one ST1.

CONCLUSION

The contamination rate in the PIF and FUF has stayed at a relatively high level. The contamination rate of PIF was significantly lower than FUF. The isolates had high susceptibility to the antibiotics tested, except cefoxitin. There were polymorphisms between the Cronobacter spp. as indicated by pulsed‐field gel electrophoresis and multilocus sequence typing. Therefore, contamination with Cronobacter spp. remains a current issue for commercial infant formulas in China. © 2016 Society of Chemical Industry
Effects of licury cake in young Nellore bull diets: salted sun‐dried meat is preferred rather than fresh meat by consumers despite similar physicochemical characteristics
Authors: Gouvêa Ana AL , Oliveira Ronaldo L , Leão André G , Bezerra Leilson R , Assis Dallyson YC , Albuquerque Italo RR , Pellegrini Caius B , Rocha Tiago C
Published: September 2016

BACKGROUND

Salted Sun‐dried meat is a traditional process of meat salting that can improve quality and overall acceptance. The present study compared the physicochemical and sensory attributes of fresh and salted sun‐dried meat from Nellore Zebu (Bos taurus indicus) bulls (n = 32) and evaluated diets containing different levels (0%, 7%, 14% and 21%) of licury cake in diets provided to Nellore finished in a feedlot.

RESULTS

Salted sun‐dried meat decreased moisture (P < 0.0001) and ether extract (P = 0.0002) contents but increased ash (P < 0.0001) and protein (P < 0.0001) contents compared to fresh meat. The addition of licury resulted in linear increases in moisture (P = 0.02) and quadratic effects on Warner–Bratzler shear force (P < 0.03) in fresh meat. Cooking weight loss (P < 0.0001) and Warner–Bratzler shear force (P = 0.03) were reduced by the manufacturing process of sun‐dried meat. Sun‐dried meat presented greater color index L* (P = 0.0032), a* (P < 0.0001) and c* (P < 0.0001) values but a lower index color b* (P < 0.0001) value compared to fresh meat. Salted sun‐dried meat presented greater sensory characteristic scores compared to fresh meat (P > 0.05).

CONCLUSION

Licury cake can be used in 21% of dry matter in diets to finish animals in feedlot without lessening the quality fresh meat or sundried meat. Salted sun‐dried meat presented a greater overall acceptance. © 2016 Society of Chemical Industry
Higher‐order Sobolev‐type embeddings on Carnot–Carathéodory spaces
Authors: Franců Martin
Published: September 2016

A sufficient condition for higher‐order Sobolev‐type embeddings on bounded domains of Carnot–Carathéodory spaces is established for the class of rearrangement‐invariant function spaces. The condition takes form of a one‐dimensional inequality for suitable integral operators depending on the isoperimetric function relative to the Carnot–Carathéodory structure of the relevant sets. General results are then applied to particular Sobolev spaces built upon Lebesgue, Lorentz and Orlicz spaces on John domains in the Heisenberg group. In the case of the Heisenberg group, the condition is shown to be necessary as well.
Optimized AIR and investigational MOLLI cardiac T1 mapping pulse sequences produce similar intra‐scan repeatability in patients at 3T
Authors: Hong KyungPyo , Collins Jeremy , Lee Daniel C. , Wilcox Jane E. , Markl Michael , Carr James , Kim Daniel
Published: September 2016

This study was conducted to improve the precision of arrhythmia‐insensitive rapid (AIR) cardiac T1 mapping through pulse sequence optimization and then evaluate the intra‐scan repeatability in patients at 3T against investigational modified Look–Locker inversion recovery (MOLLI) T1 mapping. In the first development phase (five human subjects), we implemented and tested centric‐pair k‐space ordering to suppress image artifacts associated with eddy currents. In the second development phase (15 human subjects), we determined optimal flip angles to reduce the measurement variation in T1 maps. In the validation phase (35 patients), we compared the intra‐scan repeatability between investigational MOLLI and optimized AIR. In 23 cardiac planes, conventional centric k‐space ordering (3.7%) produced significantly (p < 0.05) more outliers as a fraction of left ventricular cavity area than optimal centric k‐space ordering (1.4%). In 15 human subjects, for each of four types of measurement (native myocardial T1, native blood T1, post‐contrast myocardial T1, post‐contrast blood T1), flip angles of 55–65° produced lower measurement variation while producing results that are not significantly different from those produced with the previously used flip angle of 35° (p > 0.89, intra‐class correlation coefficient ≥ 0.95 for all four measurement types). Compared with investigational MOLLI (coefficient of repeatability, CR = 40.0, 77.2, 26.5, and 25.9 ms for native myocardial, native blood, post‐contrast myocardial, and post‐contrast blood T1, and 2.0% for extracellular volume (ECV) measurements, respectively), optimized AIR (CR = 54.3, 89.7, 30.5, and 14.7 ms for native myocardial, native blood, post‐contrast myocardial, and post‐contrast blood T1, and 1.6% for ECV measurements, respectively) produced similar absolute intra‐scan repeatability in all 35 patients in the validation phase. High repeatability is critically important for longitudinal studies, where the goal is to monitor physiologic/pathologic changes, not measurement variation. Optimized AIR cardiac T1 mapping is likely to yield high scan–retest repeatability for pre‐clinical and clinical applications.
XFEM‐based element subscale refinement for detailed representation of crack propagation in large‐scale analyses
Authors: Mostofizadeh S. , Fagerström M. , Larsson R.
Published: September 2016

In the present paper, we address the delicate balance between computational efficiency and level of detailing at the modelling of ductile fracture in thin‐walled structures. To represent the fine‐scale nature of the ductile process, we propose a new extended finite element method‐based enrichment of the displacement field to allow for crack tips that end or kink within an element. The idea is to refine the crack tip element locally in a way such that the macroscale node connectivity is unaltered. This allows for a better representation of the discontinuous kinematics without affecting the macroscale solution procedure, which would be a direct consequence of a regular mesh refinement. The method is first presented in a general 3D setting, and thereafter, it is specialised to shell theory for the modelling of crack propagation in thin‐walled structures. The paper is concluded by a number of representative examples showing the accuracy of the method. We conclude that the ideas proposed in the paper enhance the current methodology for the analysis of ductile fracture of thin‐walled large‐scale structures under high strain rates. Copyright © 2016 John Wiley & Sons, Ltd.
Probabilistic bias analysis in pharmacoepidemiology and comparative effectiveness research: a systematic review
Authors: Hunnicutt Jacob N. , Ulbricht Christine M. , Chrysanthopoulou Stavroula A. , Lapane Kate L.
Published: September 2016

Purpose

We systematically reviewed pharmacoepidemiologic and comparative effectiveness studies that use probabilistic bias analysis to quantify the effects of systematic error including confounding, misclassification, and selection bias on study results.

Methods

We found articles published between 2010 and October 2015 through a citation search using Web of Science and Google Scholar and a keyword search using PubMed and Scopus. Eligibility of studies was assessed by one reviewer. Three reviewers independently abstracted data from eligible studies.

Results

Fifteen studies used probabilistic bias analysis and were eligible for data abstraction—nine simulated an unmeasured confounder and six simulated misclassification. The majority of studies simulating an unmeasured confounder did not specify the range of plausible estimates for the bias parameters. Studies simulating misclassification were in general clearer when reporting the plausible distribution of bias parameters. Regardless of the bias simulated, the probability distributions assigned to bias parameters, number of simulated iterations, sensitivity analyses, and diagnostics were not discussed in the majority of studies.

Conclusion

Despite the prevalence and concern of bias in pharmacoepidemiologic and comparative effectiveness studies, probabilistic bias analysis to quantitatively model the effect of bias was not widely used. The quality of reporting and use of this technique varied and was often unclear. Further discussion and dissemination of the technique are warranted. Copyright © 2016 John Wiley & Sons, Ltd.
A probabilistic bias analysis for misclassified categorical exposures, with application to oral anti‐hyperglycaemic drugs
Authors: Arfè Andrea , Nicotra Federica , Ghirardi Arianna , Simonetti Monica , Lapi Francesco , Sturkenboom Miriam , Corrao Giovanni
Published: September 2016

Purpose

The effect of drug exposure misclassification generally receives little attention in pharmacoepidemiological research. In this paper, we illustrate a probabilistic bias analysis approach for misclassified categorical exposures and apply it in a database study of oral anti‐hyperglycaemic drugs (OADs).

Methods

A cohort study based on the Health Search Database general‐practice database was carried out by including 12 640 adult (≥40 years) patients newly treated with OADs during 2003–2010. The proportion of days covered by OADs prescriptions during the first year of follow‐up was evaluated for each individual, either by means of the prescribed daily dose or the defined daily dose. The effect of misclassification on hypothetical OAD–outcome association profiles was assessed through the proposed probabilistic bias analysis approach, taking advantage of available exposure validation data.

Results

During the first year of follow‐up, the average (SD) number of months with OADs available was 7 (4) months and 5 (3) months according to the prescribed daily dose and defined daily dose metrics, respectively. Probabilistic bias analysis results based on validation data suggest that the effect of misclassification is complex, as conventional exposure–outcome association estimates may be of greater or lower magnitude than their misclassification‐adjusted values.

Conclusions

Misclassification should be taken into account in database studies on the safety of prescribed medications. To this aim, investigators should take advantage of external exposure validation data in sensitivity analysis approaches such as ours. Copyright © 2016 John Wiley & Sons, Ltd.
Photoinitiated polymerization in ionic liquids and its application
Authors: Andrzejewska Ewa
Published: September 2016

Ionic liquids (ILs) are low‐melting organic salts often liquid at room temperature, whose unique properties are the reason of increasing interest for their applications as solvents, reaction media and functional additives. The exceptional properties ofILshave proved to be particularly useful in polymer science giving the potential to produce polymeric materials with improved properties or to immobilizeILsin polymer matrices while keeping their special characteristics. One of the possibilities is polymerization inILswhich can also affect positively polymerization reactions. An especially attractive technique is photopolymerization due to the ease of process control, short reaction time and ambient working temperature. This review gives a literature survey of developments in photopolymerization processes carried out inILsas well as applications of these processes. It covers both the photopolymerizationinILsas well as photopolymerizationofILmonomers. The first part presents a short overview of physicochemical and photochemical properties ofILs; it includes also photochemical reactions and photoinitiation of polymerization inILs. The second part covers both the basic research (kinetics of photopolymerization including polymerization rate coefficients and polymerization ofILmonomers) as well as applications ofUV‐induced polymerization inILs. © 2016 Society of Chemical Industry
Economic competitiveness of III–V on silicon tandem one‐sun photovoltaic solar modules in favorable future scenarios
Authors: Bobela David C. , Gedvilas Lynn , Woodhouse Michael , Horowitz Kelsey A. W. , Basore Paul A.
Published: September 2016

Tandem modules combining a III–V top cell with a Si bottom cell offer the potential to increase the solar energy conversion efficiency of one‐sun photovoltaic modules beyond 25%, while fully utilizing the global investment that has been made in Si photovoltaics manufacturing. At present, the cost of III–V cells is far too high for this approach to be competitive for one‐sun terrestrial power applications. We investigated the system‐level economic benefits of both GaAs/Si and InGaP/Si tandem modules in favorable future scenarios where the cost of III–V cells is substantially reduced, perhaps to less than the cost of Si cells. We found, somewhat unexpectedly, that these tandems can reduce installed system cost only when the area‐related balance‐of‐system cost is high, such as for area‐constrained residential rooftop systems in the USA. When area‐related balance‐of‐system cost is lower, such as for utility‐scale systems, the tandem module offers no benefit. This is because a system using tandem modules is more expensive than one using single‐junction Si modules when III–V cells are expensive, and a system using tandem modules is more expensive than one using single‐junction III–V modules when III–V cells are inexpensive. Copyright © 2016 John Wiley & Sons, Ltd.
Quantum‐Mechanical Calculations of Cross Sections for Electron Collisions With Atoms and Molecules
Authors: Bartschat Klaus , Tennyson Jonathan , Zatsarinny Oleg
Published: September 2016

An overview of quantum‐mechanical methods to generate cross‐section data for electron collisions with atoms and molecules is presented. Particular emphasis is placed on the time‐independent close‐coupling approach, since it is particularly suitable for low‐energy collisions and also allows for systematic improvements as well as uncertainty estimates. The basic ideas are illustrated with examples for electron collisions with argon atoms and methane. For many atomic systems, such as e‐Ar collisions, highly reliable cross sections can now be computed with quantified uncertainties. On the other hand, while electron collision calculations with molecules do provide key input data for plasma models, the methods, and computer codes presently used require further development to make these inputs robust.
Shock Initiation of the CL‐20‐Based Explosive C‐1 Measured with Embedded Electromagnetic Particle Velocity Gauges
Authors: Chen Lang , Pi Zheng‐Di , Liu Dan‐Yang , Yang Kun , Wu Jun‐Ying
Published: September 2016

Hexanitrohexaazaisowurtzitane (CL‐20) is a high‐energy material with high shock sensitivity. The evolution of shock into the detonation of CL‐20 deserves academic attention and research. An embedded electromagnetic particle velocity gauge was used to study the shock initiation of detonation in a pressed solid explosive formulation, C‐1, containing 94 wt‐% epsilon phase CL‐20 and 6 wt‐% fluororubber (FPM). In conventional experiments, the magnetic field was generated using a pair of electromagnets with a complex structure and operation. A new device was designed to solve complex problems. This device comprised NdFeB magnets, pole shoes and magnetic yokes; using this technique, a uniform magnetic field could be created. A series of shock initiation experiments on high‐explosive C‐1 was performed, and the explosive samples were initiated at different intensity input shocks by an explosive driven flyer plate. In situ magnetic particle velocity gauges were utilized to detail the growth from an input shock to detonation, and the attenuation of particle velocity in unreacted C‐1 was also obtained in low‐intensity shock initiation experiments. Hugoniot data for C‐1 in the form of shock velocity D vs. particle velocity Up were obtained. A simulation model for shock initiation of C‐1 was established, and the particle velocity data from several experiments were used to determine the parameters required for the unreacted equation of state and ignition and growth reactive flow model for C‐1. These coefficients were then applied in the calculation of the initial shock pressure−distance to detonation relationship (Pop‐plot) for the explosive. Based on the results of experiments and simulations, the shock sensitivity characteristic of C‐1 was described.
Investigation of various optical transitions in GaAs/Al0.3Ga0.7As double quantum ring grown by droplet epitaxy
Authors: Kim Jong Su
Published: September 2016

This work examines the optical transitions of a GaAs double quantum ring (DQR) embedded in Al0.3Ga0.7As matrix by photoreflectance spectroscopy (PR). The GaAs DQR was grown by droplet epitaxy (DE). The optical properties of the DQR were investigated by excitation‐intensity and temperature‐dependent PR. The various optical transitions were observed in PR spectra, whereas the photoluminescence (PL) spectrum shows only the DQR and GaAs band emissions. The various optical transitions were identified for the GaAs near‐band‐edge transition, surface confined state (SCS), DQR confined state, wetting layer (WL), spin–orbital split (EGaAs + Δo), and AlGaAs band transition. PR spectroscopy can identify various optical transitions that are invisible in PL. The PR results show that the GaAs/AlGaAs DQR has complex electronic structures due to the various interfaces resulting from DE.
Enhanced dielectric properties of polyvinylidene fluoride with addition of SnO2 nanoparticles
Authors: Liu Zhe , Wang Fanghui , Zhu Hong
Published: September 2016

In this letter, SnO2/polyvinylidene fluoride (PVDF) nanocomposites with outstanding dielectric properties were fabricated. The SEM and TEM images showed that SnO2 nanoparticles with size of 5–7 nm dispersed homogeneously in polymer matrix. The significantly improved dielectric constant was well explained by percolation theory. The nanocompo‐ sites can retain a certain value of breakdown field. The maximum energy density of SnO2/PVDF nanocomposites was 5.4 J/cm3, two times that of the pure polyvinylidene fluoride. These findings suggest that SnO2/PVDF nanocomposites are suitable candidates for energy storage applications. (© 2016 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
Theoretical investigation on the passivation layer with linearly graded bandgap for the amorphous/crystalline silicon heterojunction solar cell
Authors: Zhao Lei , Wang Guanghong , Diao Hongwei , Wang Wenjing
Published: September 2016

Passivation layer with linearly graded bandgap (LGB) was proposed to improve the performance of amorphous/crystalline silicon heterojunction (SHJ) solar cell by eliminating the large abrupt energy band uncontinuity at the a‐Si:H/c‐Si interface. Theoretical investigation on the a‐Si:H(p)/the LGB passivation layer(i)/c‐Si(n)/a‐Si:H(i)/a‐Si:H(n+) solar cell via AFORS‐HET simulation show that such LGB passivation layer could improve the solar cell efficiency (η) by enhancing the fill factor (FF) greatly, especially when the a‐Si:H(p) emitter was not efficiently doped and the passivation layer was relatively thick. But gap defects in the LGB passivation layer could make the improvement discounted due to the open‐circuit voltage (VOC) decrease induced by recombination. To overcome this, it was quite effective to keep the gap defects away from the middle of the bandgap by widening the minimum bandgap of the LGB passivation layer to be a little larger than that of the c‐Si base. The underlying mechanisms were analysed in detail. How to achieve the LGB passivation layer experimentally was also discussed. (© 2016 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
Dynamical downscaling and variable resolution in limited‐area models
Authors: Davies Terry
Published: September 2016

Limited‐area models (LAMs) are widely used in numerical weather prediction and regional climate modelling to obtain high‐resolution results which would be too expensive computationally to acquire using a global model. This is often referred to as downscaling. To run LAMs requires lateral boundary conditions (LBCs) which are normally obtained from a global model or a lower‐resolution LAM containing the domain of the smaller LAM. Using a large‐domain high‐resolution LAM as the control, smaller‐domain LAMs were run using LBCs from a low‐resolution LAM run over the large domain. The results from the smaller‐domain LAMs were used to assess the errors due to the LBCs by taking differences against the large domain control. These differences were also used to understand how downscaling occurs and to assess the impact of increasing the domain size. Tests using variable‐resolution LAMs were conducted to determine whether errors arising from LBCs could be reduced. Investigations were made into the appearance of noise over steep orography at boundaries and possible mitigation strategies are discussed.
Investigation of non‐covalent complexations of Ca(II) and Mg(II) ions with insulin by using electrospray ionization mass spectrometry
Authors: Gülfen Mustafa , Özdemir Abdil , Lin Jung‐Lee , Chen Chung‐Hsuan
Published: September 2016

Rationale

Insulin is a peptide hormone secreted by pancreatic β‐cells. Ca(II) and Mg(II) ions play an important role in the secretion of insulin. There is no study about a direct complexation of Ca(II) or Mg(II) with insulin and their equilibrium constants. Electrospray ionization mass spectrometry (ESI‐MS) is a practical method for the monitoring of non‐covalent complexes such as Ca(II)‐insulin and Mg(II)‐insulin. Here, the equilibrium constants of Ca(II)‐insulin and Mg(II)‐insulin non‐covalent complexes have been calculated after ESI‐MS measurements in aqueous solutions.

Methods

The effects of pH, competitive binding, ion exchange, and Na(I) and K(I) ions on Ca(II)‐insulin and Mg(II)‐insulin complexation have been examined by measuring by ESI‐MS. The dissociation equilibrium constants (K1 and K2) of Ca(II)‐insulin and Mg(II)‐insulin complexes were calculated from the binomial graph derived from the ESI‐MS normalized peak intensities. The MS/MS spectra of the complexes have been examined.

Results

The dissociation equilibrium constants were found to K1: 1.29 × 10−4 M and K2: 9.69 × 10−4 M for the Ca(II)‐insulin complexes, and K1: 1.37 × 10−4 M and K2: 9.12 × 10−4 M for Mg(II)‐insulin complexes. Ca(II) ions have higher complexation capability with insulin than Mg(II) ions.

Conclusions

The binding equilibrium constants of Ca(II)‐ and Mg(II)‐insulin non‐covalent complexes have been determined successfully by ESI‐MS. Ca(II) and Mg(II) ions are involved in the insulin secretion by forming non‐covalent complexes. Copyright © 2016 John Wiley & Sons, Ltd.
Nitrogen stable isotope variability in tissues of juvenile tilapia Oreochromis aureus: empirical and modelling results
Authors: Wang Yinping , Gu Xiaohong , Zeng Qingfei , Mao Zhigang , Wang Wenxia
Published: September 2016

Rationale

Studies on diet or trophic interactions of organisms based on stable isotopes require accurate estimates of how quickly stable isotope ratios change in the investigated tissues. However, rates of isotope turnover in fish tissues, especially in omnivorous species, are poorly understood.

Methods

We conducted a diet‐shift study using juvenile tilapia to (i) empirically estimate the isotopic turnover rates of nitrogen in the dorsal muscle, liver, fin and backbone; (ii) model the relative contributions of metabolism and growth to the total isotopic turnover in each tissue; and (iii) develop a non‐lethal approach for estimating body nitrogen stable isotope ratios for threatened or endangered species. Isotopic analyses were performed using a Flash EA CN elemental analyser coupled to a ThermoFinnigan Delta Plus mass spectrometer.

Results

Nitrogen isotopic turnover rates were consistently ranked in the order backbone > liver > muscle > fin due to the relatively lower metabolic rates of muscle and fin tissue. Backbone tissue turned over significantly faster than other tissues, suggesting the potential for a multiple‐tissue stable isotope approach to the study of movement and trophic position over different time scales for omnivorous fish. However, fin tissue had the longest half‐life, at 57.81 days, indicating that this tissue is more useful than muscle as a long‐term dietary indicator.

Conclusions

The change in nitrogen isotope ratios in dorsal muscle was mainly regulated by somatic growth, but metabolic activity markedly stimulated the turnover rate of backbone. This study is one of a few to demonstrate significant variation in the δ15N turnover rates among multiple tissues of a single organism, especially for omnivorous fish. Our results, to some extent, also indirectly contribute to the conservation of threatened or endangered species. Copyright © 2016 John Wiley & Sons, Ltd.
Influence of carboxylation on osteocalcin detection by mass spectrometry
Authors: Cleland Timothy P. , Thomas Corinne J. , Gundberg Caren M. , Vashishth Deepak
Published: September 2016

Rationale

Osteocalcin is a small, abundant bone protein that is difficult to detect using high‐throughput tandem mass spectrometry (MS/MS) proteomic approaches from bone protein extracts, and is predominantly detected by non‐MS immunological methods. Here, we analyze bovine osteocalcin and its post‐translational modifications to determine why a protein of this size goes undetected.

Methods

Osteocalcin was purified from cow bone using well‐established methods. Intact osteocalcin or trypsin‐digested osteocalcin were separated using an Agilent 1200 series high‐performance liquid chromatography (HPLC) system and analyzed using a ThermoScientific LTQ‐Orbitrap XL after fragmentation with higher‐energy collision dissociation. Data were analyzed using Mascot or Prosight Lite.

Results

Our results support previous findings that the cow osteocalcin has up to three carboxylations using both intact osteocalcin and digested forms. Using Mascot, we were able to detect osteocalcin peptides, but no fragments that localized the carboxylations. Full annotation using Prosight Lite of the intact (three carboxylations), N‐terminal peptide (one carboxylation), and middle peptide (two carboxylations) showed complete fragmentation was present, but complete neutral loss was observed.

Conclusions

Osteocalcin carboxylation, and its associated neutral losses, makes high‐throughput detection of this protein challenging; however, alternative fragmentation or limited purification can overcome these challenges. Copyright © 2016 John Wiley & Sons, Ltd.
Lujo viral hemorrhagic fever: considering diagnostic capacity and preparedness in the wake of recent Ebola and Zika virus outbreaks
Authors: Simulundu Edgar , Mweene Aaron S. , Changula Katendi , Monze Mwaka , Chizema Elizabeth , Mwaba Peter , Takada Ayato , Ippolito Guiseppe , Kasolo Francis , Zumla Alimuddin , Bates Matthew
Published: September 2016

Lujo virus is a novel Old World arenavirus identified in Southern Africa in 2008 as the cause of a viral hemorrhagic fever (VHF) characterized by nosocomial transmission with a high case fatality rate of 80% (4/5 cases). Whereas this outbreak was limited, the unprecedented Ebola virus disease outbreak in West Africa, and recent Zika virus disease epidemic in the Americas, has brought into acute focus the need for preparedness to respond to rare but potentially highly pathogenic outbreaks of zoonotic or arthropod‐borne viral infections. A key determinant for effective control of a VHF outbreak is the time between primary infection and diagnosis of the index case. Here, we review the Lujo VHF outbreak of 2008 and discuss how preparatory measures with respect to developing diagnostic capacity might be effectively embedded into existing national disease control networks, such as those for human immunodeficiency virus, tuberculosis, and malaria.
Pattern‐avoiding permutations and Brownian excursion part I: Shapes and fluctuations
Authors: Hoffman Christopher , Rizzolo Douglas , Slivken Erik
Published: September 2016

Permutations that avoid given patterns are among the most classical objects in combinatorics and have strong connections to many fields of mathematics, computer science and biology. In this paper we study the scaling limits of a random permutation avoiding a pattern of length 3 and their relations to Brownian excursion. Exploring this connection to Brownian excursion allows us to strengthen the recent results of Madras and Pehlivan [25] and Miner and Pak [29] as well as to understand many of the interesting phenomena that had previously gone unexplained. © 2016 Wiley Periodicals, Inc. Random Struct. Alg., 50, 394–419, 2017
A Size‐Selective Intracellular Delivery Platform
Authors: Saung May Tun , Sharei Armon , Adalsteinsson Viktor A. , Cho Nahyun , Kamath Tushar , Ruiz Camilo , Kirkpatrick Jesse , Patel Nehal , Mino‐Kenudson Mari , Thayer Sarah P. , Langer Robert , Jensen Klavs F. , Liss Andrew S. , Love J. Christopher
Published: September 2016

Identifying and separating a subpopulation of cells from a heterogeneous mixture are essential elements of biological research. Current approaches require detailed knowledge of unique cell surface properties of the target cell population. A method is described that exploits size differences of cells to facilitate selective intracellular delivery using a high throughput microfluidic device. Cells traversing a constriction within this device undergo a transient disruption of the cell membrane that allows for cytoplasmic delivery of cargo. Unique constriction widths allow for optimization of delivery to cells of different sizes. For example, a 4 μm wide constriction is effective for delivery of cargo to primary human T‐cells that have an average diameter of 6.7 μm. In contrast, a 6 or 7 μm wide constriction is best for large pancreatic cancer cell lines BxPc3 (10.8 μm) and PANC‐1 (12.3 μm). These small differences in cell diameter are sufficient to allow for selective delivery of cargo to pancreatic cancer cells within a heterogeneous mixture containing T‐cells. The application of this approach is demonstrated by selectively delivering dextran‐conjugated fluorophores to circulating tumor cells in patient blood allowing for their subsequent isolation and genomic characterization.