bluuebunny/crossref_metadata_2025 huggingface dataset:
CCR2 Expression in Neutrophils Plays a Critical Role in Their Migration Into the Joints in Rheumatoid Arthritis
Authors: Talbot Jhimmy , Bianchini Francine J. , Nascimento Danilele C. , Oliveira Rene D. R. , Souto Fabricio O. , Pinto Larissa G. , Peres Raphael S. , Silva Jaqueline R. , Almeida Sergio C. L. , Louzada‐Junior Paulo , Cunha Thiago M. , Cunha Fernando Q. , Alves‐Filho Jose C.
Published: March 2015

Objective

Infiltration of neutrophils into the joints plays an important role in bone erosion and articular destruction in rheumatoid arthritis (RA). Neutrophil trafficking during inflammation is a process that involves activation of chemotactic receptors. Recent findings suggest that changes in chemotactic receptor patterns could occur in neutrophils under certain inflammatory conditions. The aim of this study was to evaluate the gain of responsiveness of neutrophils to CCL2 in RA patients and to assess the role of CCL2 in driving neutrophil infiltration into the joints.

Methods

Neutrophils were purified from the peripheral blood of patients with RA or from mice with antigen‐induced arthritis (AIA). Expression of CCR2 was evaluated using polymerase chain reaction, flow cytometry, and immunofluorescence analyses. In vitro chemotaxis to CCL2 was assayed to evaluate the functional significance of de novo CCR2 expression. The murine AIA model was used to evaluate the in vivo role of CCR2 in neutrophil infiltration into the joints.

Results

High CCR2 expression and responsiveness to CCL2 were observed in neutrophils from the blood of patients with early RA and in neutrophils from the blood and bone marrow of mice with AIA. Genetic deficiency or pharmacologic inhibition of CCR2 protected against the infiltration of neutrophils into the joints. This protection was not associated with an impairment of the neutrophil chemotactic ability or CXC chemokine production in the joints. Moreover, adoptive transfer of wild‐type mouse neutrophils to CCR2‐deficient mice restored neutrophil infiltration and the articular mechanical hyperalgesia associated with joint inflammation.

Conclusion

These findings suggest that CCR2 is directly involved in the detrimental infiltration of neutrophils into the joints in patients with RA, showing a new inflammatory role of CCR2 during RA flares or active disease.
The Topoisomerase I Inhibitor Irinotecan and the Tyrosyl‐DNA Phosphodiesterase 1 Inhibitor Furamidine Synergistically Suppress Murine Lupus Nephritis
Authors: Keil Andreas , Frese‐Schaper Manuela , Steiner Selina K. , Körner Meike , Schmid Ralph A. , Frese Steffen
Published: March 2015

Objective

The treatment of lupus nephritis is still an unmet medical need requiring new therapeutic approaches. Our group found recently that irinotecan, an inhibitor of topoisomerase I (topo I), reversed proteinuria and prolonged survival in mice with advanced lupus nephritis. While irinotecan is known to stabilize the complex of topo I and DNA, the enzyme tyrosyl‐DNA phosphodiesterase 1 (TDP‐1) functions in an opposing manner by releasing topo I from DNA. Therefore, we undertook this study to test whether the TDP‐1 inhibitor furamidine has an additional effect on lupus nephritis when used in combination with irinotecan.

Methods

NZB/NZW mice were treated with low‐dose irinotecan and furamidine either alone or in combination beginning at age 26 weeks. DNA relaxation was visualized using gel electrophoresis. Binding of anti–double‐stranded DNA (anti‐dsDNA) antibodies to DNA modified by topo I, TDP‐1, and the topo I inhibitor camptothecin was determined by enzyme‐linked immunosorbent assay.

Results

Compared to treatment with either agent alone, simultaneous treatment with low‐dose irinotecan and furamidine significantly improved survival of NZB/NZW mice. Similar to what has been previously shown for irinotecan alone, the combination treatment did not change the levels of anti‐dsDNA antibodies. In vitro, recombinant TDP‐1 increased topo I–mediated DNA relaxation, resulting in enhanced binding of anti‐dsDNA antibodies. In combination with topo I and camptothecin, TDP‐1 reversed the inhibitory effects of camptothecin on DNA relaxation and anti‐dsDNA binding.

Conclusion

Affecting DNA relaxation by the enzymes topo I and TDP‐1 and their inhibitors may be a promising approach for the development of new targeted therapies for systemic lupus erythematosus.
Apremilast in Patients With Active Rheumatoid Arthritis: A Phase II, Multicenter, Randomized, Double‐Blind, Placebo‐Controlled, Parallel‐Group Study
Authors: Genovese Mark C. , Jarosova Katerina , Cieślak Dorota , Alper Jeffrey , Kivitz Alan , Hough Douglas R. , Maes Peter , Pineda Lilia , Chen Mindy , Zaidi Farrukh
Published: March 2015

Objective

To study the efficacy/safety of apremilast, an oral phosphodiesterase 4 inhibitor, compared with placebo in patients with active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX).

Methods

Patients were randomized 1:1:1 to receive placebo, apremilast 20 mg twice a day, or apremilast 30 mg twice a day. Patients whose swollen and tender joint counts had not improved by ≥20% were considered nonresponders at week 16 and were required to enter the protocol‐defined early escape. At week 24, patients were transitioned in a blinded manner to receive apremilast 20 mg twice a day if they were initially randomized to receive placebo. Patients who were not initially randomized to receive placebo continued to receive their target apremilast dose. Patients were required to take a stable dose of MTX (7.5–25 mg/week) throughout the study. Magnetic resonance imaging (MRI) was performed in a subset of patients.

Results

A total of 237 patients who were receiving MTX therapy were randomized and received ≥1 dose of study medication. At week 16, similar proportions of patients receiving placebo (35%), apremilast 20 mg twice a day (28%), and apremilast 30 mg twice a day (34%) met the American College of Rheumatology criteria for 20% improvement in disease activity (the primary efficacy end point). In the MRI substudy, mean change from baseline in total joint damage scores according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system was generally similar with either apremilast dose at week 16. At week 52, no trends were noted for clinical end points by treatment group. Both apremilast doses were generally well tolerated.

Conclusion

Apremilast efficacy was not demonstrated in patients who had active RA despite stable MTX therapy.
Generating descriptive multi‐document summaries of geo‐located entities using entity type models
Authors: Aker Ahmet , Gaizauskas Robert
Published: March 2015

In this article, we investigate the application of entity type models in extractive multi‐document summarization using automatic caption generation for images of geo‐located entities (e.g., Westminster Abbey) as an application scenario. Entity type models contain sets of patterns aiming to capture the ways geo‐located entities are described in natural language. They are automatically derived from texts about geo‐located entities of the same type (e.g., churches, lakes). We integrate entity type models into a multi‐document summarizer and use them to address the 2 major tasks in extractive multi‐document summarization: sentence scoring and summary composition. We experiment with 3 different representation methods for entity type models: signature words, n‐gram language models, and dependency patterns. We evaluate the summarizer with integrated entity type models relative to (a) a summarizer using standard text‐related features commonly used in text summarization and (b) the Wikipedia location descriptions. Our results show that entity type models significantly improve the quality of output summaries over that of summaries generated using standard summarization features and Wikipedia summaries. The representation of entity type models using dependency patterns is superior to the representations using signature words and n‐gram language models.
Aluminum oxide nanoparticles alter cell cycle progression through CCND1 and EGR1 gene expression in human mesenchymal stem cells
Authors: Periasamy Vaiyapuri Subbarayan , Athinarayanan Jegan , Alshatwi Ali A.
Published: March 2015

Aluminum oxide nanoparticles (Al2O3‐NPs) are important ceramic materials that have been used in a variety of commercial and industrial applications. However, the impact of acute and chronic exposure to Al2O3‐NPs on the environment and on human health has not been well studied. In this investigation, we evaluated the cytotoxic effects of Al2O3‐NPs on human mesenchymal stem cells (hMSCs) by using a cell viability assay and observing cellular morphological changes, analyzing cell cycle progression, and monitoring the expression of cell cycle response genes (PCNA, EGR1, E2F1, CCND1, CCNC, CCNG1, and CYCD3). The Al2O3‐NPs reduced hMSC viability in a dose‐ and time‐dependent manner. Nuclear condensation and fragmentation, chromosomal DNA fragmentation, and cytoplasmic vacuolization were observed in Al2O3‐NP‐exposed cells. The nuclear morphological changes indicated that Al2O3‐NPs alter cell cycle progression and gene expression. The cell cycle distribution revealed that Al2O3‐NPs cause cell cycle arrest in the sub‐G0‐G1 phase, and this is associated with a reduction in the cell population in the G2/M and G0/G1 phases. Moreover, Al2O3‐NPs induced the upregulation of cell cycle response genes, including EGR1, E2F1, and CCND1. Our results suggested that exposure to Al2O3‐NPs could cause acute cytotoxic effects in hMSCs through cell cycle regulatory genes.
Carboxymethyl starch/alginate microspheres containing diamine oxidase for intestinal targeting
Authors: Blemur Lindsay , Le Tien Canh , Marcocci Lucia , Pietrangeli Paola , Mateescu Mircea Alexandru
Published: March 2015

The association of carboxymethyl starch (CMS) and alginate is proposed as a novel matrix for the entrapment of bioactive agents in microspheres affording their protection against gastrointestinal degradation. In this study, the enzyme diamine oxidase (DAO) from white pea (Lathyrus sativus) was immobilized by inclusion in microspheres formed by ionotropic gelation of CMS/alginate by complexation with Ca2+. The association of CMS to alginate generated a more compact structure presenting a lesser porosity, thus decreasing the access of gastric fluid inside the microspheres and preventing the loss of entrapped enzyme. Moreover, the immobilized enzyme remained active and was able to oxidize the polyamine substrates even in the presence of degrading proteases of pancreatin. The inclusion yield in terms of entrapped protein was of about 82%–95%. The DAO entrapped in calcium CMS/alginate beads retained up to 70% of its initial activity in simulated gastric fluid (pH 2.0). In simulated intestinal fluid (pH 7.2) with pancreatin, an overall retention of 65% of activity for the immobilized DAO was observed over 24 H, whereas in similar conditions the free enzyme was totally inactivated. Our project proposes the vegetal DAO as an antihistaminic agent orally administered to treat food histaminosis and colon inflammation.
Preparation, characterization, and silanization of 3D microporous PDMS structure with properly sized pores for endothelial cell culture
Authors: Zargar Reyhaneh , Nourmohammadi Jhamak , Amoabediny Ghassem
Published: March 2015

Nowadays, application of porous polydimethylsiloxane (PDMS) structure in biomedical is becoming widespread, and many methods have been established to create such structure. Although the pores created through these methods are mostly developed on the outer surface of PDMS membrane, this study offers a simple and cost‐efficient technique for creating three‐dimensional (3D) microporous PDMS structure with appropriate pore size for endothelial cell culture. In this study, combination of gas foaming and particulate leaching methods, with NaHCO3 as effervescent salt and NaCl as progen are used to form a 3D PDMS sponge. The in situ chemical reaction between NaHCO3 and HCl resulted in the formation of small pores and channels. Moreover, soaking the samples in HCl solution temporarily improved the hydrophilicity of PDMS, which then facilitated the penetration of water for further leaching of NaCl. The surface chemical modification process was performed by (3‐aminopropyl)triethoxysilane to culture endothelial cells on porous PDMS matrix. The results are an indication of positive response of endothelial cells to the fabricated PDMS sponge. Because of simplicity and practicality of this method for preparing PDMS sponge with appropriate pore size and biological properties, the fabricated matrix can perfectly be applied to future studies in blood‐contacting devices.
Family structure instability and the educational persistence of young people in England
Authors: Hampden‐Thompson Gillian , Galindo Claudia
Published: March 2015

Research in the area of family structure and educational outcomes has often failed to account for instability in family structure. Furthermore, prior research in this area has been dominated by North American studies with a smaller body emerging from Europe. This study draws upon 10,783 young people and their parents from the Longitudinal Study of Young People in England to examine the association between family structure and family structure instability on post‐16 educational persistence. Multivariate models indicate that family structure instability has a negative impact on educational persistence. After controlling for covariates, young people who had experienced family structure instability were 33% less likely to stay in education than young people who resided in married biological families during the four years prior to the end of compulsory schooling. The findings of this research provide evidence that young people who have experienced a change in family circumstances during these four years are potentially at risk of dropping out of school – this is the case irrespective of the nature of the change. Once covariates were accounted for, young people who resided in stable lone‐parent households were just as likely as those in stable married biological families to continue to post‐16 education. Analyses were also conducted to determine the educational persistence of young people from biological vs step‐cohabitating families.
Meta-analysis of the predictive value of C-reactive protein for infectious complications in abdominal surgery
Authors: Adamina M , Steffen T , Tarantino I , Beutner U , Schmied B M , Warschkow R
Published: March 2015

Background

The aim of this analysis was to assess the predictive value of C-reactive protein (CRP) for the early detection of postoperative infectious complications after a variety of abdominal operations.

Methods

A meta-analysis of seven cohort studies from a single institution was performed. Laparoscopic gastric bypass and colectomies, as well as open resections of cancer of the colon, rectum, pancreas, stomach and oesophagus, were included. The predictive value of CRP was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.

Results

Of 1986 patients, 577 (29·1 (95 per cent c.i. 27·1 to 31·3) per cent) had at least one postoperative infectious complication. Patients undergoing laparoscopic gastric bypass (383 patients) or colectomy (285), and those having open gastric (97) or colorectal (934) resections were combined in a meta-analysis. Patients who had resection for cancer of the oesophagus (41) or pancreas (246) were analysed separately owing to heterogeneity. CRP levels 4 days after surgery had the highest diagnostic accuracy (AUC 0·76, 95 per cent c.i. 0·73 to 0·78). Sensitivity and specificity were 68·5 (60·6 to 75·5) and 71·6 (66·6 to 76·0) per cent respectively. Positive and negative predictive values were 50·4 (46·0 to 54·8) and 84·3 (80·8 to 87·3) per cent. The threshold CRP varied according to the procedure performed.

Conclusion

The negative predictive value of serum CRP concentration on day 4 after surgery facilitates reliable exclusion of postoperative infectious complications.
Outcome after surgical resection for duodenal adenocarcinoma in the UK
Authors: Solaini L , Jamieson N B , Metcalfe M , Abu Hilal M , Soonawalla Z , Davidson B R , McKay C , Kocher H M ,   UK Duodenal Cancer Study Group, Tamburrini R , Spoletini G , Shamali A , Thomasset S
Published: March 2015

Background

Factors influencing long-term outcome after surgical resection for duodenal adenocarcinoma are unclear.

Methods

A prospectively created database was reviewed for patients undergoing surgery for duodenal adenocarcinoma in six UK hepatopancreaticobiliary centres from 2000 to 2013. Factors influencing overall survival and disease-free survival (DFS) were identified by regression analysis.

Results

Resection with curative intent was performed in 150 (84·3 per cent) of 178 patients. The postoperative morbidity rate for these patients was 40·0 per cent and the in-hospital mortality rate was 3·3 per cent. Patients who underwent resection had a better median survival than those who had a palliative surgical procedure (84 versus 8 months; P < 0·001). The 1-, 3- and 5-year overall survival rates for patients who underwent resection were 83·9, 66·7 and 51·2 per cent respectively. Median DFS was 53 months, and 1- and 3-year DFS rates were 80·8 and 56·5 per cent respectively. Multivariable analysis revealed that node status (hazard ratio 1·73, 95 per cent c.i. 1·07 to 2·79; P = 0·006) and lymphovascular invasion (hazard ratio 3·49, 1·83 to 6·64; P = 0·003) were associated with overall survival.

Conclusion

Resection of duodenal adenocarcinoma in specialist centres is associated with good long-term survival. Lymphovascular invasion and nodal metastases are independent prognostic indicators.
DNA methylation and hydroxymethylation in stem cells
Authors: Cheng Ying , Xie Nina , Jin Peng , Wang Tao
Published: March 2015

In mammals, DNA methylation and hydroxymethylation are specific epigenetic mechanisms that can contribute to the regulation of gene expression and cellular functions. DNA methylation is important for the function of embryonic stem cells and adult stem cells (such as haematopoietic stem cells, neural stem cells and germline stem cells), and changes in DNA methylation patterns are essential for successful nuclear reprogramming. In the past several years, the rediscovery of hydroxymethylation and the TET enzymes expanded our insights tremendously and uncovered more dynamic aspects of cytosine methylation regulation. Here, we review the current knowledge and highlight the most recent advances in DNA methylation and hydroxymethylation in embryonic stem cells, induced pluripotent stem cells and several well‐studied adult stems cells. Our current understanding of stem cell epigenetics and new advances in the field will undoubtedly stimulate further clinical applications of regenerative medicine in the future. Copyright © 2015 John Wiley & Sons, Ltd.
Effectiveness of purging on preventing gas emission buildup in wood pellet storage
Authors: Yazdanpanah Fahimeh , Sokhansanj Shahab , Lim Choon Jim , Lau Anthony , Bi Xiaotao
Published: March 2015

Storage of wood pellets has resulted in deadly accidents in connection with off‐gassing and self‐heating. A forced ventilation system should be in place to sweep the off‐gases and control the thermal conditions. In this study, multiple purging tests were conducted in a pilot scale silo to evaluate the effectiveness of a purging system and quantify the time and volume of the gas needed to sweep the off‐gases. To identify the degree of mixing, residence time distribution of the tracer gas was also studied experimentally. Large deviations from plug flow suggested strong gas mixing for all superficial velocities. As the velocity increased, the system dispersion number became smaller, which indicated less degree of mixing with increased volume of the purging gas. One‐dimensional modelling and numerical simulation of the off‐gas concentration profile gave the best agreement with the measured gas concentration at the bottom and middle of the silo.
Detection of decomposition for high pressure ethylene/vinyl acetate copolymerization in autoclave reactor using principal component analysis on heat balance model
Authors: Sivalingam G. , Soni Nipun J. , Vakil Suketu M.
Published: March 2015

An autoclave reactor offers flexibility in producing specialty grades of ethylene/vinyl acetate copolymer at a temperature range of 150–230 °C and pressure range of 1400–2000 kg/cm2. At such conditions, copolymerization is accompanied by decomposition of reactants which increases the risk of thermal runaway. The runaway reaction is initiated by local hot spots in the reactor which are generated by process/equipment disturbances or imperfect mixing in the reactor. It is hard to predict decomposition, due to the extremely fast dynamics of the event. A decomposition detection method was developed based on the overall energy balance around the reactor. During normal steady state operations, the heat balance error should be within reasonable limits. If abnormal conditions generate excess heat in the reactor, the heat balance error will exceed the limit, indicating the possibility of an impending decomposition. Principal component analysis (PCA) was used for model identification and to get the unknown parameters in the model. An iterative PCA technique was used to confirm the selection of the model. Long term plant operation data over a period of six months were used for training and testing of the model. Data validation rules were applied and false alarms associated with operating condition fluctuations were minimized by applying appropriate equations for conversion at various operating conditions. The model was validated with an actual plant steady state decomposition case where the model could predict decomposition with a few seconds of lead time.
Fear of Self and Unacceptable Thoughts in Obsessive–Compulsive Disorder
Authors: Melli Gabriele , Aardema Frederick , Moulding Richard
Published: March 2015

Cognitive‐behavioural models have linked unacceptable or repugnant thoughts in obsessive–compulsive disorder (OCD) with vulnerable self‐themes and fear‐of‐self concerns. To investigate this notion, Aardema and coworkers recently developed and validated the Fear of Self‐Questionnaire (FSQ) in non‐clinical samples, finding it had strong internal inconsistency, and good divergent and convergent validity, including strong relationships to obsessional symptoms and with other processes implicated in cognitive models of OCD (e.g., obsessive beliefs and inferential confusion). The current article describes two studies that aim to replicate and extend these findings in clinical OCD and non‐clinical samples. Study 1 investigated the psychometric properties of an Italian translation of the FSQ in a non‐clinical sample (n = 405). Results of confirmatory factor analysis supported the unidimensionality of the scale; the FSQ also showed very good internal consistency and temporal stability. Study 2 investigated the role of fear of self in OCD symptoms, and unacceptable thoughts and repugnant obsessions in particular, using a clinical OCD sample (n = 76). As expected, fear of self was a unique, major predictor of unacceptable thoughts independent of negative mood states and obsessive beliefs. Moreover, even when considered with obsessive beliefs, anxiety and depression, the feared self was the only unique predictor of obsessionality, providing support for the notion that self‐themes could explain why some intrusions convert into obsessions, whereas others do not. Implications for current cognitive‐behavioural models are discussed. Copyright © 2015 John Wiley & Sons, Ltd.

Key Practitioner Message

Unacceptable thoughts in OCD have been linked with vulnerable self‐themes and a fear of self.

Aardema and coworkers recently developed and validated the Fear of Self‐Questionnaire (FSQ).

Study 1 investigated the Psychometric properties of an Italian translation of the FSQ in a non‐clinical sample.

Study 2 investigated the role of fear of self in unacceptable thoughts, using a clinical OCD sample.

Fear of self was a unique, major predictor of unacceptable thoughts in OCD over and beyond obsessive beliefs.
Regulation of ABC transporters at the blood–brain barrier
Authors: Miller DS
Published: March 2015

ATP binding cassette (ABC) transporters at the blood–brain barrier function as ATP‐driven xenobiotic efflux pumps and limit delivery of small molecule drugs to the brain. Here I review recent progress in understanding the regulation of the expression and transport activity of these transporters and comment on how this new information might aid in improving drug delivery to the brain.
Crystal structure of aluminum sulfate hexadecahydrate and its morphology
Authors: Sun Xiaoxue , Sun Yuzhu , Yu Jianguo
Published: March 2015

A single‐crystal structure of aluminum sulfate hexadecahydrate (Al2(SO4)3·16H2O) was captured with a polarizing microscope. The structure was similar to a hexagonal plate and consistent with the predicted morphology derived from the modified AE model. An octagonal plate morphology was first obtained in a vacuum but was transformed into hexagonal plate‐like when the effect of the solvent with two disappearing {1 1 0} and {1 0 −1} faces was considered.
The immunosuppressive enzyme IL4I1 promotes FoxP3+ regulatory T lymphocyte differentiation
Authors: Cousin Céline , Aubatin Aude , Le Gouvello Sabine , Apetoh Lionel , Castellano Flavia , Molinier‐Frenkel Valérie
Published: March 2015

IL4I1 (interleukin‐4‐induced gene 1) is a phenylalanine oxidase produced mainly by APCs of myeloid origin, and converts phenylalanine (Phe) to phenylpyruvate, hydrogen peroxide, and ammonia. We have previously shown that IL4I1 is highly expressed by tumor‐associated macrophages from various human cancers and facilitates immune evasion from the cytotoxic response in a murine tumor model. Indeed, IL4I1 inhibits T‐cell proliferation via hydrogen peroxide toxicity on effector/memory T cells. Here, we explored the effect of IL4I1 on naïve CD4+ T‐cell differentiation. We show that IL4I1 stimulates the generation of Foxp3+ regulatory T (Treg) cells in vitro from human and mouse T cells. This effect was observed with IL4I1 from different sources, including the naturally produced enzyme. Conversely, IL4I1 limits Th1 and Th2 polarization while modifying the Th17 phenotype, in particular, by inducing its own production. Analysis of Treg‐cell induction under conditions of Phe deprivation and hydrogen peroxide addition suggests that Phe consumption by the enzyme participates in Treg‐cell enrichment. In line with this hypothesis, IL4I1 inhibits mTORC1 signaling shortly after T‐cell activation. Thus, the IL4I1 enzyme may act on T cells both by direct inhibition of effector cell proliferation and by indirect immunoregulation mediated by Treg‐cell induction.
Regression‐based covariance functions for nonstationary spatial modeling
Authors: Risser Mark D. , Calder Catherine A.
Published: March 2015

In many environmental applications involving spatially‐referenced data, limitations on the number and locations of observations motivate the need for practical and efficient models for spatial interpolation, or kriging. A key component of models for continuously‐indexed spatial data is the covariance function, which is traditionally assumed to belong to a parametric class of stationary models. However, stationarity is rarely a realistic assumption. Alternative methods that more appropriately model the nonstationarity present in environmental processes often involve high‐dimensional parameter spaces, which lead to difficulties in model fitting and interpretability. To overcome this issue, we build on the growing literature of covariate‐driven nonstationary spatial modeling. Using process convolution techniques, we propose a Bayesian model for continuously‐indexed spatial data based on a flexible parametric covariance regression structure for a convolution‐kernel covariance matrix. The resulting model is a parsimonious representation of the kernel process, and we explore properties of the implied model, including a description of the resulting nonstationary covariance function and the interpretational benefits in the kernel parameters. Furthermore, we demonstrate that our model provides a practical compromise between stationary and highly parameterized nonstationary spatial covariance functions that do not perform well in practice. We illustrate our approach through an analysis of annual precipitation data. Copyright © 2015 John Wiley & Sons, Ltd.
Does Disagreement Amongst Forecasters Have Predictive Value?
Authors: Legerstee Rianne , Franses Philip Hans
Published: March 2015

In the present study we examine the predictive power of disagreement amongst forecasters. In our empirical work, we find that in some situations this variable can signal upcoming structural and temporal changes in an economic process and in the predictive power of the survey forecasts. We examine a variety of macroeconomic variables, and we use different measurements for the degree of disagreement, together with measures for location of the survey data and autoregressive components. Forecasts from simple linear models and forecasts from Markov regime‐switching models with constant and with time‐varying transition probabilities are constructed in real time and compared on forecast accuracy. Copyright © 2015 John Wiley & Sons, Ltd.
Analysis of Leakages in a Solid Oxide Fuel Cell Stack in a System Environment
Authors: Halinen M. , Pennanen J.
Published: March 2015

A solid oxide fuel cell (SOFC) stack can exhibit both anodic and cathodic leakages, i.e. a fuel leak from the anode side and an air leak from the cathode side of the stack, respectively. This study describes the results of an in‐situ leakage analysis conducted for a planar SOFC stack during 2000 hours of operation in an actual system environment. The leakages are quantified experimentally at nominal system operating conditions by conducting composition analysis and flow metering of gases for both fuel and air subsystems. Based on the calculated atomic hydrogen‐to‐carbon ratio of the fuel and air gases, it is found that the fuel leakages are mostly selective by nature: the leaking fuel gas does not have the same composition as the fuel system gas. A simple diffusive leakage model, based on the leakage being driven by concentration differences weighted by diffusion coefficients, is applied to quantify the amount of leakages. The leakage model provides a good correspondence with the experimental results of the gas analysis.
Assessing the fit of biotic ligand model validation data in a risk management decision context
Authors: McLaughlin Douglas B
Published: March 2015

Biotic ligand models (BLMs) have advanced the ability to predict the concentrations of metals in surface waters likely to harm aquatic organisms. BLMs have been developed for several metals including Cu, Zn, Cd, and Ag. Additionally, the US Environmental Protection Agency has published guidance on the use of a BLM to develop water quality criteria for Cu. To validate the predictive performance of many BLMs, model predictions based on test water quality have been compared with corresponding laboratory toxicity measurements. Validation results are typically described in the published literature in terms of the proportion of predicted effect concentrations that fall within a factor of 2 of measured values. In this article, an alternative is presented using a receiver operating characteristics approach and regression prediction limit analyses, quantifying the probabilities of true and false predictions of excess toxicity risk based on toxic unit calculations and a risk management threshold of 1. The approaches are applied to a published Zn BLM and 3 simulated data sets that reflect attributes of other published BLM validation data. The overall accuracy of the unified Zn BLM is estimated to be 80% to 90%, and analyses of simulated data suggest a similar level of accuracy for other published BLMs. Further application of these validation methods to other BLMs may provide more complete and transparent information on their possible predictive value when used in the management of risks due to aqueous metals. Integr Environ Assess Manag 2015;9999:1–8. © 2015 SETAC

Key Points

Biotic Ligand Models are used increasingly in the assessment of risks to aquatic life due to metals. BLM validation results have typically been described in the literature in terms of the proportion of predicted effect concentrations that fall within a factor of 2 of measured values. This paper presents an alternative which quantifies model accuracy and prediction error rates for a toxicity threshold of 1 toxic unit. Such performance metrics may be more directly relevant to risk managers considering the use of BLMs.
Bonding charge density from atomic perturbations
Authors: Wang Yi , Wang William Yi , Chen Long‐Qing , Liu Zi‐Kui
Published: March 2015

Charge transfer among individual atoms is the key concept in modern electronic theory of chemical bonding. In this work, we present a first‐principles approach to calculating the charge transfer. Based on the effects of perturbations of an individual atom or a group of atoms on the electron charge density, we determine unambiguously the amount of electron charge associated with a particular atom or a group of atoms. We computed the topological electron loss versus gain using ethylene, graphene, MgO, and SrTiO3 as examples. Our results verify the nature of chemical bonds in these materials at the atomic level. © 2015 Wiley Periodicals, Inc.
Gaseous emissions and soil fertility of homegardens in the Nuba Mountains, Sudan
Authors: Goenster Sven , Wiehle Martin , Predotova Martina , Gebauer Jens , Ali Abdalla Mohamed , Buerkert Andreas
Published: March 2015

Intensification of homegardens in the Nuba Mountains may lead to increases in C and nutrient losses from these small‐scale land‐use systems and potentially threaten their sustainability. This study, therefore, aimed at determining gaseous C and N fluxes from homegarden soils of different soil moisture, temperature, and C and N status. Emissions of CO2, NH3, and N2O from soils of two traditional and two intensified homegardens and an uncultivated control were recorded bi‐weekly during the rainy season in 2010. Flux rates were determined with a portable dynamic closed chamber system consisting of a photo‐acoustic multi‐gas field monitor connected to a PTFE coated chamber. Topsoil moisture and temperature were recorded simultaneously to the gas measurements. Across all homegardens emissions averaged 4,527 kg CO2‐C ha−1, 22 kg NH3‐N ha−1, and 11 kg N2O‐N ha−1 for the observation period from June to December. Flux rates were largely positively correlated with soil moisture and predominantly negatively with soil temperature. Significant positive, but weak (rs < 0.34) correlations between increasing management intensity and emissions were noted for CO2‐C. Similarly, morning emissions of NH3 and increasing management intensity were weakly correlated (rs = 0.17). The relatively high gaseous C and N losses in the studied homegardens call for effective management practices to secure the soil organic C status of these traditional land‐use systems.
Optimisation of α‐terpineol production by limonene biotransformation using Penicillium digitatumDSM 62840
Authors: Tai Ya‐Nan , Xu Min , Ren Jing‐Nan , Dong Man , Yang Zi‐Yu , Pan Si‐yi , Fan Gang
Published: March 2015

BACKGROUND

In this study, (R)‐(+)‐limonene biotransformation using three fungal strains was compared. Penicillium digitatum DSM 62840 was distinguished for its capacity to transform limonene into α‐terpineol with high regioselectivity. Growth kinetics in submerged liquid culture and the effects of growth phase and contact time on biotransformation were studied using this strain. Substrate concentration, co‐solvent selection, and cultivation conditions were subsequently optimised.

RESULTS

The maximum concentration of α‐terpineol (833.93 mg L−1) was obtained when the pre‐culture medium was in medium log‐phase by adding 840 mg L−1 substrate dissolved in ethanol and cultivation was performed at 24 °C, 150 rpm, and pH 6.0 for 12 h. Addition of small amounts of (R)‐(+)‐limonene (84 mg L−1) at the start of fungal log‐phase growth yielded a 1.5‐fold yield of α‐terpineol, indicating that the enzyme was inducible.

CONCLUSION

Among these three strains tested, P. digitatum DSM 62840 was proved to be an efficient biocatalyst to transform (R)‐(+)‐limonene to α‐terpineol. Further studies revealed that the optimal growth phase for biotransformation was in the medium log phase of this strain. The biotransformation represented a wide tolerance of temperature; α‐terpineol concentration underwent no significant change at 8–32 °C. The biotransformation could also be performed using resting cells. © 2015 Society of Chemical Industry
Homoclinic solutions for a class of second order Hamiltonian systems
Authors: Zhang Qingye
Published: March 2015

In this paper, we study homoclinic solutions for the nonperiodic second order Hamiltonian systems

urn:x-wiley:0025584X:media:mana201200293:mana201200293-math-0001where L is unnecessarily coercive or uniformly positively definite, and is only locally defined near the origin with respect to u. Under some general conditions on L and W, we show that the above system has infinitely many homoclinic solutions near the origin. Some related results in the literature are extended and generalized.
Late Emergence of Parkinsonian Phenotype and Abnormal Dopamine Transporter Scan in Chorea‐Acanthocytosis
Authors: Nagy Anna , Noyce Alastair , Velayos‐Baeza Antonio , Lees Andrew J. , Warner Thomas T. , Ling Helen
Published: March 2015

Chorea‐acanthocytosis (ChAc) is a neurodegenerative condition predominantly manifesting with chorea and often acanthocytes on peripheral blood film. Abnormal appearances with 123I‐FP‐CIT single‐photon emission computed tomography (SPECT) have not previously been reported in ChAc. We describe 2 cases with typical presentations of ChAc and late development of parkinsonism with asymmetric reduction in presynaptic striatal uptake on 123I‐FP‐CIT SPECT. Case 1, a 50‐year‐old male, developed micrographia and limb bradykinesia 14 years after initial presentation at the age of 30. Case 2, a 42‐year‐old female presenting with vocal tics and generalized dystonia at the age of 25, developed tremor, bradykinesia, and rigidity 11 years into the disease course. These cases represent the best description to date of the natural history of ChAc, in which the early hyperkinetic clinical syndromes give way to a parkinsonian phenotype. This is consistent with a gradual deterioration of presynaptic nigrostriatal projections, reflected in the clinical parkinsonism and abnormal 123I FP‐CIT SPECT.
Revisiting the Syndrome of “Obsessional Slowness”
Authors: Ganos Christos , Kassavetis Panagiotis , Cerdan Maria , Erro Roberto , Balint Bettina , Price Gary , Edwards Mark J. , Bhatia Kailash P.
Published: March 2015

Background

Obsessional slowness (OS) denotes a rare condition of disablingly slow motor performance. It was originally described in patients with obsessive‐compulsive disorder as a “primary” condition; however, subsequent reports have included heterogeneous clinical populations. We wished to reassess patients with this diagnosis at our own institution and also revisit the literature to provide an overview of this condition.

Methods

Clinical documentation and videos of 3 patients diagnosed with OS in the National Hospital for Neurology and Neurosurgery (London, UK) were reviewed. One of the patients was clinically reappraised. A systematic review of published articles with sufficient clinical patient information was also conducted.

Results

Our 3 cases were male with symptom onset in adolescence or early adulthood. Motor slowness with poverty of movement and a history of obsessive‐compulsive symptoms were characteristic. Poor speech production, bizarre postures, mannerisms, echophenomena, and oculogyric tics were also noted. Dopaminergic imaging was normal in 2 cases. One case had autistic features. Systematic literature review identified 77 further cases. Male preponderance with symptom onset mainly during the second decade and presence of obsessive‐compulsive symptoms were noted. Additional motor and neuropsychiatric features were often present.

Conclusion

The existence of OS as a “primary” condition is doubtful. This diagnosis has been given to characterize different clinical presentations ranging from obsessive‐compulsive disorder with motor slowness resulting from covert obsessive‐compulsive symptoms to catatonia. Clinicians should be aware of this syndrome to separate it from juvenile parkinsonism and other causes of motor slowness given that diagnostic approaches and treatment strategies differ.
Lymph node flap transfer for patients with secondary lower limb lymphedema
Authors: Batista Bernardo N. , Germain Michel , Faria José Carlos M. , Becker Corinne
Published: March 2015

Background

Previous authors have shown benefits from the use of lymph node flap transfer (LNFT) to treat lymphedema of the arms, but there is little evidence for its use for lower limb lymphedema. We performed a retrospective analysis of a series of patients suffering from secondary lower limb lymphedema treated with a free LNFT.

Methods

52 cases of LNFT to treat 41 legs in 38 patients with secondary lymphedema were retrospectively reviewed. The causes of the lymphedema included lymphedema secondary to hysterectomy for uterine cancer, melanoma resections on the leg, lymphoma treatment and testicular cancer, cosmetic surgery to the limb, lipoma resection at the inguinal region, and a saphenectomy. Patients had been suffering with lymphedema for an average of 9.1 ± 7.3 years at the time of LNFT.

Results

Eleven patients (28.9%) presented with minor complications treated conservatively. For 23 legs there was enough data to follow limb volume evolution after a single LNFT. Total volume reduction in eight legs (two patients with no measures of the healthy limb and three bilateral) was 7.1 ± 8.6%. Another group of 15 patients with unilateral lymphedema had an average 46.3 ± 34.7% reduction of excess volume. Better results (>30% REV) were associated with smaller preoperative excess volume (P = 0.045).

Conclusion

Patients with secondary leg lymphedema can benefit from LNFT. Results in patients with mild presentations seem to be better than in more severe cases. © 2014 Wiley Periodicals, Inc. Microsurgery 37:29–33, 2017.
Fréchet differentiability of the elasto‐acoustic scattered field with respect to Lipschitz domains
Authors: Barucq Helene , Djellouli Rabia , Estecahandy Elodie
Published: March 2015

We analyse the dependence with respect to a given domain of the solution of a fluid‐structure interaction scattering problem. We establish that the scattered field is continuously Fréchet differentiable with respect to the shape of the elastic scatterer. Our proof assumes that the boundary of the scatterer as well as the admissible perturbations to be only Lipschitzian. Given the applied nature of this problem and its prevalence in engineering and numerical literature, this new result appears to be of practical interest. Copyright © 2015 John Wiley & Sons, Ltd.
LC‐MS/MS‐based serum proteomics for identification of candidate biomarkers for hepatocellular carcinoma
Authors: Tsai Tsung‐Heng , Song Ehwang , Zhu Rui , Di Poto Cristina , Wang Minkun , Luo Yue , Varghese Rency S. , Tadesse Mahlet G. , Ziada Dina Hazem , Desai Chirag S. , Shetty Kirti , Mechref Yehia , Ressom Habtom W.
Published: March 2015

Associating changes in protein levels with the onset of cancer has been widely investigated to identify clinically relevant diagnostic biomarkers. In the present study, we analyzed sera from 205 patients recruited in the United States and Egypt for biomarker discovery using label‐free proteomic analysis by LC‐MS/MS. We performed untargeted proteomic analysis of sera to identify candidate proteins with statistically significant differences between hepatocellular carcinoma (HCC) and patients with liver cirrhosis. We further evaluated the significance of 101 proteins in sera from the same 205 patients through targeted quantitation by MRM on a triple quadrupole mass spectrometer. This led to the identification of 21 candidate protein biomarkers that were significantly altered in both the United States and Egyptian cohorts. Among the 21 candidates, ten were previously reported as HCC‐associated proteins (eight exhibiting consistent trends with our observation), whereas 11 are new candidates discovered by this study. Pathway analysis based on the significant proteins reveals upregulation of the complement and coagulation cascades pathway and downregulation of the antigen processing and presentation pathway in HCC cases versus patients with liver cirrhosis. The results of this study demonstrate the power of combining untargeted and targeted quantitation methods for a comprehensive serum proteomic analysis, to evaluate changes in protein levels and discover novel diagnostic biomarkers. All MS data have been deposited in the ProteomeXchange with identifier PXD001171 (http://proteomecentral.proteomexchange.org/dataset/PXD001171).
Effects of intentional oxygen and carbon doping in MOVPE‐grown GaN layers on photoelectric properties
Authors: Wang Yaxin , Teramoto Takashi , Ohkawa Kazuhiro
Published: March 2015

In order to qualitatively and quantitatively analyze the effects of N source impurity species and concentrations on the properties of epitaxial GaN layers, we intentionally introduced the oxygen‐containing species CO and CO2 into GaN layers during growth. Subsequently, we determined the impurities or elements that had a strong effect on the photoelectric properties of the GaN layers and investigated the doping mechanism. The results of this study show that changes in the carrier density are more sensitive to CO2 than to CO. Oxygen as the main donor was found to affect the carrier density and photoluminescence (PL) emission intensities of CO and CO2‐doped GaN, and the carbon incorporation efficiency of these molecules was found to be lower than the oxygen incorporation efficiency. In order to obtain ideal epitaxial GaN layers with a reduced carrier density of 1013 cm−3, the CO and CO2 concentrations in the ammonia source should be less than 100 ppb (CO) and 10−1 ppb (CO2).
Comparative Cytotoxicity of Glycyrrhiza glabra Roots from Different Geographical Origins Against Immortal Human Keratinocyte (HaCaT), Lung Adenocarcinoma (A549) and Liver Carcinoma (HepG2) Cells
Authors: Basar Norazah , Oridupa Olayinka Ayotunde , Ritchie Kenneth J. , Nahar Lutfun , Osman Nashwa Mostafa M. , Stafford Angela , Kushiev Habibjon , Kan Asuman , Sarker Satyajit D.
Published: March 2015

Glycyrrhiza glabra L. (Fabaceae), commonly known as ‘liquorice’, is a well‐known medicinal plant. Roots of this plant have long been used as a sweetening and flavouring agent in food and pharmaceutical products, and also as a traditional remedy for cough, upper and lower respiratory ailments, kidney stones, hepatitis C, skin disorder, cardiovascular diseases, diabetes, gastrointestinal ulcers and stomach ache. Previous pharmacological and clinical studies have revealed its antitussive, antiinflammatory, antiviral, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and cardioprotective properties. While glycyrrhizin, a sweet‐tasting triterpene saponin, is the principal bioactive compound, several bioactive flavonoids and isoflavonoids are also present in the roots of this plant. In the present study, the cytotoxicity of the methanol extracts of nine samples of the roots of G. glabra, collected from various geographical origins, was assessed against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cell lines using the in vitro 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazoliumbromide cell toxicity/viability assay. Considerable variations in levels of cytotoxicity were observed among various samples of G. glabra. Copyright © 2015 John Wiley & Sons, Ltd.