bluuebunny/crossref_metadata_2025 huggingface dataset:
Imputation of Missing Data for a Continuous Variable with an Ordinal form of Risk Function: When to Apply the Transformation?
Authors: Baneshi Mohammad Reza , Garrusi Behshid , Haji-Maghsoudi Saiedeh
Published: November 2014

Introduction: Imputation of missing data and selection of appropriate risk function are of importance . Sometimes a variable with continuous nature will be offered to the regression model as an ordinal variable. Our aim is to investigate whether to offer the continuous form of the variable to the imputation phase and its ordinal from to the modeling phase, or whether to offer the ordinal version to both phases.
Material and Methods: The outcome and main variable of interest was use of diet as a body change approach, and Body Mass Index (BMI). We randomly deleted 10%, 20%, and 40% of BMI values. In strategies 1 and 2, BMI was offered to the imputation phase as a continuous (BMIC) and ordinal variable (BMIO). Missing data were imputed using linear and polytomous regression respectively. In strategy 1, after imputation, BMIC was categorized (named BMICO) and offered to the modeling phase. In strategy 2, after imputation of BMIO values, this variable was offered to the logistic model (named BMIOO). We compared two strategies at Event Per Variables (EPV) of 75, 10, and 5.
Result: At EPVs of 75 and 10 no remarkable difference was seen. However, at EPV of 5, strategy 2 was superior. At 20% and 40% missing rates, strategy 1 was 2.21 and 3.67 times more likely to produce Severe Relative Bias. At high missing rate, power was higher in strategy2 (90% versus 83%).
Conclusions: When EPV is low and missing rate is high, categorizing of variable before imputation of missing data produces less SRB and leads to higher power.
Avoiding Inferential Errors in Public Health Research: The Statistical Modelling of Physical Activity Behavior
Authors: Amuta Ann O. , Jr. Dudley Poston
Published: November 2014

Background: A review of the health behavior literature on the statistical modeling of days of physical activity (PA) indicates that in many instances linear regression models have been used. It is inappropriate statistically to model a count dependent variable such as days of physical activity with Ordinary Least Squares (OLS). Many count variables have skewed distributions, and, also, have a preponderance of zeroes. Count variables should not be treated as continuous and unbounded. If OLS is used, estimations of the regression will frequently turn out to be inefficient, inconsistent and biased, and such outcomes could well have incorrect impacts on health programs and policies.
Methods: We considered three statistical methods for modelling the distribution of days of PA data for respondents in the 2013 Health Information Trends Survey (HINTS). The three regression models analyzed were: Ordinary Least Squares (OLS), Negative Binomial (NBRM), and Zero-inflated Negative Binomial (ZINB). We used the exact same predictor variables in the three models. Our results illustrate the differences in the results.
Results: Our analyses of the PA data demonstrated that the ZINB model fits the observed PA data better than either the OLS or the NBRM models. The coefficients and standard errors differed in the zero-inflated count models from the other models. For instance, the ZINB coefficient for the association between income and PA behavior was not statistically significant (p>0.05), whereas in the NBRM and in the OLS models, it was statistically significant (p<0.05).
Conclusions: The inappropriate use of regression models could well lead to wrong statistical inferences. Our analyses of the number of days of moderate PA demonstrated that the ZINB count model fits the observed PA data much better than the OLS model and the NBRM.
Remembering Sir Francis Drake: Travel, Commemoration and National Identity in the Work of Henry Robarts
Authors: Ord Melanie
Published: November 2014

Henry Robarts is a little-known writer whose work includes prose romances, records of state entertainments, and commendatory pamphlets on travel. This article pays particular attention to his celebrations of Sir Francis Drake, which form part of a sub-genre of writing on travel and which provide insights into how voyages of discovery figured in the late-sixteenth-century popular imagination. It considers how Robarts theorises the act of commemoration in these and other texts, and looks at the crucial role he imagines both it and travel to play in shaping England's national identity.
Facing Life as We Have Known it: Virginia Woolf and the Women's Co-operative Guild
Authors: Wood Alice
Published: November 2014

This article explores Leonard and Virginia Woolf's early interactions with the Women's Co-operative Guild and supplies a contextualised analysis of Virginia Woolf's preface to Life as We Have Known It (1931). Written to introduce a volume of autobiographical sketches by Co-operative Guildswomen and published in a variant form in the Yale Review, this essay has generated conflicting debate in Woolf studies. In this article I argue that the essay fictionalises Virginia Woolf's relationship with the Guild, concealing her familiarity with Guild activities to better engage an anticipated middle-class readership and promote frank interrogation of class prejudice.
George Orwell, Internment and the Illusion of Liberty
Authors: Robinson Emma
Published: November 2014

George Orwell's initial response to wartime internment is characterised by his silence. Uncertainty, desire for government work, wartime necessity, political prejudice and faith in English reasonableness contributed to his toleration of the policy, in the specific context of total war. Orwell worried that criticising internment could undermine public trust in civil liberties, which performatively protected England from the excesses of totalitarianism. Unlike others on the Left, he therefore placed his faith not in the vigilance of parliament, but in an illusion embraced by the English people: that they remained guardians of civil liberties, despite a need in wartime to curtail them.
‘Hauntings of Celticism’: Fionn Mac Colla and the Myth of History
Authors: Lyall Scott
Published: November 2014

Fionn Mac Colla's ideas of history can be characterised as postcolonial in their critique of historical determinism, Cartesian dualism and Whig progressivism. He utilises his theories, which encompass the psychological implications for individuals and nations of historical deficit, to oppose Scottish Reformation doctrine and the ostensible schisms of Scottish history, particularly the racial polarities promoted through Arnoldian Celticism. Mac Colla seeks to unify what he perceives as a divided Scottish history and identity through the adoption of Thomist religious philosophy.
Connect and Divide
Authors: Heine Eike-Christian
Published: November 2014

The Kiel Canal (built between 1886 and 1895) connects the North Sea and the Baltic for seagoing vessels, yet, being 100 km long, about 10 m deep and 100 m wide, it also divides a landscape. This finding is the starting point for analysing the effects of infrastructure that facilitates communication and exchange but also produces obstructions and rivalries. This article explores the ambiguous effects this piece of infrastructure had on politics, technology, labour, trade and military strategy. The ‘deep ditch’ also had severe environmental consequences that were palpable until well into the twentieth century. By considering both the ‘positive’ and the ‘negative’ of the waterway, the narrative of ‘connect-and-divide’ avoids the still-too-often told affirmative story of transport infrastructure. Instead, it and opens the outlook to a multi-faceted history of transport infrastructures.
Maintaining neural stem cell identity in the brain
Authors: Jiang Yanrui , Reichert Heinrich
Published: November 2014

In the developing fruit fly brain, a protein called Trithorax increases the number of neural cells produced from a single stem cell, in part by regulating the transcription of the target genes buttonhead and pointed.
Neuroimaging biomarkers for Parkinson disease: Facts and fantasy
Authors: Perlmutter Joel S. , Norris Scott A.
Published: November 2014

In this grand rounds, we focus on development, validation, and application of neuroimaging biomarkers for Parkinson disease (PD). We cover whether such biomarkers can be used to identify presymptomatic individuals (probably yes), provide a measure of PD severity (in a limited fashion, but frequently done poorly), investigate pathophysiology of parkinsonian disorders (yes, if done carefully), play a role in differential diagnosis of parkinsonism (not well), and investigate pathology underlying cognitive impairment (yes, in conjunction with postmortem data). Along the way, we clarify several issues about definitions of biomarkers and surrogate endpoints. The goal of this lecture is to provide a basis for interpreting current literature and newly proposed clinical tools in PD. In the end, one should be able to critically distinguish fact from fantasy. Ann Neurol 2014;76:769–783
Longitudinal diffusion tensor imaging in frontotemporal dementia
Authors: Mahoney Colin J. , Simpson Ivor J. A. , Nicholas Jennifer M. , Fletcher Phillip D. , Downey Laura E. , Golden Hannah L. , Clark Camilla N. , Schmitz Nicole , Rohrer Jonathan D. , Schott Jonathan M. , Zhang Hui , Ourselin Sebastian , Warren Jason D. , Fox Nick C.
Published: November 2014

Objective

Novel biomarkers for monitoring progression in neurodegenerative conditions are needed. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. Here we report trajectories of WM change using serial DTI in a cohort with behavioral variant frontotemporal dementia (bvFTD).

Methods

Twenty‐three patients with bvFTD (12 having genetic mutations), and 18 age‐matched control participants were assessed using DTI and neuropsychological batteries at baseline and ∼1.3 years later. Baseline and follow‐up DTI scans were registered using a groupwise approach. Annualized rates of change for DTI metrics, neuropsychological measures, and whole brain volume were calculated. DTI metric performances were compared, and sample sizes for potential clinical trials were calculated.

Results

In the bvFTD group as a whole, rates of change in fractional anisotropy (FA) and mean diffusivity (MD) within the right paracallosal cingulum were greatest (FA: −6.8%/yr, p < 0.001; MD: 2.9%/yr, p = 0.01). MAPT carriers had the greatest change within left uncinate fasciculus (FA: −7.9%/yr, p < 0.001; MD: 10.9%/yr, p < 0.001); sporadic bvFTD and C9ORF72 carriers had the greatest change within right paracallosal cingulum (sporadic bvFTD, FA: −6.7%/yr, p < 0.001; MD: 3.8%/yr, p = 0.001; C9ORF72, FA: −6.8%/yr, p = 0.004). Sample size estimates using FA change were substantially lower than neuropsychological or whole brain measures of change.

Interpretation

Serial DTI scans may be useful for measuring disease progression in bvFTD, with particular trajectories of WM damage emerging. Sample size calculations suggest that longitudinal DTI may be a useful biomarker in future clinical trials. ANN NEUROL 2015;77:33–46
Controlled dispersion of a porphyrin/fullerene donor‐acceptor complex in semiconducting polymer thin films: Intermolecular interactions of polymers with porphyrin and fullerene
Authors: Natori Itaru , Natori Shizue , Hanawa Naoki , Ogino Kenji
Published: November 2014

Thin films composed of semiconducting polymers [poly(2‐vinyl naphthalene), poly(4‐diphenyl aminostyrene), poly(1‐vinyl pyrene), and poly(3‐hexyl thiophene‐2,5‐diyl)], zinc(II)−5,10,15,20‐tetra‐(2‐naphthyl)porphyrin, and [6,6]‐phenyl‐C61‐butyric acid methyl ester blends were prepared to investigate the controlled dispersion of porphyrin molecules in semiconducting polymer thin films. Tailoring the intermolecular interactions between the polymer/fullerene, polymer/porphyrin, and porphyrin/fullerene systems was found to be an effective method of controlling the dispersion. When the polymer/porphyrin interactions were enhanced, intermixed porphyrin/fullerene donor–acceptor complex domains were formed, whereas under conditions where the polymer/porphyrin interactions were weakened, the complex assembled at the borders between the polymer and fullerene phases. This concept could potentially be applied to various combinations of porphyrin/fullerene systems in semiconducting polymer thin films to develop polymer solar cells with excellent performance. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41629.
Essential dynamics analysis captures the concerted motion of the integrin‐binding site in jerdostatin, an RTS disintegrin
Authors: Calvanese Luisa , Falcigno Lucia , D'Auria Gabriella
Published: November 2014

Disintegrins, small molecular weight proteins contained in the venom of vipers and rattlesnakes, are high‐affinity and selectivity integrin antagonists. Disintegrins inhibitory epitope mainly consists in a tripeptide sequence localized in a mobile loop protruding from the protein core. RTS and/or KTS tripeptide characterizes the most recently discovered group of disintegrins that selectively block α1β1 integrin receptor. A NMR study dedicated to structure and dynamics properties of jerdostatin, an RTS disintegrin, demonstrated that the substitution of the native RTS with KTS motif impaired flexibility and inhibitory activity of the molecule. Here we add atomic details to the experimental profiles of jerdostatin and its R24K mutant by analyzing the dynamics behavior of the molecules through computational methods. For jerdostatin wild type, molecular dynamics simulations and essential dynamics analyses showed that Y31 residue acts as hinge element in the concerted motions involving the active loop and the C‐terminal tail. R24 side chain ability to engage both cation–π and H‐bond interactions with Y31 residue was found crucial for that breathing mechanism. Less significant loop‐tail concerted motions were observed for the R24K mutant. The description at atomic resolution of jerdostatin dynamics is useful for decoding the influence of specific residues on disintegrin functional properties. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 158–166, 2015.
Correlation between membrane translocation and analgesic efficacy in kyotorphin derivatives
Authors: Serrano Isa D. , Ramu Vasanthakumar G. , Pinto Antónia R. T. , Freire João M. , Tavares Isaura , Heras Montserrat , Bardaji Eduard R. , Castanho Miguel A. R. B.
Published: November 2014

Amidated kyotorphin (l‐Tyr‐l‐Arg‐NH2; KTP‐NH2) causes analgesia when systemically administered. The lipophilic ibuprofen‐conjugated derivative of KTP‐NH2 has improved analgesic efficacy. However, fast degradation by peptidases impacts negatively in the pharmacodynamics of these drugs. In this work, selected derivatives of KTP and KTP‐NH2 were synthesized to combine lipophilicity and resistance to enzymatic degradation. Eight novel structural modifications were tested for the potential to transverse lipid membranes and to evaluate their efficacy in vivo. The rationale behind the design of the pool of the eight selected molecules consisted in the addition of individual group at the N‐terminus, namely the tert‐butyloxycarbonyl (Boc), γ‐aminobutyric acid (GABA), acetyl, butanoyl, and propanoyl or in the substitution of the tyrosine residue by an indole moiety and in the replacement of the peptidic bond by a urea‐like bond in some cases. All the drugs used in the study are intrinsically fluorescent, which enables the use of spectrofluorimetry to sample the drugs in the permeation assays. The results show that the BOC and indolyl derivatives of KTP‐NH2 have maximal ability to permeate membranes with concomitant maximal analgesic power. Overall, the results demonstrate that membrane permeation is correlated with analgesic efficacy. However, this is not the only factor accounting for analgesia. KTP‐NH2 for instance has low passive permeation but is known to have central action. In this case, hypothetical transcytosis over the blood‐brain barrier seems to depend on dipeptide transporters. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 1–10, 2015.
Beaded nanofibers assembled from double‐hydrophobic elastin‐like block polypeptides: Effects of trifluoroethanol
Authors: Le Duc H. T. , Okubo Tatsuya , Sugawara‐Narutaki Ayae
Published: November 2014

A “double‐hydrophobic” elastin‐like triblock polypeptide GPG has been constructed by mimicking the localization of proline‐ and glycine‐rich hydrophobic domains of native elastin, a protein that provides elasticity and resilience to connective tissues. In this study, the effects of trifluoroethanol (TFE), an organic solvent that strongly affects secondary structures of polypeptides on self‐assembly of GPG in aqueous solutions were systematically studied. Beaded nanofiber formation of GPG, where nanoparticles are initially formed by coacervation of the polypeptides followed by their connection into one‐dimensional nanostructures, is accelerated by the addition of TFE at the concentrations up to 30% (v/v), whereas aggregates of nanoparticles are formed at 60% TFE. The concentration‐dependent assembly pattern discussed is based on the influence of TFE on the secondary structures of GPG. Well‐defined nanofibers whose diameter and secondary structures are controlled by TFE concentration may be ideal building blocks for constructing bioelastic materials in tissue engineering. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 175–185, 2015.
The structure and mechanical properties of the proteins of lamprey cartilage
Authors: Green Ellen M. , Peter Winlove C.
Published: November 2014

The cyanogen bromide‐resistant proteins of lamprey cartilage are biochemically related to the mammalian elastic protein, elastin. This study investigates their mechanical properties and enquires whether, like elastin, long‐range elasticity arises in them from a combination of entropic and hydrophobic mechanisms. Branchial and pericardial proteins resembled elastin mechanically, with elastic moduli of 0.13–0.35 MPa, breaking strains of 50%, and low hysteresis. Annular and piston proteins had higher elastic moduli (0.27–0.75 MPa) and larger hysteresis. Exchanging solvent water for trifluoroethanol increased the elastic moduli, whereas increasing temperature lowered the elastic moduli. Raman microspectrometry showed small differences in side‐chain modes consistent with reported biochemical differences. Decomposition of the amide I band indicated that the secondary structures were like those of elastin, preponderantly unordered, which probably confer the conformational flexibility necessary for entropy elasticity. Piston and annular proteins showed the strongest interactions with water, suggesting, together with the mechanical testing data, a greater role of hydrophobic interactions in their mechanics. Two‐photon imaging of intrinsic fluorescence and dye injection experiments showed that annular and piston proteins formed closed‐cell honeycomb structures, whereas the branchial and pericardial proteins formed open‐cell structures, which may account for the differences in mechanical properties. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 187–202, 2015.
Engineering cellular redox balance in Saccharomyces cerevisiae for improved production of L‐lactic acid
Authors: Lee Ju Young , Kang Chang Duk , Lee Seung Hyun , Park Young Kyoung , Cho Kwang Myung
Published: November 2014

Owing to the growing market for the biodegradable and renewable polymer, polylactic acid, world demand for lactic acid is rapidly increasing. However, the very high concentrations desired for industrial production of the free lactic acid create toxicity and low pH concerns for manufacturers. Saccharomyces cerevisiae is the most well characterized eukaryote, a preferred microbial cell factory for the largest industrial biotechnology product (bioethanol), and a robust, commercially compatible workhorse to be exploited for the production of diverse chemicals. S. cerevisiae has also been explored as a host for lactic acid production because of its high acid tolerance. Here, we constructed an L‐lactic acid‐overproducing S. cerevisiae by redirecting cellular metabolic fluxes to the production of L‐lactic acid. To this end, we deleted the S. cerevisiae genes encoding pyruvate decarboxylase 1 (PDC1), L‐lactate cytochrome‐c oxidoreductase (CYB2), and glycerol‐3‐phosphate dehydrogenase (GPD1), replacing them with a heterologous L‐lactate dehydrogenase (LDH) gene. Two new target genes encoding isoenzymes of the external NADH dehydrogenase (NDE1 and NDE2), were also deleted from the genome to re‐engineer the intracellular redox balance. The resulting strain was found to produce L‐lactic acid more efficiently (32.6% increase in final L‐lactic acid titer). When tested in a bioreactor in fed‐batch mode, this engineered strain produced 117 g/L of L‐lactic acid under low pH conditions. This result demonstrates that the redox balance engineering should be coupled with the metabolic engineering in the construction of L‐lactic acid‐overproducing S. cerevisiae. Biotechnol. Bioeng. 2015;112: 751–758. © 2014 Wiley Periodicals, Inc.
Metabolic process engineering of Clostridium tyrobutyricum Δack–adhE2 for enhanced n‐butanol production from glucose: Effects of methyl viologen on NADH availability, flux distribution, and fermentation kinetics
Authors: Du Yinming , Jiang Wenyan , Yu Mingrui , Tang I‐Ching , Yang Shang‐Tian
Published: November 2014

Butanol biosynthesis through aldehyde/alcohol dehydrogenase (adhE2) is usually limited by NADH availability, resulting in low butanol titer, yield, and productivity. To alleviate this limitation and improve n‐butanol production by Clostridium tyrobutyricum Δack–adhE2 overexpressing adhE2, the NADH availability was increased by using methyl viologen (MV) as an artificial electron carrier to divert electrons from ferredoxin normally used for H2 production. In the batch fermentation with the addition of 500 μM MV, H2, acetate, and butyrate production was reduced by more than 80–90%, while butanol production increased more than 40% to 14.5 g/L. Metabolic flux analysis revealed that butanol production increased in the fermentation with MV because of increased NADH availability as a result of reduced H2 production. Furthermore, continuous butanol production of ∼55 g/L with a high yield of ∼0.33 g/g glucose and extremely low ethanol, acetate, and butyrate production was obtained in fed‐batch fermentation with gas stripping for in situ butanol recovery. This study demonstrated a stable and reliable process for high‐yield and high‐titer n‐butanol production by metabolically engineered C. tyrobutyricum by applying MV as an electron carrier to increase butanol biosynthesis. Biotechnol. Bioeng. 2015;112: 705–715. © 2014 Wiley Periodicals, Inc.
Highly efficient targeted chromosome deletions using CRISPR/Cas9
Authors: He Zuyong , Proudfoot Chris , Mileham Alan J. , McLaren David G. , Whitelaw C. Bruce A. , Lillico Simon G.
Published: November 2014

The CRISPR/Cas9 system has emerged as an intriguing new technology for genome engineering. It utilizes the bacterial endonuclease Cas9 which, when delivered to eukaryotic cells in conjunction with a user‐specified small guide RNA (gRNA), cleaves the chromosomal DNA at the target site. Here we show that concurrent delivery of gRNAs designed to target two different sites in a human chromosome introduce DNA double‐strand breaks in the chromosome and give rise to targeted deletions of the intervening genomic segment. Predetermined genomic DNA segments ranging from several‐hundred base pairs to 1 Mbp can be precisely deleted at frequencies of 1–10%, with no apparent correlation between the size of the deleted fragment and the deletion frequency. The high efficiency of this technique holds promise for large genomic deletions that could be useful in generation of cell and animal models with engineered chromosomes. Biotechnol. Bioeng. 2015;112: 1060–1064. © 2014 Wiley Periodicals, Inc.
Advanced tools for fluid and fouling layer characterization applied to the description of membrane fouling phenomena for particle‐organic matter mixtures
Authors: Loulergue Patrick , Teychene Benoit , Weckert Marie , Cabassud Corinne , Guigui Christelle
Published: November 2014

Fouling by the formation of a complex cake remains a major hindrance of membrane bioreactors. One approach to fouling mitigation is to add particles within the biofluid in order to improve sludge filterability. Despite a number of studies dealing with this topic, fouling mechanisms are still not clear. This study reports the use of an original methodology for better fouling understanding and mitigation. This original approach is based on in situ characterization of cake local structural properties together with a detailed fluid characterization using size exclusion chromatography and the monitoring of global filtration performances.

In order to obtain comprehensive elements, the impact of particle addition within cakes having markedly different behaviours (slightly and highly compressible cake, different specific resistance) was investigated considering different biofluids and membranes. The results demonstrated that a potential beneficial effect of particles on filtration performance depended on the cake properties in the absence of particles. It was found that particle addition could only improve biofluid filterability when the fouling layer was highly compressible and consisted mainly of macromolecular protein. In addition, in situ characterization revealed that particles within the fouling layer strongly influenced organic matter deposition at the membrane. It also showed that the effect of particles on fouling mitigation depended on the environment surrounding them within the fouling layer.
Modified multiscale permutation entropy algorithm and its application for multiscroll chaotic systems
Authors: Shaobo He , Kehui Sun , Huihai Wang
Published: November 2014

To analyze the complexity of continuous chaotic systems better, the modified multiscale permutation entropy (MMPE) algorithm is proposed. Characteristics and parameter choices of the MMPE algorithm are investigated. The comparative study between MPE and MMPE shows that MMPE has better robustness for identifying different chaotic systems when the scale factor τ takes large values. Compared with MPE, MMPE algorithm is more suitable for analyzing the complexity of time series as it has τ time series. For its application, MMPE algorithm is used to calculate the complexity of multiscroll chaotic systems. Results show that complexity of multiscroll chaotic systems does not increase as scroll number increases. Discussions based on first‐order difference operation present a reasonable explanation on why the complexity does not increase. This complexity analysis method lays a theoretical as well as experimental basis for the applications of multiscroll chaotic systems. © 2014 Wiley Periodicals, Inc. Complexity 21: 52–58, 2016
Sox5 controls dorsal progenitor and interneuron specification in the spinal cord
Authors: Quiroga Alejandra C. , Stolt C. Claus , del Corral Ruth Diez , Dimitrov Spas , Pérez‐Alcalá Siro , Sock Elisabeth , Barbas Julio A. , Wegner Michael , Morales Aixa V.
Published: November 2014

The basic organization of somatosensory circuits in the spinal cord is already setup during the initial patterning of the dorsal neural tube. Extrinsic signals, such as Wnt and TGF‐β pathways, activate combinatorial codes of transcription factors that are responsible for generating a pattern of discrete domains of dorsal progenitors (dp). These progenitors will give rise to distinct dorsal interneurons (dI). The Wnt/ βcatenin signaling pathway controls specification of dp/dI1–3 progenitors and interneurons. According to the current model in the field, Wnt/βcatenin activity seems to act in a graded fashion in the spinal cord, as different relative levels determine the identity of adjacent progenitors. However, it is not clear how this activity gradient is controlled and how the identities of dI1–3 are differentially regulated by Wnt signalling. We have determined that two SoxD transcription factors, Sox5 and Sox6, are expressed in restricted domains of dorsal progenitors in the neural tube. Using gain‐ and loss‐of function approaches in chicken embryos, we have established that Sox5 controls cell fate specification of dp2 and dp3 progenitors and, as a result, controls the correct number of the corresponding dorsal interneurons (dI2 and dI3). Furthermore, Sox5 exerts its function by restricting dorsally Wnt signaling activity via direct transcriptional induction of the negative Wnt pathway regulator Axin2. By that way, Sox5 acts as a Wnt pathway modulator that contributes to sharpen the dorsal gradient of Wnt/βcatenin activity to control the distinction of two functionally distinct types of interneurons, dI2 and dI3 involved in the somatosensory relay. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 522–538, 2015
Differential regulation of Hes/Hey genes during inner ear development
Authors: Petrovic Jelena , Gálvez Hector , Neves Joana , Abelló Gina , Giraldez Fernando
Published: November 2014

Notch signaling plays a crucial role during inner ear development and regeneration. Hes/Hey genes encode for bHLH transcription factors identified as Notch targets. We have studied the expression and regulation of Hes/Hey genes during inner ear development in the chicken embryo. Among several Hes/Hey genes examined, only Hey1 and Hes5 map to the sensory regions, although with salient differences. Hey1 expression follows Jag1 expression except at early prosensory stages while Hes5 expression corresponds well to Dl1 expression throughout otic development. Although Hey1 and Hes5 are direct Notch downstream targets, they differ in the level of Notch required for activation. Moreover, they also differ in mRNA stability, showing different temporal decays after Notch blockade. In addition, Bmp, Wnt and Fgf pathways also modify Hey1 and Hes5 expression in the inner ear. Particularly, the Wnt pathway modulates Hey1 and Jag1 expression. Finally, gain of function experiments show that Hey1 and Hes5 cross‐regulate each other in a complex manner. Both Hey1 and Hes5 repress Dl1 and Hes5 expression, suggesting that they prevent the transition to differentiation stages, probably by preventing Atoh1 expression. In spite of its association with Jag1, Hey1 does not seem to be instrumental for lateral induction as it does not promote Jag1 expression. We suggest that, besides being both targets of Notch, Hey1 and Hes5 are subject to a rather complex regulation that includes the stability of their transcripts, cross regulation and other signaling pathways. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 703–720, 2015
Conjugated bile acid–activated S1P receptor 2 is a key regulator of sphingosine kinase 2 and hepatic gene expression
Authors: Nagahashi Masayuki , Takabe Kazuaki , Liu Runping , Peng Kesong , Wang Xiang , Wang Yun , Hait Nitai C. , Wang Xuan , Allegood Jeremy C. , Yamada Akimitsu , Aoyagi Tomoyoshi , Liang Jie , Pandak William M. , Spiegel Sarah , Hylemon Phillip B. , Zhou Huiping
Published: November 2014

Bile acids are important hormones during the feed/fast cycle, allowing the liver to coordinately regulate nutrient metabolism. How they accomplish this has not been fully elucidated. Conjugated bile acids activate both the ERK1/2 and AKT signaling pathways via sphingosine 1‐phosphate receptor 2 (S1PR2) in rodent hepatocytes and in vivo. Here, we report that feeding mice a high‐fat diet, infusion of taurocholate into the chronic bile fistula rat, or overexpression of the gene encoding S1PR2 in mouse hepatocytes significantly upregulated hepatic sphingosine kinase 2 (SphK2) but not SphK1. Key genes encoding nuclear receptors/enzymes involved in nutrient metabolism were significantly downregulated in livers of S1PR2–/– and SphK2–/– mice. In contrast, overexpression of the gene encoding S1PR2 in primary mouse hepatocytes differentially increased SphK2, but not SphK1, and mRNA levels of key genes involved in nutrient metabolism. Nuclear levels of sphingosine‐1‐phosphate, an endogenous inhibitor of histone deacetylases 1 and 2, as well as the acetylation of histones H3K9, H4K5, and H2BK12 were significantly decreased in hepatocytes prepared from S1PR2–/– and SphK2–/– mice. Conclusion: Both S1PR2–/– and SphK2–/– mice rapidly developed fatty livers on a high‐fat diet, suggesting the importance of conjugated bile acids, S1PR2, and SphK2 in regulating hepatic lipid metabolism. (Hepatology 2015;61:1216–1226)
CCAAT/enhancer binding protein α predicts poorer prognosis and prevents energy starvation–induced cell death in hepatocellular carcinoma
Authors: Lu Guo‐Dong , Ang Yang Huey , Zhou Jing , Tamilarasi Jegadeesan , Yan Benedict , Lim Yaw Chyn , Srivastava Supriya , Salto‐Tellez Manuel , Hui Kam M. , Shen Han‐Ming , Nguyen Long N. , Tan Bryan C. , Silver David L. , Hooi Shing Chuan
Published: November 2014

CCAAT enhancer binding protein α (C/EBPα) plays an essential role in cellular differentiation, growth, and energy metabolism. Here, we investigate the correlation between C/EBPα and hepatocellular carcinoma (HCC) patient outcomes and how C/EBPα protects cells against energy starvation. Expression of C/EBPα protein was increased in the majority of HCCs examined (191 pairs) compared with adjacent nontumor liver tissues in HCC tissue microarrays. Its upregulation was correlated significantly with poorer overall patient survival in both Kaplan‐Meier survival (P = 0.017) and multivariate Cox regression (P = 0.028) analyses. Stable C/EBPα‐silenced cells failed to establish xenograft tumors in nude mice due to extensive necrosis, consistent with increased necrosis in human C/EBPα‐deficient HCC nodules. Expression of C/EBPα protected HCC cells in vitro from glucose and glutamine starvation–induced cell death through autophagy‐involved lipid catabolism. Firstly, C/EBPα promoted lipid catabolism during starvation, while inhibition of fatty acid beta‐oxidation significantly sensitized cell death. Secondly, autophagy was activated in C/EBPα‐expressing cells, and the inhibition of autophagy by ATG7 knockdown or chloroquine treatment attenuated lipid catabolism and subsequently sensitized cell death. Finally, we identified TMEM166 as a key player in C/EBPα‐mediated autophagy induction and protection against starvation. Conclusion: The C/EBPα gene is important in that it links HCC carcinogenesis to autophagy‐mediated lipid metabolism and resistance to energy starvation; its expression in HCC predicts poorer patient prognosis. (Hepatology 2015;61:965–978)
Childhood cancer incidence patterns by race, sex and age for 2000–2006: A report from the South African National Cancer Registry
Authors: Erdmann Friederike , Kielkowski Danuta , Schonfeld Sara J. , Kellett Patricia , Stanulla Martin , Dickens Caroline , Kaatsch Peter , Singh Elvira , Schüz Joachim
Published: November 2014

Higher childhood cancer incidence rates are generally reported for high income countries although high quality information on descriptive patterns of childhood cancer incidence for low or middle income countries is limited, particularly in Sub‐Saharan Africa. There is a need to quantify global differences by cancer types, and to investigate whether they reflect true incidence differences or can be attributed to under‐diagnosis or under‐reporting. For the first time, we describe childhood cancer data reported to the pathology report‐based National Cancer Registry of South Africa in 2000–2006 and compare our results to incidence data from Germany, a high income country. The overall age‐standardized incidence rate (ASR) for South Africa in 2000–2006 was 45.7 per million children. We observed substantial differences by cancer types within South Africa by racial group; ASRs tended to be 3–4‐fold higher in South African Whites compared to Blacks. ASRs among both Black and White South Africans were generally lower than those from Germany with the greatest differences observed between the Black population in South Africa and Germany, although there was marked variation between cancer types. Age‐specific rates were particularly low comparing South African Whites and Blacks with German infants. Overall, patterns across South African population groups and in comparison to Germans were similar for boys and girls. Genetic and environmental reasons may probably explain rather a small proportion of the observed differences. More research is needed to understand the extent to which under‐ascertainment and under‐diagnosis of childhood cancers drives differences in observed rates.
Enhanced immunosuppression by therapy‐exposed glioblastoma multiforme tumor cells
Authors: Authier Astrid , Farrand Kathryn J. , Broadley Kate W.R. , Ancelet Lindsay R. , Hunn Martin K. , Stone Sarrabeth , McConnell Melanie J. , Hermans Ian F.
Published: November 2014

Glioblastoma multiforme (GBM) is a highly malignant brain tumor with an extremely short time to relapse following standard treatment. Since recurrent GBM is often resistant to subsequent radiotherapy and chemotherapy, immunotherapy has been proposed as an alternative treatment option. Although it is well established that GBM induces immune suppression, it is currently unclear what impact prior conventional therapy has on the ability of GBM cells to modulate the immune environment. In this study, we investigated the interaction between immune cells and glioma cells that had been exposed to chemotherapy or irradiation in vitro. We demonstrate that treated glioma cells are more immunosuppressive than untreated cells and form tumors at a faster rate in vivo in an animal model. Cultured supernatant from in vitro‐treated primary human GBM cells were also shown to increase suppression, which was independent of accessory suppressor cells or T regulatory cell generation, and could act directly on CD4+ and CD8+ T cell proliferation. While a number of key immunosuppressive cytokines were overexpressed in the treated cells, including IL‐10, IL‐6 and GM‐CSF, suppression could be alleviated in a number of treated GBM lines by inhibition of prostaglandin E2. These results reveal for the first time that conventional therapies can alter immunosuppressive pathways in GBM tumor cells, a finding with important implications for the combination of immunotherapy with standard treatment.
Characteristics associated with clinician diagnosis of aspiration pneumonia: A descriptive study of afflicted patients and their outcomes
Authors: Lanspa Michael J. , Peyrani Paula , Wiemken Timothy , Wilson Emily L. , Ramirez Julio A. , Dean Nathan C.
Published: November 2014

BACKGROUND

Aspiration pneumonia is a common disease, although less well characterized than other pneumonia syndromes.

OBJECTIVE

We analyzed patient‐level covariates associated with clinician‐defined aspiration pneumonia.

METHODS

We used the Community‐Acquired Pneumonia Organization database, a multicenter, international population of patients with community‐acquired pneumonia, using data from 2001 to 2012. Aspiration pneumonia was determined by the treating clinician. We analyzed covariates associated with clinician‐defined diagnosis of aspiration pneumonia using logistic regression. We compared aspiration pneumonia patients to propensity‐matched cases with nonaspiration pneumonia.

RESULTS

We studied 5185 patients. Four hundred fifty‐one of these patients had aspiration pneumonia. Patients with aspiration pneumonia were older, had greater disease severity, and more comorbidities than patients with nonaspiration pneumonia. They were more likely cared for in the intensive care unit (19% vs 13%, P = 0.002), had longer unadjusted hospital length of stay (9 vs 7 days, P < 0.001), and took longer to achieve clinical stability (unadjusted 8 vs 4 days, P < 0.001). Confusion, nursing home residence, and cerebrovascular disease were most associated with clinician diagnosis of aspiration pneumonia (odds ratio: 4.4, 2.9, 2.3, respectively). Unadjusted inpatient mortality was higher (23% vs 9%, P < 0.001). Aspiration pneumonia conferred a 2.3 odds ratio for inpatient mortality after adjusting for age, disease severity, and comorbidities.

CONCLUSIONS

Among pneumonia patients, confusion, nursing home residence, and cerebrovascular disease are associated with a clinician diagnosis of aspiration. Aspiration pneumonia is associated with greater mortality among patients with community‐acquired pneumonia, which is not explained by older age, measured indices of severity, or comorbidities. Journal of Hospital Medicine 2015;10:90–96. © 2014 Society of Hospital Medicine
Invasive group AStreptococcus resulting in sepsis and abdominal wall abscess after adenotonsillectomy
Authors: Wilson Paul F. , Wannemuehler Todd J. , Matt Bruce H.
Published: November 2014

Systemic infectious complications following adenotonsillectomy are exceedingly rare. We describe an otherwise healthy 2‐year‐old patient who developed group A beta‐hemolytic Streptococcus sepsis and presumptive scarlet fever 3 days after an uncomplicated adenotonsillectomy. After resolution of fever, rash, and discharge home on antibiotics, the patient returned on postoperative day 10 with an abdominal wall abscess. This is the first reported case of an abdominal wall abscess as a complication of adenotonsillectomy. This case demonstrates that an awareness of unexpected infectious complications of adenotonsillectomy should be a part of postsurgical management. Laryngoscope, 125:1230–1232, 2015
Low‐level laser therapy associated with high intensity resistance training on cardiac autonomic control of heart rate and skeletal muscle remodeling in wistar rats
Authors: Paolillo Fernanda Rossi , Arena Ross , Dutra Daniela Bassi , de Cassia Marqueti Durigan Rita , de Araujo Heloisa Selistre , de Souza Hugo Celso Dutra , Parizotto Nivaldo Antonio , Cipriano Gerson , Chiappa Gaspar , Borghi‐Silva Audrey
Published: November 2014

Background and Objective

Phototherapy plus dynamic exercise can enhance physical performance and improve health. The aim of our study was to evaluate the effect of low‐level laser therapy (LLLT) associated with high intensity resistance training (HIT) on cardiac autonomic and muscle metabolic responses in rats.

Study Design/Materials and Methods

Forty Wistar rats were randomized into 4 groups: sedentary control (CG), HIT, LLLT and HIT + LLLT. HIT was performed 3 times/week for 8 weeks with loads attached to the tail of the animal. The load was gradually increased by 10% of body mass until reaching a maximal overload. For LLLT, irradiation parameters applied to the tibialis anterior (TA) muscle were as follows: infrared laser (780 nm), power of 15 mW for 10 seconds, leading to an irradiance of 37.5 mW/cm2, energy of 0.15 J per point and fluency of 3.8 J/cm2. Blood lactate (BL), matrix metalloproteinase gelatinase A (MMP−2) gene expression and heart rate variability (HRV) indices were performed.

Results

BL significantly increased after 8‐weeks for HIT, LLLT and HIT + LLLT groups. However, peak lactate when normalized by maximal load was significantly reduced for both HIT and HIT + LLLT groups (P<0.05). MMP−2 in the active form was significantly increased after HIT, LLLT and HIT + LLLT compared tom the CG (P<0.05). There was a significant reduction in low frequency [LF (ms2)] and increase in high frequency [HF (un)] and HF (ms2)] for the HIT, LLLT and HIT + LLLT groups compared with the CG (P < 0.05). However, the LF/HF ratio was further reduced in the LLLT and HIT + LLLT groups compared to the CG and HIT group (P < 0.05).

Conclusion

These results provide evidence for the positive benefits of LLLT and HIT with respect to enhanced muscle metabolic and cardiac autonomic function in Wistar rats. Lasers Surg. Med. 46:796–803, 2014. © 2014 Wiley Periodicals, Inc.
Bisphenol S and bisphenol A cyanate ester/barium metaborate composites
Authors: Şen Ferhat , Şentürk İsmail İlkkan , Kahraman Memet Vezir
Published: November 2014

The aim of this study was to improve thermal stability and surface properties of bisphenol A dicyanate ester (BADCy) by adding bisphenol S dicyanate ester (BSDCy) and Ba(BO2)2. Bisphenol S and bisphenol A cyanate ester/barium metaborate composites having various ratios of BADCy, BSDCy, and Ba(BO2)2 were prepared. Thermal stability of the samples was evaluated by thermogravimetric analysis and differential scanning calorimetry. Hydrophobicity of the samples was determined by the contact angle measurements. The samples were characterized with the following analysis; gel content, water absorption capacity. Moreover, the surface morphology of the samples was investigated by a scanning electron microscopy. The obtained results prove that the cyanate ester containing sulfonyl/Ba(BO2)2 composites have good thermal and surface properties and they can be used in many applications such as electronic devices, materials engineering, and other emergent. POLYM. COMPOS., 37:1312–1317, 2016. © 2014 Society of Plastics Engineers
Inducing Effect of Clofibric Acid on Stearoyl‐CoA Desaturase in Intestinal Mucosa of Rats
Authors: Yamazaki Tohru , Kadokura Makiko , Mutoh Yuki , Sakamoto Takeshi , Okazaki Mari , Mitsumoto Atsushi , Kawashima Yoichi , Kudo Naomi
Published: November 2014

Fibrates have been reported to elevate the hepatic proportion of oleic acid (18:1n‐9) through inducing stearoyl‐CoA desaturase (SCD). Despite abundant studies on the regulation of SCD in the liver, little is known about this issue in the small intestine. The present study aimed to investigate the effect of clofibric acid on the fatty acid profile, particularly monounsaturated fatty acids (MUFA), and the SCD expression in intestinal mucosa. Treatment of rats with a diet containing 0.5 % (w/w) clofibric acid for 7 days changed the MUFA profile of total lipids in intestinal mucosa; the proportion of 18:1n‐9 was significantly increased, whereas those of palmitoleic (16:1n‐7) and cis‐vaccenic (18:1n‐7) acids were not changed. Upon the treatment with clofibric acid, SCD was induced and the gene expression of SCD1, SCD2, and fatty acid elongase (Elovl) 6 was up‐regulated, but that of Elovl5 was unaffected. Fat‐free diet feeding for 28 days increased the proportions of 16:1n‐7 and 18:1n‐7, but did not effectively change that of 18:1n‐9, in intestinal mucosa. Fat‐free diet feeding up‐regulated the gene expression of SCD1, but not that of SCD2, Elovl6, or Elovl5. These results indicate that intestinal mucosa significantly changes its MUFA profile in response to challenges by clofibric acid and a fat‐free diet and suggest that up‐regulation of the gene expression of SCD along with Elovl6 is indispensable to elevate the proportion of 18:1n‐9 in intestinal mucosa.
A Comparative Study of Phospholipase A1 and Phospholipase C on Soybean Oil Degumming
Authors: Jiang Xiaofei , Chang Ming , Wang Xiaosan , Jin Qingzhe , Wang Xingguo
Published: November 2014

The degumming of crude soybean oil with phospholipase A1 (PLA1) and phospholipase C (PLC) was studied, and optimal conditions were obtained for each enzyme. During degumming with PLA1, more fatty acid was found in the oil than would be expected by hydrolysis of only the terminal fatty acid chains, and glycerophosphophorylcholine and glycerophosphoethanolamine were detected in the gums. These observations indicate that acyl‐migration of phospholipid fatty acids occurred during PLA1 degumming. In addition, results showed that PLA1 degumming was capable of reducing the phosphorus content in the oil to levels acceptable for physical refining (<10 mg/kg). During degumming with PLC, an increase of 1,2‐diacylglycerol was found, as most phosphatidylcholine and phosphatidylethanolamine were hydrolyzed by this enzyme. Treatment with either enzyme slightly decreased the oxidative stability of the oil and most metals were separated with the gums fraction.