bluuebunny/crossref_metadata_2025 huggingface dataset:
Axitinib blocks Wnt/β-catenin signaling and directs asymmetric cell division in cancer
Authors: Qu Yi , Gharbi Naouel , Yuan Xing , Olsen Jan Roger , Blicher Pernille , Dalhus Bjørn , Brokstad Karl A. , Lin Biaoyang , Øyan Anne Margrete , Zhang Weidong , Kalland Karl-Henning , Ke Xisong
Published: August 2016

Significance

The Wnt (wingless)/β-catenin signaling pathway is an attractive target for cancer therapy. However, known Wnt inhibitors are still far from clinical use. Here we report that the clinically approved drug axitinib strongly inhibits Wnt/β-catenin signaling in vitro and in vivo. In particular, a phenotype of Wnt inhibition called “Wnt asymmetry” was revealed in axitinib-treated cancer cells. The identification of E3 ubiquitin ligase SHPRH (SNF2, histone-linker, PHD and RING finger domain-containing helicase) as the functional target implies that axitinib blocking of Wnt signaling is independent of genetic mutations that are frequently observed in cancer patients. Collectively, our results suggest a mechanism of nuclear β-catenin regulation and highlight axitinib as a promising therapeutic agent for cancer patients with aberrant Wnt/β-catenin signaling.
Timing and causes of mid-Holocene mammoth extinction on St. Paul Island, Alaska
Authors: Graham Russell W. , Belmecheri Soumaya , Choy Kyungcheol , Culleton Brendan J. , Davies Lauren J. , Froese Duane , Heintzman Peter D. , Hritz Carrie , Kapp Joshua D. , Newsom Lee A. , Rawcliffe Ruth , Saulnier-Talbot Émilie , Shapiro Beth , Wang Yue , Williams John W. , Wooller Matthew J.
Published: August 2016

Significance

St. Paul Island, Alaska, is famous for its late-surviving population of woolly mammoth. The puzzle of mid-Holocene extinction is solved via multiple independent paleoenvironmental proxies that tightly constrain the timing of extinction to 5,600 ± 100 y ago and strongly point to the effects of sea-level rise and drier climates on freshwater scarcity as the primary extinction driver. Likely ecosystem effects of the mega-herbivore extinction include reduced rates of watershed erosion by elimination of crowding around water holes and a vegetation shift toward increased abundances of herbaceous taxa. Freshwater availability may be an underappreciated driver of island extinction. This study reinforces 21st-century concerns about the vulnerability of island populations, including humans, to future warming, freshwater availability, and sea level rise.
Extensive phosphorylation of AMPA receptors in neurons
Authors: Diering Graham H. , Heo Seok , Hussain Natasha K. , Liu Bian , Huganir Richard L.
Published: August 2016

Significance

Decades of research from many laboratories has established a model in which phosphorylation of the GluA1 AMPA-type glutamate receptor subunit plays a significant role modulating long-term potentiation and depression, homeostatic and neuromodulator-regulated plasticity, spatial memory, fear/extinction, and appetitive incentive learning. However, a recent study suggests that GluA1 phosphorylation is exceedingly low, even in synaptic fractions. Here, we address this controversy using in vitro and in vivo techniques. We find a large fraction of excitatory synapses are positive for phosphorylated GluA1. Moreover, phosphorylated species make up a significant fraction of the population and are highly responsive to numerous physiologically relevant stimuli. This characterization reaffirms a large body of work defining a prominent role of AMPA receptor phosphorylation in synapse biology and synaptic plasticity.
Protein Structural Features in Winter Wheat: Benchmarking Diversity in Ontario Hard and Soft Winter Wheat
Authors: Cao Wei , Falk Duane , Bock Jayne E.
Published: August 2016

A set of 32 winter wheat lines and varieties was selected to benchmark Ontario winter wheat as a first step toward improving quality. Protein secondary structure, total and accessible thiols, rheological properties, gluten aggregation kinetics, and network forming capabilities of different polymers were determined for each wheat line. Results revealed that there were statistically significant differences among the lines selected (P < 0.05). The differences between hard and soft wheat classes were not as large as would be expected, however, despite the range of quality parameters measured. Benchmarks revealed that several soft wheat lines outperformed hard wheat lines in standard breadmaking quality measures. Protein conformation changed significantly as the moisture content of the samples increased to mimic different model product systems: flour, dough, and batter. The conformation of the flour samples exhibited different patterns between hard and soft wheat classes, although these differences became narrower in the dough and batter states. Principal component analysis (PCA) factors included most quality parameters measured, with the notable exceptions of solvent retention capacity tests and total thiols. Protein conformation and accessible thiols were significant PCA factors that tended to override the rheological measures of quality they represented, suggesting that protein secondary structure and disulfide bonding patterns are fundamental aspects of rheological quality measures.
Biodiversity analysis in the digital era
Authors: La Salle John , Williams Kristen J. , Moritz Craig
Published: August 2016

This paper explores what the virtual biodiversity e-infrastructure will look like as it takes advantage of advances in ‘Big Data’ biodiversity informatics and e-research infrastructure, which allow integration of various taxon-level data types (genome, morphology, distribution and species interactions) within a phylogenetic and environmental framework. By overcoming the data scaling problem in ecology, this integrative framework will provide richer information and fast learning to enable a deeper understanding of biodiversity evolution and dynamics in a rapidly changing world. The Atlas of Living Australia is used as one example of the advantages of progressing towards this future. Living in this future will require the adoption of new ways of integrating scientific knowledge into societal decision making.

This article is part of the themed issue ‘From DNA barcodes to biomes’.
Bayesian Inference of Two-Dimensional Contrast Sensitivity Functions
Authors: Wang Xiaoxiao , Wang Huan , Huang Jinfeng , Tzvetanov Tzvetomir , Zhou Yifeng
Published: August 2016

The contrast sensitivity function (CSF) is crucial in predicting functional vision both in research and clinical areas. Recently, a group of novel strategies, multi-dimensional adaptive methods, were proposed and allowed more rapid measurements when compared to usual methods such as Ψ or staircase. Our study further presents a multi-dimensional Bayesian framework to estimate parameters of the CSF from experimental data obtained by classical sampling. We extensively simulated the framework’s performance as well as validated the results in a psychophysical experiment. The results showed that the Bayesian framework significantly improves the accuracy and precision of parameter estimates from usual strategies, and requires about the same number of observations as the novel methods to obtain reliable inferences. Additionally, the improvement with the Bayesian framework was maintained when the prior poorly matched the observer’s CSFs. The results indicated that the Bayesian framework is flexible and sufficiently precise for estimating CSFs.
Different combinations of ErbB receptor dimers generate opposing signals that regulate cell proliferation in cardiac valve development
Authors: Iwamoto Ryo , Mine Naoki , Mizushima Hiroto , Mekada Eisuke
Published: August 2016

HB-EGF plays an indispensable role in suppression of cell proliferation in mouse valvulogenesis. However, ligands of the EGF receptor (EGFR/ErbB1), including HB-EGF, are generally considered as growth-promoting factors, as shown in cancers. HB-EGF binds to and activates ErbB1 and ErbB4. We investigated the role of ErbB receptors in valvulogenesis in vivo using ErbB1- and ErbB4-deficient mice, and an ex vivo model of endocardial cushion explants. We show that HB-EGF suppresses valve mesenchymal cell proliferation through a heterodimer of ErbB1 and ErbB4, and an ErbB1 ligand(s) promotes cell proliferation through a homodimer of ErbB1. Moreover, a rescue experiment with cleavable or uncleavable isoforms of ErbB4 inERBB4null cells suggests that the cytoplasmic intracellular domain of ErbB4, rather than the membrane-anchored tyrosine kinase, achieves this suppression. Our study demonstrates that opposing signals generated by different ErbB dimer combinations function in the same cardiac cushion mesenchymal cells for proper cardiac valve formation.

Summary statement

In valvulogenesis, opposing signals generated by different combinations of ErbB-dimers elaborately regulate cell proliferation, in which proteolytically released intracellular domain of ErbB4 activated by HB-EGF is required to suppress proliferation.
Changes in Stomatal Behavior and Guard Cell Cytosolic Free Calcium in Response to Oxidative Stress
Authors: McAinsh M. R. , Clayton H. , Mansfield T. A. , Hetherington A. M.
Published: August 2016

We have investigated the cellular basis for the effects of oxidative stress on stomatal behavior using stomatal bioassay and ratio photometric techniques. Two oxidative treatments were employed in this study: (a) methyl viologen, which generates superoxide radicals, and (b) H2O2. Both methyl viologen and H2O2 inhibited stomatal opening and promoted stomatal closure. At concentrations [less than or equal to]10–5 M, the effects of methyl viologen and H2O2 on stomatal behavior were reversible and were abolished by 2 mM EGTA or 10 [mu]M verapamil. In addition, at 10–5 M, i.e. the maximum concentration at which the effects of the treatments were prevented by EGTA or verapamil, methyl viologen and H2O2 caused an increase in guard cell cytosolic free Ca2+ ([Ca2+]i), which was abolished in the presence of EGTA. Therefore, at low concentrations of methyl viologen and H2O2, removal of extracellular Ca2+ prevented both the oxidative stress-induced changes in stomatal aperture and the associated increases in [Ca2+]i. This suggests that in this concentration range the effects of the treatments are Ca2+-dependent and are mediated by changes in [Ca2+]i. In contrast, at concentrations of methyl viologan and H2O2 > 10–5 M, EGTA and verapamil had no effect. However, in this concentration range the effects of the treatments were irreversible and correlated with a marked reduction in membrane integrity and guard cell viability. This suggests that at high concentrations the effects of methyl viologen and H2O2 may be due to changes in membrane integrity. The implications of oxidative stress-induced increases in [Ca2+]i and the possible disruption of guard-cell Ca2+ homeostasis are discussed in relation to the processes of Ca2+-based signal transduction in stomatal guard cells and the control of stomatal aperture.
Characterization of Glutathione Uptake in Broad Bean Leaf Protoplasts
Authors: Jamai A. , Tommasini R. , Martinoia E. , Delrot S.
Published: August 2016

Transport of reduced glutathione (GSH) and oxidized glutathione (GSSG) was studied with broad bean (Vicia faba L.) leaf tissues and protoplasts. Protoplasts and leaf discs took up GSSG at a rate about twice the uptake rate of GSH. Detailed studies with protoplasts indicated that GSH and GSSG uptake exhibited the same sensitivity to the external pH and to various chemical reagents. GSH uptake was inhibited by GSSG and glutathione conjugates. GSSG uptake was inhibited by GSH and GS conjugates, and the uptake of metolachlor-GS was inhibited by GSSG. Various amino acids (L-glutamic acid, L-glutamine, L-cysteine, L-glycine, L-methionine) and peptides (glycine-glycine, glycine-glycine-glycine) affected neither the transport of GSH nor GSSG. Uptake kinetics indicate that GSH is taken up by a single saturable transporter, with an apparent Km of 0.4 mM, whereas GSSG uptake exhibits two saturable phases, with an apparent Km of 7 [mu]M and 3.7 mM. It is concluded that the plasma membrane of leaf cells contains a specific transport system for glutathione, which takes up GSSG and GS conjugates preferentially over GSH. Proton flux measurements and electrophysiological measurements indicate that GSH and GSSG are taken up with proton symport. However, a detailed analysis of these measurements suggests that the ion movements induced by GSSG differ from those induced by GSH.
Evidence That the Pathway of Dimethylsulfoniopropionate Biosynthesis Begins in the Cytosol and Ends in the Chloroplast
Authors: Trossat C. , Nolte K. D. , Hanson A. D.
Published: August 2016

In the flowering plant Wollastonia biflora (L.) DC. the first step in 3-dimethylsulfoniopropionate (DMSP) synthesis is conversion of methionine to S-methylmethionine (SMM) and the last is oxidation of 3-dimethylsulfoniopropionaldehyde (DMSP-ald) (F. James, L. Paquet, S.A. Sparace, D.A. Gage, A.D. Hanson [1995] Plant Physiol 108: 1439–1448). DMSP-ald was shown to undergo rapid, spontaneous decomposition to dimethylsulfide and acrolein. However, it was stable enough (half-life [greater than or equal to] 1 h) in tertiary amine buffers to use as a substrate for enzyme assays. A dehydrogenase catalyzing DMSP-ald oxidation was detected in extracts of W. biflora mesophyll protoplasts. This enzyme had a high affinity for DMSP-ald (Km = 1.5 [mu]M), was subject to substrate inhibition, preferred NAD to NADP, and was immunologically related to plant betaine aldehyde dehydrogenases. After fractionation of protoplast lysates, [greater than or equal to]90% of DMSP-ald dehydrogenase activity was recovered from the chloroplast stromal fraction, whereas the enzyme that mediates SMM synthesis, S-adenosylmethionine:methionine S-methyltransferase, was found exclusively in the cytosolic fraction. Immunohistochemical analysis confirmed that the S-methyltransferase was cytosolic. Intact W. biflora chloroplasts were able to metabolize supplied [35S]SMM to [35S]DMSP. These findings indicate that SMM is made in the cytosol, imported into the chloroplast, and there converted successively to DMSP-ald and DMSP.
Photosynthetic Gene Expression in Meristems and during Initial Leaf Development in a C4 Dicotyledonous Plant
Authors: Ramsperger V. C. , Summers R. G. , Berry J. O.
Published: August 2016

Immunolocalization and fluorescent in situ hybridization were used with confocal microscopy to examine patterns of photosynthetic gene expression during initial stages of leaf development in the C4 dicot Amaranthus hypochondriacus. mRNAs encoding the large and small subunit of ribulose-1,5-bisphosphate carboxylase were present in the apical dome and in all cells of the leaf primordia. In contrast, these polypeptides were detected only in cells of the ground meristem, with no accumulation detected in the apical dome or in other leaf primordia cells. The ribulose-1,5-bisphosphate carboxylase transcripts showed very little cell-type specificity as leaf structures began to differentiate, whereas their polypeptides accumulated primarily in bundle-sheath precursor cells. Phosphoenolpyruvate carboxylase and pyruvate orthophosphate dikinase mRNAs were abundant in meristems and leaf primordia, although their corresponding polypeptides did not accumulate in leaves until the leaf vascular system began to differentiate. These polypeptides were mostly restricted to premesophyll cells from their earliest detection, whereas their transcripts remained present in nearly all leaf cells. These findings indicate that individual C4 genes are independently regulated as they become initially localized to their appropriate cell types. Furthermore, posttranscriptional regulation plays a major role in determining early patterns of C4 gene expression.
Comparative analysis of book tags: a cross-lingual perspective
Authors: Lu Chao , Zhang Chengzhi , He Daqing
Published: August 2016

Purpose

In the era of social media, users all over the world annotate books with social tags to express their preferences and interests. The purpose of this paper is to explore different tagging behaviours by analysing the book tags in different languages.

Design/methodology/approach

This investigation collected nearly 56,000 tags of 1,200 books from one Chinese and two English online bookmarking systems; it combined content analysis and machine-processing methods to evaluate the similarities and differences between different tagging systems from a cross-lingual perspective. Jaccard’s coefficient was adopted to evaluate the similarity level.

Findings

The results show that the similarity between mono-lingual tags of the same books is higher than that of cross-lingual tags in different systems and the similarity between tags of books written for specialties is higher than that of books written for the general public.

Research limitations/implications

Those who have more in common annotate books with more similar tags. The similarity between users in tagging systems determines the similarity of the tag sets.

Practical implications

The results and conclusion of this study will benefit users’ cross-lingual information retrieval and cross-lingual book recommendation for online bookmarking systems.

Originality/value

This study may be one of the first to compare cross-lingual tags. Its methodology can be applied to tag comparison between any two languages. The insights of this study will help develop cross-lingual tagging systems and improve information retrieval.
Preference of Bangladesh university students for searching the library catalogue
Authors: Yesmin Shamima , Ahmed S.M. Zabed
Published: August 2016

Purpose

The aim of this paper was to compare university students’ preferences for searching the library catalogue via the library’s Koha online public access catalogue (OPAC) or its discovery tool VuFind.

Design/methodology/approach

A total of 175 students responded to a questionnaire-based survey through which their demographic data, duration (years) of computer use and their self-reported levels of computer skills were obtained. Students were asked what interfaces they use for catalogue searching and to rate their opinion on the relevant interfaces on a seven-point Likert scale. Mann–Whitney and Kruskal–Wallis tests were conducted to statistically compare the differences between students’ demographic/individual characteristics and their ratings on the respective interfaces. For those students who used both systems, differences between their Likert ratings were assessed using a one-tailed Wilcoxon signed rank test.

Findings

The results showed that there were no significant differences among students in terms of their ratings on either the OPAC or VuFind interfaces. Wilcoxon signed ranks test indicated that significantly more students thought that VuFind was more usable than the Koha OPAC.

Originality/value

This is a pioneering study of the current use of the OPAC and discovery tools by university students and their preferences for searching catalogue information through these systems. It is hoped that the findings of this study will encourage researchers to conduct task-based usability studies with various cataloguing tools and this could yield new and improved interaction designs for library catalogue searching.
Geographic variation and trade‐offs in parasitoid virulence
Authors: Fors Lisa , Markus Robert , Theopold Ulrich , Ericson Lars , Hambäck Peter A.
Published: August 2016

Host–parasitoid systems are characterized by a continuous development of new defence strategies in hosts and counter‐defence mechanisms in parasitoids. This co‐evolutionary arms race makes host–parasitoid systems excellent for understanding trade‐offs in host use caused by evolutionary changes in host immune responses and parasitoid virulence. However, knowledge obtained from natural host–parasitoid systems on such trade‐offs is still limited.

In this study, the aim was to examine trade‐offs in parasitoid virulence in Asecodes parviclava (Hymenoptera: Eulophidae) when attacking three closely related beetles: Galerucella pusilla, Galerucella calmariensis and Galerucella tenella (Coleoptera: Chrysomelidae). A second aim was to examine whether geographic variation in parasitoid infectivity or host immune response could explain differences in parasitism rate between northern and southern sites.

More specifically, we wanted to examine whether the capacity to infect host larvae differed depending on the previous host species of the parasitoids and if such differences were connected to differences in the induction of host immune systems. This was achieved by combining controlled parasitism experiments with cytological studies of infected larvae.

Our results reveal that parasitism success in A. parviclava differs both depending on previous and current host species, with a higher virulence when attacking larvae of the same species as the previous host. Virulence was in general high for parasitoids from G. pusilla and low for parasitoids from G. calmariensis. At the same time, G. pusilla larvae had the strongest immune response and G. calmariensis the weakest. These observations were linked to changes in the larval hemocyte composition, showing changes in cell types important for the encapsulation process in individuals infected by more or less virulent parasitoids.

These findings suggest ongoing evolution in parasitoid virulence and host immune response, making the system a strong candidate for further studies on host race formation and speciation.
Testing the apparent resistance of three dominant plants to chronic drought on the Colorado Plateau
Authors: Hoover David L. , Duniway Michael C. , Belnap Jayne
Published: August 2016

Many drylands, including the south‐western United States, are projected to become more water‐limited as these regions become warmer and drier with climate change. Such chronic drought may push individual species or plant functional types beyond key thresholds leading to reduced growth or even mortality. Indeed, recent observational and experimental evidence from the Colorado Plateau suggests that C3 grasses are the most vulnerable to chronic drought, while C4 grasses and C3 shrubs appear to have greater resistance.

The effects of chronic, or press‐drought are predicted to begin at the physiological level and translate up to higher hierarchical levels. To date, the drought resistance of C4 grasses and C3 shrubs in this region has been only evaluated at the community level and thus we lack information on whether there are sensitivities to drought at lower hierarchical levels. In this study, we tested the apparent drought resistance of three dominant species (Pleuraphis jamesii, a C4 rhizomatous grass; Coleogyne ramosissima, a C3 drought‐deciduous shrub; and Ephedra viridis, a C3 evergreen shrub) to an ongoing experimental press‐drought (‐35% precipitation) by comparing individual‐level responses (ecophysiology and growth dynamics) to community‐level responses (plant cover).

For all three species, we observed consistent responses across all hierarchical levels: P. jamesii was sensitive to drought across all measured variables, while the shrubs C. ramosissima and E. viridis had little to no responses to the experimental press‐drought at any given level.

Synthesis. Our findings suggest that the apparent drought resistance at higher hierarchical levels, such as cover, may serve as good proxies for lower‐level responses. Furthermore, it appears the shrubs are avoiding drought, possibly by utilizing moisture at deeper soil layers, while the grasses are limited to shallower layers and must endure the drought conditions. Give this differential sensitivity to drought, a future with less precipitation and higher temperatures may increase the dominance of shrubs on the Colorado Plateau, as grasses succumb to chronic water stress.
Effects of soil heterogeneity and clonal integration on Alternanthera philoxeroides populations with a radial ramet aggregation
Authors: Liu Lu , Dong Bi‐Cheng
Published: August 2016

Some clonal plants can spread their ramet populations radially, and soil heterogeneity and clonal integration may greatly affect the establishment of these types of populations. We constructed Alternanthera philoxeroides populations with a radial ramet aggregation, allowing old ramets of clonal fragments to concentrate in central pots and younger ramets to root in peripheral pots. The peripheral pots were supplemented either with three different levels (high, medium and low) of soil nutrients to simulate a heterogeneous soil environment, or only one medium level of soil nutrients to simulate a homogeneous environment. Stolon connections between the central older ramets and the peripheral younger ramets were left intact or severed to test the effect of clonal integration. The maintenance of stolon connection could induce the division of labor between different‐aged ramets, by increasing the root investment in central ramets and the above‐ground growth in peripheral ramets. The maintenance of stolon connection could improve the growth of the central and peripheral ramets, clonal fragments and even the whole population. However, the positive consequence in peripheral ramets and whole fragments was only detected in the high‐nutrient patch of heterogeneous treatment. In sum, in the population with the radial ramet aggregation, clonal integration can play a key role in the rapid recruitment of young ramets of A. philoxeroides fragments, as well as the expansion of the whole population. The magnitude of clonal integration also became more obvious in the peripheral young ramets and whole fragments that experienced high‐nutrient patches.
The (in)complete organelle genome: exploring the use and nonuse of available technologies for characterizing mitochondrial and plastid chromosomes
Authors: Sanitá Lima Matheus , Woods Laura C. , Cartwright Matthew W. , Smith David Roy
Published: August 2016

Not long ago, scientists paid dearly in time, money and skill for every nucleotide that they sequenced. Today, DNA sequencing technologies epitomize the slogan ‘faster, easier, cheaper and more’, and in many ways, sequencing an entire genome has become routine, even for the smallest laboratory groups. This is especially true for mitochondrial and plastid genomes. Given their relatively small sizes and high copy numbers per cell, organelle DNAs are currently among the most highly sequenced kind of chromosome. But accurately characterizing an organelle genome and the information it encodes can require much more than DNA sequencing and bioinformatics analyses. Organelle genomes can be surprisingly complex and can exhibit convoluted and unconventional modes of gene expression. Unravelling this complexity can demand a wide assortment of experiments, from pulsed‐field gel electrophoresis to Southern and Northern blots to RNA analyses. Here, we show that it is exactly these types of ‘complementary’ analyses that are often lacking from contemporary organelle genome papers, particularly short ‘genome announcement’ articles. Consequently, crucial and interesting features of organelle chromosomes are going undescribed, which could ultimately lead to a poor understanding and even a misrepresentation of these genomes and the genes they express. High‐throughput sequencing and bioinformatics have made it easy to sequence and assemble entire chromosomes, but they should not be used as a substitute for or at the expense of other types of genomic characterization methods.
Low‐cost fluctuating‐temperature chamber for experimental ecology
Authors: Greenspan Sasha E. , Morris Wayne , Warburton Russell , Edwards Lexie , Duffy Richard , Pike David A. , Schwarzkopf Lin , Alford Ross A.
Published: August 2016

Commercially available fluctuating‐temperature chambers are large and costly. This poses a challenge to experimental ecologists endeavouring to recreate natural temperature cycles in the laboratory because the large number of commercial chambers required for replicated study designs is prohibitively expensive to purchase, requires a large amount of space and consumes a great deal of energy.

We developed and validated a design for economical, programmable fluctuating‐temperature chambers based on a relatively small (23 L) commercially manufactured constant temperature chamber ($140US) modified with a customized, user‐friendly microcontroller ($15US).

Over a 1‐week trial, these chambers reliably reproduced a real‐world fluctuating (13·1–35·5 °C) body temperature regime of an individual frog, with a near‐perfect 1 : 1 fit between target and actual temperatures (y = 1·0036x + 0·1366, R2 = 0·9977, 95% confidence interval for slope = 1·0026, 1·0046). Over 30‐day trials, they also reliably produced a simpler daily fluctuating‐temperature scheme (sine wave fluctuating between 10 and 25 °C each 24 h) and a range of constant temperature regimes.

The design is inexpensive and simple to assemble in large numbers, enabling genuine replication of even highly complex, many treatment study designs. For example, it is possible to simultaneously examine in replicate chambers the responses of organisms to constant regimes, regimes that fluctuate following the means experienced by populations and regimes that exactly mimic fluctuations measured over any length of time for particular individuals that differ in behaviour or microhabitat use. These chambers thus vastly expand the pool of resources available for manipulative experiments in thermal biology and ecology.
Joint Partially Linear Model for Longitudinal Data with Informative Drop-Outs
Authors: Kim Sehee , Zeng Donglin , Taylor Jeremy M. G.
Published: August 2016

In biomedical research, a steep rise or decline in longitudinal biomarkers may indicate latent disease progression, which may subsequently cause patients to drop out of the study. Ignoring the informative drop-out can cause bias in estimation of the longitudinal model. In such cases, a full parametric specification may be insufficient to capture the complicated pattern of the longitudinal biomarkers. For these types of longitudinal data with the issue of informative drop-outs, we develop a joint partially linear model, with an aim to find the trajectory of the longitudinal biomarker. Specifically, an arbitrary function of time along with linear fixed and random covariate effects is proposed in the model for the biomarker, while a flexible semiparametric transformation model is used to describe the drop-out mechanism. Advantages of this semiparametric joint modeling approach are the following: 1) it provides an easier interpretation, compared to standard nonparametric regression models, and 2) it is a natural way to control for common (observable and unobservable) prognostic factors that may affect both the longitudinal trajectory and the drop-out process. We describe a sieve maximum likelihood estimation procedure using the EM algorithm, where the Akaike information criterion (AIC) and Bayesian information criterion (BIC) are considered to select the number of knots. We show that the proposed estimators achieve desirable asymptotic properties through empirical process theory. The proposed methods are evaluated by simulation studies and applied to prostate cancer data.
Case of Morvan syndrome with anti‐Ma2/Ta antibodies
Authors: Nishioka Kenya , Hoshino Yasunobu , Kanai Kauzuaki , Ueno Shinichi , Nakazato Tomoko , Takanashi Masashi , Tanaka Ryota , Yokoyama Kazumasa , Arimura Kimiyoshi , Kuwabara Satoshi , Hattori Nobutaka
Published: August 2016

Background

The anti‐paraneoplastic (Ma2/Ta) antibody is related to testicular, lung and ovarian cancers, and might cause paraneoplastic neurological disorders.

Case presentation

We present a 25‐year‐old woman presenting various neurological symptoms of myokymia, chronic widespread pain, tremor, excessive daytime sleepiness, impaired eye of movements, and seizures and autonomic symptoms related to anti‐Ma2/Ta antibodies. Needle electromyography showed spontaneous multiplet and myokymic discharges in the left vestus lateralis. Thus, we diagnosed her as Morvan syndrome. After initiation of steroids, plasma exchange and dantrolene, her symptoms partially improved with decreasing intensity of the antigen of anti‐Ma2/Ta antibodies, from moderate strong to borderline.

Conclusions

The present case expands the clinical spectrum of anti‐Ma2/Ta antibodies‐related disorders to include the existence of neuroimmune activation and Morvan syndrome.
Long‐term outcomes of implants placed after vertical alveolar ridge augmentation in partially edentulous patients: a 10‐year prospective clinical study
Authors: Roccuzzo Mario , Savoini Matteo , Dalmasso Paola , Ramieri Guglielmo
Published: August 2016

Aim

The aim of this study was to evaluate the long‐term clinical results around non‐submerged implants placed after vertical alveolar ridge augmentation.

Material and methods

The original population consisted of two groups of partially edentulous patients (Clinical Oral Implants Research, 15, 2004, 73; Clinical Oral Implants Research, 18, 2007, 286), receiving a total of 82 implants, after a vertical bone augmentation of at least 4 mm. Following cementation of the fixed dental prostheses, patients were asked to follow an individualized supportive periodontal therapy (SPT) program for an appropriate clinical and radiographic follow‐up.

Results

At the 10‐year examination, seven of the 41 patients were lost to follow‐up. During SPT, additional antibiotic and/or surgical therapy was necessary in 18 implants, and four of these implants were removed for biological complications. The overall implant survival rate was 94.1%. The mean interproximal bone loss (BL) was 0.58 ± 0.57 mm.

Conclusions

The results of this study confirmed that implants, placed after vertical augmentation and followed by an adequate SPT, offer predictable long‐term results. Nevertheless, patients whose bone atrophy was consequence of a previous history of periodontitis presented a statistically significant greater BL.
Naltrexone/Bupropion extended release‐induced weight loss is independent of nausea in subjects without diabetes
Authors: Hong K. , Herrmann K. , Dybala C. , Halseth A. E. , Lam H. , Foreyt J. P.
Published: August 2016

Naltrexone/bupropion extended release (NB) is indicated as an adjunct to a reduced‐calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index of ≥30 or ≥27 kg m−2 and ≥1 weight‐related comorbidity (e.g. hypertension, type 2 diabetes and dyslipidaemia). In phase 3 clinical studies, nausea occurred in significantly higher proportions of subjects randomized to NB vs. placebo (PBO). In this pooled analysis of three phase 3, 56‐week, PBO‐controlled studies, we characterized nausea and weight loss in NB‐ and PBO‐treated subjects without diabetes. Subjects receiving NB (n = 1778) lost significantly more weight than those receiving PBO (n = 1160). Weight change was not significantly different between subjects reporting and not reporting nausea in either treatment arm. Severity of nausea was mild to moderate in ≥95% of all cases. In the NB arm, the highest incidence of nausea onset (9%) was reported during week 1. The median duration of mild, moderate and severe nausea in subjects receiving NB was 14, 9 and 13 days, respectively. Our results demonstrate that nausea associated with NB is rarely severe, primarily occurs early in treatment and is not a contributor to weight loss.
Social Media and Language Processing: How Facebook and Twitter Provide the Best Frequency Estimates for Studying Word Recognition
Authors: Herdağdelen Amaç , Marelli Marco
Published: August 2016

Corpus‐based word frequencies are one of the most important predictors in language processing tasks. Frequencies based on conversational corpora (such as movie subtitles) are shown to better capture the variance in lexical decision tasks compared to traditional corpora. In this study, we show that frequencies computed from social media are currently the best frequency‐based estimators of lexical decision reaction times (up to 3.6% increase in explained variance). The results are robust (observed for Twitter‐ and Facebook‐based frequencies on American English and British English datasets) and are still substantial when we control for corpus size.
A computational continuum damage mechanics model for predicting transverse cracking and splitting evolution in open hole cross‐ply composite laminates
Authors: Babaei R. , Farrokhabadi A.
Published: August 2016

The present study focuses on a computational constitutive model which predicts the matrix cracking evolution and fibre breakage in cross‐ply composite laminates with open hole under in‐plane loading. To consider the effects of matrix cracking on the nonlinear response of laminates, a simplified crack density based model is applied which evaluates the representative damage parameters of matrix cracking. Furthermore, a developed subroutine based on continuum damage mechanics concepts is applied in ANSYS code which is capable to consider the transverse cracking/splitting evolution and predict the final failure load of mentioned laminate under monotonic loading in a progressive damage analyses. It is shown that the obtained stress–strain behaviours and the damage evaluation of considered laminates are in good agreement with the available experimental results.
AMiscanthusplantation can be carbon neutral without increasing soil carbon stocks
Authors: Robertson Andy D. , Whitaker Jeanette , Morrison Ross , Davies Christian A. , Smith Pete , McNamara Niall P.
Published: August 2016

National governments and international organizations perceive bioenergy, from crops such asMiscanthus, to have an important role in mitigating greenhouse gas (GHG) emissions and combating climate change. In this research, we address three objectives aimed at reducing uncertainty regarding the climate change mitigation potential of commercialMiscanthusplantations in the United Kingdom: (i) to examine soil temperature and moisture as potential drivers of soilGHGemissions through four years of parallel measurements, (ii) to quantify carbon (C) dynamics associated with soil sequestration using regular measurements of topsoil (0–30 cm) C and the surface litter layer and (iii) to calculate a life cycleGHGbudget using site‐specific measurements, enabling theGHGintensity ofMiscanthusused for electricity generation to be compared against coal and natural gas. Our results show that methane (CH4) and nitrous oxide (N2O) emissions contributed little to the overallGHGbudget ofMiscanthus, while soil respiration offset 30% of the crop's net aboveground C uptake. Temperature sensitivity of soil respiration was highest during crop growth and lowest during winter months. We observed no significant change in topsoil C or nitrogen stocks following 7 years ofMiscanthuscultivation. The depth of litter did, however, increase significantly, stabilizing at approximately 7 tonnes dry biomass per hectare after 6 years. The cradle‐to‐farm gateGHGbudget of this crop indicated a net removal of 24.5 tCO2‐eq ha−1 yr−1from the atmosphere despite no detectable C sequestration in soils. When scaled up to consider the full life cycle,Miscanthusfared very well in comparison with coal and natural gas, suggesting considerableCO2offsetting perkWh generated. Although the comparison does not account for the land area requirements of the energy generated,Miscanthusused for electricity generation can make a significant contribution to climate change mitigation even when combusted in conventional steam turbine power plants.
A phase III clinical trial of a mixture agent of plasma‐derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors
Authors: Shinkoda Y. , Shirahata A. , Fukutake K. , Takamatsu J. , Shima M. , Hanabusa H. , Mugishima H. , Takedani H. , Kawasugi K. , Taki M. , Matsushita T. , Tawa A. , Nogami K. , Higasa S. , Kosaka Y. , Fujii T. , Sakai M. , Migita M. , Uchiba M. , Kawakami K. , Sameshima K. , Ohashi Y. , Saito H.
Published: August 2016

Introduction

MC710, a 1:10 protein weight ratio mixture of plasma‐derived activated factor VII (FVIIa) and factor X (FX), is a novel bypassing agent for haemostasis in haemophilia patients with inhibitors. We evaluated the haemostatic efficacy and safety of one to two administrations of MC710 in 21 joint, muscle, and subcutaneous bleeding episodes in 14 male patients, in a multi‐centre, open‐label, non‐randomized clinical trial.

Methods

Subjects were intravenously administered one or two doses of 60 or 120 μg kg−1 MC710 (as FVIIa) once or twice (to a maximum of 180 μg kg−1) over up to five bleeding episodes per subject. The haemostatic efficacy of MC710 was determined for each episode by investigator evaluation, using changes in visual analogue scale (VAS) for pain relief, and/or knee joint or muscle circumference for swelling reduction, and range of motion (ROM) for improvement of joint mobility.

Results

In 21 treatments for bleeding episodes, 19 were rated “excellent” or “effective” 8 h after the last treatment. VAS significantly decreased over time, and ROM significantly improved over time compared with the values before treatment. One mild adverse reaction, decreased blood potassium, and two serious adverse events, both knee joint bleeding, were observed within 1 week after first administration, with no significant effect on safety. Furthermore, diagnostic markers did not show any signs of disseminated intravascular coagulation (DIC).

Conclusion

These results show that MC710 has sufficient haemostatic efficacy and safety, and can be used as a potential bypassing agent to control bleeding in haemophilia patients with inhibitors.
Towards Strategic Actorhood? The Execution of Institutional Positioning Strategies at Finnish Universities of Applied Sciences
Authors: Vuori Johanna
Published: August 2016

Given the emerging interest in institutional positioning and to augment the small number of empirical studies in this field, this paper presents discussion about how Finnish universities of applied sciences implement their profiling strategies. The analysis is based on an examination of documents recently submitted by these institutions when reapplying for operating licences. The paper discusses how institutions refer to their positioning statements when introducing or responding to changes in their internal or external environments and questions whether or not positioning paves the way to strategic actorhood. The results suggest that the universities of applied sciences that most often refer to profiling statements have built different kinds of networks to support their positioning activities. Moreover, they have made considerable structural changes to implement their positioning strategies. The restructuring of human resource capacity required to execute the positioning strategy is discussed in the reapplication documents, albeit with a lesser emphasis.
Autonomy and Identity in the Cities of Norman Italy, c. 1050–c. 1200
Authors: Oldfield Paul
Published: August 2016

Understandings on the medieval cities of southern Italy and Sicily have for long been shaped by the so‐called ‘Southern Question’ and problematic comparisons with the cities of North and Central Italy. An over‐arching conventional position emerged suggesting that the political and cultural dynamism of the cities of the South was drastically impaired by the arrival of the Normans and the creation of a monarchy. However, a corpus of revisionist, interdisciplinary work has been produced since the late 20th century. It has substantially reframed our perception of the types of autonomies and identities present within the cities of southern Italy and Sicily. This essay briefly tracks some of the most salient aspects of these recent historiographical developments.
Recent trends and patterns in HIV‐1 transmitted drug resistance in the United Kingdom
Authors: Tostevin A , White E , Dunn D , Croxford S , Delpech V , Williams I , Asboe D , Pozniak A , Churchill D , Geretti AM , Pillay D , Sabin C , Leigh‐Brown A , Smit E ,   the UK HIV Drug Resistance Database
Published: August 2016

Objectives

Transmission of drug‐resistant HIV‐1 has decreased in the UK since the early 2000s. This analysis reports recent trends and characteristics of transmitted drug resistance (TDR) in the UK from 2010 to 2013.

Methods

Resistance tests conducted in antiretroviral treatment (ART)‐naïve individuals between 2010 and 2013 were analysed for the presence of transmitted drug resistance mutations (TDRMs), defined as any mutations from a modified 2009 World Health Organization surveillance list, or a modified 2013 International Antiviral Society‐USA list for integrase tests. Logistic regression was used to examine associations between demographics and the prevalence of TDRMs.

Results

TDRMs were observed in 1223 (7.5%) of 16 425 individuals; prevalence declined from 8.1% in 2010 to 6.6% in 2013 (P = 0.02). The prevalence of TDRMs was higher among men who have sex with men (MSM) compared with heterosexual men and women (8.7% versus 6.4%, respectively) with a trend for decreasing TDRMs among MSM (P = 0.008) driven by a reduction in nucleoside reverse transcriptase inhibitor (NRTI)‐related mutations. The most frequently detected TDRMs were K103N (2.2%), T215 revertants (1.6%), M41L (0.9%) and L90M (0.7%). Predicted phenotypic resistance to first‐line ART was highest to the nonnucleoside reverse transcriptase inhibitors (NNRTIs) rilpivirine and efavirenz (6.2% and 3.4%, respectively) but minimal to NRTIs, including tenofovir, and protease inhibitors (PIs). No major integrase TDRMs were detected among 101 individuals tested while ART‐naïve.

Conclusions

We observed a decrease in TDRMs in recent years. However, this was confined to the MSM population and rates remained stable in those with heterosexually acquired HIV infection. Resistance to currently recommended first‐line ART, including integrase inhibitors, remained reassuringly low.
The versatility of the medial thigh lift for defect coverage in the genito‐perineal region
Authors: Djedovic Gabriel , Del Frari Barbara , Matiasek Johannes , Schiltz David , Engelhardt Timm O , Pierer Gerhard , Rieger Ulrich M
Published: August 2016

Soft tissue defects in the genito‐perineal region are predominantly because of trauma, infections, neoplasms or iatrogenic causes. As a result of the region's urological, reproductive and gastrointestinal function, defects in this area may cause devastating physical and psychological consequences as well as diminished sexual functioning. The purpose of this study was to examine the efficacy of implementing a medial thigh lift for defect coverage in the perineal region.

A retrospective analysis of all medial thigh lift procedures for defect coverage in the genito‐perineal region between November 2010 and March 2015 was conducted at three institutions.

Ten consecutive patients underwent a medial thigh lift for defect coverage in the genito‐perineal region. Nine patients were male, and one was female. The causative factors were Fournier's gangrene in eight patients, one patient had a straddle injury, and one suffered from extramammary Paget's disease. The mean follow‐up time was 19·8 months. The average total defect size was 11·1 × 11 cm (length × width).

The medial thigh lift procedure is a safe, technically easy and reliable technique with discrete scars. Outstanding aesthetic and functional outcomes result in a high rate of patient satisfaction. Through immediate wound closure, a reduction of recovery time can be achieved.
Why can we not Predict Earthquakes?
Authors: Matthews Robert
Published: August 2016

Hundreds of people have been killed since the start of the year as a result of earthquakes. With all the data we have on these natural disasters, why can we not reliably predict their occurrence?
The Drugs don't Work … or do they?
Authors: Baayen Corine
Published: August 2016

When testing new drugs, researchers are asked to specify their statistical analysis plan before seeing their results. This can be a gamble if little is known about how a drug might work. But there is a way for researchers to keep their analysis options open, says Corine Baayen