bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of magnetic islands on turbulent transport in the WEGA stellarator
Authors: Marsen S. , Otte M. , Wolf R. 
Published: May 2012

Abstract
The role of the magnetic field topology for the complex interplay between turbulence and zonal flows (ZFs) leading to the formation of transport barriers is a recent topic in fusion research. Gaining knowledge on their relation in experiments requires a flexible magnetic configuration and a good diagnostic access with high temporal and spatial resolution. WEGA as a small classical stellarator with moderate plasma parameters is well suited for such experiments. Stationary n = 1 islands can be modified in size by external error field compensation coils. Configurations with m/n = 5/1 islands at the plasma edge are compared with configurations showing no major resonances (i.e. no islands). The spatio-temporal structure of fluctuations was studied with Langmuir-probe arrays at different toroidal and poloidal positions.
In low density discharges ZF-like patterns were observed in potential fluctuations. A characteristic feature of these oscillations is a long range correlation (LRC) with fluctuations being symmetric on a flux surface. It was shown for the first time that the presence of magnetic islands alters the structure of these low frequency fluctuations. At r < r
island the LRCs were still observed. Inside the islands the fluctuations showed up more like meso-scale structures with finite poloidal wave number. The poloidal correlation length was shown to be decreased with increasing islands width. Frequency resolved measurements of the turbulent transport across the island's X-point showed that these structures do not significantly contribute to the transport due to their nearly symmetric character. However, their decorrelation goes together with an increase in transport in the frequency range of the ambient turbulence.
Stable isotopes reveal age-dependent trophic level and spatial segregation during adult marine feeding in populations of salmon
Authors: MacKenzie Kirsteen M. , Trueman Clive N. , Palmer Martin R. , Moore Andy , Ibbotson Anton T. , Beaumont William R. C. , Davidson Ian C. 
Published: May 2012

AbstractMacKenzie, K. M., Trueman, C. N., Palmer, M. R., Moore, A., Ibbotson, A. T., Beaumont, W. R. C., and Davidson, I. C. 2012. Stable isotopes reveal age-dependent trophic level and spatial segregation during adult marine feeding in populations of salmon from the UK. – ICES Journal of Marine Science, 69: 1637–1645. Locating and differentiating the marine feeding areas used by adult salmon (Salmo salar) is essential to stock-based management and conservation, but traditional tagging studies are limited and influenced by the uneven distribution of the fisheries or research vessel surveys. Here, a novel approach is used, based on the observation that the isotopic composition of animal tissues is intrinsically linked to the environmental conditions during tissue growth, which allows for the distinction of pelagic fish feeding in different locations. This isotopic approach is applied using archived collections of salmon scales and shows that (i) salmon act as size-structured pelagic predators, (ii) adult salmon from different natal origins within the UK (and hence components of the southern European stock complex) feed in different oceanic regions before their return, (iii) one-sea-winter (1SW) and multi-sea-winter salmon returning to some rivers in the UK are separated in their marine feeding areas, whereas those from others are not, and (iv) salmon from the rivers sampled are not feeding in regions of the Northwest Atlantic used by 1SW salmon returning to rivers in Newfoundland. Therefore, the stable isotope approach allows for retrospective investigations of marine diet, location, and migration at stock- and cohort-specific levels.
How Homophily Affects the Speed of Learning and Best-Response Dynamics
Authors: Golub Benjamin , Jackson Matthew O. 
Published: May 2012

AbstractWe examine how the speed of learning and best-response processes depends on homophily: the tendency of agents to associate disproportionately with those having similar traits. When agents' beliefs or behaviors are developed by averaging what they see among their neighbors, then convergence to a consensus is slowed by the presence of homophily but is not influenced by network density (in contrast to other network processes that depend on shortest paths). In deriving these results, we propose a new, general measure of homophily based on the relative frequencies of interactions among different groups. An application to communication in a society before a vote shows how the time it takes for the vote to correctly aggregate information depends on the homophily and the initial information distribution.
Dissecting Arabidopsis Gβ Signal Transduction on the Protein Surface
Authors: Jiang Kun , Frick-Cheng Arwen , Trusov Yuri , Delgado-Cerezo Magdalena , Rosenthal David M. , Lorek Justine , Panstruga Ralph , Booker Fitzgerald L. , Botella José Ramón , Molina Antonio , Ort Donald R. , Jones Alan M. 
Published: May 2012

Abstract
The heterotrimeric G-protein complex provides signal amplification and target specificity. The Arabidopsis (Arabidopsis thaliana) Gβ-subunit of this complex (AGB1) interacts with and modulates the activity of target cytoplasmic proteins. This specificity resides in the structure of the interface between AGB1 and its targets. Important surface residues of AGB1, which were deduced from a comparative evolutionary approach, were mutated to dissect AGB1-dependent physiological functions. Analysis of the capacity of these mutants to complement well-established phenotypes of Gβ-null mutants revealed AGB1 residues critical for specific AGB1-mediated biological processes, including growth architecture, pathogen resistance, stomata-mediated leaf-air gas exchange, and possibly photosynthesis. These findings provide promising new avenues to direct the finely tuned engineering of crop yield and traits.
Pharmacokinetic and pharmacodynamic profiling of a P2X7 receptor allosteric modulator GSK1482160 in healthy human subjects
Authors: Ali Zahid , Laurijssens Bart , Ostenfeld Thor , McHugh Simon , Stylianou Anastasia , Scott‐Stevens Paul , Hosking Louise , Dewit Odile , Richardson Jill C. , Chen Chao 
Published: May 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• P2X7 receptors are involved in the production of pro‐inflammatory cytokines, such as Il‐1β, by central and peripheral immune cells. Il‐1β has been implicated as an important mediator of inflammation. Therefore, the P2X7 receptor is an attractive therapeutic target for inflammatory diseases.WHAT THIS STUDY ADDS• Findings in pharmacokinetics, pharmacodynamics, safety and tolerability of a P2X7 receptor modulator, GSK1482160, from the first human study for the molecule are described. A pharmacokinetic/pharmacodynamic model for LPS‐stimulated ATP‐induced Il‐1β production in blood allowed the integration of all relevant data and provided in vivo evidence of the nature of the drug–receptor interaction. The model has the potential to be used to simulate future trials.AIMS This paper describes findings from the first‐in‐human study for GSK1482160, an orally available allosteric P2X7 receptor modulator. The study aimed to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of the compound in healthy subjects.METHODS Escalating single doses of up to 1 g were administered to healthy subjects in a single‐blind and placebo‐controlled fashion. Safety, tolerability, blood drug concentrations and ex vivo Il‐1β production in blood were evaluated.RESULTS Drug concentration peaked within 3.5 h of dosing under fasting conditions and declined thereafter with a relatively short half‐life of less than 4.5 h. Exposure was proportional to dose with between subject variability of less than 60%. A PK/PD model quantified Il‐1β as a function of drug exposure. The model allowed simulation of in vivo pharmacology for various untested dose levels and regimens. Furthermore, the mechanistic model supported the hypothesis that the compound reduces the efficacy of ATP at the P2X7 receptor without affecting its affinity. No major safety or tolerability concerns were identified in this small study (n= 29), except for one case of asymptomatic accelerated idioventricular rhythm at the top dose.CONCLUSION The model‐based approach maximized analysis power by integrating all biomarker data and revealed mechanistic insight into the pharmacology of P2X7 modulation by GSK1482160. Simulations by this model ultimately led to the discontinuation of the development of this compound. The therapeutic relevance of the P2X7 receptor remains to be tested in patients. The mechanistic‐model‐based approach can be applied widely to drug development.
ID1 expression associates with other molecular markers and is not an independent prognostic factor in cytogenetically normal acute myeloid leukaemia
Authors: Damm Frederik , Wagner Katharina , Görlich Kerstin , Morgan Michael , Thol Felicitas , Yun Haiyang , Delwel Ruud , Valk Peter J. M. , Löwenberg Bob , Heuser Michael , Ganser Arnold , Krauter Jürgen 
Published: May 2012

SummaryIn acute myeloid leukaemia with normal karyotype (CN‐AML), gene mutations (e.g. NPM1, FLT3, CEBPA) as well as deregulated gene expression affect outcome. High expression of ID1 was described as a negative prognostic factor. We have shown that CEBPA regulates ID1 expression. Therefore, we analysed the prognostic impact of ID1 expression in 269 patients (aged 16–60 years) with CN‐AML in the context of other molecular markers, particularly CEBPA mutations. ID1high status was an independent negative prognostic factor for overall survival (OS) in multivariate analysis when analysed together with age, extramedullary disease, platelets, expression of BAALC and WT1, FLT3‐internal tandem duplication, NPM1, WT1 single nucleotide polymorphism rs16754 and IDH1. ID1 expression was higher in CEBPA wildtype patients than in patients with monoallelic CEBPA mutations and these patients showed higher ID1 expression compared to patients with biallelic CEBPA mutations. Thus, when CEBPA mutations were considered, ID1 expression lost its prognostic impact. Likewise, the negative impact of ID1high status on relapse‐free survival (RFS) was lost when CEBPA mutations were included in the analysis. In CEBPA wildtype patients, ID1 expression had no impact on complete remission‐rate, OS or RFS. In conclusion, CEBPA mutations seem to deregulate ID1 expression. Therefore, ID1 expression is not an independent prognostic factor in CN‐AML.
An alternative allergen:adjuvant formulation potentiates the immunogenicity and reduces allergenicity of a novel subcutaneous immunotherapy product for treatment of grass‐pollen allergy
Authors: Rask C. , Lund L. , Lund G. , Heydenreich B. , Wurtzen P. , Bellinghausen I. , Saloga J. , Lund K. 
Published: May 2012

AbstractBackgroundSubcutaneous specific immunotherapy (SCIT) has proven sustained clinical efficacy against allergy. The recommended regimen for SCIT is a gradual updosing over a period of weeks. Commonly, in commercial products for SCIT, the specific allergen is formulated with an adjuvant, most often in the form of aluminium hydroxide (AlOH). It has been shown that allergen‐specific IgG antibodies are induced as a result of successful SIT.ObjectiveTo investigate the possibility of optimizing the formulation of AlOH‐based grass‐pollen allergy vaccines for SCIT in a way that allows for shorter updosing regimens while maintaining the immunogenicity of the vaccine.MethodsMice were immunized with various concentrations of Phleum pratense (Phl p) allergen extract and AlOH or a fixed dilution of the maintenance doses of one conventional and one alternatively formulated vaccine. The kinetics of Phl p‐specific IgG antibody responses in serum and spleen T cell responses were determined. Allergenicity, measured as the ability of the formulations to activate human basophils, was also determined. In addition, human T cell responses and the expression of dendritic cell surface markers after vaccine challenge in vitro were analysed.ResultsSpecific IgG antibody responses were shown to depend on the AlOH concentration, but not on the allergen concentrations. The immunogenicity of the conventional formulation and the alternative formulation was shown to be similar with regard to the in vivo‐induced IgG and T cell responses. In contrast, the allergenicity of the alternative formulation was significantly reduced compared with the conventional formulation.ConclusionThe optimization of the formulation allows for administration of a lower dose of allergen while maintaining the immunogenicity of the product and at the same time reducing allergenicity.Clinical RelevanceThis study indicates that the optimization of the allergen and the adjuvant formulation could benefit the safety/efficacy profile and allow for shorter updosing.
HIF‐1α up‐regulation is associated with adverse clinicopathological and biological factors in neuroblastomas
Authors: Dungwa Josiah V , Hunt Linda P , Ramani Pramila 
Published: May 2012

Dungwa J V, Hunt L P & Ramani P (2012) Histopathology 61, 417–427HIF‐1α up‐regulation is associated with adverse clinicopathological and biological factors in neuroblastomasAims:  To study the expression of hypoxia‐inducible factor 1α (HIF‐1α) in clinical neuroblastoma (NB) samples and its association with the clinicopathological features, biological features and survival of NB patients.Methods and results:  Immunohistochemistry indicated that elevated HIF‐1α expression was present in 30 of 90 (33%) NBs. This expression was correlated significantly and positively with higher clinical stage (P = 0.002), ≥18 months of age at presentation (P = 0.020), high‐risk group (P = 0.005), unfavourable pathology (P = 0.002), MYCN amplification (P < 0.001), 1p deletion (P = 0.004) and 17q gain (P = 0.002). Enzyme‐linked immunosorbent assays showed that total HIF‐1α protein was significantly higher in NBs of patients with all examined adverse prognostic factors except for age. Univariate survival analysis revealed that higher‐than‐median HIF‐1α total protein levels were associated significantly with a decrease in event‐free survival (EFS) (P = 0.017), but not in overall survival (OS) (P = 0.12). HIF‐1α immunoexpression by ≥10% of tumour cells was associated significantly with decreased OS and EFS (P = 0.002 and P = 0.004, respectively), but not in multivariate analysis after adjusting for the high‐risk group (P = 0.16 and P = 0.19, respectively).Conclusions:  HIF‐1α was increased significantly in patients with NB associated with unfavourable characteristics. HIF‐1α is a prognostic indicator of poor OS and EFS and defines subgroups of NBs with aggressive clinical behaviour.
Size‐related variation in protein abundance in the brain and abdominal tissue of bumble bee workers
Authors: Wolschin F. , Shpigler H. , Amdam G. V. , Bloch G. 
Published: May 2012

AbstractFemale bumble bee workers of the same species often show a profound body size variation that is linked to a division of labour. Large individuals are more likely to forage whereas small individuals are more likely to perform in‐nest activities. A higher sensory sensitivity, stronger circadian rhythms as well as better learning and memory performances appear to better equip large individuals for outdoor activities compared to their smaller siblings. The molecular mechanisms underlying worker functional polymorphism remain unclear. Proteins are major determinants of an individual's morphology and behaviour. We hypothesized that the abundance of proteins such as metabolic enzymes as well as proteins involved in neuronal functions would differ with body size and provide insights into the mechanisms underlying size‐dependent physiological specialization in bumble bee workers. We conducted protein quantification measurements based on liquid chromatography coupled with tandem mass spectrometry on tissue samples derived from small and large Bombus impatiens and Bombus terrestris workers. Proteins found to differ significantly in abundance between small and large workers belong to the categories of structure, energy metabolism and stress response. These findings provide the first proteomic insight into mechanisms associated with size‐based division of labour in social insects.
Interactions among fire, grazing, harvest and abiotic conditions shape palm demographic responses to disturbance
Authors: Mandle Lisa , Ticktin Tamara 
Published: May 2012

Summary1. Determining the drivers of plant demography is integral to understanding the processes that shape plant species abundances and distributions. Despite recognition that interactions among drivers have important effects on demographic processes, few demographic studies test for interactions among multiple drivers in plants.2. We used a factorial‐design experiment to study the interactive effects among three common forms of disturbance in the tropics (fire history, grazing and leaf harvest by humans) on the vital rates of Phoenix loureiri (mountain date palm) in South India. In addition, we tested for interactive effects among these disturbances, abiotic conditions and plant size. We also tested for non‐consumptive effects of grazing and harvest, such as trampling, by measuring the intensities of grazing and harvest in plots open to these disturbances.3. Intensities of leaf harvest and grazing varied with abiotic conditions and disturbance. Leaf harvest decreased with increasing grazing intensity, suggesting that the net effect of harvest on palm populations is less where it co‐occurs with grazing. In areas without fire, plots with lower soil moisture had higher grazing intensities.4. We found multiple significant main and interactive effects of disturbance on palm vital rates. Palm mortality increased with fire and grazing. Grazing and harvest reduced growth, but growth increased following fire. The negative impact of harvest on palm individuals was reduced when harvest occurred in plots with fire.5. We found evidence of non‐consumptive effects of grazing and harvest on palm growth, likely from trampling. Studies inferring the effects of grazing by comparing grazed and ungrazed individuals within an area where grazing occurs will likely underestimate grazing effects.6. Synthesis. Our findings reveal that P. loureiri demographic rates are driven by interactive effects among multiple forms of disturbance and abiotic factors and that the intensities of disturbance are themselves driven by interactions between other forms of disturbance and abiotic factors. These results illustrate that understanding the effects of, and interactions among, multiple drivers will be key in attempts to mitigate the effects of environmental change on plant species declines.
Species–genetic diversity correlations in habitat fragmentation can be biased by small sample sizes
Authors: NAZARENO ALISON G. , JUMP ALISTAIR S. 
Published: May 2012

AbstractPredicted parallel impacts of habitat fragmentation on genes and species lie at the core of conservation biology, yet tests of this rule are rare. In a recent article in Ecology Letters, Struebig et al. (2011) report that declining genetic diversity accompanies declining species diversity in tropical forest fragments. However, this study estimates diversity in many populations through extrapolation from very small sample sizes. Using the data of this recent work, we show that results estimated from the smallest sample sizes drive the species–genetic diversity correlation (SGDC), owing to a false‐positive association between habitat fragmentation and loss of genetic diversity. Small sample sizes are a persistent problem in habitat fragmentation studies, the results of which often do not fit simple theoretical models. It is essential, therefore, that data assessing the proposed SGDC are sufficient in order that conclusions be robust.
A Shift from Underweight to Overweight and Obesity in Asian Children and Adolescents with Congenital Heart Disease
Authors: Chen Chun‐An , Wang Jou‐Kou , Lue Hung‐Chi , Hua Yu‐Chuan , Chang Mei‐Hwei , Wu Mei‐Hwan 
Published: May 2012

AbstractBackground:  In Western countries, obesity is a common problem in children with congenital heart disease (CHD). However, this problem may have racial difference, and little is known about the shift of this trend as patients grow up. The present study sought to investigate the prevalence and trends of being underweight, overweight and obesity in an Asian CHD cohort using a 5‐year citywide school survey database.Methods:  Patient group consisted of 705 first grade elementary school students (children) and 219 first grade senior high school students (adolescents), while 18753 healthy children and 15014 healthy adolescents served as controls. Body mass index (BMI) percentile was calculated to define underweight (BMI < 15th percentile) and overweight (BMI 85th–95th percentile)/obesity (BMI ≥ 95th percentile).Results:  In CHD children, the prevalence of underweight and overweight/obesity was 21.0% (control 16%, P < 0.001) and 14.5% (control 19.8%, P < 0.001), respectively. Children with moderate to severe CHD, especially cyanotic CHD, were more underweight and less overweight/obese than children with non‐cyanotic CHD. The prevalence of underweight (23.3%) and overweight/obesity (26.5%) in CHD adolescents became close to that in controls. From childhood to adolescence, different shifts in BMI distribution were noted; controls became more underweight and overweight/obese for males and more underweight and less overweight/obese for females, while CHD patients became more overweight/obese for both genders, including cyanotic CHD.Conclusions:  In this Asian CHD cohort, we demonstrates a shift of BMI distribution from more underweight and less overweight/obese compared with healthy children, to a pattern similar to that in healthy adolescents.
Functional analyses of AGAMOUS family members in Nicotiana benthamiana clarify the evolution of early and late roles of C‐function genes in eudicots
Authors: Fourquin Chloé , Ferrándiz Cristina 
Published: May 2012

SummaryThe C‐function, according to the ABC model of floral organ identity, is required for stamen and carpel development and to provide floral meristem determinacy. Members of the AG lineage of the large MADS box gene family specify the C‐function in a broadly conserved manner in angiosperms. In core eudicots, two sub‐lineages co‐exist, euAG and PLE, which have been extensively characterized in Antirrhinum majus and Arabidopsis thaliana, where strong sub‐functionalization has led to highly divergent contributions of the respective paralogs to the C‐function. Various scenarios have been proposed to reconstruct the evolutionary history of the euAG and PLE lineages in eudicots, but detailed functional analyses of the roles of these genes in additional representative species to validate evolutionary hypotheses are scarce. Here, we report functional characterization of euAG‐ and PLE‐like genes in Nicotiana benthamiana through expression analyses and phenotypic characterization of the defects caused by their specific down‐regulation. We show that both paralogs redundantly contribute to the C‐function in this species, providing insights on the likely evolution of these gene lineages following divergence of the major groups within the eudicots (rosids and asterids). Moreover, we have demonstrated a conserved role for the PLE‐like genes in controlling fruit dehiscence, which strongly supports the ancestral role of PLE‐like genes in late fruit development and suggests a common evolutionary origin of late developmental processes in dry (dehiscent) and fleshy (ripening) fruits.