bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of stratosphere‐troposphere coupling in the occurrence of extreme winter cold spells over northern Europe
Authors: Tomassini Lorenzo , Gerber Edwin P. , Baldwin Mark P. , Bunzel Felix , Giorgetta Marco 
Published: September 2012

Extreme cold spells over Northern Europe during winter are examined in order to address the question to what degree and in which ways stratospheric dynamics may influence the state of the troposphere. The study is based on 500 years of a pre‐industrial control simulation with a comprehensive global climate model which well resolves the stratosphere, the MPI Earth System Model. Geopotential height anomalies leading to cold air outbreaks leave imprints throughout the atmosphere including the middle and lower stratosphere. A significant connection between tropospheric winter cold spells over Northern Europe and erosion of the stratospheric polar vortex is detected up to 30 hPa. In about 40 percent of the cases, the extreme cold spells are preceded by dynamical disturbances in the stratosphere. The strong warmings associated with the deceleration of the stratospheric jet cause the tropopause height to decrease over high latitudes. The compression of the tropospheric column below favors the development of high pressure anomalies and blocking signatures over polar regions. This in turn leads to the advection of cold air towards Northern Europe and the establishment of a negative annular mode pattern in the troposphere. Anomalies in the residual mean meridional circulation during the stratospheric weak vortex events contribute to the warming of the lower stratosphere, but are not key in the mechanism through which the stratosphere impacts the troposphere.
Combined targeting of MEK/MAPK and PI3K/Akt signalling in multiple myeloma
Authors: Steinbrunn Torsten , Stühmer Thorsten , Sayehli Cyrus , Chatterjee Manik , Einsele Hermann , Bargou Ralf C. 
Published: September 2012

SummarySo‐called RAS‐dependent pathways, such as those signalling via mitogen‐activated protein kinase kinase (MEK)/mitogen‐activated protein kinase (MAPK) and phosphoinositide‐3 kinase (PI3K)/Akt, are implicated in proliferation and survival of multiple myeloma (MM) cells. However, the effects of their combined blockade and its potential therapeutic utility for the treatment of RAS‐mutated MM have not systematically been analysed. Here, we tested the functional consequences of single versus combined inhibition of the MEK/MAPK and PI3K/Akt pathways in a large series of primary MM samples (n = 55) and MM cell lines (n = 11). Additionally, the anti‐myeloma activity of different treatments was analysed with respect to the RAS mutation status. PI3K/Akt blockade was generally more pro‐apoptotic than blockade of MEK/MAPK both in cell lines and in primary MM samples. Simultaneous blockade of both pathways led to significantly enhanced anti‐myeloma activity in 75% of primary MM samples, whereas the remainder was largely resistant. Resistance to combination blockade was exclusively observed in RAS wildtype cases, whereas sensitivity was noted in RAS wildtype and in RAS mutated MM. These results suggest that oncogenic RAS is a predictor of sensitivity to combination treatment with PI3K/Akt and MEK/MAPK inhibitors and that such an approach might therefore be beneficial for this genetically well‐defined subgroup of MM patients.
Coda with aFinalTwist:theVivaceCodetta in theFirstMovement ofBrahms'sCello sonata inFmajor
Authors: Wu Nelson 
Published: September 2012

ABSTRACTIn music theory, a coda is generally understood as an appendage or an epilogue to a musical structure. This is perhaps the reason that, as Joseph Kerman writes, ‘[m]usical analysts who deal with ... sonata‐form movements generally ... do less well ... in accounting for actual musical experience when dealing with codas than with other sections of the form.’The first movement of Brahms's Cello Sonata in F major, Op. 99, is one of the most‐analysed works in the tonal repertoire. Yet its peculiar final twist, thevivacecodetta, has drawn little analytical comment. This re‐examination of the Allegro vivace aims to go beyond the ostensibly deeper element of melody and harmony by focussing on how prominent expository surface details (anacrusis, metre, articulation and texture) are manipulated in thevivacecodetta. This energetic ending manifests the persistent struggle between duple and triple rhythmic units, as well as the ambiguity between the perceived metre and the notated metre, by synthesising the two main thematic ideas in a sophisticated metrical framework. This approach sheds a new light on the significance of a seemingly negligible ‘coda to a coda’.
Transcriptional reprogramming by root knot and migratory nematode infection in rice
Authors: Kyndt Tina , Denil Simon , Haegeman Annelies , Trooskens Geert , Bauters Lander , Van Criekinge Wim , De Meyer Tim , Gheysen Godelieve 
Published: September 2012

Summary

Rice is one of the most important staple crops worldwide, but its yield is compromised by different pathogens, including plant‐parasitic nematodes. In this study we have characterized specific and general responses of rice (Oryza sativa) roots challenged with two endoparasitic nematodes with very different modes of action.

Local transcriptional changes in rice roots upon root knot (Meloidogyne graminicola) and root rot nematode (RRN, Hirschmanniella oryzae) infection were studied at two time points (3 and 7 d after infection, dai), using mRNA‐seq.

Our results confirm that root knot nematodes (RKNs), which feed as sedentary endoparasites, stimulate metabolic pathways in the root, and enhance nutrient transport towards the induced root gall. The migratory RRNs, on the other hand, induce programmed cell death and oxidative stress, and obstruct the normal metabolic activity of the root. While RRN infection causes up‐regulation of biotic stress‐related genes early in the infection, the sedentary RKNs suppress the local defense pathways (e.g. salicylic acid and ethylene pathways). Interestingly, hormone pathways mainly involved in plant development were strongly induced (gibberellin) or repressed (cytokinin) at 3 dai.

These results uncover previously unrecognized nematode‐induced expression profiles related to their specific infection strategy.
Evaluating the peripheral optical effect of multifocal contact lenses
Authors: Rosén Robert , Jaeken Bart , Lindskoog Petterson Anna , Artal Pablo , Unsbo Peter , Lundström Linda 
Published: September 2012

AbstractPurposeMultifocal soft contact lenses have been used to decrease the progression of myopia, presumably by inducing relative peripheral myopia at the same time as the central image is focused on the fovea. The aim of this study was to investigate how the peripheral optical effect of commercially available multifocal soft contact lenses can be evaluated from objective wavefront measurements.MethodsTwo multifocal lenses with high and low add and one monofocal design were measured over the ±40° horizontal field, using a scanning Hartmann–Shack wavefront sensor on four subjects. The effect on the refractive shift, the peripheral image quality, and the depth of field of the lenses was evaluated using the area under the modulation transfer function as the image quality metric.ResultsThe multifocal lenses with a centre distance design and 2 dioptres of add induced about 0.50 dioptre of relative peripheral myopia at 30° in the nasal visual field. For larger off‐axis angles the border of the optical zone of the lenses severely degraded image quality. Moreover, these multifocal lenses also significantly reduced the image quality and increased the depth of field for angles as small as 10°–15°.ConclusionsThe proposed methodology showed that the tested multifocal soft contact lenses gave a very small peripheral myopic shift in these four subjects and that they would need a larger optical zone and a more controlled depth of field to explain a possible treatment effect on myopia progression.
Scleral changes induced by atropine in chicks as an experimental model of myopia
Authors: Gallego Patricia , Martínez‐García Carmen , Pérez‐Merino Pablo , Ibares‐Frías Lucía , Mayo‐Iscar Agustín , Merayo‐Lloves Jesús 
Published: September 2012

AbstractPurposeTo determine the effects of intravitreal atropine on scleral growth in the form‐deprived chick as an experimental model of myopia.MethodsFive groups of five chicks were studied from day 0–12 post‐hatching. One group remained untreated (C), and four were form‐deprived by monocular light diffusers to induce myopia. Two groups (RLand A) wore diffusers for 9 days, and the other two groups (D and D + A) wore diffusers throughout the study. Group D received no further treatment (myopia positive control). Groups A and D + A received intravitreal injections of atropine for days 9–12. Measurements of refractive error and axial length were performed on days 0, 9, and 12. Sclera changes were assessed in cartilaginous and fibrous layers by histological analysis.ResultsAll form‐deprived eyes had a myopic refractive error on day 9. All atropine‐treated groups were hyperopic on day 12. The effect of atropine was most evident in Group D + A in which diffusers were maintained throughout treatment and changes in refractive error were statistically significant. The observed changes in axial length were in line with the changes in refractive error. The scleral fibrous layer thickness increased, and the sceral cartilaginous layer underwent a slight thinning compared to Group D, the myopia positive control.ConclusionsIf the signals that induce growth remain during atropine treatment, morphological changes in sclera are produced: the scleral fibrous layer thickened, and the sceral cartilaginous layer thinned. These changes resulted in refractive error recovery, and the ocular growth was stopped. The data suggested the atropine was acting throughout the scleral fibrous layer.
Dietitians as leaders, past, present and future
Authors: CAPRA Sandra 
Published: September 2012

AbstractAim:  Dietetics as a form of study predates medicine, but the profession did not emerge until the nineteenth century and is still in an emergent stage today in many parts of the world. This paper seeks to demonstrate how the impact of leaders has been critical in terms of the growth and development of the profession.Methods:  A narrative review was formed from searching the published literature.Results:  The published literature is silent on many aspects of dietetics. In modern times, the majority of written works have come from North America and Western Europe. No work on historical or developmental aspects of dietetics from other parts of the world could be located. Leadership within the profession is well researched, but leadership by the profession in the broader arena of national and international policy and practice is harder to identify. There are calls for curricula to keep pace with the needs of modern healthcare systems if the profession is to flourish.Conclusion:  Despite all the changes and the evolution of the profession, much remains unchanged. There are recurring themes throughout the literature reviewed here, those of the breadth of dietetics, the need for evolving curricula, the need for business acumen, the need for diversity and, in more recent times, the ability to work with interdisciplinary teams. But the profession has what it takes. It has within its ranks leaders of today and tomorrow. It is up to the profession to allow those leaders to emerge and take the profession to the next level.
Disruption of subcellular Arc/Arg 3.1 mRNA expression in striatal efferent neurons following partial monoamine loss induced by methamphetamine
Authors: Barker‐Haliski Melissa L. , Oldenburger Katharina , Keefe Kristen A. 
Published: September 2012

AbstractThe immediate‐early gene Arc (activity‐regulated cytoskeleton‐associated protein) is provocative in the context of neuroplasticity because of its experience‐dependent regulation and mRNA transport to and translation at activated synapses. Normal rats have more preproenkephalin‐negative (ppe‐neg; presumed striatonigral) neurons with cytoplasmic Arc mRNA than ppe‐positive (ppe‐pos; striatopallidal) neurons, despite equivalent numbers of these neurons showing novelty‐induced transcriptional activation of Arc. Furthermore, rats with partial monoamine loss induced by methamphetamine (METH) show impaired Arc mRNA expression in both ppe‐neg and ppe‐pos neurons relative to normal animals following response‐reversal learning. In this study, Arc expression induced by exposure to a novel environment was used to assess transcriptional activation and cytoplasmic localization of Arc mRNA in striatal efferent neuron subpopulations subsequent to METH‐induced neurotoxicity. Partial monoamine depletion significantly altered Arc expression. Specifically, basal Arc expression was elevated, but novelty‐induced transcriptional activation was abolished. Without novelty‐induced Arc transcription, METH‐pre‐treated rats also had fewer neurons with cytoplasmic Arc mRNA expression, with the effect being greater for ppe‐neg neurons. Thus, METH‐induced neurotoxicity substantially alters striatal efferent neuron function at the level of Arc transcription, suggesting a long‐term shift in basal ganglia neuroplasticity processes subsequent to METH‐induced neurotoxicity. Such changes potentially underlie striatally based learning deficits associated with METH‐induced neurotoxicity.
Do mesenchymal stem cells function across species barriers? Relevance for xenotransplantation
Authors: Li Jiang , Ezzelarab Mohamed B. , Cooper David K. C. 
Published: September 2012

Li J, Ezzelarab MB, Cooper DKC. Do mesenchymal stem cells function across species barriers? Relevance for xenotransplantation. Xenotransplantation 2012; 19: 273–285. © 2012 John Wiley & Sons A/S.Abstract: Background: Allogeneic mesenchymal stem (stromal) cells (MSC) are a promising therapy for various pathological conditions. Genetically modified pig MSC have been demonstrated to downregulate the human T‐cell response to pig antigens in vitro. Before genetically modified pig MSC can be used clinically, however, evidence needs to be provided to indicate whether they will survive in a human (xenogeneic) host.Literature Search and Results: A literature search through the end of 2011 identified 94 reports of the in vivo cross‐species administration of MSC in a variety of experimental models. The majority (n = 89) involved the use of human MSC in various other species, with an occasional study using pig, rat, or guinea‐pig MSC. When human MSC were used, they were largely derived from the bone marrow, adipose tissue, or umbilical cord blood. The routes of administration were varied, although almost half of the studies utilized the intravenous route. In 88 experiments (93.6%), there was evidence that the MSC engrafted and functioned across the species barrier, and in only six cases (6.4%) was there evidence of failure to function. Importantly, MSC function was confirmed in several different cross‐species models. For example, human MSC functioned in no fewer than seven different recipient species.Conclusions: The data provided by this literature search strengthen the hypothesis that pig MSC will function satisfactorily in a different species, for example, humans. The data also suggest that our own in vitro observations on the efficacy of pig MSC in downregulating the strength of the human T‐cell response to pig antigens will likely be reproduced in vivo in pre‐clinical large animal models and in clinical trials.
PS12 Diabetes and Pre-Diabetes Prevalence Rates in the Survey of Lifestyles, Attitude and Nutrition (Slan) in the Republic of Ireland
Authors: Buckley CM , Kearney PM , McHugh S , Harrington J , Bradley CP , Perry IJ 
Published: September 2012

BackgroundTo date estimates of the prevalence of diabetes in Ireland have been based on models of UK data. Since 2009 the International Expert Committee has recommended that the diagnosis of diabetes and pre-diabetes can be made on the basis of HbA1c levels. The objectives of this study are to estimate the prevalence of diabetes and pre-diabetes in a nationally representative sample of adults living in private households in Ireland and to assess whether the discrepancy between self-report and objective diabetes status is influenced by socio-demographic characteristics.MethodsEstimates were based on a nationally representative sample of participants in the Survey of Lifestyles, Attitude and Nutrition (SLAN) whom provided a blood sample at the physical examination. Diabetes was diagnosed based on an HbA1C level ≥6.5% or self-report of occurrence of diabetes or reporting of diabetes medications. Pre-diabetes was diagnosed based on HbA1c level ≥5.7% and <6.5% and no self-report of diabetes or diabetes medications. Prevalences are reported with their 95% confidence intervals. Comparisons between men and women were carried out using the design-adjusted chi2test. A p-value of less than 0.05 was considered statistically significant.ResultsThe overall response rate among eligible adults (18+ years) was 62% for the main survey (n=10,364) and 66% for the physical examination substudy (aged 45+, n=1202). Among the 1202 participants who underwent a physical examination, 8 were excluded because they did not complete the questions on diabetes history and 65 were excluded from the analysis because they did not have HbA1c measurements. Among the remaining 1132 participants, 54 had diagnosed diabetes and 34 had undiagnosed diabetes based on HbA1c levels. Based on the HbA1c threshold, prediabetes was found in 214 individuals. The overall prevalence of diabetes was 7.7% (95% CI 6.2–9.4) and of pre-diabetes was 18.7% (95% CI 16.5–21). Prevalence of both diabetes and pre-diabetes were higher among men than women. A logistic regression model was used to investigate risk factors for undiagnosed diabetes.ConclusionThe prevalence of diabetes and pre-diabetes in this study is high. Pre-diabetes is a well-established risk factor for progression to diabetes and of cardiovascular disease. Despite efforts to increase awareness and screening for diabetes, some individuals with diabetes remain undiagnosed. Undiagnosed diabetes is highest in younger men (46–64 years). Increased efforts are required to improve detection of diabetes and pre-diabetes and thus, identify and manage this high-risk population.
The Role of Mesoscale Convective Complexes in Southern Africa Summer Rainfall
Authors: Blamey R. C. , Reason C. J. C. 
Published: September 2012

AbstractA combination of numerous factors, including geographic position, regional orography, and local sea surface temperatures, means that subtropical southern Africa experiences considerable spatial and temporal variability in rainfall and is prone to both frequent flooding and drought events. One system that may contribute to rainfall variability in the region is the mesoscale convective complex (MCC). In this study, Tropical Rainfall Measuring Mission (TRMM) Multisatellite Precipitation Analysis (TMPA) data is used to document the precipitation produced by MCCs over southern Africa for the 1998–2006 period.Most of the rainfall associated with MCCs is found to occur over central Mozambique, extending southward to eastern South Africa. High precipitation totals associated with these systems also occur over the neighboring southwest Indian Ocean, particularly off the northeast coast of South Africa. MCCs are found to contribute up to 20% of the total summer rainfall (November–March) in parts of the eastern region of southern Africa. If the month of March is excluded from the analysis, then the contribution increases up to 24%. In general, the MCC summer rainfall contribution for most of the eastern region is approximately between 8% and 16%. Over the western interior and Botswana and Namibia, the MCC contribution is much less (&lt;6%). It is also evident that there is considerable interannual variability associated with the contribution that these systems make to the total warm season rainfall.
Efficient experimental design and analysis strategies for the detection of differential expression using RNA-Sequencing
Authors: Robles José A , Qureshi Sumaira E , Stephen Stuart J , Wilson Susan R , Burden Conrad J , Taylor Jennifer M 
Published: September 2012

Abstract

Background
RNA sequencing (RNA-Seq) has emerged as a powerful approach for the detection of differential gene expression with both high-throughput and high resolution capabilities possible depending upon the experimental design chosen. Multiplex experimental designs are now readily available, these can be utilised to increase the numbers of samples or replicates profiled at the cost of decreased sequencing depth generated per sample. These strategies impact on the power of the approach to accurately identify differential expression. This study presents a detailed analysis of the power to detect differential expression in a range of scenarios including simulated null and differential expression distributions with varying numbers of biological or technical replicates, sequencing depths and analysis methods.

Results
Differential and non-differential expression datasets were simulated using a combination of negative binomial and exponential distributions derived from real RNA-Seq data. These datasets were used to evaluate the performance of three commonly used differential expression analysis algorithms and to quantify the changes in power with respect to true and false positive rates when simulating variations in sequencing depth, biological replication and multiplex experimental design choices.

Conclusions
This work quantitatively explores comparisons between contemporary analysis tools and experimental design choices for the detection of differential expression using RNA-Seq. We found that the DESeq algorithm performs more conservatively than edgeR and NBPSeq. With regard to testing of various experimental designs, this work strongly suggests that greater power is gained through the use of biological replicates relative to library (technical) replicates and sequencing depth. Strikingly, sequencing depth could be reduced as low as 15% without substantial impacts on false positive or true positive rates.
Quantitative global and gene-specific promoter methylation in relation to biological properties of neuroblastomas
Authors: Kiss Nimrod B , Kogner Per , Johnsen John Inge , Martinsson Tommy , Larsson Catharina , Geli Janos 
Published: September 2012

AbstractBackgroundIn this study we aimed to quantify tumor suppressor gene (TSG) promoter methylation densities levels in primary neuroblastoma tumors and cell lines. A subset of these TSGs is associated with a CpG island methylator phenotype (CIMP) in other tumor types.MethodsThe study panel consisted of 38 primary tumors, 7 established cell lines and 4 healthy references. Promoter methylation was determined by bisulphate Pyrosequencing for 14 TSGs; andLINE-1repeat element methylation was used as an indicator of global methylation levels.ResultsOverall mean TSG Z-scores were significantly increased in cases with adverse outcome, but were unrelated to globalLINE-1methylation. CIMP with hypermethylation of three or more gene promoters was observed in 6/38 tumors and 7/7 cell lines. Hypermethylation of one or more TSG (comprising TSGsBLU,CASP8,DCR2,CDH1,RASSF1Aand RASSF2) was evident in 30/38 tumors. By contrast only very low levels of promoter methylation were recorded forAPC,DAPK1,NORE1A,P14,P16,TP73,PTENandRARB. Similar involvements of methylation instability were revealed between cell line models and neuroblastoma tumors. Separate analysis of two proposedCASP8regulatory regions revealed frequent and significant involvement of CpG sites between exon 4 and 5, but modest involvement of the exon 1 region.Conclusions/significanceThe results highlight the involvement of TSG methylation instability in neuroblastoma tumors and cell lines using quantitative methods, support the use of DNA methylation analyses as a prognostic tool for this tumor type, and underscore the relevance of developing demethylating therapies for its treatment.