Transforming growth factor-beta renders ageing microglia inhibitory to oligodendrocyte generation by CNS progenitors.

It is now well-established that the macrophage and microglial response to CNS demyelination influences remyelination by removing myelin debris and secreting a variety of signaling molecules that influence the behaviour of oligodendrocyte progenitor cells (OPCs). Previous studies have shown that changes in microglia contribute to the age-related decline in the efficiency of remyelination. In this study, we show that microglia increase their expression of the proteoglycan NG2 with age, and that this is associated with an altered micro-niche generated by aged, but not young, microglia that can divert the differentiation OPCs from oligodendrocytes into astrocytes in vitro. We further show that these changes in ageing microglia are generated by exposure to high levels of TGFβ. Thus, our findings suggest that the rising levels of circulating TGFβ known to occur with ageing contribute to the age-related decline in remyelination by impairing the ability of microglia to promote oligodendrocyte differentiation from OPCs, and therefore could be a potential therapeutic target to promote remyelination.This work was supported by funding from the UK Multiple Sclerosis Society, Medimmune, The Adelson Medical Research Foundation and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institut

Exact field ionization rates in the barrier suppression-regime from numerical TDSE calculations

Numerically determined ionization rates for the field ionization of atomic hydrogen in strong and short laser pulses are presented. The laser pulse intensity reaches the so-called "barrier suppression ionization" regime where field ionization occurs within a few half laser cycles. Comparison of our numerical results with analytical theories frequently used shows poor agreement. An empirical formula for the "barrier suppression ionization"-rate is presented. This rate reproduces very well the course of the numerically determined ground state populations for laser pulses with different length, shape, amplitude, and frequency. Number(s): 32.80.RmComment: Enlarged and newly revised version, 22 pages (REVTeX) + 8 figures in ps-format, submitted for publication to Physical Review A, WWW: http://www.physik.tu-darmstadt.de/tqe

Efficiency-Effectiveness Trade-offs in Recommendation Systems

Throughout the years, numerous recommendation algorithms have been developed to address the information filtering problem by leveraging users’ tastes through implicit or explicit feedback. In this paper, we present the work undertaken as part of a PhD thesis focused on exploring new evaluation dimensions centred around the efficiency-effectiveness trade-offs present in state-of-the-art recommendation systems. Firstly, we highlight the lack of efficiency-oriented studies and we formulate the research problem. Then, we propose a mapping of the design space and a classification of the recommendation algorithms/models with respect to salient attributes and characteristics. At the same time, we explain why and how assessing the recommendations on an accuracy versus training cost curve would advance the current knowledge in the area of evaluation, as well as open new research avenues for exploring parameter configurations within well-known algorithms. Finally, we make the case for a comprehensive methodology that incorporates predictive efficiency-effectiveness models, which illustrate the performance and behaviour of the recommendation systems under different recommendation tasks, while satisfying user-defined quality of service constraints and goals

Sounding Situated Knowledges - Echo in Archaeoacoustics

This article proposes that feminist epistemologies via Donna Haraway's “Situated Knowledges” can be productively brought to bear upon theories of sonic knowledge production, as “sounding situated knowledges.” Sounding situated knowledges re-reads debates around the “nature of sound” with a Harawayan notion of the “natureculture of sound.” This aims to disrupt a traditional subject-object relation which I argue has perpetuated a pervasive “sonic naturalism” in sound studies. The emerging field of archaeoacoustics (acoustic archaeology), which examines the role of sound in human behaviour in archaeology, is theorized as an opening with potentially profound consequences for sonic knowledge production which are not currently being realized. The echo is conceived as a material-semiotic articulation, which akin to Haraway's infamous cyborg, serves as a feminist figuration which enables this renegotiation. Archaeoacoustics research, read following Haraway both reflectively and diffractively, is understood as a critical juncture for sound studies which exposes the necessity of both embodiedness and situatedness for sonic knowledge production. Given the potential opened up by archaeoacoustics through the figure of echo, a critical renegotiation of the subject-object relation in sound studies is suggested as central in further developing theories of sonic knowledge production

Neural Aspects of Sentence Comprehension: Syntactic Complexity, Reversibility, and Reanalysis

Broca's area is preferentially activated by reversible sentences with complex syntax, but various linguistic factors may be responsible for this finding, including syntactic movement, working-memory demands, and post hoc reanalysis. To distinguish between these, we tested the interaction of syntactic complexity and semantic reversibility in a functional magnetic resonance imaging study of sentence–picture matching. During auditory comprehension, semantic reversibility induced selective activation throughout the left perisylvian language network. In contrast, syntactic complexity (object-embedded vs. subject-embedded relative clauses) within reversible sentences engaged only the left inferior frontal gyrus (LIFG) and left precentral gyrus. Within irreversible sentences, only the LIFG was sensitive to syntactic complexity, confirming a unique role for this region in syntactic processing. Nonetheless, larger effects of reversibility itself occurred in the same regions, suggesting that full syntactic parsing may be a nonautomatic process applied as needed. Complex reversible sentences also induced enhanced signals in LIFG and left precentral regions on subsequent picture selection, but with additional recruitment of the right hemisphere homolog area (right inferior frontal gyrus) as well, suggesting that post hoc reanalysis of sentence structure, compared with initial comprehension, engages an overlapping but larger network of brain regions. These dissociable effects may offer a basis for studying the reorganization of receptive language function after brain damage

Single nucleotide polymorphism discovery in elite north american potato germplasm

BACKGROUND: Current breeding approaches in potato rely almost entirely on phenotypic evaluations; molecular markers, with the exception of a few linked to disease resistance traits, are not widely used. Large-scale sequence datasets generated primarily through Sanger Expressed Sequence Tag projects are available from a limited number of potato cultivars and access to next generation sequencing technologies permits rapid generation of sequence data for additional cultivars. When coupled with the advent of high throughput genotyping methods, an opportunity now exists for potato breeders to incorporate considerably more genotypic data into their decision-making. RESULTS: To identify a large number of Single Nucleotide Polymorphisms (SNPs) in elite potato germplasm, we sequenced normalized cDNA prepared from three commercial potato cultivars: 'Atlantic', 'Premier Russet' and 'Snowden'. For each cultivar, we generated 2 Gb of sequence which was assembled into a representative transcriptome of (~)28-29 Mb for each cultivar. Using the Maq SNP filter that filters read depth, density, and quality, 575,340 SNPs were identified within these three cultivars. In parallel, 2,358 SNPs were identified within existing Sanger sequences for three additional cultivars, 'Bintje', 'Kennebec', and 'Shepody'. Using a stringent set of filters in conjunction with the potato reference genome, we identified 69,011 high confidence SNPs from these six cultivars for use in genotyping with the Infinium platform. Ninety-six of these SNPs were used with a BeadXpress assay to assess allelic diversity in a germplasm panel of 248 lines; 82 of the SNPs proved sufficiently informative for subsequent analyses. Within diverse North American germplasm, the chip processing market class was most distinct, clearly separated from all other market classes. The round white and russet market classes both include fresh market and processing cultivars. Nevertheless, the russet and round white market classes are more distant from each other than processing are from fresh market types within these two groups. CONCLUSIONS: The genotype data generated in this study, albeit limited in number, has revealed distinct relationships among the market classes of potato. The SNPs identified in this study will enable high-throughput genotyping of germplasm and populations, which in turn will enable more efficient marker-assisted breeding efforts in potato

Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study)

Background: Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications. The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas. Methods/design. Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma 3 cm, located between 115 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane i

Measurement of hadronic event shapes in high-p T multijet final states at √s = 13 TeV with the ATLAS detector

A measurement of event-shape variables in proton-proton collisions at large momentum transfer is presented using data collected at s = 13 TeV with the ATLAS detector at the Large Hadron Collider. Six event-shape variables calculated using hadronic jets are studied in inclusive multijet events using data corresponding to an integrated luminosity of 139 fb−1. Measurements are performed in bins of jet multiplicity and in different ranges of the scalar sum of the transverse momenta of the two leading jets, reaching scales beyond 2 TeV. These measurements are compared with predictions from Monte Carlo event generators containing leading-order or next-to-leading order matrix elements matched to parton showers simulated to leading-logarithm accuracy. At low jet multiplicities, shape discrepancies between the measurements and the Monte Carlo predictions are observed. At high jet multiplicities, the shapes are better described but discrepancies in the normalisation are observed. [Figure not available: see fulltext.