Perturbation Theory with a Variational Basis: the Generalized Gaussian Effective Potential

The perturbation theory with a variational basis is constructed and analyzed.The generalized Gaussian effective potential is introduced and evaluated up to the second order for selfinteracting scalar fields in one and two spatial dimensions. The problem of the renormalization of the mass is discussed in details. Thermal corrections are incorporated. The comparison between the finite temperature generalized Gaussian effective potential and the finite temperature effective potential is critically analyzed. The phenomenon of the restoration at high temperature of the symmetry broken at zero temperature is discussed.Comment: RevTex, 49 pages, 16 eps figure

Identification of the NF-κB activating protein-like locus as a risk locus for rheumatoid arthritis

Objective: To fine-map the NF-κB activating protein-like (NKAPL) locus identified in a prior genome-wide study as a possible rheumatoid arthritis (RA) risk locus and thereby delineate additional variants with stronger and/or independent disease association. Methods: Genotypes for 101 SNPs across the NKAPL locus on chromosome 6p22.1 were obtained on 1368 Canadian RA cases and 1471 controls. Single marker associations were examined using logistic regression and the most strongly associated NKAPL locus SNPs then typed in another Canadian and a US-based RA case/control cohort. Results: Fine-mapping analyses identified six NKAPL locus variants in a single haplotype block showing association with p≤5.6×10−8 in the combined Canadian cohort. Among these SNPs, rs35656932 in the zinc finger 193 gene and rs13208096 in the NKAPL gene remained significant after conditional logistic regression, contributed independently to risk for disease, and were replicated in the US cohort (Pcomb=4.24×10−10 and 2.44×10−9, respectively). These associations remained significant after conditioning on SNPs tagging the HLA-shared epitope (SE) DRB1*0401 allele and were significantly stronger in the HLA-SE negative versus positive subgroup, with a significant negative interaction apparent between HLA-DRB1 SE and NKAPL risk alleles. Conclusions: By illuminating additional NKAPL variants with highly significant effects on risk that are distinct from, but interactive with those arising from the HLA-DRB1 locus, our data conclusively identify NKAPL as an RA susceptibility locus

An Assessment of Geophysical Survey Techniques for Characterising the Subsurface Around Glacier Margins, and Recommendations for Future Applications

Geophysical surveys provide an efficient and non-invasive means of studying subsurface conditions in numerous sedimentary settings. In this study, we explore the application of three geophysical methods to a proglacial environment, namely ground penetrating radar (GPR), seismic refraction and multi-channel analysis of surface waves (MASW). We apply these geophysical methods to three glacial landforms with contrasting morphologies and sedimentary characteristics, and we use the various responses to assess the applicability and limitations of each method for these proglacial targets. Our analysis shows that GPR and seismic (refraction and MASW) techniques can provide spatially extensive information on the internal architecture and composition of moraines, but careful survey designs are required to optimise data quality in these geologically complex environments. Based on our findings, we define a number of recommendations and a potential workflow to guide future geophysical investigations in analogous settings. We recommend the initial use of GPR in future studies of proglacial environments to inform (a) seismic survey design and (b) the selection of seismic interpretation techniques. We show the benefits of using multiple GPR antenna frequencies (e.g., 25 and 100 MHz) to provide decimetre scale imaging in the near surface (e.g., < 15 m) while also enabling signal penetration to targets at up to ∼40 m depth (e.g., bedrock). This strategy helps to circumvent changes in radar signal penetration resulting from variations in substrate conductivity or abundant scatterers. Our study also demonstrates the importance of combining multiple geophysical methods together with ground-truthing through sedimentological observations to reduce ambiguity in interpretations. Implementing our recommendations will improve geophysical survey practice in the field of glacial geology and allow geophysical methods to play an increasing role in the interpretation of glacial landforms and sediments.publishedVersio

Sulfation patterns of glycosaminoglycans encode molecular recognition and activity

Although glycosaminoglycans contribute to diverse physiological processes, an understanding of their molecular mechanisms has been hampered by the inability to access homogeneous glycosaminoglycan structures. Here, we assembled well-defined chondroitin sulfate oligosaccharides using a convergent, synthetic approach that permits installation of sulfate groups at precise positions along the carbohydrate backbone. Using these defined structures, we demonstrate that specific sulfation motifs function as molecular recognition elements for growth factors and modulate neuronal growth. These results provide both fundamental insights into the role of sulfation and direct evidence for a 'sulfation code' whereby glycosaminoglycans encode functional information in a sequence-specific manner analogous to that of DNA, RNA and proteins

Entanglement-assisted quantum low-density parity-check codes

This paper develops a general method for constructing entanglement-assisted quantum low-density parity-check (LDPC) codes, which is based on combinatorial design theory. Explicit constructions are given for entanglement-assisted quantum error-correcting codes (EAQECCs) with many desirable properties. These properties include the requirement of only one initial entanglement bit, high error correction performance, high rates, and low decoding complexity. The proposed method produces infinitely many new codes with a wide variety of parameters and entanglement requirements. Our framework encompasses various codes including the previously known entanglement-assisted quantum LDPC codes having the best error correction performance and many new codes with better block error rates in simulations over the depolarizing channel. We also determine important parameters of several well-known classes of quantum and classical LDPC codes for previously unsettled cases.Comment: 20 pages, 5 figures. Final version appearing in Physical Review

The Radio Properties of Composite LINER/HII Galaxies

Arcsec-resolution VLA observations -- newly obtained as well as published -- of 40 nearby galaxies are discussed, completing a study of the radio properties of a magnitude-limited sample of nearby galaxies of the composite LINER/HII type. Our results reveal an overall detection rate of at least 25% AGN candidates among these composite sources. The general properties of these AGN candidates, as compared to non-AGN composite sources and HII galaxies, are discussed.Comment: Accepted for publication in ApJ

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Antonio Gramsci’s impact on critical pedagogy

This paper provides an account of Antonio Gramsci’s impact on the area of critical pedagogy. It indicates the Gramscian influence on the thinking of major exponents of the field. It foregrounds Gramsci's ideas and then indicates how they have been taken up by a selection of critical pedagogy exponents who were chosen on the strength of their identification and engagement with Gramsci's ideas, some of them even having written entire essays on Gramsci. The essay concludes with a discussion concerning an aspect of Gramsci's concerns, the question of powerful knowledge, which, in the present author's view, provides a formidable challenge to critical pedagogues.peer-reviewe

Objectively measured physical activity, sedentary behaviour and all-cause mortality in older men: does volume of activity matter more than pattern of accumulation?

OBJECTIVES: To understand how device-measured sedentary behaviour and physical activity are related to all-cause mortality in older men, an age group with high levels of inactivity and sedentary behaviour. METHODS: Prospective population-based cohort study of men recruited from 24 UK General Practices in 1978-1980. In 2010-2012, 3137 surviving men were invited to a follow-up, 1655 (aged 71-92 years) agreed. Nurses measured height and weight, men completed health and demographic questionnaires and wore an ActiGraph GT3x accelerometer. All-cause mortality was collected through National Health Service central registers up to 1 June 2016. RESULTS: After median 5.0 years' follow-up, 194 deaths occurred in 1181 men without pre-existing cardiovascular disease. For each additional 30 min in sedentary behaviour, or light physical activity (LIPA), or 10 min in moderate to vigorous physical activity (MVPA), HRs for mortality were 1.17 (95% CI 1.10 to 1.25), 0.83 (95% CI 0.77 to 0.90) and 0.90 (95% CI 0.84 to 0.96), respectively. Adjustments for confounders did not meaningfully change estimates. Only LIPA remained significant on mutual adjustment for all intensities. The HR for accumulating 150 min MVPA/week in sporadic minutes (achieved by 66% of men) was 0.59 (95% CI 0.43 to 0.81) and 0.58 (95% CI 0.33 to 1.00) for accumulating 150 min MVPA/week in bouts lasting ≥10 min (achieved by 16% of men). Sedentary breaks were not associated with mortality. CONCLUSIONS: In older men, all activities (of light intensity upwards) were beneficial and accumulation of activity in bouts ≥10 min did not appear important beyond total volume of activity. Findings can inform physical activity guidelines for older adults