Consistent Interactions between Gauge Fields and Local BRST Cohomology : The Example of Yang-Mills Models

Recent results on the cohomological reformulation of the problem of consistent interactions between gauge fields are illustrated in the case of the Yang-Mills models. By evaluating the local BRST cohomology through descent equation techniques, it is shown (i) that there is a unique local, Poincar\'e invariant cubic vertex for free gauge vector fields which preserves the number of gauge symmetries to first order in the coupling constant; and (ii) that consistency to second order in the coupling constant requires the structure constants appearing in the cubic vertex to fulfill the Jacobi identity. The known uniqueness of the Yang-Mills coupling is therefore rederived through cohomological arguments.Comment: 6 pages in LaTeX, ULB-PMIF/930

Reciprocal knock-in mice to investigate the functional redundancy of lamin B1 and lamin B2.

Lamins B1 and B2 (B-type lamins) have very similar sequences and are expressed ubiquitously. In addition, both Lmnb1- and Lmnb2-deficient mice die soon after birth with neuronal layering abnormalities in the cerebral cortex, a consequence of defective neuronal migration. The similarities in amino acid sequences, expression patterns, and knockout phenotypes raise the question of whether the two proteins have redundant functions. To investigate this topic, we generated "reciprocal knock-in mice"-mice that make lamin B2 from the Lmnb1 locus (Lmnb1(B2/B2)) and mice that make lamin B1 from the Lmnb2 locus (Lmnb2(B1/B1)). Lmnb1(B2/B2) mice produced increased amounts of lamin B2 but no lamin B1; they died soon after birth with neuronal layering abnormalities in the cerebral cortex. However, the defects in Lmnb1(B2/B2) mice were less severe than those in Lmnb1-knockout mice, indicating that increased amounts of lamin B2 partially ameliorate the abnormalities associated with lamin B1 deficiency. Similarly, increased amounts of lamin B1 in Lmnb2(B1/B1) mice did not prevent the neurodevelopmental defects elicited by lamin B2 deficiency. We conclude that lamins B1 and B2 have unique roles in the developing brain and that increased production of one B-type lamin does not fully complement loss of the other

The hidden costs of dietary restriction: Implications for its evolutionary and mechanistic origins

Dietary restriction (DR) extends life span across taxa. Despite considerable research, universal mechanisms of DR have not been identified, limiting its translational potential. Guided by the conviction that DR evolved as an adaptive, pro-longevity physiological response to food scarcity, biomedical science has interpreted DR as an activator of pro-longevity molecular pathways. Current evolutionary theory predicts that organisms invest in their soma during DR, and thus when resource availability improves, should outcompete rich-fed controls in survival and/or reproduction. Testing this prediction in Drosophila melanogaster (N > 66,000 across 11 genotypes), our experiments revealed substantial, unexpected mortality costs when flies returned to a rich diet following DR. The physiological effects of DR should therefore not be interpreted as intrinsically pro-longevity, acting via somatic maintenance. We suggest DR could alternatively be considered an escape from costs incurred under nutrient-rich conditions, in addition to costs associated with DR

Palmoplantar keratoderma along with neuromuscular and metabolic phenotypes in Slurp1-deficient mice.

Mutations in SLURP1 cause mal de Meleda, a rare palmoplantar keratoderma (PPK). SLURP1 is a secreted protein that is expressed highly in keratinocytes but has also been identified elsewhere (e.g., spinal cord neurons). Here, we examined Slurp1-deficient mice (Slurp1(-/-)) created by replacing exon 2 with β-gal and neo cassettes. Slurp1(-/-) mice developed severe PPK characterized by increased keratinocyte proliferation, an accumulation of lipid droplets in the stratum corneum, and a water barrier defect. In addition, Slurp1(-/-) mice exhibited reduced adiposity, protection from obesity on a high-fat diet, low plasma lipid levels, and a neuromuscular abnormality (hind-limb clasping). Initially, it was unclear whether the metabolic and neuromuscular phenotypes were due to Slurp1 deficiency, because we found that the targeted Slurp1 mutation reduced the expression of several neighboring genes (e.g., Slurp2, Lypd2). We therefore created a new line of knockout mice (Slurp1X(-/-) mice) with a simple nonsense mutation in exon 2. The Slurp1X mutation did not reduce the expression of adjacent genes, but Slurp1X(-/-) mice exhibited all of the phenotypes observed in the original line of knockout mice. Thus, Slurp1 deficiency in mice elicits metabolic and neuromuscular abnormalities in addition to PPK

The client satisfaction with device: a Rasch validation of the Arabic version in patients with upper and lower limb amputation

BACKGROUND: The Client Satisfaction with Devices (CSD) module of the Orthotics and Prosthetics Users' Survey is an extensively used questionnaire that measures patients' satisfaction with orthosis and prosthesis. However, the validated version for Arabic speakers (CSD-Ar) is only applicable for orthosis users. OBJECTIVES: The aim of this study was to evaluate the psychometric proprieties of the CSD-Ar for prosthetics users. METHODS: The study used a convenience sample of prosthesis users from Saudi Arabia and Turkey (N\u2009=\u2009183), who completed the CSD-Ar. The collected data were analysed using Rasch analysis to evaluate item fit, reliability indices, item difficulty, local item dependency, and differential item functioning (DIF) using WINSTEPS version 4.6.1. RESULTS: Based on the analysis, the four-response Likert-scale was acceptable, as shown by the category functioning test, All eight items did achieve a fit to the Rasch Model [(infit) and (outfit) mean-square 0.75 to 1.3]. Person separation reliability was 0.76, and item separation reliability was 0.94. A principal component analysis (PCA) showed satisfactory unidimensionality and no local item dependency. The DIF analysis showed no notable dependency among items on participant characteristics in terms of age, gender, duration of use, country, and level of amputation. CONCLUSION: This study contributes to the confidence of using CSD-Ar to evaluate users' satisfaction with different prostheses, affirming the need for further refinement of the quality of the outcome measure

Regulation of fibroblast growth factor receptor signalling and trafficking by Src and Eps8

Fibroblast growth factor receptors (FGFRs) mediate a wide spectrum of cellular responses that are crucial for development and wound healing. However, aberrant FGFR activity leads to cancer. Activated growth factor receptors undergo stimulated endocytosis, but can continue to signal along the endocytic pathway. Endocytic trafficking controls the duration and intensity of signalling, and growth factor receptor signalling can lead to modifications of trafficking pathways. We have developed live-cell imaging methods for studying FGFR dynamics to investigate mechanisms that coordinate the interplay between receptor trafficking and signal transduction. Activated FGFR enters the cell following recruitment to pre-formed clathrin-coated pits (CCPs). However, FGFR activation stimulates clathrin-mediated endocytosis; FGF treatment increases the number of CCPs, including those undergoing endocytosis, and this effect is mediated by Src and its phosphorylation target Eps8. Eps8 interacts with the clathrin-mediated endocytosis machinery and depletion of Eps8 inhibits FGFR trafficking and immediate Erk signalling. Once internalized, FGFR passes through peripheral early endosomes en route to recycling and degredative compartments, through an Src- and Eps8-dependent mechanism. Thus Eps8 functions as a key coordinator in the interplay between FGFR signalling and trafficking. This work provides the first detailed mechanistic analysis of growth factor receptor clustering at the cell surface through signal transduction and endocytic trafficking. As we have characterised the Src target Eps8 as a key regulator of FGFR signalling and trafficking, and identified the early endocytic system as the site of Eps8-mediated effects, this work provides novel mechanistic insight into the reciprocal regulation of growth factor receptor signalling and trafficking

Flavor Structure in F-theory Compactifications

F-theory is one of frameworks in string theory where supersymmetric grand unification is accommodated, and all the Yukawa couplings and Majorana masses of right-handed neutrinos are generated. Yukawa couplings of charged fermions are generated at codimension-3 singularities, and a contribution from a given singularity point is known to be approximately rank 1. Thus, the approximate rank of Yukawa matrices in low-energy effective theory of generic F-theory compactifications are minimum of either the number of generations N_gen = 3 or the number of singularity points of certain types. If there is a geometry with only one E_6 type point and one D_6 type point over the entire 7-brane for SU(5) gauge fields, F-theory compactified on such a geometry would reproduce approximately rank-1 Yukawa matrices in the real world. We found, however, that there is no such geometry. Thus, it is a problem how to generate hierarchical Yukawa eigenvalues in F-theory compactifications. A solution in the literature so far is to take an appropriate factorization limit. In this article, we propose an alternative solution to the hierarchical structure problem (which requires to tune some parameters) by studying how zero mode wavefunctions depend on complex structure moduli. In this solution, the N_gen x N_gen CKM matrix is predicted to have only N_gen entries of order unity without an extra tuning of parameters, and the lepton flavor anarchy is predicted for the lepton mixing matrix. We also obtained a precise description of zero mode wavefunctions near the E_6 type singularity points, where the up-type Yukawa couplings are generated.Comment: 148 page

Extending and validating a human papillomavirus (HPV) knowledge measure in a national sample of Canadian parents of boys

As the human papillomavirus (HPV) vaccine is now recommended for males, a reliable, comprehensive HPV knowledge measurement tool which addresses issues relevant to males is needed. We aimed to replicate, validate and test the comprehensiveness of an existing general HPV and an HPV vaccination knowledge scale in English and French. We also measured parental HPV knowledge and changes over time. An online questionnaire was administered in February (Time 1; T1) and November 2014 (Time 2; T2) to a nationally representative sample of Canadian parents of boys. Dimensionality, internal consistency and model fit were evaluated at both time points and separately in English and French sub-samples. Differences in knowledge scores were measured. Analyses were performed on 3117 participants at T1 and 1427 at T2. The 25-item HPV general knowledge and an 11-item HPV vaccination scale were unidimensional, showed high internal consistency (α>0.87, α>0.73) and had good model fit. Both general HPV and vaccine-specific knowledge significantly increased over time in both languages, but remained low at T2, with only about half of the items being answered correctly. Correct responses at T2 are best explained by correct responses at T1, with some small changes from 'Don't know' at T1 to correct at T2. The extended general and vaccine-specific knowledge scales are valid, reliable and comprehensive, and could be used among parents of boys, in both English and French. Educational interventions could target specific knowledge gaps and focus on providing information rather than correcting misconceptions

Play it Again: Evolved Audio Effects and Synthesizer Programming

Automatic programming of sound synthesizers and audio devices to match a given, desired sound is examined and a Genetic Algorithm (GA) that functions independent of specific synthesis techniques is proposed. Most work in this area has focused on one synthesis model or synthesizer, designing the GA and tuning the operator parameters to obtain optimal results. The scope of such inquiries has been limited by available computing power, however current software (Ableton Live, herein) and commercially available hardware is shown to quickly find accurate solutions, promising a practical application for music creators. Both software synthesizers and audio effects processors are examined, showing a wide range of performance times (from seconds to hours) and solution accuracy, based on particularities of the target devices. Random oscillators, phase synchronizing, and filters over empty frequency ranges are identified as primary challenges for GA based optimization

Anthropometric measurements of the orbita and gender prediction with three-dimensional computed tomography images

Background: The aim of the study was to investigate the orbital anthropometric variations in the normal population using three-dimensional computed tomography (3D-CT) images and to define the effects of age and gender on orbital anthropometry.Materials and methods: Three-dimensional orbita CT of 280 patients, obtained for various reasons, were retrospectively evaluated in 772-bed referral and tertiary-care hospital between April 2011 and June 2012. Using 3D images, orbital width, height, biorbital-interorbital diameter and orbital index were measured. Measurements were obtained comparing right and left sides and male to female. The relation of the results with age and gender was analysed.Results: Right orbit was found to be wider than left (p < 0.0001). Male patients had wider (p < 0.0001) and higher (p = 0.0001) orbits. Right orbital index was found to be smaller than the left one (p = 0.005). No differences were found between the genders in terms of right and left orbital indexes (p > 0.05). Biorbital (p < 0.0001) and interorbital (p = 0.01) widths were found to be higher in males. There was no relation between the age change and the parameters defined (p > 0.05).Conclusions: No relation was found between age and orbital measurements. It was concluded that orbital images obtained with 3D-CT may be used as a method for gender evaluation