447 research outputs found
Genetic Association of rs1021188 and DNA Methylation Signatures of TNFSF11 in the Risk of Conductive Hearing Loss
Otosclerosis (OTSC) is a complex bone disorder of the otic capsule, which causes conductive hearing impairment in human adults. The dysregulation of the signaling axis mediated by the receptor activator of nuclear factor-kappa-B (RANK), RANK ligand (RANKL), and osteoprotegerin has been widely attributed to the context of metabolic bone disorders. While genetic associations and epigenetic alterations in the TNFSF11 gene (RANKL) have been well-linked to metabolic bone diseases of the skeleton, particularly osteoporosis, they have never been addressed in OTSC. This study aimed to assess whether the genetic association of rs1021188 polymorphism in the upstream of TNFSF11 and the DNA methylation changes in its promoter CpG-region reveal the susceptibility of OTSC. Peripheral blood DNA samples were collected from unrelated Tunisian-North African subjects for genotyping (109 cases and 120 controls) and for DNA methylation analysis (40 cases and 40 controls). The gender-stratified analysis showed that the TNFSF11 rs1021188 C/T was associated with OTSC in men (p = 0.023), but not in women (p = 0.458). Individuals with CC genotype were more susceptible to OTSC, suggesting an increased risk to disease development. Using publicly available data, the rs1021188 was within a cluster grouping the subpopulations with African ethnicity. Moreover, 26 loci in the TNFSF11 gene were in linkage disequilibrium with rs1021188, revealing relative similarities between different populations. Significant differences in both DNA methylation and unmethylation status were detected with 4.53- and 4.83-fold decreases in the global DNA methylation levels in female and male OTSC groups, respectively. These changes could contribute to an increased risk of OTSC development. Bioinformatic analyses indicated that each of the rs1021188 variations and the DNA methylation changes in the promoter CpG-sites within TNFSF11 may play an important role in its transcription regulation. To our knowledge, this is the first study that investigates an independent effect of the rs1021188 polymorphism and DNA hypomethylation of TNFSF11 promoter in OTSC. Genetic and epigenetic changes in the regulatory regions of TNFSF11 could offer new molecular insights into the understanding of the complexity of OTSC
Frequency and genome load of Epstein-Barr virus in 509 breast cancers from different geographical areas
Since the few data exploring a possible association between Epstein–Barr virus (EBV) and breast cancer are conflicting, we investigated this association together with the influences of geographical areas. 509 breast cancers were sampled from areas with varying risks of nasopharynx carcinoma (NPC) such as North Africa (Algeria and Tunisia, high-risk area); southern France (Marseille, intermediate-risk area); and northern Europe (northern France, the Netherlands and Denmark; low-risk areas). Polymerase chain reaction (PCR) of a subregion of EBV BamHIC encoding the EBERs demonstrated that 31.8% of the tumours contained the viral genome. No significant differences were observed among the geographical areas. However, positive samples showed higher loads of the EBV genome in the NPC high- and intermediate-risk areas than in the low-risk areas. EBV type 1 was the dominant strain. In situ hybridization studies using a35S-labelled riboprobe for EBER1 and a laser capture microdissection, combined with quantitative PCR, showed that EBV localization was restricted to some tumour epithelial cell clusters. EBV could not be detected in the stroma. Considering the whole population covered, the presence of the EBV genome was not correlated with age, menopausal status, tumour, size, nodal status or histological grade. © 2001 Cancer Research Campaign http://www. bjcancer.co
Asymptotic analysis for radial sign-changing solutions of the Brezis-Nirenberg problem in low dimensions
We consider the classical Brezis-Nirenberg problem in the unit ball of
, and analyze the asymptotic behavior of nodal radial
solutions in the low dimensions as the parameter converges to some
limit value which naturally arises from the study of the associated ordinary
differential equation
Blow-up solutions for linear perturbations of the Yamabe equation
For a smooth, compact Riemannian manifold (M,g) of dimension N \geg 3, we
are interested in the critical equation where \Delta_g is the Laplace--Beltrami
operator, S_g is the Scalar curvature of (M,g), , and
is a small parameter
Molecular analysis of HBV genotypes and subgenotypes in the Central-East region of Tunisia
<p>Abstract</p> <p>Background</p> <p>In Tunisia, country of intermediate endemicity for Hepatitis B virus (HBV) infection, most molecular studies on the virus have been carried out in the North of the country and little is known about other regions. The aim of this study was to determine HBV genotype and subgenotypes in Central-East Tunisia. A total of 217 HBs antigen positive patients were enrolled and determination of genotype was investigated in 130 patients with detectable HBV DNA. HBV genotyping methods were: PCR-RFLP on the pre-S region, a PCR using type-specific primers in the S region (TSP-PCR) and partial sequencing in the pre-S region.</p> <p>Results</p> <p>Three genotypes (D, B and A) were detected by the PCR-RFLP method and two (D and A) with the TSP-PCR method, the concordance between the two methods was 93%. Sequencing and phylogenetic analysis of 32 strains, retrieved the same genotype (D and A) for samples with concordant results and genotype D for samples with discordant results. The sequences of discordant genotypes had a restriction site in the pre-S gene which led to erroneous result by the PCR-RFLP method. Thus, prevalence of genotype D and A was 96% and 4%, respectively. Phylogenetic analysis showed the predominance of two subgenotypes D1 (55%) and D7 (41%). Only one strain clustered with D3 subgenotype (3%).</p> <p>Conclusions</p> <p>Predominance of subgenotype D7 appears to occur in northern regions of Africa with transition to subgenotype D1 in the East of the continent. HBV genetic variability may lead to wrong results in rapid genotyping methods and sequence analysis is needed to clarify atypical results.</p
Après une décennie de « buzz » : quelle pertinence pour le concept de modèle d’affaires en stratégie?
Une dizaine d’années après la renaissance manifeste de l’intérêt des praticiens, puis des chercheurs, pour le concept de modèle d’affaires (business model), la question de sa pertinence au regard des concepts et des outils existants en stratégie persiste. Concept polysémique? Concept « valise »? Concept utile? Concept durable? Autant de questions qui, au-delà de la popularité du concept, nous invitent à porter un regard à la fois critique et constructif sur le modèle d’affaires dans le champ du management stratégique.Alors que notre pratique d’enseignement de la stratégie et d’accompagnement de projets d’innovation nous amenait à questionner la pertinence du concept/outil du modèle d’affaires, il nous sembla qu’un tour de table s’imposait pour tenter de répondre aux questions soulevées. Ce tour de table s’est tenu le 8 juin 2011 lors de la XXe conférence de l’Association Internationale de Management Stratégique (AIMS) à Nantes. Ce petit ouvrage a pour but de faire partager au lecteur l’intégralité des propos échangés ce jour-là
Aerodynamic investigations of ventilated brake discs.
The heat dissipation and performance of a ventilated brake disc strongly depends
on the aerodynamic characteristics of the flow through the rotor passages. The
aim of this investigation was to provide an improved understanding of ventilated
brake rotor flow phenomena, with a view to improving heat dissipation, as well
as providing a measurement data set for validation of computational fluid
dynamics methods. The flow fields at the exit of four different brake rotor
geometries, rotated in free air, were measured using a five-hole pressure probe
and a hot-wire anemometry system. The principal measurements were taken using
two-component hot-wire techniques and were used to determine mean and unsteady
flow characteristics at the exit of the brake rotors. Using phase-locked data
processing, it was possible to reveal the spatial and temporal flow variation
within individual rotor passages. The effects of disc geometry and rotational
speed on the mean flow, passage turbulence intensity, and mass flow were
determined. The rotor exit jet and wake flow were clearly observed as
characterized by the passage geometry as well as definite regions of high and
low turbulence. The aerodynamic flow characteristics were found to be reasonably
independent of rotational speed but highly dependent upon rotor geometry
Influence of plasma turbulence on microwave propagation
It is not fully understood how electromagnetic waves propagate through plasma
density fluctuations when the size of the fluctuations is comparable with the
wavelength of the incident radiation. In this paper, the perturbing effect of a
turbulent plasma density layer on a traversing microwave beam is simulated with
full-wave simulations. The deterioration of the microwave beam is calculated as
a function of the characteristic turbulence structure size, the turbulence
amplitude, the depth of the interaction zone and the size of the waist of the
incident beam. The maximum scattering is observed for a structure size on the
order of half the vacuum wavelength. The scattering and beam broadening was
found to increase linearly with the depth of the turbulence layer and
quadratically with the fluctuation strength. Consequences for experiments and
3D effects are considered.Comment: 16 pages, 13 figures. This is an author-created, un-copyedited
version of an article submitted for publication in Plasma Physics and
Controlled Fusion. IoP Publishing Ltd is not responsible for any errors or
omissions in this version of the manuscript or any version derived from i
Review article: MHD wave propagation near coronal null points of magnetic fields
We present a comprehensive review of MHD wave behaviour in the neighbourhood
of coronal null points: locations where the magnetic field, and hence the local
Alfven speed, is zero. The behaviour of all three MHD wave modes, i.e. the
Alfven wave and the fast and slow magnetoacoustic waves, has been investigated
in the neighbourhood of 2D, 2.5D and (to a certain extent) 3D magnetic null
points, for a variety of assumptions, configurations and geometries. In
general, it is found that the fast magnetoacoustic wave behaviour is dictated
by the Alfven-speed profile. In a plasma, the fast wave is focused
towards the null point by a refraction effect and all the wave energy, and thus
current density, accumulates close to the null point. Thus, null points will be
locations for preferential heating by fast waves. Independently, the Alfven
wave is found to propagate along magnetic fieldlines and is confined to the
fieldlines it is generated on. As the wave approaches the null point, it
spreads out due to the diverging fieldlines. Eventually, the Alfven wave
accumulates along the separatrices (in 2D) or along the spine or fan-plane (in
3D). Hence, Alfven wave energy will be preferentially dissipated at these
locations. It is clear that the magnetic field plays a fundamental role in the
propagation and properties of MHD waves in the neighbourhood of coronal null
points. This topic is a fundamental plasma process and results so far have also
lead to critical insights into reconnection, mode-coupling, quasi-periodic
pulsations and phase-mixing.Comment: 34 pages, 5 figures, invited review in Space Science Reviews => Note
this is a 2011 paper, not a 2010 pape
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