1,910 research outputs found
Selective ablation of pillar and deiters' cells severely affects cochlear postnatal development and hearing in mice.
Mammalian auditory hair cells (HCs) are inserted into a well structured environment of supporting cells (SCs) and acellular matrices. It has been proposed that when HCs are irreversibly damaged by noise or ototoxic drugs, surrounding SCs seal the epithelial surface and likely extend the survival of auditory neurons. Because SCs are more resistant to damage than HCs, the effects of primary SC loss on HC survival and hearing have received little attention. We used the Cre/loxP system in mice to specifically ablate pillar cells (PCs) and Deiters' cells (DCs). In Prox1CreER(T2)+/-;Rosa26(DTA/+) (Prox1DTA) mice, Cre-estrogen receptor (CreER) expression is driven by the endogenous Prox1 promoter and, in presence of tamoxifen, removes a stop codon in the Rosa26(DTA/+) allele and induces diphtheria toxin fragment A (DTA) expression. DTA produces cell-autonomous apoptosis. Prox1DTA mice injected with tamoxifen at postnatal days 0 (P0) and P1 show significant DC and outer PC loss at P2-P4, that reaches ∼70% by 1 month. Outer HC loss follows at P14 and is almost complete at 1 month, while inner HCs remain intact. Neural innervation to the outer HCs is disrupted in Prox1DTA mice and auditory brainstem response thresholds in adults are 40-50 dB higher than in controls. The hearing deficit correlates with loss of cochlear amplification. Remarkably, in Prox1DTA mice, the auditory epithelium preserves the ability to seal the reticular lamina and spiral ganglion neuron counts are normal, a key requirement for cochlear implant success. In addition, our results show that cochlear SC pools should be appropriately replenished during HC regeneration strategies
Holographic Kondo Model in Various Dimensions
We study the addition of localised impurities to U(N) Supersymmetric
Yang-Mills theories in (p+1)-dimensions by using the gauge/gravity
correspondence. From the gravity side, the impurities are introduced by
considering probe D(8-p)-branes extendingalong the time and radial directions
and wrapping an (7-p)-dimensional submanifold of the internal (8-p)-sphere, so
that the degrees of freedom are point-like from the gauge theory perspective.
We analyse both the configuration in which the branes generate straight flux
tubes -corresponding to actual single impurities - and the one in which
connected flux tubes are created- corresponding to dimers. We discuss the
thermodynamics of both the configurations and the related phase transition. In
particular, the specific heat of the straight flux-tube configuration is
negative for p<3, while it is never the case for the connected one. We study
the stability of the system by looking at the impurity fluctuations. Finally,
we characterise the theory by computing one- and two-point correlators of the
gauge theory operators dual to the impurity fluctuations. Because of the
underlying generalised conformal structure, such correlators can be expressed
in terms of an effective coupling constant (which runs because of its
dimensionality) and a generalised conformal dimension.Comment: 56 pages, 3 figures; v2: typos correcte
Challenges of Profile Likelihood Evaluation in Multi-Dimensional SUSY Scans
Statistical inference of the fundamental parameters of supersymmetric
theories is a challenging and active endeavor. Several sophisticated algorithms
have been employed to this end. While Markov-Chain Monte Carlo (MCMC) and
nested sampling techniques are geared towards Bayesian inference, they have
also been used to estimate frequentist confidence intervals based on the
profile likelihood ratio. We investigate the performance and appropriate
configuration of MultiNest, a nested sampling based algorithm, when used for
profile likelihood-based analyses both on toy models and on the parameter space
of the Constrained MSSM. We find that while the standard configuration is
appropriate for an accurate reconstruction of the Bayesian posterior, the
profile likelihood is poorly approximated. We identify a more appropriate
MultiNest configuration for profile likelihood analyses, which gives an
excellent exploration of the profile likelihood (albeit at a larger
computational cost), including the identification of the global maximum
likelihood value. We conclude that with the appropriate configuration MultiNest
is a suitable tool for profile likelihood studies, indicating previous claims
to the contrary are not well founded.Comment: 21 pages, 9 figures, 1 table; minor changes following referee report.
Matches version accepted by JHE
Nonthermal Emission from Star-Forming Galaxies
The detections of high-energy gamma-ray emission from the nearby starburst
galaxies M82 & NGC253, and other local group galaxies, broaden our knowledge of
star-driven nonthermal processes and phenomena in non-AGN star-forming
galaxies. We review basic aspects of the related processes and their modeling
in starburst galaxies. Since these processes involve both energetic electrons
and protons accelerated by SN shocks, their respective radiative yields can be
used to explore the SN-particle-radiation connection. Specifically, the
relation between SN activity, energetic particles, and their radiative yields,
is assessed through respective measures of the particle energy density in
several star-forming galaxies. The deduced energy densities range from O(0.1)
eV/cm^3 in very quiet environments to O(100) eV/cm^3 in regions with very high
star-formation rates.Comment: 17 pages, 5 figures, to be published in Astrophysics and Space
Science Proceeding
Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.
BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721
In vitro activities of natural products against oral Candida isolates from denture wearers
Background: Candida-associated denture stomatitis is a frequent infectious disease. Treatment of this oral condition is difficult because failures and recurrences are common. The aim of this study was to test the in vitro antifungal activity of pure constituents of essentials oils. --
Methods: Eight terpenic derivatives (carvacrol, farnesol, geraniol, linalool, menthol, menthone, terpinen-4-ol, and aterpineol), a phenylpropanoid (eugenol), a phenethyl alcohol (tyrosol) and fluconazole were evaluated against 38 Candida isolated from denture-wearers and 10 collection Candida strains by the CLSI M27-A3 broth microdilution method. -- Results: Almost all the tested compounds showed antifungal activity with MIC ranges of 0.03-0.25% for eugenol and linalool, 0.03-0.12% for geraniol, 0.06-0.5% for menthol, a-terpineol and terpinen-4-ol, 0.03-0.5% for carvacrol, and 0.06-4% for menthone. These compounds, with the exception of farnesol, menthone and tyrosol, showed important in vitro activities against the fluconazole-resistant and susceptible-dose dependent Candida isolates. -- Conclusions: Carvacrol, eugenol, geraniol, linalool and terpinen-4-ol were very active in vitro against oral Candida isolates. Their fungistatic and fungicidal activities might convert them into promising alternatives for the topic treatment of oral candidiasis and denture stomatitis.Funding: this work has been funded in part by projects GIC07 123-IT-222-07 (Departamento de Educacion, Universidades e Investigacion, Gobierno Vasco), S-PR09UN01 and S-PR10UN03 (Saiotek 2009 and 2010, Departamento de Industria, Comercio y Turismo, Gobierno Vasco)
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Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients
The RPS6KB1 gene is amplified and overexpressed in approximately 10% of breast carcinomas and has been found associated with poor prognosis. We studied the prognostic significance of P70 S6 kinase protein (PS6K) overexpression in a series of 452 node-negative premenopausal early-stage breast cancer patients (median follow-up: 10.8 years). Immunohistochemistry was used to assess PS6K expression in the primary tumour, which had previously been analysed for a panel of established prognostic factors in breast cancer. In a univariate analysis, PS6K overexpression was associated with worse distant disease-free survival as well as impaired locoregional control (HR 1.80, P 0.025 and HR 2.50, P 0.006, respectively). In a multivariate analysis including other prognostic factors, PS6K overexpression remained an independent predictor for poor locoregional control (RR 2.67, P 0.003). To our knowledge, P70 S6 kinase protein is the first oncogenic marker that has prognostic impact on locoregional control and therefore may have clinical implications in determining the local treatment strategy in early-stage breast cancer patients
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