6,289 research outputs found

    Study of resonance light scattering for remote optical probing

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    Enhanced scattering and fluorescence processes in the visible and UV were investigated which will enable improved remote measurements of gas properties. The theoretical relationship between scattering and fluorescence from an isolated molecule in the approach to resonance is examined through analysis of the time dependence of re-emitted light following excitation of pulsed incident light. Quantitative estimates are developed for the relative and absolute intensities of fluorescence and resonance scattering. New results are obtained for depolarization of scattering excited by light at wavelengths within a dissociative continuum. The experimental work was performed in two separate facilities. One of these utilizes argon and krypton lasers, single moded by a tilted etalon, and a 3/4 meter double monochromator. This facility was used to determine properties of the re-emission from NO2, I2 and O3 excited by visible light. The second facility involves a narrow-line dye laser, and a 3/4 meter single monochromator. The dye laser produces pulsed light with 5 nsec pulse duration and 0.005 nm spectral width

    Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure

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    Noise induced hearing loss (NIHL) is a disease that affects millions of Americans. Identifying genetic pathways that influence recovery from noise exposure is an important step forward in understanding NIHL. The transcription factor Foxo3 integrates the cellular response to oxidative stress and plays a role in extending lifespan in many organisms, including humans. Here we show that Foxo3 is required for auditory function after noise exposure in a mouse model system, measured by ABR. Absent Foxo3, outer hair cells are lost throughout the middle and higher frequencies. SEM reveals persistent damage to some surviving outer hair cell stereocilia. However, DPOAE analysis reveals that some function is preserved in low frequency outer hair cells, despite concomitant profound hearing loss. Inner hair cells, auditory synapses and spiral ganglion neurons are all present after noise exposure in the Foxo3KO/KO fourteen days post noise (DPN). We also report anti-Foxo3 immunofluorescence in adult human outer hair cells. Taken together, these data implicate Foxo3 and its transcriptional targets in outer hair cell survival after noise damage. An additional role for Foxo3 in preserving hearing is likely, as low frequency auditory function is absent in noise exposed Foxo3KO/KOs even though all cells and structures are present

    The identification of mitochondrial DNA variants in glioblastoma multiforme

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    Background: Mitochondrial DNA (mtDNA) encodes key proteins of the electron transfer chain (ETC), which produces ATP through oxidative phosphorylation (OXPHOS) and is essential for cells to perform specialised functions. Tumor-initiating cells use aerobic glycolysis, a combination of glycolysis and low levels of OXPHOS, to promote rapid cell proliferation and tumor growth. Glioblastoma multiforme (GBM) is an aggressively malignant brain tumor and mitochondria have been proposed to play a vital role in GBM tumorigenesis. Results: Using next generation sequencing and high resolution melt analysis, we identified a large number of mtDNA variants within coding and non-coding regions of GBM cell lines and predicted their disease-causing potential through in silico modeling. The frequency of variants was greatest in the D-loop and origin of light strand replication in non-coding regions. ND6 was the most susceptible coding gene to mutation whilst ND4 had the highest frequency of mutation. Both genes encode subunits of complex I of the ETC. These variants were not detected in unaffected brain samples and many have not been previously reported. Depletion of HSR-GBM1 cells to varying degrees of their mtDNA followed by transplantation into immunedeficient mice resulted in the repopulation of the same variants during tumorigenesis. Likewise, de novo variants identified in other GBM cell lines were also incorporated. Nevertheless, ND4 and ND6 were still the most affected genes. We confirmed the presence of these variants in high grade gliomas. Conclusions: These novel variants contribute to GBM by rendering the ETC. partially dysfunctional. This restricts metabolism to anaerobic glycolysis and promotes cell proliferation

    The effect of surface character on flows in microchannels

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    A technique for quantifying velocity profiles of fluids flowing in circular microchannels is presented. The primary purpose of this technique is to provide a robust method for quantifying the effect Of Surface character on the bulk fluid behaviour. A laser-scanning confocal microscope has been used to obtain fluorescent particle images from a 1 micron thick plane along the centreline of hydrophobic and hydrophilic glass capillaries. The velocities of fluorescent particles being carried in pressure-driven laminar flow of a Newtonian fluid have been evaluated at the centreplane of 57.5 micron capillaries using a variation of particle tracking velocimetry (PTV). This work aims to clarify inconsistencies in previously reported [1-12] slip velocities observed in water over hydrophobically modified surfaces at micron and submicron lengthscales. A change in the velocity profile is observed for water flowing in hydrophobic capillaries, although the behaviour appears to be a result of an optical distortion at the fluid-wall interface. This may point to previous suggestions of a thin layer of air adsorbing to the surface. Notwithstanding, the results do not confidently suggest evidence of slip of water on hydrophobic surfaces in microchannels

    Stratorotational instability in MHD Taylor-Couette flows

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    The stability of dissipative Taylor-Couette flows with an axial stable density stratification and a prescribed azimuthal magnetic field is considered. Global nonaxisymmetric solutions of the linearized MHD equations with toroidal magnetic field, axial density stratification and differential rotation are found for both insulating and conducting cylinder walls. Flat rotation laws such as the quasi-Kepler law are unstable against the nonaxisymmetric stratorotational instability (SRI). The influence of a current-free toroidal magnetic field depends on the magnetic Prandtl number Pm: SRI is supported by Pm > 1 and it is suppressed by Pm \lsim 1. For too flat rotation laws a smooth transition exists to the instability which the toroidal magnetic field produces in combination with the differential rotation. This nonaxisymmetric azimuthal magnetorotational instability (AMRI) has been computed under the presence of an axial density gradient. If the magnetic field between the cylinders is not current-free then also the Tayler instability occurs and the transition from the hydrodynamic SRI to the magnetic Tayler instability proves to be rather complex. Most spectacular is the `ballooning' of the stability domain by the density stratification: already a rather small rotation stabilizes magnetic fields against the Tayler instability. An azimuthal component of the resulting electromotive force only exists for density-stratified flows. The related alpha-effect for magnetic SRI of Kepler rotation appears to be positive for negative d\rho/dz <0.Comment: 10 pages, 13 figures, submitted to Astron. Astrophy

    Effect of drying on the reproducibility of DIAGNOdent to detect caries-like lesions

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    The aim of this study was to verify the drying effect on the reproducibility of DIAGNOdent (Dd) devices to detect caries-like lesions. Three areas were created in each of the 34 bovine incisors: sound (S), demineralized (DE) and remineralized (RE). One examiner measured each area with two Dd devices (denominated X and Y), twice under humid, and twice under dry condition. Intra-rater agreement according each device and inter-device agreement were estimated by kappa statistics (k). Intra-rater agreement for device Y was substantial under humid (k DE=0.68 and k RE+S=0.68) and dry condition (k DE=0.64 and k RE+S=0.67). For device X, it was substantial under humid condition (k DE=0.57 and k RE+S=0.49), and it was almost perfect after air drying (k DE=1.0 and kRE+S=1.0). Inter-device agreement was slight (k =0.17) under humid condition, and it was substantial under dry condition (k =0.62). As reproducibility increased under dry condition, drying is advised to detect caries-like lesions on free smooth surfaces when different devices are used.Este estudo verificou o efeito da secagem sobre o resultado de reprodutibilidade de aparelhos laser DIAGNOdent (Dd) no diagnóstico de cárie artificial. Três áreas foram produzidas em cada um dos 34 incisivos bovinos: hígida (S), desmineralizada (DE) e remineralizada (RE). Um examinador mediu cada área com dois aparelhos Dd (denominados X e Y), sendo duas vezes sob a condição úmida e duas vezes sob a condição seca. A concordância intra-examinador segundo cada aparelho, e a concordância entre aparelhos foram estimadas por meio da estatística kappa (k). A reprodutibilidade intra para o aparelho Y foi substancial sob a condição úmida (kDE=0,68 e k RE+S=0,68) e seca (k DE=0,64 e k RE+S=0,67). Para o aparelho X, a concordância foi substancial sob a condição úmida (kDE=0,57 e k RE+S=0,49) e foi quase perfeita após a secagem (kDE=1,0 e k RE+S+1,0). A concordância entre aparelhos foi fraca (k=0,17) na condição úmida, porém foi substancial na condição seca (k=0,62). Como a reprodutibilidade foi melhor sob a condição seca, a secagem da superfície dentária é aconselhada para se detectar lesões de cárie incipientes em superfícies lisas livres, quando mais de um aparelho é utilizado no diagnóstico

    Salford postgraduate annual research conference (SPARC) 2012 proceedings

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    These proceedings bring together a selection of papers from the 2012 Salford Postgraduate Annual Research Conference (SPARC). They reflect the breadth and diversity of research interests showcased at the conference, at which over 130 researchers from Salford, the North West and other UK universities presented their work. 21 papers are collated here from the humanities, arts, social sciences, health, engineering, environment and life sciences, built environment and business

    Transmission of mitochondrial DNA following assisted reproduction and nuclear transfer

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    Review of the articleMitochondria are the organelles responsible for producing the majority of a cell's ATP and also play an essential role in gamete maturation and embryo development. ATP production within the mitochondria is dependent on proteins encoded by both the nuclear and the mitochondrial genomes, therefore co-ordination between the two genomes is vital for cell survival. To assist with this co-ordination, cells normally contain only one type of mitochondrial DNA (mtDNA) termed homoplasmy. Occasionally, however, two or more types of mtDNA are present termed heteroplasmy. This can result from a combination of mutant and wild-type mtDNA molecules or from a combination of wild-type mtDNA variants. As heteroplasmy can result in mitochondrial disease, various mechanisms exist in the natural fertilization process to ensure the maternal-only transmission of mtDNA and the maintenance of homoplasmy in future generations. However, there is now an increasing use of invasive oocyte reconstruction protocols, which tend to bypass mechanisms for the maintenance of homoplasmy, potentially resulting in the transmission of either form of mtDNA heteroplasmy. Indeed, heteroplasmy caused by combinations of wild-type variants has been reported following cytoplasmic transfer (CT) in the human and following nuclear transfer (NT) in various animal species. Other techniques, such as germinal vesicle transfer and pronuclei transfer, have been proposed as methods of preventing transmission of mitochondrial diseases to future generations. However, resulting embryos and offspring may contain mtDNA heteroplasmy, which itself could result in mitochondrial disease. It is therefore essential that uniparental transmission of mtDNA is ensured before these techniques are used therapeutically

    Randomized, Controlled Trial of the Long Term Safety, Immunogenicity and Efficacy of RTS,S/AS02(D) Malaria Vaccine in Infants Living in a Malaria-Endemic Region.

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    The RTS,S/AS malaria candidate vaccine is being developed with the intent to be delivered, if approved, through the Expanded Programme on Immunization (EPI) of the World Health Organization. Safety, immunogenicity and efficacy of the RTS,S/AS02(D) vaccine candidate when integrated into a standard EPI schedule for infants have been reported over a nine-month surveillance period. This paper describes results following 20 months of follow up. This Phase IIb, single-centre, randomized controlled trial enrolled 340 infants in Tanzania to receive three doses of RTS,S/AS02(D) or hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received DTPw/Hib (diphtheria and tetanus toxoids, whole-cell pertussis vaccine, conjugated Haemophilus influenzae type b vaccine) at the same timepoints. The study was double-blinded to month 9 and single-blinded from months 9 to 20. From month 0 to 20, at least one SAE was reported in 57/170 infants who received RTS,S/AS02(D) (33.5%; 95% confidence interval [CI]: 26.5, 41.2) and 62/170 infants who received hepatitis B vaccine (36.5%; 95% CI: 29.2, 44.2). The SAE profile was similar in both vaccine groups; none were considered to be related to vaccination. At month 20, 18 months after completion of vaccination, 71.8% of recipients of RTS,S/AS02(D) and 3.8% of recipients of hepatitis B vaccine had seropositive titres for anti-CS antibodies; seroprotective levels of anti-HBs antibodies remained in 100% of recipients of RTS,S/AS02(D) and 97.7% recipients of hepatitis B vaccine. Anti-HBs antibody GMTs were higher in the RTS,S/AS02(D) group at all post-vaccination time points compared to control. According to protocol population, vaccine efficacy against multiple episodes of malaria disease was 50.7% (95% CI: -6.5 to 77.1, p = 0.072) and 26.7% (95% CI: -33.1 to 59.6, p = 0.307) over 12 and 18 months post vaccination, respectively. In the Intention to Treat population, over the 20-month follow up, vaccine efficacy against multiple episodes of malaria disease was 14.4% (95% CI: -41.9 to 48.4, p = 0.545). The acceptable safety profile and good tolerability of RTS,S/AS02(D) in combination with EPI vaccines previously reported from month 0 to 9 was confirmed over a 20 month surveillance period in this infant population. Antibodies against both CS and HBsAg in the RTS,S/AS02(D) group remained significantly higher compared to control for the study duration. Over 18 months follow up, RTS,S/AS02(D) prevented approximately a quarter of malaria cases in the study population. CLINICAL TRIALS: Gov identifier: NCT00289185
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