249 research outputs found
The World Radiation Monitoring Center of the Baseline Surface Radiation Network - Status April 2017
The Baseline Surface Radiation Network and the World Radiation Monitoring Center - Status March 2018
Optical properties of structurally-relaxed Si/SiO superlattices: the role of bonding at interfaces
We have constructed microscopic, structurally-relaxed atomistic models of
Si/SiO superlattices. The structural distortion and oxidation-state
characteristics of the interface Si atoms are examined in detail. The role
played by the interface Si suboxides in raising the band gap and producing
dispersionless energy bands is established. The suboxide atoms are shown to
generate an abrupt interface layer about 1.60 \AA thick. Bandstructure and
optical-absorption calculations at the Fermi Golden rule level are used to
demonstrate that increasing confinement leads to (a) direct bandgaps (b) a blue
shift in the spectrum, and (c) an enhancement of the absorption intensity in
the threshold-energy region. Some aspects of this behaviour appear not only in
the symmetry direction associated with the superlattice axis, but also in the
orthogonal plane directions. We conclude that, in contrast to Si/Ge, Si/SiO
superlattices show clear optical enhancement and a shift of the optical
spectrum into the region useful for many opto-electronic applications.Comment: 11 pages, 10 figures (submitted to Phys. Rev. B
GCH1 deficiency activates brain innate immune response and impairs tyrosine hydroxylase homeostasis
The Parkinsonâs disease (PD) risk gene GTP cyclohydrolase 1 (GCH1) catalyzes the rate-limiting step in tetrahydrobiopterin (BH4) synthesis, an essential cofactor in the synthesis of monoaminergic neurotransmitters. To investigate the mechanisms by which GCH1 deficiency may contribute to PD, we generated a loss of function zebrafish gch1 mutant (gch1-/-), using CRISPR/Cas technology. gch1-/- zebrafish develop marked monoaminergic neurotransmitter deficiencies by 5 dpf, movement deficits by 8 dpf and lethality by 12 dpf. Tyrosine hydroxylase protein levels were markedly reduced without loss of ascending dopaminergic (DAergic) neurons. L-Dopa treatment of gch1-/- larvae improved survival without ameliorating the motor phenotype. RNAseq of gch1-/- larval brain tissue identified highly upregulated transcripts involved in innate immune response. Subsequent experiments provided morphological and functional evidence of microglial activation in gch1-/-. The results of our study suggest that GCH1 deficiency may unmask early, subclinical parkinsonism and only indirectly contribute to neuronal cell death via immune-mediated mechanisms. Our work highlights the importance of functional validation for GWAS risk factors and further emphasises the important role of inflammation in the pathogenesis of PD
Shelf ice-associated cryo-benthos and environmental features
Incidences of cryo-benthic communities beneath ice shelves are rare and recent discoveries. Combined seal- and ROV-borne imagery and novel sampling technologies allowed for a re-assessment and augmentation of earlier findings on a cryo-benthic isopod community (Antarcturus cf. spinacoronatus), being attached head-down to the underside of floating shelf ice at depths of around 80-150m. The shelf ice-associated cryo-benthos was discovered at Drescher Inlet (-72.83667 -19.15300), Riiser-Larsen Ice Shelf (eastern Weddell Sea). The inlet constitutes a 25km long and between 2 and 4km wide crack in the surrounding shelf ice, which is associated with certain environmental features. Here we compile all available local physical, biological, and biogeochemical data and discuss their relevance in the wider regional context for this faunal hotspot. These include data on shelf, sea and platelet ice, seafloor topography, hydrography and water chemistry, as well as associated pelagic and benthic marine life, in particular affinities of the cryo-benthic isopod community to related fauna occurring in nearby seabed communities using molecular barcoding
TP53 mutated glioblastoma stem-like cell cultures are sensitive to dual mTORC1/2 inhibition while resistance in TP53 wild type cultures can be overcome by combined inhibition of mTORC1/2 and Bcl-2
Mycobacterial Acid Tolerance Enables Phagolysosomal Survival and Establishment of Tuberculous Infection In Vivo.
The blockade of phagolysosomal fusion is considered a critical mycobacterial strategy to survive in macrophages. However, viable mycobacteria have been observed in phagolysosomes during infection of cultured macrophages, and mycobacteria have the virulence determinant MarP, which confers acid resistance in vitro. Here we show in mice and zebrafish that innate macrophages overcome mycobacterial lysosomal avoidance strategies to rapidly deliver a substantial proportion of infecting bacteria to phagolysosomes. Exploiting the optical transparency of the zebrafish, we tracked the fates of individual mycobacteria delivered to phagosomes versus phagolysosomes and discovered that bacteria survive and grow in phagolysosomes, though growth is slower. MarP is required specifically for phagolysosomal survival, making it an important determinant for the establishment of mycobacterial infection in their hosts. Our work suggests that if pathogenic mycobacteria fail to prevent lysosomal trafficking, they tolerate the resulting acidic environment of the phagolysosome to establish infection.National Institutes of Health (Grant IDs: R37AI054503, R01 AI076327, 5T32HD007233, 5F30HL110455), Wellcome Trust, National Institute of Health Research Cambridge Biomedical Research CentreThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.chom.2016.07.00
TP53 mutated glioblastoma stem-like cell cultures are sensitive to dual mTORC1/2 inhibition while resistance in TP53 wild type cultures can be overcome by combined inhibition of mTORC1/2 and Bcl-2
Background: Glioblastoma is the most malignant tumor of the central nervous system and still lacks effective treatment. This study explores mutational biomarkers of 11 drugs targeting either the RTK/Ras/PI3K, the p53 or the Rb pathway using 25 patient-derived glioblastoma stem-like cell cultures (GSCs). Results: We found that TP53 mutated GSCs were approximately 3.5 fold more sensitive to dual inhibition of mammalian target of rapamycin complex 1 and 2 (mTORC1/2) compared to wild type GSCs. We identified that Bcl-2(Thr56/Ser70) phosphorylation contributed to the resistance of TP53 wild type GSCs against dual mTORC1/2 inhibition. The Bcl-2 inhibitor ABT-263 (navitoclax) increased sensitivity to the mTORC1/2 inhibitor AZD8055 in TP53 wild type GSCs, while sensitivity to AZD8055 in TP53 mutated GSCs remained unchanged. Conclusion: Our data suggest that Bcl-2 confers resistance to mTORC1/2 inhibitors in TP53 wild type GSCs and that combined inhibition of both mTORC1/2 and Bcl-2 is worthwhile to explore further in TP53 wild type glioblastomas, whereas in TP53 mutated glioblastomas dual mTORC1/2 inhibitors should be explored
All-sky Search for High-Energy Neutrinos from Gravitational Wave Event GW170104 with the ANTARES Neutrino Telescope
Advanced LIGO detected a significant gravitational wave signal (GW170104)
originating from the coalescence of two black holes during the second
observation run on January 4, 2017. An all-sky high-energy
neutrino follow-up search has been made using data from the ANTARES neutrino
telescope, including both upgoing and downgoing events in two separate
analyses. No neutrino candidates were found within s around the GW
event time nor any time clustering of events over an extended time window of
months. The non-detection is used to constrain isotropic-equivalent
high-energy neutrino emission from GW170104 to less than
erg for a spectrum
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