188 research outputs found
Formation of Carbon Nanostructures with Ge and SiC Nanoparticles Prepared by Direct Current and Radio Frequency Hybrid Arc Discharge
A long gamma-ray burst from a merger of compact objects
Gamma-ray bursts (GRBs) are flashes of high-energy radiation arising from
energetic cosmic explosions. Bursts of long (>2 s) duration are produced by the
core-collapse of massive stars, those of short (< 2 s) duration by the merger
of two neutron stars (NSs). A third class of events with hybrid high-energy
properties was identified, but never conclusively linked to a stellar
progenitor. The lack of bright supernovae rules out typical core-collapse
explosions, but their distance scales prevent sensitive searches for direct
signatures of a progenitor system. Only tentative evidence for a kilonova has
been presented. Here we report observations of the exceptionally bright
GRB211211A that classify it as a hybrid event and constrain its distance scale
to only 346 Mpc. Our measurements indicate that its lower-energy (from
ultraviolet to near-infrared) counterpart is powered by a luminous (~1E42
erg/s) kilonova possibly formed in the ejecta of a compact binary merger.Comment: original version, accepted for publication after revisio
Meteorological and evaluation datasets for snow modelling at ten reference sites: description of in situ and bias-corrected reanalysis data
Prognostic value of tissue-type plasminogen activator (tPA) and its complex with the type-1 inhibitor (PAI-1) in breast cancer
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Adeno-associated viral vector-mediated human vascular endothelial growth factor gene transfer stimulates angiogenesis and wound healing in the genetically diabetic mouse
Characteristics of surface “melt potential” over Antarctic ice shelves based on regional atmospheric model simulations of summer air temperature extremes from 1979/80 to 2018/19
We calculate a regional surface “melt potential” index (MPI) over Antarctic ice shelves that describes the frequency (MPI-freq, %) and intensity (MPI-int, K) of daily maximum summer temperatures exceeding a melt threshold of 273.15 K. This is used to determine which ice shelves are vulnerable to melt-induced hydrofracture and is calculated using near-surface temperature output for each summer from 1979/80 to 2018/19 from two high-resolution regional atmospheric model hindcasts (using the MetUM and HIRHAM5). MPI is highest for Antarctic Peninsula ice shelves (MPI-freq 23-35%, MPI-int 1.2-2.1 K), lowest (2-3%, < 0 K) for Ronne-Filchner and Ross ice shelves, and around 10-24% and 0.6-1.7 K for the other West and East Antarctic ice shelves. Hotspots of MPI are apparent over many ice shelves, and they also show a decreasing trend in MPI-freq. The regional circulation patterns associated with high MPI values over West and East Antarctic ice shelves are remarkably consistent for their respective region but tied to different large-scale climate forcings. The West Antarctic circulation resembles the central Pacific El Niño pattern with a stationary Rossby wave and a strong anticyclone over the high-latitude South Pacific. By contrast, the East Antarctic circulation comprises a zonally symmetric negative Southern Annular Mode pattern with a strong regional anticyclone on the plateau and enhanced coastal easterlies/weakened Southern Ocean westerlies. Values of MPI are 3-4 times larger for a lower temperature/melt threshold of 271.15 K used in a sensitivity test, as melting can occur at temperatures lower than 273.15 K depending on snowpack properties
Heart Failure-Inducible Gene Therapy Targeting Protein Phosphatase 1 Prevents Progressive Left Ventricular Remodeling
BACKGROUND: The targeting of Ca(2+) cycling has emerged as a potential therapy for the treatment of severe heart failure. These approaches include gene therapy directed at overexpressing sarcoplasmic reticulum (SR) Ca(2+) ATPase, or ablation of phospholamban (PLN) and associated protein phosphatase 1 (PP1) protein complexes. We previously reported that PP1β, one of the PP1 catalytic subunits, predominantly suppresses Ca(2+) uptake in the SR among the three PP1 isoforms, thereby contributing to Ca(2+) downregulation in failing hearts. In the present study, we investigated whether heart-failure-inducible PP1β-inhibition by adeno-associated viral-9 (AAV9) vector mediated gene therapy is beneficial for preventing disease progression in genetic cardiomyopathic mice. METHODS: We created an adeno-associated virus 9 (AAV9) vector encoding PP1β short-hairpin RNA (shRNA) or negative control (NC) shRNA. A heart failure inducible gene expression system was employed using the B-type natriuretic protein (BNP) promoter conjugated to emerald-green fluorescence protein (EmGFP) and the shRNA sequence. AAV9 vectors (AAV9-BNP-EmGFP-PP1βshRNA and AAV9-BNP-EmGFP-NCshRNA) were injected into the tail vein (2×10(11) GC/mouse) of muscle LIM protein deficient mice (MLPKO), followed by serial analysis of echocardiography, hemodynamic measurement, biochemical and histological analysis at 3 months. RESULTS: In the MLPKO mice, BNP promoter activity was shown to be increased by detecting both EmGFP expression and the induced reduction of PP1β by 25% in the myocardium. Inducible PP1βshRNA delivery preferentially ameliorated left ventricular diastolic function and mitigated adverse ventricular remodeling. PLN phosphorylation was significantly augmented in the AAV9-BNP-EmGFP-PP1βshRNA injected hearts compared with the AAV9-BNP-EmGFP-NCshRNA group. Furthermore, BNP production was reduced, and cardiac interstitial fibrosis was abrogated at 3 months. CONCLUSION: Heart failure-inducible molecular targeting of PP1β has potential as a novel therapeutic strategy for heart failure
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