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

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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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