Are Swift gamma-ray bursts consistent with the Ghirlanda relation?

A few tight correlations linking several properties of gamma-ray bursts (GRBs), namely the spectral peak energy, the total radiated energy, and the afterglow break time, have been discovered with pre-Swift GRBs. They were used to constrain the cosmological parameters, together with type-Ia supernovae. However, the tightness of these correlations is a challenge to GRB models. We explore the effect of adding Swift bursts to the Ghirlanda and Liang-Zhang relations. Although they are both still valid, they become somewhat weakened mostly due to the presence of significant outliers, which otherwise are apparently normal GRBs so difficult to distinguish. The increased dispersion of the relations makes them less reliable for purposes of precision cosmology.Comment: Paper accepted for publication on A&A (7 pages, 2 figures). Small changes after comment

Nonlocal field correlations and dynamical Casimir-Polder forces between one excited- and two ground-state atoms

The problem of nonlocality in the dynamical three-body Casimir-Polder interaction between an initially excited and two ground-state atoms is considered. It is shown that the nonlocal spatial correlations of the field emitted by the excited atom during the initial part of its spontaneous decay may become manifest in the three-body interaction. The observability of this new phenomenon is discussed.Comment: 17 pages, 1 figure, sub. to Phys. Rev.

TESTING the BINARY TRIGGER HYPOTHESIS in FUors

We present observations of three FU Orionis objects (hereafter, FUors) with nonredundant aperture-mask interferometry at 1.59 μm and 2.12 μm that probe for binary companions on the scale of the protoplanetary disk that feeds their accretion outbursts. We do not identify any companions to V1515 Cyg or HBC 722, but we do resolve a close binary companion to V1057 Cyg that is at the diffraction limit ($\rho =58.3\pm 1.4$ mas or 30 ± 5 au) and currently much fainter than the outbursting star (${\rm{\Delta }}K^{\prime} =3.34\pm 0.10$ mag). Given the flux excess of the outbursting star, we estimate that the mass of the companion ($M\sim 0.25{M}_{\odot }$) is similar to or slightly below that of the FUor itself, and therefore it resembles a typical T Tauri binary system. Our observations only achieve contrast limits of ${\rm{\Delta }}K^{\prime} \sim 4$ mag, and hence we are only sensitive to companions that were near or above the pre-outburst luminosity of the FUors. It remains plausible that FUor outbursts could be tied to the presence of a close binary companion. However, we argue from the system geometry and mass reservoir considerations that these outbursts are not directly tied to the orbital period (i.e., occurring at periastron passage), but instead must only occur infrequently

The endogenous caspase-8 inhibitor c-FLIPL regulates ER morphology and crosstalk with mitochondria

Components of the death receptors-mediated pathways like caspase-8 have been identified in complexes at intracellular membranes to spatially restrict the processing of local targets. In this study, we report that the long isoform of the cellular FLICE-inhibitory protein (c-FLIPL), a well- known inhibitor of the extrinsic cell death initiator caspase-8, localizes at the endoplasmic reticulum (ER) and mitochondria-associated membranes (MAMs). ER morphology was disrupted and ER Ca2+-release as well as ER-mitochondria tethering were decreased in c-FLIP-/- mouse embryonic fibroblasts (MEFs). Mechanistically, c-FLIP ablation resulted in enhanced basal caspase-8 activation and in caspase-mediated processing of the ER-shaping protein reticulon-4 (RTN4) that was corrected by re-introduction of c-FLIPL and caspase inhibition, resulting in the recovery of a normal ER morphology and ER-mitochondria juxtaposition. Thus, the caspase-8 inhibitor c-FLIPL emerges as a component of the MAMs signaling platforms, where caspases appear to regulate ER morphology and ER-mitochondria crosstalk by impinging on ER-shaping proteins like the RTN4

Identification and functional validation of FDA-approved positive and negative modulators of the mitochondrial calcium uniporter

The mitochondrial calcium uniporter (MCU), the highly selective channel responsible for mitochondrial Ca2+ entry, plays important roles in physiology and pathology. However, only few pharmacological compounds directly and selectively modulate its activity. Here, we perform high-throughput screening on a US Food and Drug Administration (FDA)-approved drug library comprising 1,600 compounds to identify molecules modulating mitochondrial Ca2+ uptake. We find amorolfine and benzethonium to be positive and negative MCU modulators, respectively. In agreement with the positive effect of MCU in muscle trophism, amorolfine increases muscle size, and MCU silencing is sufficient to blunt amorolfine-induced hypertrophy. Conversely, in the triple-negative breast cancer cell line MDA-MB-231, benzethonium delays cell growth and migration in an MCU-dependent manner and protects from ceramide-induced apoptosis, in line with the role of mitochondrial Ca2+ uptake in cancer progression. Overall, we identify amorolfine and benzethonium as effective MCU-targeting drugs applicable to a wide array of experimental and disease conditions

Validation of the CogDrisk Instrument as Predictive of Dementia in Four General Community-Dwelling Populations

Background: Lack of external validation of dementia risk tools is a major limitation for generalizability and translatability of prediction scores in clinical practice and research. Objectives: We aimed to validate a new dementia prediction risk tool called CogDrisk and a version, CogDrisk-AD for predicting Alzheimer’s disease (AD) using cohort studies. Design, Setting, Participants and Measurements: Four cohort studies were identified that included majority of the dementia risk factors from the CogDrisk tool. Participants who were free of dementia at baseline were included. The predictors were component variables in the CogDrisk tool that include self-reported demographics, medical risk factors and lifestyle habits. Risk scores for Any Dementia and AD were computed and Area Under the Curve (AUC) was assessed. To examine modifiable risk factors for dementia, the CogDrisk tool was tested by excluding age and sex estimates from the model. Results: The performance of the tool varied between studies. The overall AUC and 95% CI for predicting dementia was 0.77 (0.57, 0.97) for the Swedish National study on Aging and Care in Kungsholmen, 0.76 (0.70, 0.83) for the Health and Retirement Study - Aging, Demographics and Memory Study, 0.70 (0.67,0.72) for the Cardiovascular Health Study Cognition Study, and 0.66 (0.62,0.70) for the Rush Memory and Aging Project. Conclusions: The CogDrisk and CogDrisk-AD performed well in the four studies. Overall, this tool can be used to assess individualized risk factors of dementia and AD in various population settings

Ripple oscillations in the left temporal neocortex are associated with impaired verbal episodic memory encoding

Background: We sought to determine if ripple oscillations (80-120Hz), detected in intracranial EEG (iEEG) recordings of epilepsy patients, correlate with an enhancement or disruption of verbal episodic memory encoding. Methods: We defined ripple and spike events in depth iEEG recordings during list learning in 107 patients with focal epilepsy. We used logistic regression models (LRMs) to investigate the relationship between the occurrence of ripple and spike events during word presentation and the odds of successful word recall following a distractor epoch, and included the seizure onset zone (SOZ) as a covariate in the LRMs. Results: We detected events during 58,312 word presentation trials from 7,630 unique electrode sites. The probability of ripple on spike (RonS) events was increased in the seizure onset zone (SOZ, p<0.04). In the left temporal neocortex RonS events during word presentation corresponded with a decrease in the odds ratio (OR) of successful recall, however this effect only met significance in the SOZ (OR of word recall 0.71, 95% CI: 0.59-0.85, n=158 events, adaptive Hochberg p<0.01). Ripple on oscillation events (RonO) that occurred in the left temporal neocortex non-SOZ also correlated with decreased odds of successful recall (OR 0.52, 95% CI: 0.34-0.80, n=140, adaptive Hochberg , p<0.01). Spikes and RonS that occurred during word presentation in the left middle temporal gyrus during word presentation correlated with the most significant decrease in the odds of successful recall, irrespective of the location of the SOZ (adaptive Hochberg, p<0.01). Conclusion: Ripples and spikes generated in left temporal neocortex are associated with impaired verbal episodic memory encoding