Can gravitational waves be detected in quasar microlensing?

Studies of the lensed quasar ${\rm Q}0957+561 {\rm A,B}$ have shown evidence for microlensing in the brightness history of the quasar images. It had been suggested that a frequency offset between the brightness fluctuations in each of the two images might possibly be caused by gravitational radiation generated by a massive black hole binary at the center of the lensing galaxy. This paper demonstrates that the fluctuations produced by such a source of gravitational waves will be too small to account for the observed frequency offsets.Comment: 10 pages, 1 fig; submitted to Ap

Direct Microlensing-Reverberation Observations of the Intrinsic magnetic Structure of AGN in Different Spectral States: A Tale of Two Quasars

We show how direct microlensing-reverberation analysis performed on two well-known Quasars (Q2237 - The Einstein Cross and Q0957 - The Twin) can be used to observe the inner structure of two quasars which are in significantly different spectral states. These observations allow us to measure the detailed internal structure of quasar Q2237 in a radio quiet high-soft state, and compare it to quasar Q0957 in a radio loud low-hard state. We find that the observed differences in the spectral states of these two quasars can be understood as being due to the location of the inner radii of their accretion disks relative to the co-rotation radii of rotating intrinsically magnetic supermassive compact objects in the centers of these quasars.Comment: 26 page manuscript with 2 tables and 2 figures, submitted to Astronomical Journa

Pleistocene Deposits in the Southern Egyptian Sahara: Lithostratigraphic Relationships of Sediments and Landscape Dynamics at Bir Tarfawi

The sedimentological and lithostratigraphic record from north-central Bir Tarfawi documents the presence of Pleistocene basin-fill deposits. Three topographic basins were created as a result of deflation during climate episodes associated with lowering of the local groundwater table. In each case, the three deflational basins or topographic depressions were subsequently filled with sediments; these basin aggradations coincided with changes from arid climate conditions to wetter conditions and a rise in the groundwater table. The oldest and highest sedimentary remnant is associated with Acheulian artifacts and may reflect spring-fed pond and marsh conditions during a Middle Pleistocene wet climate episode. Lithofacies for a lower stratigraphic sequence (the “White Lake”) documents deposition in a perennial lake that varied in extent and depth and is associated with Middle Paleolithic artifacts. A third episode of deflation created a topographic low that has been filled with Late Pleistocene sediments that are associated with Middle Paleolithic artifacts and fossil remains. Lateral and vertical variations in the lithofacies of this basin-fill sequence and the sediments of the “grey-green” lake phases provide a record of changing hydrologic conditions. These hydrologic conditions appear to reflect variations in water-table levels related to groundwater recharge and, at times, local rains

Functional analysis of a missense mutation in the serine protease inhibitor SPINT2 associated with congenital sodium diarrhea.

Membrane-bound serine proteases play important roles in different biological processes. Their regulation by endogenous inhibitors is poorly understood. A Y163C mutation in the SPINT2 gene encoding the serine protease inhibitor Hepatocyte Growth Factor Inhibitor HAI-2 is associated with a congenital sodium diarrhea. The functional consequences of this mutation on HAI-2 activity and its physiological targets are unknown. We established a cellular assay in Xenopus laevis oocytes to study functional interactions between HAI-2 and candidate membrane-bound serine proteases expressed in the gastro-intestinal tract. We found that the wild-type form of HAI-2 is a potent inhibitor of nine gastro-intestinal serine proteases. The Y163C mutation in the second Kunitz domain of HAI-2 resulted in a complete loss of inhibitory activity on two intestinal proteases, prostasin and tmprss13. The effect of the mutation of the homologous Y68C in the first Kunitz domain of HAI-2 is consistent with a differential contribution of the two Kunitz domains of HAI-2 in the inhibition of serine proteases. By contrast to the Tyr to Cys, the Tyr to Ser substitution did not change the inhibitory potency of HAI-2, indicating that the thiol-group of the cysteine rather than the Tyr deletion is responsible for the HAI-2 loss of function. Our functional assay allowed us to identify membrane-bound serine proteases as cellular target for inhibition by HAI-2 wild type and mutants, and to better define the role of the Tyr in the second Kunitz domain in the inhibitory activity of HAI-2

Proton and non-proton activation of ASIC channels.

The Acid-Sensing Ion Channels (ASIC) exhibit a fast desensitizing current when activated by pH values below 7.0. By contrast, non-proton ligands are able to trigger sustained ASIC currents at physiological pHs. To analyze the functional basis of the ASIC desensitizing and sustained currents, we have used ASIC1a and ASIC2a mutants with a cysteine in the pore vestibule for covalent binding of different sulfhydryl reagents. We found that ASIC1a and ASIC2a exhibit two distinct currents, a proton-induced desensitizing current and a sustained current triggered by sulfhydryl reagents. These currents differ in their pH dependency, their sensitivity to the sulfhydryl reagents, their ionic selectivity and their relative magnitude. We propose a model for ASIC1 and ASIC2 activity where the channels can function in two distinct modes, a desensitizing mode and a sustained mode depending on the activating ligands. The pore vestibule of the channel represents a functional site for binding non-proton ligands to activate ASIC1 and ASIC2 at neutral pH and to prevent channel desensitization

No credible evidence for links between 2D:4D and COVID-19 outcomes: A probabilistic perspective on digit ratio, ACE variants, and national case fatalities

Research into COVID-19 susceptibility and outcomes are critical, but claims must be carefully evaluated to inform policy decisions. In a recent series of articles, Manning and Fink [1–3] use national-level data to describe associations between case-fatality ratios and male and female finger ratios (2D:4D), a suggested measure of prenatal androgen exposure, as well as angiotensin-converting enzyme (ACE) allele and genotype frequencies. The authors suggest that 2D:4D is linked with ACE variant prevalence, and that higher male 2D:4D is associated with higher case fatality ratios, and point to 2D:4D as a useful prognostic measure for COVID-19 susceptibility. A critical review and robust Bayesian analysis of the hypothesis is described here, finding no conclusive evidence of COVID-19 mortality and 2D:4D, nor associations between 2D:4D and ACE1 allele or ACE2 genotype frequency. This absence of evidence is present for data taken from the second wave of COVID-19 in October 2020. Problematic theoretical grounding, individual-level conclusions drawn from national-level data, and issues with statistical inference in the original articles are discussed. Taken together, the current data offer no clear utility of 2D:4D in determining COVID-19 outcomes

The Human Acid-Sensing Ion Channel ASIC1a: Evidence for a Homotetrameric Assembly State at the Cell Surface.

The chicken acid-sensing ion channel ASIC1 has been crystallized as a homotrimer. We address here the oligomeric state of the functional ASIC1 in situ at the cell surface. The oligomeric states of functional ASIC1a and mutants with additional cysteines introduced in the extracellular pore vestibule were resolved on SDS-PAGE. The functional ASIC1 complexes were stabilized at the cell surface of Xenopus laevis oocytes or CHO cells either using the sulfhydryl crosslinker BMOE, or sodium tetrathionate (NaTT). Under these different crosslinking conditions ASIC1a migrates as four distinct oligomeric states that correspond by mass to multiples of a single ASIC1a subunit. The relative importance of each of the four ASIC1a oligomers was critically dependent on the availability of cysteines in the transmembrane domain for crosslinking, consistent with the presence of ASIC1a homo-oligomers. The expression of ASIC1a monomers, trimeric or tetrameric concatemeric cDNA constructs resulted in functional channels. The resulting ASIC1a complexes are resolved as a predominant tetramer over the other oligomeric forms, after stabilization with BMOE or NaTT and SDS-PAGE/western blot analysis. Our data identify a major ASIC1a homotetramer at the surface membrane of the cell expressing functional ASIC1a channel

On the optical counterpart of NGC300 X-1 and the global Wolf-Rayet content of NGC300

(Conext:) Surveys of Wolf-Rayet (WR) populations in nearby galaxies provide tests of evolutionary models plus Type Ib/c supernova progenitors. This spectroscopic study complements the recent imaging survey of the spiral galaxy NGC 300 by Schild et al. (Aims): Revisions to the known WR content of NGC 300 are presented. We investigate the WR nature of candidate #41 from Schild et al. which is spatially coincident with the bright X-ray point source NGC 300 X-1; (Methods:) VLT/FORS2 multi-object spectroscopy of WR candidates in NGC 300 is obtained; (Results:) We establish an early-type WN nature of #41, i.e. similar to the optical counterpart of IC 10 X-1, which closely resembles NGC 300 X-1. We confirm 9 new WR stars, bringing the current WR census of the inner disk to 31, with N(WC)/N(WN)~0.9. (Conclusions:) If #41 is the optical counterpart for NGC 300 X-1, we estimate a WR mass of 38 Msun based upon ground-based photometry, from which a black hole mass of > 10 Msun results from the 32.8 hr period of the system and WR wind velocity of 1250 km/s. We estimate an 95% completeness among WC stars and 70% among WN stars, such that the total WR content is ~40, with N(WC)/N(WN)~0.7. From the Halpha-derived star formation rate of the inner galaxy, we infer N(WR)/N(O)~0.04Comment: 5 pages, 5 figures, accepted for A&A Letter