Observing supermassive black holes with deci-Hz gravitational-wave detectors

The most massive black holes in our Universe form binaries at the centre of merging galaxies. The recent evidence for a gravitational-wave (GW) background from pulsar timing may constitute the first observation that these supermassive black hole binaries (SMBHBs) merge. Yet, the most massive SMBHBs are out of reach of interferometric detectors and are exceedingly difficult to resolve individually with pulsar timing. These limitations call for unexplored strategies to detect individual SMBHBs in the uncharted frequency band $\lesssim10^{-5}\,\rm Hz$ in order to establish their abundance and decipher the coevolution with their host galaxies. Here we show that SMBHBs imprint detectable long-term modulations on GWs from stellar-mass binaries residing in the same galaxy. We determine that proposed deci-Hz GW interferometers sensitive to numerous stellar-mass binaries will uncover modulations from $\sim\mathcal{O}(10^{-1}$ - $10^4)$ SMBHBs with masses $\sim\mathcal{O}(10^7$ - $10^9)\,\rm M_\odot$ out to redshift $z\sim3.5$. This offers a unique opportunity to map the population of SMBHBs through cosmic time, which might remain inaccessible otherwise.Comment: 16 pages, 4 figures, comments welcom

ACE-versus chymase-dependent angiotensin II generation in human coronary arteries: a matter of efficiency?

OBJECTIVE: The objective of this study was to investigate ACE- and chymase-dependent angiotensin I-to-II conversion in human coronary arteries (HCAs). METHODS AND RESULTS: HCA rings were mounted in organ baths, and concentration-response curves to angiotensin II, angiotensin I, and the chymase-specific substrate Pro(11)-D-Ala(12)-angiotensin I (PA-angiotensin I) were constructed. All angiotensins displayed similar efficacy. For a given vasoconstriction, bath (but not interstitial) angiotensin II during angiotensin I and PA-angiotensin I was lower than during angiotensin II, indicating that interstitial (and not bath) angiotensin II determines vasoconstriction. PA-angiotensin I increased interstitial angiotensin II less efficiently than angiotensin I. Separate inhibition of ACE (with captopril) and chymase (with C41 or chymostatin) shifted the angiotensin I concentration-response curve approximately 5-fold to the right, whereas a 10-fold shift occurred during combined ACE and chymase inhibition. Chymostatin, but not captopril and/or C41, reduced bath angiotensin II and abolished PA-Ang I-induced vasoconstriction. Perfused HCA segments, exposed luminally or adventitially to angiotensin I, released angiotensin II into the luminal and adventitial fluid, respectively, and this release was blocked by chymostatin. CONCLUSIONS: Both ACE and chymase contribute to the generation of functionally active angiotensin II in HCAs. However, because angiotensin II loss in the organ bath is chymase-dependent, ACE-mediated conversion occurs more efficiently (ie, closer to AT(1) receptors) than chymase-mediated conversion

Simultaneous observations of PKS 2155-304 with H.E.S.S., Fermi, RXTE and ATOM: spectral energy distributions and variability in a low state

We report on the first simultaneous observations that cover the optical, X-ray, and high energy gamma-ray bands of the BL Lac object PKS 2155-304. The gamma-ray bands were observed for 11 days, between 25 August and 6 September 2008, jointly with the Fermi Gamma-ray Space Telescope and the H.E.S.S. atmospheric Cherenkov array, providing the first simultaneous MeV-TeV spectral energy distribution with the new generation of gamma-ray telescopes. The ATOM telescope and the RXTE and Swift observatories provided optical and X-ray coverage of the low-energy component over the same time period. The object was close to the lowest archival X-ray and Very High Energy state, whereas the optical flux was much higher. The light curves show relatively little (~30%$) variability overall when compared to past flaring episodes, but we find a clear optical/VHE correlation and evidence for a correlation of the X-rays with the high energy spectral index. Contrary to previous observations in the flaring state, we do not find any correlation between the X-ray and VHE components. Although synchrotron self-Compton models are often invoked to explain the SEDs of BL Lac objects, the most common versions of these models are at odds with the correlated variability we find in the various bands for PKS 2155-304.Comment: Accepted for publication in the Astrophysical Journa

Early intervention, treatment and rehabilitation of employees with common mental disorders by using psychotherapeutic consultation at work: study protocol of a randomised controlled multicentre trial (friaa project)

Background: Common mental disorders are one of the leading causes for sickness absence and early retirement due to reduced health. Furthermore, a treatment gap for common mental disorders has been described worldwide. Within this study, psychotherapeutic consultation at work defined as a tailored, module-based and work-related psychotherapeutic intervention will be applied to improve mental health care. Methods: This study comprises a randomized controlled multicentre trial with 1:1 allocation to an intervention and control group. In total, 520 employees with common mental disorders shall be recruited from companies being located around five study centres in Germany. Besides care as usual, the intervention group will receive up to 17 sessions of psychotherapy. The first session will include basics diagnostics and medical indication of treatment, and the second session will include work-related diagnostics. Then, participants of the intervention group may receive work-related psychotherapeutic consultation for up to ten sessions. Further psychotherapeutic consultation during return to work for up to five sessions will be offered where appropriate. The control group will receive care as usual and the first intervention session of basic diagnostics and medical indication of treatment. After enrollment to the study, participants will be followed up after nine (first follow-up) and fifteen (second follow-up) months. Self-reported days of sickness absence within the last 6 months at the second follow-up will be used as the primary outcome and self-efficacy at the second follow-up as the secondary outcome. Furthermore, a cost-benefit assessment related to costs of common mental disorders for social insurances and companies will be performed. Discussion: Psychotherapeutic consultation at work represents a low threshold care model aiming to overcome treatment gaps for employees with common mental disorders. If successfully implemented and evaluated, it might serve as a role model to the care of employees with common mental disorders and might be adopted in standard care in cooperation with sickness and pension insurances in Germany. Trial registration: The friaa project was registered at the German Clinical Trial Register (DRKS) at 01.03.2021 (DRKS00023049): https://www.drks.de/drks web/navigate.do?navigationId=trial.HTML&TRIAL ID=DRKS00023049

Acerca de los sentidos de la palabra "Mística"

An improved knowledge of iron biogeochemistry is needed to better understand key controls on the functioning of high-nitrate low-chlorophyll (HNLC) oceanic regions. Iron budgets for HNLC waters have been constructed using data from disparate sources ranging from laboratory algal cultures to ocean physics. In summer 2003 we conducted FeCycle, a 10-day mesoscale tracer release in HNLC waters SE of New Zealand, and measured concurrently all sources (with the exception of aerosol deposition) to, sinks of iron from, and rates of iron recycling within, the surface mixed layer. A pelagic iron budget (timescale of days) indicated that oceanic supply terms (lateral advection and vertical diffusion) were relatively small compared to the main sink (downward particulate export). Remote sensing and terrestrial monitoring reveal 13 dust or wildfire events in Australia, prior to and during FeCycle, one of which may have deposited iron at the study location. However, iron deposition rates cannot be derived from such observations, illustrating the difficulties in closing iron budgets without quantification of episodic atmospheric supply. Despite the threefold uncertainties reported for rates of aerosol deposition (Duce et al., 1991), published atmospheric iron supply for the New Zealand region is ∼50-fold (i.e., 7-to 150-fold) greater than the oceanic iron supply measured in our budget, and thus was comparable (i.e., a third to threefold) to our estimates of downward export of particulate iron. During FeCycle, the fluxes due to short term (hours) biological iron uptake and regeneration were indicative of rapid recycling and were tenfold greater than for new iron (i.e. estimated atmospheric and measured oceanic supply), giving an fe ratio (uptake of new iron/ uptake of new + regenerated iron) of 0.17 (i.e., a range of 0.06 to 0.51 due to uncertainties on aerosol iron supply), and an Fe ratio (biogenic Fe export/uptake of new + regenerated iron) of 0.09 (i.e., 0.03 to 0.24). Copyright 2005 by the American Geophysical Union

Inhibition of T lymphocyte activation in mice heterozygous for loss of the IMPDH II gene

Inosine 5′-monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in the de novo synthesis of guanine nucleotides, which are also synthesized from guanine by a salvage reaction catalyzed by the X chromosome–linked enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Since inhibitors of IMPDH are in clinical use as immunosuppressive agents, we have examined the consequences of knocking out the IMPDH type II enzyme by gene targeting in a mouse model. Loss of both alleles of the gene encoding this enzyme results in very early embryonic lethality despite the presence of IMPDH type I and HPRT activities. Lymphocytes from IMPDH II(+/–) heterozygous mice are normal with respect to subpopulation distribution and respond normally to a variety of mitogenic stimuli. However, mice with an IMPDH II(+/–), HPRT(–/o) genotype demonstrate significantly decreased lymphocyte responsiveness to stimulation with anti-CD3 and anti-CD28 antibodies and show a 30% mean reduction in GTP levels in lymphocytes activated by these antibodies. Furthermore, the cytolytic activity of their T cells against allogeneic target cells is significantly impaired. These results demonstrate that a moderate decrease in the ability of murine lymphocytes to synthesize guanine nucleotides during stimulation results in significant impairment in T-cell activation and function