Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Structure and biological activity of a conformational constrained apolipoprotein A-I-derived helical peptide targeting the protein haptoglobin

The development of novel pharmacological treatments for atherosclerosis is an active research field in medicinal chemistry. It has been shown that the acute phase protein haptoglobin (Hpt) plays a role in modulating the reverse cholesterol transport binding to the HDL-major protein Apolipoprotein A-I, and it also plays a role in impairing the activity of the lecithin-cholesterol acyltransferase (LCAT). We reported that the peptide P2a in vitro and in vivo restores the LCAT activity in the presence of Hpt. Now, we have designed and characterized a conformational constrained P2a analogue, ApoAib, with the intention of improving Hpt binding and metabolic stability. Using non-proteogenic aminoisobutyric acid residues, we have obtained a well folded α-helical peptide with high proteolytic stability in serum. It binds to Hpt, impairs haptoglobin binding to HDL, and restores LCAT activity in the presence of haptoglobin. Furthermore, an interaction analysis using NMR revealed the peptide binding site involved in haptoglobin molecular recognition. In conclusion, ApoAib represents a promising candidate to improve reverse cholesterol transport for application in cardiovascular diseases. This journal i

Structure and biological activity of a conformational constrained apolipoprotein A-I-derived helical peptide targeting the protein haptoglobin

The development of novel pharmacological treatments for atherosclerosis is an active research field in medicinal chemistry. It has been shown that the acute phase protein haptoglobin (Hpt) plays a role in modulating the reverse cholesterol transport binding to the HDL-major protein Apolipoprotein A-I, and it also plays a role in impairing the activity of the lecithin-cholesterol acyltransferase (LCAT). We reported that the peptide P2a in vitro and in vivo restores the LCAT activity in the presence of Hpt. Now, we have designed and characterized a conformational constrained P2a analogue, ApoAib, with the intention of improving Hpt binding and metabolic stability. Using non-proteogenic aminoisobutyric acid residues, we have obtained a well folded α-helical peptide with high proteolytic stability in serum. It binds to Hpt, impairs haptoglobin binding to HDL, and restores LCAT activity in the presence of haptoglobin. Furthermore, an interaction analysis using NMR revealed the peptide binding site involved in haptoglobin molecular recognition. In conclusion, ApoAib represents a promising candidate to improve reverse cholesterol transport for application in cardiovascular diseases. This journal i

Int J Cancer

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person‐years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382–523), 136 in Latin America (95% CI: 85–219), 76 in North America (95% CI: 48–119) and 66 in Europe (95% CI: 57–77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27–4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73–16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37–1.71). Overall, ICC rates increased with age (>50 years vs. 16–30 years, aHR: 1.57, 95% CI: 1.03–2.40) and lower CD4 cell counts at ART initiation (per 100 cell/μl decrease, aHR: 1.25, 95% CI: 1.15–1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer‐related health inequities

Designing a broad-spectrum integrative approach for cancer prevention and treatment.

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered.Multiple funders. See acknowledgments within article for details.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.semcancer.2015.09.00