Constraining the primordial black hole scenario with Bayesian inference and machine learning: the GWTC-2 gravitational wave catalog

Primordial black holes (PBHs) might be formed in the early Universe and could comprise at least a fraction of the dark matter. Using the recently released GWTC-2 dataset from the third observing run of the LIGO-Virgo Collaboration, we investigate whether current observations are compatible with the hypothesis that all black hole mergers detected so far are of primordial origin. We constrain PBH formation models within a hierarchical Bayesian inference framework based on deep learning techniques, finding best-fit values for distinctive features of these models, including the PBH initial mass function, the fraction of PBHs in dark matter, and the accretion efficiency. The presence of several spinning binaries in the GWTC-2 dataset favors a scenario in which PBHs accrete and spin up. Our results indicate that PBHs may comprise only a fraction smaller than $0.3 \%$ of the total dark matter, and that the predicted PBH abundance is still compatible with other constraints.Comment: 14 pages, 5 figures. v2: matching published versio

Developing Cyber-risk Centric Courses and Training Material for Cyber Ranges: A Systematic Approach

The use of cyber ranges to train and develop cybersecurity skills and awareness is attracting more attention, both in public and private organizations. However, cyber ranges typically focus mainly on hands-on exercises and do not consider aspects such as courses, learning goals and learning objectives, specific skills to train and develop, etc. We address this gap by proposing a method for developing courses and training material based on identified roles and skills to be trained in cyber ranges. Our method has been used by people with different background grouped in academia, critical infrastructure, research, and service providers who have developed 22 courses including hands-on exercises. The developed courses have been tried out in pilot studies by SMEs. Our assessment shows that the method is feasible and that it considers learning and educational aspects by facilitating the development of courses and training material for specific cybersecurity roles and skills.acceptedVersio

Immunometabolism Modulation by Extracts from Pistachio Stalks Formulated in Phospholipid Vesicles

Several studies have demonstrated the effectiveness of plant extracts against various diseases, especially skin disorders; namely, they exhibit overall protective effects. The Pistachio (Pistacia vera L.) is known for having bioactive compounds that can effectively contribute to a person’s healthy status. However, these benefits may be limited by the toxicity and low bioavailability often inherent in bioactive compounds. To overcome these problems, delivery systems, such as phospholipid vesicles, can be employed. In this study, an essential oil and a hydrolate were produced from P. vera stalks, which are usually discarded as waste. The extracts were characterized by liquid and gas chromatography coupled with mass spectrometry and formulated in phospholipid vesicles intended for skin application. Liposomes and transfersomes showed small size (<100 nm), negative charge (approximately −15 mV), and a longer storage stability for the latter. The entrapment efficiency was determined via the quantification of the major compounds identified in the extracts and was >80%. The immune-modulating activity of the extracts was assayed in macrophage cell cultures. Most interestingly, the formulation in transfersomes abolished the cytotoxicity of the essential oil while increasing its ability to inhibit inflammatory mediators via the immunometabolic citrate pathway

Quantifying the evidence for primordial black holes in LIGO/Virgo gravitational-wave data

With approximately 50 binary black hole events detected by LIGO/Virgo to date and many more expected in the next few years, gravitational-wave astronomy is shifting from individual-event analyses to population studies. We perform a hierarchical Bayesian analysis on the GWTC-2 catalog by combining several astrophysical formation models with a population of primordial black holes. We compute the Bayesian evidence for a primordial population compared to the null hypothesis, and the inferred fraction of primordial black holes in the data. We find that these quantities depend on the set of assumed astrophysical models: the evidence for primordial black holes against an astrophysical-only multichannel model is decisively favored in some scenarios, but it is significantly reduced in the presence of a dominant stable-mass-transfer isolated formation channel. The primordial channel can explain mergers in the upper mass gap such as GW190521, but (depending on the astrophysical channels we consider) a significant fraction of the events could be of primordial origin even if we neglected GW190521. The tantalizing possibility that LIGO/Virgo may have already detected black holes formed after inflation should be verified by reducing uncertainties in astrophysical and primordial formation models, and it may ultimately be confirmed by third-generation interferometers.Comment: 12 pages, 7 figures. v2: Version submitted to journal. The Bayesian analysis was extended to additional astrophysical channels by taking into account feedback from the community, and the conclusions were revised accordingl

Association of neovascular age-related macular degeneration with month and season of birth in Italy

In order to investigate the influence of season and month of birth on the risk of neovascular age-related macular degeneration (n-AMD) in Italy, we evaluated the month birth and sex of all patients, recorded in the anti-vascular endothelial growth factor (VEGF) monitoring registry of the Italian Medicines Agency, born between 1925-1944, who received intravitreal anti-VEGF injections for n-AMD between January 1, 2013 and July 29, 2015. The numbers of all births in Italy in the same years, extracted from the Italian National Institute of Statistics, were used to calculate the expected number of n-AMD cases. Overall, 45,845 patients (19,207 men, 26,638 women) received intravitreal anti-VEGF for n-AMD; in the same years, 20,140,426 people (10,334,262 male, 9,806,164 female) were born in Italy. Comparing the observed number of n-AMD cases with the expected number of n- AMD cases in each season, we found that the season-specific risk for n-AMD was 2.5% higher for those born in summer (OR=1.03, Bonferroni-corrected P=0.008) and 3% lower for those born in winter (OR=0.96, Bonferroni-corrected P=0.0004). When considering the month of birth, the risk of n-AMD was 5.9% lower for people born in January (OR=0.93, Bonferroni-corrected P=0.0012). The factors causing such differences should be determined

Antitumor Agents. 1. Synthesis, Biological Evaluation, and Molecular Modeling of 5H-Pyrido[3,2-a]phenoxazin-5-one, a Compound with Potent Antiproliferative Activity

The iminoquinone is an important moiety of a large number of antineoplastic drugs and plays a significant role in the nucleus of actinomycins, powerful, highly toxic, natural antibiotics that target DNA as intercalating agents. A series of polycyclic iminoquinonic compounds, 2-amino-3H-phenoxazin-3-one (1), 2-amino-1,9-diacetyl-3H-phenoxazin-3-one (2), 2-acetylamino- 3H-phenoxazin-3-one (3), 3H-phenoxazin-3-one (4), 5H-pyrido[3,2-a]phenoxazin-5-one (5), and 5H-pyrido[3,2-a]phenothiazin-5-one (6), strictly related to the actinomycin chromophore, were synthesized for developing new anticancer intercalating drugs. The antiproliferative activity of these compounds, evaluated against representative human liquid and solid neoplastic cell lines, showed that 5 and its isoster 6 were the most active compounds inhibiting cell proliferation in a submicromolar range. Compound 5 was also evaluated against KB subclones (KBMDR, KB7D, and KBV20C), which overexpress the MDR1/P-glycoprotein drug efflux pump responsible for drug resistance. All the above KB subclones did not show altered sensitivity to the antiproliferative activity of 5. UV-vis and 1H NMR spectroscopy experiments support the phenoxazinone 5/DNA binding. Molecular mechanics methods were used to build a three-dimensional model of the 5/[d(GAAGCTTC)]2 complex. Electrostatic interactions between the hydrogen of the positively charged pyridine nitrogen of 5 and the negatively charged oxygen atoms (O4¢ and O5¢) of the cytosine C5 residue together with stacking forces contribute to the high antiproliferative activity. The metal(II)-assisted synthesis procedure of 5 is described, and the formation mechanism is proposed

Accumulation of neutral lipids in peripheral blood mononuclear cells as a distinctive trait of Alzheimer patients and asymptomatic subjects at risk of disease

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease is the most common progressive neurodegenerative disease. In recent years, numerous progresses in the discovery of novel Alzheimer's disease molecular biomarkers in brain as well as in biological fluids have been made. Among them, those involving lipid metabolism are emerging as potential candidates. In particular, an accumulation of neutral lipids was recently found by us in skin fibroblasts from Alzheimer's disease patients. Therefore, with the aim to assess whether peripheral alterations in cholesterol homeostasis might be relevant in Alzheimer's disease development and progression, in the present study we analyzed lipid metabolism in plasma and peripheral blood mononuclear cells from Alzheimer's disease patients and from their first-degree relatives.</p> <p>Methods</p> <p>Blood samples were obtained from 93 patients with probable Alzheimer's disease and from 91 of their first-degree relatives. As controls we utilized 57, cognitively normal, over-65 year-old volunteers and 113 blood donors aged 21-66 years, respectively. Data are reported as mean ± standard error. Statistical calculations were performed using the statistical analysis software Origin 8.0 version. Data analysis was done using the Student t-test and the Pearson test.</p> <p>Results</p> <p>Data reported here show high neutral lipid levels and increased ACAT-1 protein in about 85% of peripheral blood mononuclear cells freshly isolated (<it>ex vivo</it>) from patients with probable sporadic Alzheimer's disease compared to about 7% of cognitively normal age-matched controls. A significant reduction in high density lipoprotein-cholesterol levels in plasma from Alzheimer's disease blood samples was also observed. Additionally, correlation analyses reveal a negative correlation between high density lipoprotein-cholesterol and cognitive capacity, as determined by Mini Mental State Examination, as well as between high density lipoprotein-cholesterol and neutral lipid accumulation. We observed great variability in the neutral lipid-peripheral blood mononuclear cells data and in plasma lipid analysis of the subjects enrolled as Alzheimer's disease-first-degree relatives. However, about 30% of them tend to display a peripheral metabolic cholesterol pattern similar to that exhibited by Alzheimer's disease patients.</p> <p>Conclusion</p> <p>We suggest that neutral lipid-peripheral blood mononuclear cells and plasma high density lipoprotein-cholesterol determinations might be of interest to outline a distinctive metabolic profile applying to both Alzheimer's disease patients and asymptomatic subjects at higher risk of disease.</p