KEMTUB012-NI2, a novel potent tubulysin analog that selectively targets hypoxic cancer cells and is potentiated by cytochrome p450 reductase downregulation

Peer reviewedPublisher PD

Coffee-based colloids for direct solar absorption

Despite their promising thermo-physical properties for direct solar absorption, carbon-based nanocolloids present some drawbacks, among which the unpleasant property of being potentially cytotoxic and harmful to the environment. In this work, a sustainable, stable and inexpensive colloid based on coffee is synthesized and its photo-thermal properties investigated. The proposed colloid consists of distilled water, Arabica coffee, glycerol and copper sulphate, which provide enhanced properties along with biocompatibility. The photo-thermal performance of the proposed fluid for direct solar absorption is analysed for different dilutions and compared with that of a traditional flat-plate collector. Tailor-made collectors, opportunely designed and realized via 3D-printing technique, were used for the experimental tests. The results obtained in field conditions, in good agreement with two different proposed models, show similar performance of the volumetric absorption using the proposed coffee-based colloids as compared to the classical systems based on a highly-absorbing surface. These results may encourage further investigations on simple, biocompatible and inexpensive colloids for direct solar absorption

Development of Fluorinated Analogues of Perhexiline with Improved Pharmacokinetic Properties and Retained Efficacy

We designed and synthesized perhexiline analogues that have the same therapeutic profile as the parent cardiovascular drug but lacking its metabolic liability associated with CYP2D6 metabolism. Cycloalkyl perhexiline analogues 6a–j were found to be unsuitable for further development, as they retained a pharmacokinetic profile very similar to that shown by the parent compound. Multistep synthesis of perhexiline analogues incorporating fluorine atoms onto the cyclohexyl ring(s) provided a range of different fluoroperhexiline analogues. Of these, analogues 50 (4,4-gem-difluoro) and 62 (4,4,4′,4′-tetrafluoro) were highly stable and showed greatly reduced susceptibility to CYP2D6-mediated metabolism. In vitro efficacy studies demonstrated that a number of derivatives retained acceptable potency against CPT-1. Having the best balance of properties, 50 was selected for further evaluation. Like perhexiline, it was shown to be selectively concentrated in the myocardium and, using the Langendorff model, to be effective in improving both cardiac contractility and relaxation when challenged with high fat buffer

Spectroastrometry of rotating gas disks for the detection of supermassive black holes in galactic nuclei. II. Application to the galaxy Centaurus A (NGC 5128)

We measure the black hole mass in the nearby active galaxy Centaurus A (NGC 5128) using a new method based on spectroastrometry of a rotating gas disk. The spectroastrometric approach consists in measuring the photocenter position of emission lines for different velocity channels. In a previous paper we focused on the basic methodology and the advantages of the spectroastrometric approach with a detailed set of simulations demonstrating the possibilities for black hole mass measurements going below the conventional spatial resolution. In this paper we apply the spectroastrometric method to multiple longslit and integral field near infrared spectroscopic observations of Centaurus A. We find that the application of the spectroastrometric method provides results perfectly consistent with the more complex classical method based on rotation curves: the measured BH mass is nearly independent of the observational setup and spatial resolution and the spectroastrometric method allows the gas dynamics to be probed down to spatial scales of ~0.02", i.e. 1/10 of the spatial resolution and ~1/50 of BH sphere of influence radius. The best estimate for the BH mass based on kinematics of the ionized gas is then log(MBH (sin i)^2/M\odot)=7.5 \pm 0.1 which corresponds to MBH = 9.6(+2.5-1.8) \times 10^7 M\odot for an assumed disk inclination of i = 35deg. The complementarity of this method with the classic rotation curve method will allow us to put constraints on the disk inclination which cannot be otherwise derived from spectroastrometry. With the application to Centaurus A, we have shown that spectroastrometry opens up the possibility of probing spatial scales smaller than the spatial resolution, extending the measured MBH range to new domains which are currently not accessible: smaller BHs in the local universe and similar BHs in more distant galaxies

The effect of social media and infodemic on mental health during the COVID-19 pandemic: results from the COMET multicentric trial

On January 30, 2020, the World Health Organization (WHO) declared the status of pandemic due to the COVID-19 infection. The initial phases of the pandemic were characterized by uncertainty and public fears. In order to cope with such unexpected conditions, people adopted different coping strategies, including search for information, accessing Internet, and using social media. The present study based on the COMET collaborative research network aims to: (1) assess use of Internet and of social media among the Italian general population; (2) explore differences in web usage between people with pre-existing mental disorders and the general population; (3) identify changes over time in social media usage along the phase 1 of the pandemic; (4) identify the clinical, socio-demographic and contextual predictors of excessive use of social media. A significant increase in time spent on Internet, with an average time of 4.8 ± 0.02 h per day, was found in the global sample of 20,720 participants. Compared with the general population, Internet use was significantly higher in people with pre-existing mental disorders (5.2 ± 0.1 h vs. 4.9 ± 0.02; p < 0.005). According to the multivariate logistic regression model, the risk of excessive use of social media and Internet was significantly higher in people with moderate levels of depressive symptoms (OR: 1.26, CI 95%: 0.99 to 1.59, p < 0.0.005); while protective factors were being students (OR: 0.72, CI 95%: 0.53 to 0.96, p < 0.0029) and living in central Italy (OR: 0.46, CI 95%: 0.23 to 0.90, p < 0.002). The evaluation of social media and Internet use by the general population represents a first step for developing specific protective and supportive interventions for the general population, including practical suggestions on how to safely use Internet and social media

Enhanced Star Formation in Narrow Line Seyfert 1 AGN revealed by Spitzer

We present new low resolution Spitzer mid-infrared spectroscopy of a sample of 20 ROSAT selected local Narrow Line Seyfert 1 galaxies (NLS1s). We detect strong AGN continuum in all and clear PAH emission in 70% of the sources. The 6.2 micron PAH luminosity spans three orders of magnitudes, from ~10^(39) erg/s to ~10^(42) erg/s providing strong evidence for intense ongoing star formation in the circumnuclear regions of these sources. Using the IRS/Spitzer archive we gather a large number of additional NLS1s and their broad line counterparts (BLS1s) and constructed NLS1 and BLS1 sub-samples to compare them in various ways. The comparison shows a clear separation according to FWHM(H_beta) such that objects with narrower broad H_beta lines are the strongest PAH emitters. We test this division in various ways trying to remove biases due to luminosity and aperture size. Specifically, we find that star formation activity around NLS1 AGN is larger than around BLS1 of the same AGN luminosity. The above result seems to hold over the entire range of distance and luminosity. Moreover the star formation rate is higher in low black hole mass and high L/L_Edd systems indicating that black hole growth and star formation are occurring simultaneously.Comment: 30 pages, 11 figures, 4 tables. Now accepted in MNRA

The effect of social media and infodemic on mental health during the COVID-19 pandemic: results from the COMET multicentric trial

On January 30, 2020, the World Health Organization (WHO) declared the status of pandemic due to the COVID-19 infection. The initial phases of the pandemic were characterized by uncertainty and public fears. In order to cope with such unexpected conditions, people adopted different coping strategies, including search for information, accessing Internet, and using social media. The present study based on the COMET collaborative research network aims to: (1) assess use of Internet and of social media among the Italian general population; (2) explore differences in web usage between people with pre-existing mental disorders and the general population; (3) identify changes over time in social media usage along the phase 1 of the pandemic; (4) identify the clinical, socio-demographic and contextual predictors of excessive use of social media. A significant increase in time spent on Internet, with an average time of 4.8  ±  0.02 h per day, was found in the global sample of 20,720 participants. Compared with the general population, Internet use was significantly higher in people with pre-existing mental disorders (5.2  ± 0.1 h vs. 4.9  ±  0.02; p &lt; 0.005). According to the multivariate logistic regression model, the risk of excessive use of social media and Internet was significantly higher in people with moderate levels of depressive symptoms (OR: 1.26, CI 95%: 0.99 to 1.59, p &lt; 0.0.005); while protective factors were being students (OR: 0.72, CI 95%: 0.53 to 0.96, p &lt; 0.0029) and living in central Italy (OR: 0.46, CI 95%: 0.23 to 0.90, p &lt; 0.002). The evaluation of social media and Internet use by the general population represents a first step for developing specific protective and supportive interventions for the general population, including practical suggestions on how to safely use Internet and social media

Technology and technique for left ventricular assist device optimization: A Bi-Tech solution

Background We investigated the synergistic effect of the new cone-bearing design of Jarvik 2000 (Jarvik Heart Inc., NY) together with a minimally-invasive approach to outcomes of LVAD patients. Methods We retrospectively reviewed all patients from 5 institutions involved in the Jarvik 2000 Italian Registry, from October 2008 to October 2016. Patients were divided into three groups according to pump design and implantation technique: pin-bearing design and conventional approach (Group 1); cone-bearing and conventional approach (Group 2); cone-bearing and minimally-invasive implantation (Group 3). Results A total of 150 adult patients with end-stage heart failure were enrolled: 26 subjects in Group 1, 74 in Group 2, and 50 in Group 3. Nineteen patients (73%) in Group 1, 51 (69%) in Group 2, and 36 (72%) in Group 3 were discharged. During follow-up, 22 patients underwent transplantation, while in 3 patients the LVAD was explanted. The overall 1-year survival was 58 +/- 10%, 64 +/- 6%, and 74% +/- 7% in Groups 1, 2, and 3, respectively (p = 0.034). The competing-risks-adjusted cumulative incidence rate for adverse events was 42.1 [27-62.7] per 100 patient-years in Group 1, 35.4 [25.3-48.2] in Group 2, and 22.1 [12.4-36.4] in Group 3 (p = 0.046 for Group 1 vs. 3). Conclusions The association of the modern cone-bearing configuration of Jarvik 2000 and minimally invasive surgery improved survival and minimized the risk for cardiovascular events, as a result of combining technology and technique

Seeding black holes in cosmological simulations

We present a new model for the formation of black holes in cosmological simulations, motivated by the first star formation. Black holes form from high density peaks of primordial gas, and grow via both gas accretion and mergers. Massive black holes heat the surrounding material, suppressing star formation at the centres of galaxies, and driving galactic winds. We perform an investigation into the physical effects of the model parameters, and obtain a 'best' set of these parameters by comparing the outcome of simulations to observations. With this best set, we successfully reproduce the cosmic star formation rate history, black hole mass-velocity dispersion relation, and the size-velocity dispersion relation of galaxies. The black hole seed mass is ~103M{⊙}, which is orders of magnitude smaller than that which has been used in previous cosmological simulations with active galactic nuclei, but suggests that the origin of the seed black holes is the death of Population III stars.Peer reviewedFinal Accepted Versio