Genome-wide multi-parametric analysis of H2AX or γH2AX distributions during ionizing radiation-induced DNA damage response

Background: After induction of DNA double strand breaks (DSBs), the DNA damage response (DDR) is activated. One of the earliest events in DDR is the phosphorylation of serine 139 on the histone variant H2AX (gH2AX) catalyzed by phosphatidylinositol 3-kinases-related kinases. Despite being extensively studied, H2AX distribution[1] across the genome and gH2AX spreading around DSBs sites[2] in the context of different chromatin compaction states or transcription are yet to be fully elucidated. Materials and methods: gH2AX was induced in human hepatocellular carcinoma cells (HepG2) by exposure to 10 Gy X-rays (250 kV, 16 mA). Samples were incubated 0.5, 3 or 24 hours post irradiation to investigate early, intermediate and late stages of DDR, respectively. Chromatin immunoprecipitation was performed to select H2AX, H3 and gH2AX-enriched chromatin fractions. Chromatin-associated DNA was then sequenced by Illumina ChIP-Seq platform. HepG2 gene expression and histone modification (H3K36me3, H3K9me3) ChIP-Seq profiles were retrieved from Gene Expression Omnibus (accession numbers GSE30240 and GSE26386, respectively). Results: First, we combined G/C usage, gene content, gene expression or histone modification profiles (H3K36me3, H3K9me3) to define genomic compartments characterized by different chromatin compaction states or transcriptional activity. Next, we investigated H3, H2AX and gH2AX distributions in such defined compartments before and after exposure to ionizing radiation (IR) to study DNA repair kinetics during DDR. Our sequencing results indicate that H2AX distribution followed H3 occupancy and, thus, the nucleosome pattern. The highest H2AX and H3 enrichment was observed in transcriptionally active compartments (euchromatin) while the lowest was found in low G/C and gene-poor compartments (heterochromatin). Under physiological conditions, the body of highly and moderately transcribed genes was devoid of gH2AX, despite presenting high H2AX levels. gH2AX accumulation was observed in 5’ or 3’ flanking regions, instead. The same genes showed a prompt gH2AX accumulation during the early stage of DDR which then decreased over time as DDR proceeded. Finally, during the late stage of DDR the residual gH2AX signal was entirely retained in heterochromatic compartments. At this stage, euchromatic compartments were completely devoid of gH2AX despite presenting high levels of non-phosphorylated H2AX. Conclusions: We show that gH2AX distribution ultimately depends on H2AX occupancy, the latter following H3 occupancy and, thus, nucleosome pattern. Both H2AX and H3 levels were higher in actively transcribed compartments. However, gH2AX levels were remarkably low over the body of actively transcribed genes suggesting that transcription levels antagonize gH2AX spreading. Moreover, repair processes did not take place uniformly across the genome; rather, DNA repair was affected by genomic location and transcriptional activity. We propose that higher H2AX density in euchromaticcompartments results in high relative gH2AXconcentration soon after the activation of DDR, thus favoring the recruitment of the DNA repair machinery to those compartments. When the damage is repaired and gH2AX is removed, its residual fraction is retained in the heterochromatic compartments which are then targeted and repaired at later times

Post vaccinal temporary sensorineural hearing loss

In our systematic research we identified four studies concerning the onset of neurological adverse events following vaccination and two excluding this association. A 33-year-old Italian man, belonging to the Italian Army was hospitalized because he suffered from vertigo, nausea and sudden right hearing loss not classified (NDD), that set in 24 h after the administration of tetanus-diphtheria and meningococcal vaccines. Some neurological events arising after vaccination are very difficult to treat. In our case, the functional recovery on low and medium frequencies was possible about 6 months after the morbid event

Multi-Criteria Optimization of Real-Time DAGs on Heterogeneous Platforms under P-EDF

This paper tackles the problem of optimal placement of complex real-time embedded applications on heterogeneous platforms. Applications are composed of directed acyclic graphs of tasks, with each DAG having a minimum inter-arrival period for its activation requests, and an end-to-end deadline within which all of the computations need to terminate since each activation. The platforms of interest are heterogeneous power-aware multi-core platforms with DVFS capabilities, including big.LITTLE Arm architectures, and platforms with GPU or FPGA hardware accelerators with Dynamic Partial Reconfiguration capabilities. Tasks can be deployed on CPUs using partitioned EDF-based scheduling. Additionally, some of the tasks may have an alternate implementation available for one of the accelerators on the target platform, which are assumed to serve requests in non-preemptive FIFO order. The system can be optimized by: minimizing power consumption, respecting precise timing constraints; maximizing the applications’ slack, respecting given power consumption constraints; or even a combination of these, in a multi-objective formulation. We propose an off-line optimization of the mentioned problem based on mixed-integer quadratic constraint programming (MIQCP). The optimization provides the DVFS configuration of all the CPUs (or accelerators) capable of frequency switching and the placement to be followed by each task in the DAGs, including the software-vs-hardware implementation choice for tasks that can be hardware-accelerated. For relatively big problems, we developed heuristic solvers capable of providing suboptimal solutions in a significantly reduced time compared to the MIQCP strategy, thus widening the applicability of the proposed framework. We validate the approach by running a set of randomly generated DAGs on Linux under SCHED_DEADLINE, deployed onto two real boards, one with Arm big.LITTLE architecture, the other with FPGA acceleration, verifying that the experimental runs meet the theoretical expectations in terms of timing and power optimization goals

Nanolesions induced by heavy ions in human tissues: experimental and theoretical studies

The biological effects of energetic heavy ions are attracting increasing interest for their applications in cancer therapy and protection against space radiation. The cascade of events leading to cell death or late effects starts from stochastic energy deposition on the nanometer scale and the corresponding lesions in biological molecules, primarily DNA. We have developed experimental techniques to visualize DNA nanolesions induced by heavy ions. Nanolesions appear in cells as “streaks” which can be visualized by using different DNA repair markers. We have studied the kinetics of repair of these “streaks” also with respect to the chromatin conformation. Initial steps in the modeling of the energy deposition patterns at the micrometer and nanometer scale were made with MCHIT and TRAX models, respectively

The touristic sector in the 5G technology era: the 5G-TOURS project approach

5G mobile networks are designed to fulfill very stringent requirements and support new vertical use cases. This transition to a vertical oriented delivery model will have a strong impact in the touristic sector. In this context, the "touristic city node" of 5G-TOURS, built in the city of Turin, aims at exploiting the potential of the media vertical. The objective is to develop an innovative tourism concept based on complementary and linked trials for five specific use cases. The trials will promote an overall integrated indoor/outdoor immersive experience to the visitors using any possible device, enhancing the accessibility to the technology especially for disadvantaged and disabled people. They will also utilize 5G to drive "remote tourism" based on AR/VR experiences and bridge the gap between the physical and virtual worlds for tourism. This paper provides an overview of the 5G technology deployed in the touristic node, explaining the different services to be provided and discussing the need of 5G technology to support this vision. This work also assesses the business potential of each of the considered use cases, corroborating their potential in the context of future network services.This work was supported in part by the European Commission under the 5G-TOURS: SmarT mObility, media and e-health for toURists and citizenS (H2020-ICT-2018-2020 call, grant number 856950)

Realdo Colombo in the fifth centenary of his birth

The date of birth of Realdo Colombo is still uncertain. However, 1516 is conventionally credited as the year where he was born in Cremona. Colombo’s life can be divided into three periods, according to the cities where he worked: Padua, Pisa and Rome. A talented anatomist, in Padua Colombo became assistant of Andreas Vesalius in 1541. In 1545 he moved to Pisa at the behest of the Grand Duke Cosimo I de’ Medici. Finally, he was invited in Rome by Pope Paul III and became the physician of many important patients, including Michelangelo Buonarroti. He also performed the autopsy on the body of Saint Ignatius of Loyola. In his unique masterpiece, De re anatomica, consisting of 15 books, Colombo reported original observations. He hoped to have a text illustrated by Michelangelo that would have competed with the fabrica of Vesalius, but that purpose did not realize. Indeed, the unique engraving of the volume, published posthumously in 1559, is the frontispiece. The most important anatomical discovery attributed to Colombo is the original description of the pulmonary circulation, based on hundreds of dissections and vivisections. The Galen’s long-standing doctrine of the blood circulation from the right ventricle to the left ventricle through invisible pores of the interventricular septum was definitively rejected. Although two other figures had already described the pulmonary circulation – the thirteenth century Arabic physician Ibn al-Nafis, in the Commentary on Anatomy in Avicenna’s Canon, and the Spanish philosopher Michael Servetus, in the theological book Christianismi restitutio – Colombo seems to have arrived at his conclusions independently. He also understood the function of the cardiac valves. Colombo’s book had a profound effect on William Harvey, when he prepared his lectures on anatomy for the College of Physicians of London, and was determinant for the publication of his description of the blood circulation in De motu cordis (1628). Other anatomical observations are attributed to Colombo. He corrected previous misconceptions, demonstrating that the right kidney is lower than the left, and showing that the lens is in the anterior chamber of the eye. He recognized anatomical variants, such as the presence of palmaris longus muscle, and described congenital malformations, such as the horseshoe kidney. He also seems to have coined the term “placenta” and claimed to have been the first to describe the clitoris and its function

Proton pump inhibitors and serum magnesium levels in patients with Torsades de Pointes

Background: Torsades de pointes (TdP) is a life-threatening ventricular tachycardia occurring in long QT-syndrome patients. It usually develops when multiple QT-prolonging factors are concomitantly present, more frequently drugs and electrolyte imbalances. Since proton-pump inhibitors (PPIs)-associated hypomagnesemia is an increasingly recognized adverse event, PPIs were recently included in the list of drugs with conditional risk of TdP, despite only few cases of TdP in PPI users have been reported so far. Objectives: Aim of the present study is to evaluate whether PPI-induced hypomagnesemia actually has a significant clinical impact on the risk of TdP in the general population. Methods: Forty-eight unselected patients who experienced TdP were consecutively enrolled (2008-2017). Shortly after the first TdP episode, in those patients who did not receive magnesium sulfate and/or potassium or calcium replacement therapy, serum electrolytes were measured and their relationship with PPI usage analyzed. Results: Many patients (28/48, 58%) were under current PPI treatment when TdP occurred. Among TdP patients in whom serum electrolyte determinations were obtained before replacement therapy (27/48), those taking PPIs had significantly lower serum magnesium levels than those who did not. Hypomagnesemia occurred in ~40% of patients receiving PPIs (6/14), in all cases after an extended treatment (> 2 weeks). In patients taking PPIs the mean QT-prolonging risk factor number was significantly higher than in those who did not, a difference which was mainly driven by lower magnesium levels. Conclusions: In unselected TdP patients, PPI-induced hypomagnesemia was common and significantly contributed to their cumulative arrhythmic risk. By providing clinical support to current recommendations, our data confirm that more awareness is needed when a PPI is prescribed, specifically as regards the risk of life-threatening arrhythmias

The Far-Infrared Radiation Mobile Observation System (FIRMOS) for spectral characterization of the atmospheric emission

The Far-Infrared Radiation Mobile Observation System (FIRMOS) is a Fourier transform spectroradiometer developed to support the Far-infrared Outgoing Radiation Understanding and Monitoring (FORUM) satellite mission by validating measurement methods and instrument design concepts, both in the laboratory and in field campaigns. FIRMOS is capable of measuring the downwelling spectral radiance emitted by the atmosphere in the spectral band from 100 to 1000 cm$^{−1}$ (10–100 µm in wavelength), with a maximum spectral resolution of 0.25 cm$^{−1}$. We describe the instrument design and its characterization and discuss the geophysical products obtained by inverting the atmospheric spectral radiance measured during a campaign from the high-altitude location of Mount Zugspitze in Germany, beside the Extended-range Atmospheric Emitted Radiance Interferometer (E-AERI), which is permanently installed at the site. Following the selection of clear-sky scenes, using a specific algorithm, the water vapour and temperature profiles were retrieved from the FIRMOS spectra by applying the Kyoto protocol and Informed Management of the Adaptation (KLIMA) code. The profiles were found in very good agreement with those provided by radiosondes and by the Raman lidar operating from the Zugspitze Schneefernerhaus station. In addition, the retrieval products were validated by comparing the retrieved integrated water vapour values with those obtained from the E-AERI spectra

Empirical experiments on intrinsic motivations and action acquisition: results, evaluation, and redefinition

This document presents Deliverable D3.2 of the EU-funded Integrated Project "IM-CLeVeR - Intrinsically Motivated Cumulative Learning Versatile Robots", contract n. FP7-ICT-IP-231722.The aims of the deliverable, as given in the original IM-CLEVER proposal were to identify new key empirical phenomena and processes, allowing the design of a second set of experiments. This report covers: (1) novelty detection and discovery of when/what/how of agency in experiments with humans ("joystick experiment") and Parkinson patients. (2) how object properties that stimulate intrinsically motivated interaction and facilitate the acquisition of adaptive knowledge and skills in monkeys and children ("board experiment")