Phosphenes in space: a study on the interaction between carbon ions and rod photoreceptor

I fosfeni, o light flash, sono stati percepiti per la prima volta durante il volo verso la luna della navicella Apollo. In genere sono avvertiti al buio, prima di addormentarsi. In questa tesi si studia l'ipotesi di una eccitazione dei fotorecettori della retina da parte di ioni pesanti (carbonio). Campioni di recettori dei bastoncelli vengono irradiati, e viene studiato l'effetto degli ioni carbonio su topo, attraverso la registrazione della risposta elettrofisiologica (segnale retinico e corticale). La tesi si e' sviluppata nell'ambito del progetto ALTEA (Anomaluos Long Term Effect on Astronauts) e tutti gli esperimenti relativi a questo lavoro sono stati svolti a terra. L’obiettivo di ALTEA e’ piu’ generale e riguarda lo studio del rischio funzionale sul sistema nervoso centrale degli astronauti dovuto alla particelle ionizzanti presenti in condizioni di microgravita’ durante le missioni spaziali a lungo termine; ALTEA include sia esperimenti a terra che in orbita, a bordo della Sazione Spaziale Internazionale. La tesi inizia con una introduzione al progetto ALTEA; nel secondo capitolo e’ descritto lo studio chiamato ALTEA-MICE (Mice intermittent Irradiation with Concurrent Electrophysiological monitoring). Nel terzo capitolo sono descritto il sistema costituito dai segmenti esterni dei bastoncelli bovini in sospensione e il meccanismo di attivazione dei fotorecettori. Nel quarto capitolo e quinto capitolo mi sono occupata della interazione radiazione – materia nei tessuti e del caso specifico dell’irradiazione dei campioni dei segmenti esterni contenenti la rodopsina. Nel quinto e ultimo capitolo viene presentato un modello che spiega l’isomerizzazione (attivazione) del retinale della rodopsina come prodotto dell’azione dei radicali liberi provenienti dalla radiolisi dell’acqua.Phosphenes, or light flashes, have been reported by astronauts since the first Apollo flights to the Moon. They are usually described as occurring in the dark and typically before falling asleep. The light flashes are thought to originate as an effect of high- energy particles interacting with the visual system. The study presented in this thesis investigates the hypothesis of a direct excitation of the rod photoreceptors inside the retina and in particular the interaction between carbon ions and rods. Also the retinal and cortical electrophysiological response of mice submitted to carbon ions irradiation have been studied. This thesis has been developed as a section of the ’Anomalous Long Term Effects on Astronauts’ (ALTEA) program, and all the experiments concerning this thesis took place on ground. The objective of the ALTEA project is more general, and is aimed to assess the functional risks on the central nervous system due to particle flux in microgravity conditions during long term space mission. ALTEA includes a series of experiments both in orbit and on ground. The experiments on board International Space Station will contribute to define the causes of the anomalous phosphene perception of the astronauts by detecting the incident particles through the head of the astronauts and concurrently monitoring the central nervous system functionality. The experiments on ground include the direct irradiation with carbon ions of the outer segments of the rods, and an animal model to investigate the retina/cortex responses of mice irradiated in controlled laboratory experiments. In these experiments on ground I directly contributed in the preparation, the test and the optimization of the experiments and in the following analysis of the data. The whole project has been supported by the Italian Space Agency. The outline of this thesis includes an introduction to the interdisciplinary ALTEA program in the first chapter. In the second chapter ALTEA-MICE (Mice intermittent Irradiation with Concur- rent Electrophysiological monitoring) study is described: the experimental sessions as well as the evidences in the electrophysiological responses of the mouse retina have been described in detail. My role has been chiefly the experimental set up, and I also collaborated on the data analysis. The main results of this investigations have been published. In the third chapter the system of the rod outer segments in suspension and the mechanism of the activation of the photoreceptors are described. The fourth chapter deals with the radiation effects in the biological tissue, and in the fifth chapter there is particular regard to the effects of radiation on samples containing a suspension of rods extracted from bovine retinae. The effects on the rod photoreceptor rhodopsin has been studied: measurements have been performed irradiating with carbon ions the outer segments of the rods in suspension. The amount of the isomeric transformations (bleaching) of the molecules of chromophore into the photoreceptor gives the extent of the effects of radiation. I collaborated to the experiment and carried out the following data analysis. Finally, in the sixth chapter the process of the photo-isomerization of rhodopsin is explained by a model: the process starts with the water radiolysis and the formation of hydroxyl radicals OH in order to achieve the lipid peroxidation, then there is the subsequent emission of visible photons which are responsible for the photoreceptor bleaching. Since rhodopsin is surrounded by phospholipids, present in high concentration in the disc membranes, the effect of chemiluminescence is proposed to be the cause of the photo-transduction cascade and the light flash perception as a consequence. In order to test this hypothesis, a series of experiments was aimed at studying the effects of the hydroxyl radicals produced in an enzymatic way. The main results of this work are illustrated in chapter six, and have been published

Demographic variables, clinical aspects, and medicolegal implications in a population of patients with adjustment disorder

INTRODUCTION: Although adjustment disorder (AD) is considered as residual diagnosis and receives little attention in research, it plays an important role in clinical practice and also assumes an increasingly important role in the field of legal medicine, where the majority of diagnostic frameworks (eg, mobbing) often refer to AD. Our study aimed to look for specific stressor differences among demographic and clinical variables in a naturalistic setting of patients with AD. METHODS: A restrospective statistical analysis of the data of patients diagnosed with AD from November 2009 to September 2012, identified via manual search from the archive of the outpatient setting at the University Unit of Psychiatry "A. Fiorini" Hospital, Terracina (Latina, Italy), was performed. RESULTS: The sample consisted of 93 patients (46 males and 47 females), aged between 26 and 85, with medium-high educational level who were mainly employed. In most cases (54.80%), a diagnosis of AD with mixed anxiety and depressed mood was made. In all, 72% of the sample reported a negative family history for psychiatric disorders. In 22.60%, a previous history of psychopathology, especially mood disorders (76.19%), was reported. The main stressors linked to the development of AD were represented by working problems (32.30%), family problems (23.70%), and/or somatic disease (22.60%) with significant differences with respect to age and sex. Half of the patients were subjected to a single first examination; 24.47% requested a copy of medical records. CONCLUSION: Confirming previous data from previous reports, our results suggest that AD may have a distinct profile in demographic and clinical terms. Increased scientific attention is hoped, particularly focused on addressing a better definition of diagnostic criteria, whose correctness and accuracy are critical, especially in situations with medicolegal implications

Molecular detection of TP53, Ki-Ras and p16INK4A promoter methylation in plasma of patients with colorectal cancer and its association with prognosis. Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND:Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P <0.01), whereas only a trend towards statistical significance (P = 0.083) was observed for the TP53 mutations CONCLUSIONS: Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence. These data suggest that patients with a high risk of recurrence can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques

Dynamics in a supercooled molecular liquid: Theory and Simulations

We report extensive simulations of liquid supercooled states for a simple three-sites molecular model, introduced by Lewis and Wahnstr"om [L. J. Lewis and G. Wahnstr"om, Phys. Rev. E 50, 3865 (1994)] to mimic the behavior of ortho-terphenyl. The large system size and the long simulation length allow to calculate very precisely --- in a large q-vector range --- self and collective correlation functions, providing a clean and simple reference model for theoretical descriptions of molecular liquids in supercooled states. The time and wavevector dependence of the site-site correlation functions are compared with detailed predictions based on ideal mode-coupling theory, neglecting the molecular constraints. Except for the wavevector region where the dynamics is controlled by the center of mass (around 9 nm-1), the theoretical predictions compare very well with the simulation data.

Detection and quantification of mammaglobin in the blood of breast cancer patients: can it be useful as a potential clinical marker? Preliminary results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity and specificity of transcript MGB1 detection and to evaluate the role of MGB1 as potential clinical marker for the detection of disseminated cancer cells in the blood of BC patients. PATIENTS AND METHODS: A consecutive series of 23 BC tissues, 36 peripheral blood BC samples and 35 healthy peripheral blood samples was prospectively recruited to investigate MGB1 expression by means of a quantitative Real Time RT-PCR assay. RESULTS: MGB1 overexpression in tissue samples of BC patients is significantly associated only with high level of Ki67 (P <0.05). None of the samples from peripheral blood of 35 healthy female individuals were positive for MGB1 transcript. In contrast MGB1 mRNA expression was detected in three of 36 (8%) peripheral blood of BC patients. CONCLUSIONS: Our preliminary results demonstrate that the detection of MGB1 transcript in peripheral blood of BC patients was specific but with low sensitivity. MGB1 overexpression by itself or in combination with Ki67 might be considered an index of BC progression

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Measurements of the Higgs boson production and decay rates and coupling strengths using pp collision data at √S=7 and 8 TeV in the ATLAS experiment

Combined analyses of the Higgs boson production and decay rates as well as its coupling strengths to vector bosons and fermions are presented. The combinations include the results of the analyses of the H -> gamma gamma, ZZ*, WW*, Z gamma, b (b) over bar, tau tau and mu mu decay modes, and the constraints on the associated production with a pair of top quarks and on the off-shell coupling strengths of the Higgs boson. The results are based on the LHC proton-proton collision datasets, with integrated luminosities of up to 4.7 fb(-1) at root s = 7 TeV and 20.3 fb(-1) at root s = 8 TeV, recorded by the ATLAS detector in 2011 and 2012. Combining all production modes and decay channels, the measured signal yield, normalised to the Standard Model expectation, is 1.18(-0.14)(+0.15). The observed Higgs boson production and decay rates are interpreted in a leading-order coupling framework, exploring a wide range of benchmark coupling models both with and without assumptions on the Higgs boson width and on the Standard Model particle content in loop processes. The data are found to be compatible with the Standard Model expectations for a Higgs boson at a mass of 125.36 GeV for all models considered

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&gt;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&lt;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