Absorbed dose evaluation of Auger electron-emitting radionuclides: impact of input decay spectra on dose point kernels and S-values

The aim of this study was to investigate the impact of decay data provided by the newly developed stochastic atomic relaxation model BrIccEmis on dose point kernels (DPKs - radial dose distribution around a unit point source) and S-values (absorbed dose per unit cumulated activity) of 14 Auger electron (AE) emitting radionuclides, namely 67Ga, 80mBr, 89Zr, 90Nb, 99mTc, 111In, 117mSn, 119Sb, 123I, 124I, 125I, 135La, 195mPt and 201Tl. Radiation spectra were based on the nuclear decay data from the medical internal radiation dose (MIRD) RADTABS program and the BrIccEmis code, assuming both an isolated-atom and condensed-phase approach. DPKs were simulated with the PENELOPE Monte Carlo (MC) code using event-by-event electron and photon transport. S-values for concentric spherical cells of various sizes were derived from these DPKS using appropriate geometric reduction factors. The number of Auger and Coster-Kronig (CK) electrons and x-ray photons released per nuclear decay (yield) from MIRD-RADTABS were consistently higher than those calculated using BrIccEmis. DPKs for the electron spectra from BrIccEmis were considerably different from MIRD-RADTABS in the first few hundred nanometres from a point source where most of the Auger electrons are stopped. S-values were, however, not significantly impacted as the differences in DPKS in the sub-micrometre dimension were quickly diminished in larger dimensions. Overestimation in the total AE energy output by MIRD-RADTABS leads to higher predicted energy deposition by AE emitting radionuclides, especially in the immediate vicinity of the decaying radionuclides. This should be taken into account when MIRD-RADTABS data are used to simulate biological damage at nanoscale dimensions.Comment: 27 pages, 4 figures, 3 table

Inhibition of TXNRD or SOD1 overcomes NRF2-mediated resistance to β-lapachone

Alterations in the NRF2/KEAP1 pathway result in the constitutive activation of NRF2, leading to the aberrant induction of antioxidant and detoxification enzymes, including NQO1. The NQO1 bioactivatable agent β-lapachone can target cells with high NQO1 expression but relies in the generation of reactive oxygen species (ROS), which are actively scavenged in cells with NRF2/KEAP1 mutations. However, whether NRF2/KEAP1 mutations influence the response to β-lapachone treatment remains unknown. To address this question, we assessed the cytotoxicity of β-lapachone in a panel of NSCLC cell lines bearing either wild-type or mutant KEAP1. We found that, despite overexpression of NQO1, KEAP1 mutant cells were resistant to β-lapachone due to enhanced detoxification of ROS, which prevented DNA damage and cell death. To evaluate whether specific inhibition of the NRF2-regulated antioxidant enzymes could abrogate resistance to β-lapachone, we systematically inhibited the four major antioxidant cellular systems using genetic and/or pharmacologic approaches. We demonstrated that inhibition of the thioredoxin-dependent system or copper-zinc superoxide dismutase (SOD1) could abrogate NRF2-mediated resistance to β-lapachone, while depletion of catalase or glutathione was ineffective. Interestingly, inhibition of SOD1 selectively sensitized KEAP1 mutant cells to β-lapachone exposure. Our results suggest that NRF2/KEAP1 mutational status might serve as a predictive biomarker for response to NQO1-bioactivatable quinones in patients. Further, our results suggest SOD1 inhibition may have potential utility in combination with other ROS inducers in patients with KEAP1/NRF2 mutations

The Role of Serotonin in Fear Learning and Memory: A Systematic Review of Human Studies

Fear is characterized by distinct behavioral and physiological responses that are essential for the survival of the human species. Fear conditioning (FC) serves as a valuable model for studying the acquisition, extinction, and expression of fear. The serotonin (5-hydroxytryptamine, 5-HT) system is known to play a significant role in emotional and motivational aspects of human behavior, including fear learning and expression. Accumulating evidence from both animal and human studies suggests that brain regions involved in FC, such as the amygdala, hippocampus, and prefrontal cortex, possess a high density of 5-HT receptors, implicating the crucial involvement of serotonin in aversive learning. Additionally, studies exploring serotonin gene polymorphisms have indicated their potential influence on FC. Therefore, the objective of this work was to review the existing evidence linking 5-HT with fear learning and memory in humans. Through a comprehensive screening of the PubMed and Web of Science databases, 29 relevant studies were included in the final review. These studies investigated the relationship between serotonin and fear learning using drug manipulations or by studying 5-HT-related gene polymorphisms. The results suggest that elevated levels of 5-HT enhance aversive learning, indicating that the modulation of serotonin 5-HT2A receptors regulates the expression of fear responses in humans. Understanding the role of this neurochemical messenger in associative aversive learning can provide insights into psychiatric disorders such as anxiety and post-traumatic stress disorder (PTSD), among others

GATE simulation for medical physics with genius Web portal

présenté par C. ThiamPCSV team of the LPC laboratory in Clermont-Ferrand is involved in the deployment of biomedical applications on the grid architecture. One of these applications deals with the deployment of GATE (Geant4 Application for Tomographic Emission) for medical physics application. The aim of the developments actually performed is to enable an application of the GATE platform in clinical routine. However, this perspective is only possible if the computing time and user time are highly reduced. The new grid architecture, developed within the framework of the European project Enabling Grid for E-sciencE (EGEE) is there to answer this requirement. The use of the grid resources must be transparent easy and rapid for the medical physicists. For this perpose, we adapted the GENIUS web portal in order to facilitate the GATE simulations planning on the grid. We will present a demonstration of the GENIUS portal which integrates all the functionalities of EGEE: to create, to submit and manage GATE jobs on the grid architecture. Our GATE activities for dosimetry application entered in to direct phase of evaluation by the cancer treatment center of Clermont Ferrand (Centre Jean perrin).A work station is currently available in this center to test the use of GATE application on the grid through GENIUS. This portal will allow in a long term to use GATE application in brachytherapy and radiotherapy treatment planning using medical data (medical images, DICOM, binary data dose calculation in the heterogeneous mediums) and to analyze the results obtained in visual form. Other functionalities are under development and will make possible to register medical data on grid storages elements and to manage them. However, these data must be anonymised before their recording on the grid. Their access via the GENIUS portal must be made safe and fast (compared simulation computing time). In order to be sure that the medical data are accessible for calculations, their replication on various storage element (SE) should be possible. The grid services give the possibility of managing this information in a free way and transparently. Operations of data handling and catalogues on the grid are ensured by the Replica Manager system which integrates all tools making it possible to manage data on the grid. The computing grid give promising results and meet a definite need: reach acceptable computing time for a future use of Monte Carlo simulations for treatment planning in brachytherapy and radiotherapy

INSTALLAZIONE DI UN CLINOMETRO AD ALTA PRECISIONE IN AREA TETTONICA (SETTORE NORD-ORIENTALE DELL’ALTIPIANO IBLEO)

In questo rapporto sono riportati i dettagli dell’installazione di un clinometro profondo effettuata nel 2010 in prossimità di Pedagaggi (SR) nel settore nord-orientale dell’altipiano ibleo. L'installazione è stata possibile utilizzando uno strumento digitale autolivellante modello AGI (Applied Geomechanics Incorporated) Lily, con sensibilità pari a 0.005 microradianti. Sono illustrati i dettagli dell’installazione ed i primi dati che evidenziano la loro ottima qualità, la presenza delle componenti mareali e la minima variazione di inclinazione ottenibile ripulendo il segnale dalle stesse

Cutaneous melanoma: From pathogenesis to therapy (Review)

In less than 10 years, melanoma treatment has been revolutionized with the approval of tyrosine kinase inhibitors and immune checkpoint inhibitors, which have been shown to have a significant impact on the prognosis of patients with melanoma. The early steps of this transformation have taken place in research laboratories. The mitogen-activated protein kinase (MAPK) pathway, phosphoinositol-3-kinase (PI3K) pathway promote the development of melanoma through numerous genomic alterations on different components of these pathways. Moreover, melanoma cells deeply interact with the tumor microenvironment and the immune system. This knowledge has led to the identification of novel therapeutic targets and treatment strategies. In this review, the epidemiological features of cutaneous melanoma along with the biological mechanisms involved in its development and progression are summarized. The current state-of-the-art of advanced stage melanoma treatment strategies and the currently available evidence of the use of predictive and prognostic biomarkers are also discussed

High precision tilt observation at Mt. Etna Volcano, Italy

In 2007-2008, we installed on Mt. Etna two deep tilt stations using high resolution, self-leveling instruments. These installations are the result of accurate instrument tests, site selection, drilling and sensor positioning that has allowed detecting variations related to the principal diurnal and semidiurnal tides for first time on Mt. Etna using tilt data. We analyzed the tidal effects recorded on tilt signals and we removed tidal effects from signals, thereby allowing to detect changes of about 20 nanoradians with a considerable improvement respect to the previous installation. Tilt changes have accompanied the Mt. Etna main eruptive phases and are generally related to the rapid rise of magma and formation of dikes and eruptive fissures. However, tilt changes characterize lava fountains, earthquakes and inflation-deflation phases. The 2008-2009 eruption represents an example of the potential of these tiltmeters providing new perspectives for highly precise monitoring of ground deformation on volcanoes

EXTENDING A MOBILE DEVICE WITH LOW-COST 3D MODELING AND BUILDING-SCALE MAPPING CAPABILITIES, FOR APPLICATION IN ARCHITECTURE AND ARCHAEOLOGY

One of the most challenging problem in architecture is the automated construction of 3D (and 4D) digital models of cultural objects with the aim of implementing open data repositories, scientifically authenticated and responding to well accepted standards of validation, evaluation, preservation, publication, updating and dissemination. The realization of such an ambitious objective requires the adoption of special technological instruments. In this paper we plan to use portable devices (i.e. smartphones, tablets or PDAs eventually extended to wearable ones), extended with a small plug-in, for automatically extracting 3D models of single objects and building-scale mapping of the surrounding environment. At the same time, the device will provide the capability of inserting notes and observations. Where the instrument cannot be directly applied, for example for exploring the top of a complex building, we consider mounting our device, or using equivalent existing equipment, on a drone, in a modular approach for obtaining data de-facto interchangeable. The approach based on the expansion packs has the advantage of anticipating (or even promoting) future extensions of new mobile devices, when the spectrum of possible applications justify the corresponding increased costs. In order to experiment and verify this approach we plan to test it in two specific scenarios of the cultural heritage domain in which such devices seem particularly promising: Strada Nuova in Genoa and Palazzo Ducale in Urbino, both located in Italy