A telescope detection system for direct and high resolution spectrometry of intense neutron fields

A high energy- and spatial-resolution telescope detector was designed and constructed for neutron spectrometry of intense neutron fields. The detector is constituted by a plastic scintillator coupled to a monolithic silicon telescope (MST), in turn consisting of a DE and an E stage. The scintillator behaves as an “active” recoil-proton converter, since it measures the deposited energy of the recoil-protons generated across. The MST measures the residual energy of recoil-protons downstream of the converter and also discriminates recoil-protons from photons associated to the neutron field. The lay-out of the scintillator/MST system was optimized through an analytical model for selecting the angular range of the scattered protons. The use of unfolding techniques for reconstructing the neutron energy distribution was thus avoided with reasonable uncertainty (about 1.6% in neutron energy) and efficiency (of the order of 106 counts per unit neutron fluence). A semi-empirical procedure was also developed for correcting the non-linearity in light emission from the organic scintillator. The spectrometer was characterized with quasi-monoenergetic and continuous fields of neutrons generated at the CN Van De Graaff accelerator of the INFN-Legnaro National Laboratory, Italy, showing satisfactory agreement with literature data

Characterization of a Be(p,xn) neutron source for fission yields measurements

We report on measurements performed at The Svedberg Laboratory (TSL) to characterize a proton-neutron converter for independent fission yield studies at the IGISOL-JYFLTRAP facility (Jyv\"askyl\"a, Finland). A 30 MeV proton beam impinged on a 5 mm water-cooled Beryllium target. Two independent experimental techniques have been used to measure the neutron spectrum: a Time of Flight (TOF) system used to estimate the high-energy contribution, and a Bonner Sphere Spectrometer able to provide precise results from thermal energies up to 20 MeV. An overlap between the energy regions covered by the two systems will permit a cross-check of the results from the different techniques. In this paper, the measurement and analysis techniques will be presented together with some preliminary results.Comment: 3 pages, 3 figures, also submitted as proceedings of the International Conference on Nuclear Data for Science and Technology 201

DETERMINANTS OF HUMAN IMMUNODEFICIENCY VIRUS-1TRANSMISSION TO THE FEMALE GENITAL MUCOSA:ROLE OF CO-INFECTING PATHOGENS AND CYTOKINES IN SEMEN

Background. Nel seme Human immunodeficiency virus (HIV)-1 e co-patogeni sono presenti in una complessa rete di citochine che influenza la replicazione locale e l\u2019infettivita\u2019 dei patogeni sessualmente trasmissibili, e, allo stesso tempo, \ue8 influenzata dalle infezioni del tratto genitale maschile (MGT). La comprensione di queste interazioni richiede un'analisi approfondita dei co-patogeni che infettano il MGT e delle citochine presenti nel liquido seminale, e delle relazioni intercorrenti tra questi e HIV-1. Metodi. La carica virale di 6 herpesvirus e HIV-1 e\u2019 stata valutata nel plasma seminale e sanguigno di 83 soggetti HIV-1 infetti cronici non in terapia, e di 33 soggetti non infetti mediante real-time PCR. Un saggio multiplex basato su beads \ue8 stato utilizzato per misurare i livelli di 21 citochine. I rapporti tra citochine sono stati definiti mediante il calcolo del coefficiente di correlazione di Spearman per tutte le possibili coppie di citochine. Blocchi di tessuto cervico-vaginale e linfoide umano sono stati inoculati con HIV-1 e trattati con interleuchina (IL)-7. La replicazione di varianti HIV-1 R5 o X4 \ue8 stata monitorata mediante misurazione della produzione dell\u2019antigene p24gag. Cellule isolate da blocchi di tessuto al giorno 6 e 9 postinfezione sono state caratterizzate per l'espressione dei marcatori CD3, CD4, CD8,e HIV-1 p24gag, e l\u2019apoptosi \ue8 stata valutata misurando l'espressione delle proteine APO2.7 e Bcl-2 mediante citofluorimetria a flusso. Risultati. La maggioranza dei campioni di seme, ma non di sangue, dei soggetti HIV-1-infetti e\u2019 risultata positiva per EBV e CMV (56% e 70%). Sangue e seme sono compartimenti immunologici separati e con l\u2019infezione da HIV-1 il seme e\u2019 il compartimento interessato dai maggiori cambiamenti nella composizione citochinica (16 vs 9 citochine alterate nel sangue). La riattivazione di CMV nel MGT \ue8 associata ad un aumento dei livelli delle citochine CCL5, CCL11 e CXCL9 nel seme. L\u2019analisi dei rapporti tra citochine ha rivelato un numero maggiore di correlazioni e un aumento dell\u2019intensita\u2019 di correlazione per la maggior parte delle citochine sia nel seme che nel sangue dei soggetti HIV-1-infetti, rispetto ai non infetti. IL-7 e\u2019 risultata essere una tra le citochine pi\uf9 concentrate nel seme e l\u2019infezione da HIV-1 ne aumenta ulteriormente i livelli seminali. Abbiamo dunque utilizzato un sistema di infezione ex vivo di tessuti umani per studiare il ruolo di IL-7 nella trasmissione di HIV-1. IL-7 e\u2019 risultata promuovere la replicazione di varianti R5 e X4 di HIV-1 in modalita\u2019 dose e tempo-dipendente. In blocchi di tessuto trattati con 25 ng/mL di IL-7 e\u2019 stato osservato un numero maggiore di cellule T CD4+ infette e una riduzione della deplezione cellulare, rispetto a blocchi di tessuto non trattati con IL-7. Il trattamento con IL-7 e\u2019 risultato inoltre in una riduzione della frazione di cellule T CD4+ infette esprimenti il marcatore apoptotico APO2.7 e in un aumento dei livelli di espressione del fattore anti-apoptotico Bcl-2. Conclusioni. HIV-1 \ue8 associato ad una alterazione generale dello spettro citochinico nel seme e alla riattivazione locale di CMV e EBV nel MGT, due fenomeni che sembrano essere correlati e potrebbero dunque influenzarsi reciprocamente. La ridotta flessibilita\u2019 dei rapporti tra citochine potrebbe ulteriormente contribuire alla riattivazione di tali infezioni latenti. Tra le citochine nel seme, IL-7 esercita un effetto protettivo sulle cellule T CD4+ infette, favorendo lo stabilirisi di una infezione produttiva nel tratto genitale femminile. La comprensione di come il complesso di citochine, di concerto con i co-patogeni presenti nel seme, influenzano la trasmissione sessuale di HIV-1 sar\ue0 oggetto di ulteriori indagini.Background. In semen Human immunodeficiency virus (HIV)-1 and co-infecting pathogens are immersed in a complex network of cytokines that affects the replication and infectivity of sexually transmitted pathogens, and, at the same time, is affected by local infections in the male genital tract (MGT). Understanding the mechanisms of these interactions requires a comprehensive analysis of coinfecting pathogens and cytokines in semen, and of the relations with HIV-1. Methods. Load of HIV-1 and 6 herpesviruses in semen and blood plasma of 83 HIV-1 chronically infected individuals na\uefve to therapy and 33 HIV-uninfected individuals was evaluated by real-time PCR. A multiplex beads-based assay was used to measure the levels of 21 cytokines. The cytokine network was defined calculating the Spearman`s rank correlation coefficient for all pairwise combinations of cytokines. Human cervico-vaginal and lymphoid tissue blocks were inoculated with HIV-1 and treated with interleukin (IL)-7. Replication of R5 or X4 HIV-1 variants was monitored over a period of 12 days measuring HIV-1 p24gag antigen by a beads-based assay. Cells isolated from tissue blocks at day 6 and 9 post-infection were characterized for the expression of the markers CD3, CD4, CD8, and HIV-1 p24gag antigen, and apoptosis was evaluated measuring the expression of the proteins APO2.7 and Bcl-2 by multicolor flow cytometry. Results. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) DNA was found in semen of the majority of HIV-1-infecetd individuals (56% and 70%), but not in their blood. Blood and semen are separated immunological compartments, and with HIV-1 infection the major changes in cytokine composition occur in semen (16 vs 9 cytokine levels altered in blood). CMV reactivation in the MGT was associated with increased levels of the cytokines CCL5, CCL11 and CXCL9. Analysis of the cytokines network revealed a higher number of correlations and increase in correlation strength for most of the cytokines in semen and blood of HIV-1-infected compared to HIV-uninfected individuals. Of note, interleukin (IL)-7 resulted to be one of the most concentrated cytokines in semen and HIV-1 infection further increased seminal IL-7. Thus we employed our system of human tissues ex vivo to study the effect of IL-7 on HIV-1 replication. IL-7 enhanced the replication of R5 and X4 HIV-1 variants in dose and time-dependent manner. In tissue blocks treated with 25 ng/mL of IL-7 we observed higher number of HIV-1 infected CD4+ T cells and reduced CD4+ T cell depletion, compared with tissue blocks infected and maintained in the absence of IL-7. The fraction of HIV-1 infected CD4+ T cells expressing the apoptotic marker APO2.7 was reduced and the levels of the antiapoptotic factor Bcl-2 in infected cells were increased in the presence of IL-7. Conclusions. HIV-1 infection is associated with a general alteration of the cytokine spectrum in semen, and with the local reactivation of CMV and EBV in the MGT, two phenomena that appear to be related and may affect each other. The reduced flexibility of the cytokine network may favors the reactivation of such latent infections. Among seminal cytokines, IL-7 exerts a protective effect on HIV-1-infected CD4+ T cells in the early stages of infection, preventing their death and thus promoting the establishment of a productive infection in the female genital tract. Understanding how other cytokines in concert with co-infecting pathogens found in semen affects HIV-1 sexual transmission will be object of further investigations

A multi-targeted drug candidate with dual anti-HIV and anti-HSV activity

Human immunodeficiency virus (HIV) infection is often accompanied by infection with other pathogens, in particular herpes simplex virus type 2 (HSV-2). The resulting coinfection is involved in a vicious circle of mutual facilitations. Therefore, an important task is to develop a compound that is highly potent against both viruses to suppress their transmission and replication. Here, we report on the discovery of such a compound, designated PMEO-DAPym. We compared its properties with those of the structurally related and clinically used acyclic nucleoside phosphonates (ANPs) tenofovir and adefovir. We demonstrated the potent anti-HIV and -HSV activity of this drug in a diverse set of clinically relevant in vitro, ex vivo, and in vivo systems including (i) CD4⁺ T-lymphocyte (CEM) cell cultures, (ii) embryonic lung (HEL) cell cultures, (iii) organotypic epithelial raft cultures of primary human keratinocytes (PHKs), (iv) primary human monocyte/macrophage (M/M) cell cultures, (v) human ex vivo lymphoid tissue, and (vi) athymic nude mice. Upon conversion to its diphosphate metabolite, PMEO-DAPym markedly inhibits both HIV-1 reverse transcriptase (RT) and HSV DNA polymerase. However, in striking contrast to tenofovir and adefovir, it also acts as an efficient immunomodulator, inducing β-chemokines in PBMC cultures, in particular the CCR5 agonists MIP-1β, MIP-1α and RANTES but not the CXCR4 agonist SDF-1, without the need to be intracellularly metabolized. Such specific β-chemokine upregulation required new mRNA synthesis. The upregulation of β-chemokines was shown to be associated with a pronounced downmodulation of the HIV-1 coreceptor CCR5 which may result in prevention of HIV entry. PMEO-DAPym belongs conceptually to a new class of efficient multitargeted antivirals for concomitant dual-viral (HSV/HIV) infection therapy through inhibition of virus-specific pathways (i.e. the viral polymerases) and HIV transmission prevention through interference with host pathways (i.e. CCR5 receptor down regulation)

Numerical Modeling and Simulation of Melting Phenomena for Freeze Valve Analysis in Molten Salt Reactors

In recent years, molten salt reactors (MSRs) have gained new momentum thanks to their potential for innovation in the nuclear industry, and several studies on their compliance with all the expected safety features are currently underway. In terms of passive safety, a strategy currently envisaged in accidental scenarios is to drain by gravity the molten salt, which acts both as fuel and coolant, in an emergency draining tank, ensuring both a subcritical geometry and proper cooling. To activate the draining system, a freeze plug, made of the same salt used in the core, is expected to open when the temperature in the core reaches high values. Up to this point, the freeze valve is still a key concept in the molten salt fast reactor (MSFR), and special attention must be paid to its analysis, given the requirement for passive safety, especially focusing on melting and solidification phenomena related to the molten salt mixture. This work aims to contribute to the macroscale modeling of melting and solidification phenomena relevant to the analysis of the freeze valve behavior. In particular, the focus is on the identification of the numerical models that can be adopted to achieve the quantitative insights needed for the design of the freeze valve. Among the ones available in the literature, the most appropriate models were selected based on a compromise between accuracy and computational efficiency. A critical look at the models allows for a synthetic and consistent formulation of the numerical models and their implementation in the open-source software OpenFOAM. The code was subsequently verified using analytical and numerical solutions already well established in the literature. A good agreement between the results produced by the developed solver and the reference solutions was obtained. In the end, the code was applied to simple case studies related to the freeze valve system, focusing on recognizing whether the developed code can model physical phenomena that can occur in a freeze valve. The results of the simulations are encouraging and show that the code can be used to model single-region melting or solidification problems. As such, this work constitutes a starting point for further development of the code, intending to achieve better quantitative predictions for the design of a freeze valve

Interleukin-7 Facilitates HIV-1 Transmission to Cervico-Vaginal Tissue ex vivo

The majority of HIV-1 infections in women occur through vaginal intercourse, in which virus-containing semen is deposited on the cervico-vaginal mucosa. Semen is more than a mere carrier of HIV-1, since it contains many biological factors, in particular cytokines, that may affect HIV-1 transmission. The concentration of interleukin (IL)-7, one of the most prominent cytokines in semen of healthy individuals, is further increased in semen of HIV-1-infected men. Here, we investigated the potential role of IL-7 in HIV-1 vaginal transmission in an ex vivo system of human cervico-vaginal tissue. We simulated an in vivo situation by depositing HIV-1 on cervico-vaginal tissue in combination with IL-7 at concentrations comparable with those measured in semen of HIV-1-infected individuals. We found that IL-7 significantly enhanced virus replication in ex vivo infected cervico-vaginal tissue. Similarly, we observed an enhancement of HIV-1 replication in lymphoid tissue explants. Analysis of T cells isolated from infected tissues showed that IL-7 reduced CD4+ T cell depletion preventing apoptosis, as shown by the decrease in the number of cells expressing the apoptotic marker APO2.7 and the increase in the expression of the anti-apoptotic protein B-cell lymphoma (Bcl)-2. Also, IL-7 increased the fraction of cycling CD4+ T cells, as evidenced by staining for the nuclear factor Ki-67. High levels of seminal IL-7 in vivo may be relevant to the survival of the founder pool of HIV-1-infected cells in the cervico-vaginal mucosa at the initial stage of infection, promoting local expansion and dissemination of HIV infection

Complementary roles of slow-wave sleep and rapid eye movement sleep in emotional memory consolidation

Although rapid eye movement sleep (REM) is regularly implicated in emotional memory consolidation, the role of slow-wave sleep (SWS) in this process is largely uncharacterized. In the present study, we investigated the relative impacts of nocturnal SWS and REM upon the consolidation of emotional memories using functional magnetic resonance imaging (fMRI) and polysomnography (PSG). Participants encoded emotionally positive, negative, and neutral images (remote memories) before a night of PSG-monitored sleep. Twenty-four hours later, they encoded a second set of images (recent memories) immediately before a recognition test in an MRI scanner. SWS predicted superior memory for remote negative images and a reduction in right hippocampal responses during the recollection of these items. REM, however, predicted an overnight increase in hippocampal–neocortical connectivity associated with negative remote memory. These findings provide physiological support for sequential views of sleep-dependent memory processing, demonstrating that SWS and REM serve distinct but complementary functions in consolidation. Furthermore, these findings extend those ideas to emotional memory by showing that, once selectively reorganized away from the hippocampus during SWS, emotionally aversive representations undergo a comparably targeted process during subsequent REM

1D modelling and preliminary analysis of the coupled DYNASTY–eDYNASTY natural circulation loop

In the continuous strive to improve the safety of current-generation and next-generation nuclear power plants, natural circulation can be used to design passive safety systems to remove the decay heat during the shutdown. The Molten Salt Fast Reactor (MSFR) is a peculiar type of Gen-IV nuclear facility, where the fluid fuel is homogeneously mixed with the coolant. This design leads to natural circulation in the presence of an internally distributed heat source during the shutdown. Furthermore, to shield the environment from the highly radioactive fuel, an intermediate loop between the primary and the secondary loops, able to operate in natural circulation, is required. To analyze the natural circulation with a distributed heat source and to study the natural circulation of coupled systems and the influence of the intermediate loop on the behaviour of the primary, Politecnico di Milano designed and built the DYNASTY-eDYNASTY facility. The two facilities are coupled with a double-pipe heat exchanger, which siphons heat from DYNASTY and delivers it to the eDYNASTY loop. This work focuses on modelling the coupled DYNASTY-eDYNASTY natural circulation loops using DYMOLA2023((R)), an integrated development environment based on the Modelica Object-Oriented a-causal simulation language. The 1D Modelica approach allows for building highly reusable and flexible models easing the design effort on a complex system such as the DYNASTY-eDYNASTY case without the need to rewrite the whole model from scratch. The coupled models were developed starting from the already-validated single DYNASTY model and the double-pipe heat exchanger coupling. The models were tested during the whole development process, studying the influence of the numerical integration algorithm on the simulation behaviour. A preliminary analysis of both the adiabatic and the heat loss models analyzed the effect of the secondary natural circulation loop on the behaviour of the DYNASTY loop. The simulation results showed that the eDYNASTY loop dampens the behaviour of the primary DYNASTY loop. Furthermore, a parametric analysis of the DYNASTY and the eDYNASTY coolers highlighted the influence of the cooling configuration on the facility's behaviour. Finally, the simulation results identified the most critical aspects of the models in preparation for an experimental comparison

Development of an OpenFOAM multiphysics solver for solid fission products transport in the Molten Salt Fast Reactor

The analysis of innovative reactor concepts such as the Molten Salt Fast Reactor (MSFR) requires the development of new modeling and simulation tools. In the case of the MSFR, the strong intrinsic coupling between thermal-hydraulics, neutronics and fuel chemistry has led to the adoption of the multiphysics approach as a state-of-the-art paradigm. One of the peculiar aspects of liquid-fuel reactors such as the MSFR is the mobility of fission products (FPs) in the reactor circuit. Some FP species appear in form of solid precipitates carried by the fuel flow and can deposit on reactor boundaries (e.g., heat exchangers), potentially representing design issues related to the degradation of heat exchange performance or radioactive hotspots. The integration of transport models for solid particles in multiphysics codes is therefore relevant for the prediction of deposited fractions. To this aim, we develop a multiphysics solver based on the OpenFOAM library to address the issue of solid fission products transport. Single-phase incompressible thermal hydraulics are coupled with neutron diffusion, and advection-diffusion-decay equations are implemented for fission products concentrations. Particle deposition and precipitation are considered as well. The developed solver is tested on two different MSFR application to showcase the capabilities of the solver in steady-state simulation and to investigate the role of precipitation and turbulence modeling in the determination of particle concentration distributions

Ex vivo infection of human lymphoid tissue and female genital mucosa with human immunodeficiency virus 1 and histoculture

Histocultures allow studying intercellular interactions within human tissues, and they can be employed to model host-pathogen interactions under controlled laboratory conditions. Ex vivo infection of human tissues with human immunodeficiency virus (HIV), among other viruses, has been successfully used to investigate early disease pathogenesis, as well as a platform to test the efficacy and toxicity of antiviral drugs. In the present protocol, we explain how to process and infect with HIV-1 tissue explants from human tonsils and cervical mucosae, and maintain them in culture on top of gelatin sponges at the liquid-air interface for about two weeks. This non-polarized culture setting maximizes access to nutrients in culture medium and oxygen, although progressive loss of tissue integrity and functional architectures remains its main limitation. This method allows monitoring HIV-1 replication and pathogenesis using several techniques, including immunoassays, qPCR, and flow cytometry. Of importance, the physiologic variability between tissue donors, as well as between explants from different areas of the same specimen, may significantly affect experimental results. To ensure result reproducibility, it is critical to use an adequate number of explants, technical replicates, and donor-matched control conditions to normalize the results of the experimental treatments when compiling data from multiple experiments (i.e., conducted using tissue from different donors) for statistical analysis