HFE and transferrin directly compete for transferrin receptor in solution and at the cell surface

Transferrin receptor (TfR) is a dimeric cell surface protein that binds both the serum iron transport protein transferrin (Fe-Tf) and HFE, the protein mutated in patients with the iron overload disorder hereditary hemochromatosis. HFE and Fe-Tf can bind simultaneously to TfR to form a ternary complex, but HFE binding to TfR lowers the apparent affinity of the Fe-Tf/TfR interaction. This apparent affinity reduction could result from direct competition between HFE and Fe-Tf for their overlapping binding sites on each TfR polypeptide chain, from negative cooperativity, or from a combination of both. To explore the mechanism of the affinity reduction, we constructed a heterodimeric TfR that contains mutations such that one TfR chain binds only HFE and the other binds only Fe-Tf. Binding studies using a heterodimeric form of soluble TfR demonstrate that TfR does not exhibit cooperativity in heterotropic ligand binding, suggesting that some or all of the effects of HFE on iron homeostasis result from competition with Fe-Tf for TfR binding. Experiments using transfected cell lines demonstrate a physiological role for this competition in altering HFE trafficking patterns

Mechanism for Multiple Ligand Recognition by the Human Transferrin Receptor

Transferrin receptor 1 (TfR) plays a critical role in cellular iron import for most higher organisms. Cell surface TfR binds to circulating iron-loaded transferrin (Fe-Tf) and transports it to acidic endosomes, where low pH promotes iron to dissociate from transferrin (Tf) in a TfR-assisted process. The iron-free form of Tf (apo-Tf) remains bound to TfR and is recycled to the cell surface, where the complex dissociates upon exposure to the slightly basic pH of the blood. Fe-Tf competes for binding to TfR with HFE, the protein mutated in the iron-overload disease hereditary hemochromatosis. We used a quantitative surface plasmon resonance assay to determine the binding affinities of an extensive set of site-directed TfR mutants to HFE and Fe-Tf at pH 7.4 and to apo-Tf at pH 6.3. These results confirm the previous finding that Fe-Tf and HFE compete for the receptor by binding to an overlapping site on the TfR helical domain. Spatially distant mutations in the TfR protease-like domain affect binding of Fe-Tf, but not iron-loaded Tf C-lobe, apo-Tf, or HFE, and mutations at the edge of the TfR helical domain affect binding of apo-Tf, but not Fe-Tf or HFE. The binding data presented here reveal the binding footprints on TfR for Fe-Tf and apo-Tf. These data support a model in which the Tf C-lobe contacts the TfR helical domain and the Tf N-lobe contacts the base of the TfR protease-like domain. The differential effects of some TfR mutations on binding to Fe-Tf and apo-Tf suggest differences in the contact points between TfR and the two forms of Tf that could be caused by pH-dependent conformational changes in Tf, TfR, or both. From these data, we propose a structure-based model for the mechanism of TfR-assisted iron release from Fe-Tf

Pool temperature stratification analysis in CIRCE-ICE facility with RELAP5-3D© model and comparison with experimental tests

In the frame of heavy liquid metal (HLM) technology development, CIRCE pool facility at ENEA/Brasimone Research Center was updated by installing ICE (Integral Circulation Experiments) test section which simulates the thermal behavior of a primary system in a HLM cooled pool reactor. The experimental campaign led to the characterization of mixed convection and thermal stratification in a HLM pool in safety relevant conditions and to the distribution of experimental data for the validation of CFD and system codes. For this purpose, several thermocouples were installed into the pool using 4 vertical supports in different circumferential position for a total of 119 thermocouples [1][2]. The aim of this work is to investigate the capability of the system code RELAP5-3D (c) to simulate mixed convection and thermal stratification phenomena in a HLM pool in steady state conditions by comparing code results with experimental data. The pool has been simulated by a 3D component divided into 1728 volumes, 119 of which are centered in the exact position of the thermocouples. Three dimensional model of the pool is completed with a mono-dimensional nodalization of the primary main flow path. The results obtained by code simulations are compared with a steady state condition carried out in the experimental campaign. Results of axial, radial and azimuthal temperature profile into the pool are in agreement with the available experimental data Furthermore the code is able to well simulate operating conditions into the main flow path of the test section

Pre-test analysis of protected loss of primary pump transients in CIRCE-HERO facility

In the frame of LEADER project (Lead-cooled European Advanced Demonstration Reactor), a new configuration of the steam generator for ALFRED (Advanced Lead Fast Reactor European Demonstrator) was proposed. The new concept is a super-heated steam generator, double wall bayonet tube type with leakage monitoring [1]. In order to support the new steam generator concept, in the framework of Horizon 2020 SESAME project (thermal hydraulics Simulations and Experiments for the Safety Assessment of MEtal cooled reactors), the ENEA CIRCE pool facility will be refurbished to host the HERO (Heavy liquid mEtal pRessurized water cOoled tubes) test section to investigate a bundle of seven full scale bayonet tubes in ALFRED-like thermal hydraulics conditions. The aim of this work is to verify thermofluid dynamic performance of HERO during the transition from nominal to natural circulation condition. The simulations have been performed with RELAP5-3D© by using the validated geometrical model of the previous CIRCE-ICE test section [2], in which the preceding heat exchanger has been replaced by the new bayonet bundle model. Several calculations have been carried out to identify thermal hydraulics performance in different steady state conditions. The previous calculations represent the starting points of transient tests aimed at investigating the operation in natural circulation. The transient tests consist of the protected loss of primary pump, obtained by reducing feed-water mass flow to simulate the activation of DHR (Decay Heat Removal) system, and of the loss of DHR function in hot conditions, where feed-water mass flow rate is absent. According to simulations, in nominal conditions, HERO bayonet bundle offers excellent thermal hydraulic behavior and, moreover, it allows the operation in natural circulation

Post-test simulation of a PLOFA transient test in the CIRCE-HERO facility

CIRCE is a lead–bismuth eutectic alloy (LBE) pool facility aimed to simulate the primary system of a heavy liquid metal (HLM) cooled pool-type fast reactor. The experimental facility was implemented with a new test section, called HERO (Heavy liquid mEtal pRessurized water cOoled tubes), which consists of a steam generator composed of seven double-wall bayonet tubes (DWBT) with an active length of six meters. The experimental campaign aims to investigate HERO behavior, which is representative of the tubes that will compose ALFRED SG. In the framework of the Horizon 2020 SESAME project, a transient test was selected for the realization of a validation benchmark. The test consists of a protected loss of flow accident (PLOFA) simulating the shutdown of primary pumps, the reactor scram and the activation of the DHR system. A RELAP5-3D© nodalization scheme was developed in the pre-test phase at DIAEE of “Sapienza” University of Rome, providing useful information to the experimentalists. The model consisted to a mono-dimensional scheme of the primary flow path and the SG secondary side, and a multi-dimensional component simulating the large LBE pool. The analysis of experimental data, provided by ENEA, has suggested to improve the thermal–hydraulic model with a more detailed nodalization scheme of the secondary loop, looking to reproduce the asymmetries observed on the DWBTs operation. The paper summarizes the post-test activity performed in the frame of the H2020 SESAME project as a contribution of the benchmark activity, highlighting a global agreement between simulations and experiment for all the primary circuit physical quantities monitored. Then, the attention is focused on the secondary system operation, where uncertainties related to the boundary conditions affect the computational results

Analysis of unmitigated large break loss of coolant accidents using MELCOR code

In the framework of severe accident research activity developed by ENEA, a MELCOR nodalization of a generic Pressurized Water Reactor of 900 MWe has been developed. The aim of this paper is to present the analysis of MELCOR code calculations concerning two independent unmitigated large break loss of coolant accident transients, occurring in the cited type of reactor. In particular, the analysis and comparison between the transients initiated by an unmitigated double-ended cold leg rupture and an unmitigated double-ended hot leg rupture in the loop 1 of the primary cooling system is presented herein. This activity has been performed focusing specifically on the in-vessel phenomenology that characterizes this kind of accidents. The analysis of the thermal-hydraulic transient phenomena and the core degradation phenomena is therefore here presented. The analysis of the calculated data shows the capability of the code to reproduce the phenomena typical of these transients and permits their phenomenological study. A first sequence of main events is here presented and shows that the cold leg break transient results faster than the hot leg break transient because of the position of the break. Further analyses are in progress to quantitatively assess the results of the code nodalization for accident management strategy definition and fission product source term evaluation

Unveiling the inner morphology and gas kinematics of NGC 5135 with ALMA

The local Seyfert 2 galaxy NGC5135, thanks to its almost face-on appearance, a bulge overdensity of stars, the presence of a large-scale bar, an AGN and a Supernova Remnant, is an excellent target to investigate the dynamics of inflows, outflows, star formation and AGN feedback. Here we present a reconstruction of the gas morphology and kinematics in the inner regions of this galaxy, based on the analysis of Atacama Large Millimeter Array (ALMA) archival data. To our purpose, we combine the available $\sim$100 pc resolution ALMA 1.3 and 0.45 mm observations of dust continuum emission, the spectroscopic maps of two transitions of the CO molecule (tracer of molecular mass in star forming and nuclear regions), and of the CS molecule (tracer of the dense star forming regions) with the outcome of the SED decomposition. By applying the $^{\rm 3D}$BAROLO software (3D-Based Analysis of Rotating Object via Line Observations), we have been able to fit the galaxy rotation curves reconstructing a 3D tilted-ring model of the disk. Most of the observed emitting features are described by our kinematic model. We also attempt an interpretation for the emission in few regions that the axisymmetric model fails to reproduce. The most relevant of these is a region at the northern edge of the inner bar, where multiple velocity components overlap, as a possible consequence of the expansion of a super-bubble.Comment: 15 pages, 13 figures, resubmitted to MNRAS after moderate revision

Il fenomeno del food waste: gli sprechi alimentari da problema a risorse

Il tema degli sprechi alimentari rappresenta un problema globale nonché una preoccupazione centrale del nostro secolo. Negli ultimi anni, il fenomeno ha assunto un’importanza crescente all’interno del dibattito scientifico e delle iniziative della società civile, fino ad essere richiamato nei documenti programmatici dell’UE e delle principali organizzazioni internazionali (FAO, UNEP, USDA, G20). Tuttavia, non esiste ancora una definizione univoca di “spreco alimentare”, così come non esistono metodologie uniformi per calcolarlo; ma, gli studi concordano che il cibo è sprecato ad ogni stadio della filiera alimentare. Si stima che annualmente nel mondo gli sprechi alimentari ammontano a circa 1.3 miliardi di tonnellate (un terzo della produzione totale di cibo destinato al consumo umano). Le cause sono molteplici e si differenziano in base al livello di sviluppo economico raggiunto (Paesi industrializzati o in via di sviluppo) e in base alla particolare struttura della filiera agroalimentare (es. standard dimensionali ed estetici, norme sulla qualità dei prodotti, surplus produttivi o fattori economici). Nel panorama europeo, i Paesi che hanno già avviato azioni e programmi volti a comprendere e contrastare il fenomeno sono molti; ma solo Francia e Italia, nel 2016, hanno adottato una legislazione nazionale in materia. Gli sprechi alimentari generano impatti negativi ambientali ed economici, ma a rendere ancora più allarmante il fenomeno è la questione sociale. Infatti, a fronte di un miliardo circa di persone nel mondo che, allo stato attuale sono sottoalimentate, gli sprechi alimentari appaiono quanto mai inaccettabili. Per stimare l’impatto ambientale di un alimento sprecato è necessario considerare il suo intero ciclo di vita utilizzando indicatori specifici quali il carbon footprint, l’ecological footprint o il water footprint; mentre per quanto riguarda l’impatto economico degli sprechi, esso include la quantificazione delle esternalità negative oltre il costo o il prezzo dei prodotti gettati via. Viste le dimensioni assunte dal fenomeno e soprattutto dalla portata dei suoi impatti, gli sprechi alimentari si allontanano di molto da quelli che sono gli obiettivi di sostenibilità da intraprendere a livello mondiale. Pertanto, la promozione di iniziative di sensibilizzazione e di recupero degli sprechi (es. attraverso il recupero delle eccedenze produttive a fini solidali o per la produzione di bioenergie), oltre all’applicazione di un quadro legislativo, dovrebbe far crescere la consapevolezza di consumatori, produttori, istituzioni e politica che in un mondo in crisi economica, ambientale e sociale, lo spreco è un fenomeno totalmente insostenibile, e non è più consentito. La sostenibilità non può più essere considerata un mero concetto teorico, ma è necessario ripensare i modelli di produzione e di consumo, rivedere comportamenti e stili di vita, per intraprendere un percorso mirato verso una società compatibile con i bisogni delle attuali e delle future generazioni. In tale contesto, la Commissione europea ha presentato un pacchetto per sostenere la transizione dell’UE verso un’economia circolare, nel quale la prevenzione e la minimizzazione degli sprechi alimentari sono parte integrante.Food waste is a global issue and a central concern of our century, it is a significant phenomenon that is currently at the heart of academic debates, civil society initiatives, and political agendas (FAO, UNEP, USDA, G20). However, there is not any standardized definition of “food waste” or any homogeneous and comparable data, but all studies agree that food is wasted at every stage of the food supply chain. Annual global food waste is estimated to be about 1.3 billion tons (a third of the total food production intended for human consumption). There are many causes of waste, differentiated according to the State (industrialized or developing countries) and the various stages of the food supply chain (e.g. due to sizing and esthetic standards, product quality regulations, production surplus or economic factors). Many EU Member States have already launched actions and programmers to promote waste reduction; but only France and Italy, in 2016, have adopted a national regulation to minimize the phenomenon. Food waste have negative environmental and economic impacts and their existence raises serious questions from a social point of view. In fact, given the problem of malnutrition that is afflicting around one billion people worldwide, the food waste appears extremely unacceptable. In order to estimate the environmental impact of a wasted food, it is necessary to consider its entire life cycle using the indicators, such as carbon footprint, ecological footprint, water footprint. The economic impact of wasted food includes calculating the negative externalities, besides the cost or the price of the products thrown away. Given the scale reached by the food waste phenomenon, and above all the scope of its impacts, the food waste deviate very far from those that are the sustainability goals to be taken globally. Therefore, the promotion of awareness initiatives and waste recovery (e.g. by distribution of the productive surplus to solidarity aims or to produce bioenergy), the application of a regulatory framework, should raise consumer, producer, institution and policy awareness in a world in economic, environmental and social crisis where the waste is no longer allowed. Sustainability can no longer be considered a theoretical concept, but is necessary a rethinking of the conventional models of production and consumption, the behaviors and lifestyles, to undertake a focused path towards a society compatible with the needs of the present and the future generations. In this context, European Commission put forward to support the EU’s transition to a circular economy, where food waste prevention and minimization are an integral part

Floating-bending tensile-integrity structures

This is a conceptual work about the form-finding of a hybrid tensegrity structure. The structure was obtained from the combination of arch-supported membrane systems and diamond-type tensegrity systems. By combining these two types of structures, the resulting system features the “tensile-integrity” property of cables and membrane together with what we call “floating-bending” of the arches, a term which is intended to recall the words “floating-compression” introduced by Kenneth Snelson, the father of tensegrities. Two approaches in the form-finding calculations were followed, the Matlab implementation of a simple model comprising standard constant-stress membrane/cable elements together with the so-called stick-andspring elements for the arches, and the analysis with the commercial software WinTess, used in conjunction with Rhino and Grasshopper. The case study of a T3 floatingbending tensile-integrity structure was explored, a structure that features a much larger enclosed volume in comparison to conventional tensegrity prisms. The structural design of an outdoor pavilion of 6 m in height was carried out considering ultimate and service limit states. This study shows that floating-bending structures are feasible, opening the way to the introduction of suitable analysis and optimization procedures for this type of structure

Three-dimensional flow instability in a lid-driven isosceles triangular cavity

Linear three-dimensional modal instability of steady laminar two-dimensional states developing in a lid-driven cavity of isosceles triangular cross-section is investigated theoretically and experimentally for the case in which the equal sides form a rectangular corner. An asymmetric steady two-dimensional motion is driven by the steady motion of one of the equal sides. If the side moves away from the rectangular corner, a stationary three-dimensional instability is found. If the motion is directed towards the corner, the instability is oscillatory. The respective critical Reynolds numbers are identified both theoretically and experimentally. The neutral curves pertinent to the two configurations and the properties of the respective leading eigenmodes are documented and analogies to instabilities in rectangular lid-driven cavities are discussed