A global approach to the physics validation of simulation codes for future nuclear systems

This paper presents a global approach to the validation of the parameters that enter into the neutronics simulation tools for advanced fast reactors with the objective to reduce the uncertainties associated to crucial design parameters. This global approach makes use of sensitivity/uncertainty methods; statistical data adjustments; integral experiment selection, analysis and “representativity” quantification with respect to a reference system; scientifically based cross-section covariance data and appropriate methods for their use in multigroup calculations. This global approach has been applied to the uncertainty reduction on the criticality of the Advanced Burner Reactor (both metal and oxide core versions) presently investigated in the frame of the GNEP initiative. The results obtained are very encouraging and allow to indicate some possible improvements of the ENDF/B-VII data file.     

Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.     

Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization,Biomechanical and Biocompatibility Characterization Using New Approaches

Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients’ quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients’ quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.     

Pediatric Brain Tumors: Signatures from the Intact Proteome

The present investigation aimed to explore the intact proteome of tissues of pediatric brain tumors of different WHO grades and localizations, including medulloblastoma, pilocytic astrocytoma, and glioblastoma, in comparison with the available data on ependymoma, to contribute to the understanding of the molecular mechanisms underlying the onset and progression of these pathologies. Tissues have been homogenized in acidic water–acetonitrile solutions containing proteases inhibitors and analyzed by LC–high resolution MS for proteomic characterization and label-free relative quantitation. Tandem MS spectra have been analyzed by either manual inspection or software elaboration, followed by experimental/theoretical MS fragmentation data comparison by bioinformatic tools. Statistically significant differences in protein/peptide levels between the different tumor histotypes have been evaluated by ANOVA test and Tukey’s post-hoc test, considering a p-value > 0.05 as significant. Together with intact protein and peptide chains, in the range of molecular mass of 1.3–22.8 kDa, several naturally occurring fragments from major proteins, peptides, and proteoforms have been also identified, some exhibiting proper biological activities. Protein and peptide sequencing allowed for the identification of different post-translational modifications, with acetylations, oxidations, citrullinations, deamidations, and C-terminal truncations being the most frequently characterized. C-terminal truncations, lacking from two to four amino acid residues, particularly characterizing the β-thymosin peptides and ubiquitin, showed a different modulation in the diverse tumors studied. With respect to the other tumors, medulloblastoma, the most frequent malignant brain tumor of the pediatric age, was characterized by higher levels of thymosin β4 and β10 peptides, the latter and its des-IS form particularly marking this histotype. The distribution pattern of the C-terminal truncated forms was also different in glioblastoma, particularly underlying gender differences, according to the definition of male and female glioblastoma as biologically distinct diseases. Glioblastoma was also distinguished for the peculiar identification of the truncated form of the α-hemoglobin chain, lacking the C-terminal arginine, and exhibiting oxygen-binding and vasoconstrictive properties different from the intact form. The proteomic characterization of the undigested proteome, following the top-down approach, was challenging to originally investigate the post-translational events that differently characterize pediatric brain tumors. This study provides a contribution to elucidate the molecular profiles of the solid tumors most frequently affecting the pediatric age, and which are characterized by different grades of aggressiveness and localization.     

Host Restriction Factors Modulating HIV Latency and Replication in Macrophages

In addition to CD4⁺ T lymphocytes, myeloid cells and, particularly, differentiated macrophages are targets of human immunodeficiency virus type-1 (HIV-1) infection via the interaction of gp120Env with CD4 and CCR5 or CXCR4. Both T cells and macrophages support virus replication, although with substantial differences. In contrast to activated CD4⁺ T lymphocytes, HIV-1 replication in macrophages occurs in nondividing cells and it is characterized by the virtual absence of cytopathicity both in vitro and in vivo. These general features should be considered in evaluating the role of cell-associated restriction factors aiming at preventing or curtailing virus replication in macrophages and T cells, particularly in the context of designing strategies to tackle the viral reservoir in infected individuals receiving combination antiretroviral therapy. In this regard, we will here also discuss a model of reversible HIV-1 latency in primary human macrophages and the role of host factors determining the restriction or reactivation of virus replication in these cells.     

Multi-Prandtl correlating equations for free convection heat transfer from a horizontal tube of elliptic cross-section

Steady laminar free convection from a horizontal elliptic cylinder set in unbounded space is studied numerically under the assumption of uniform surface temperature. A specifically developed computer-code based on the SIMPLE-C algorithm is used for the solution of the mass, momentum and energy transfer governing equations. Simulations are performed for ratios between the minor and major axes of the elliptic cross-section of the cylinder in the range between 0.05 and 0.98, inclination angles of the major axis of the elliptic cross-section with respect to gravity in the range between 0° and 90°, Rayleigh numbers based on the major axis of the elliptic cross-section in the range between 10 and 10⁷, and Prandtl numbers in the range between 0.7 and 700. It is found that the heat transfer rate increases with increasing the Rayleigh and Prandtl numbers, while decreases with increasing the orientation angle of the cross-section of the cylinder, i.e., passing from the slender to the blunt configuration. In addition, a noteworthy fact is that in most cases the amount of heat exchanged at the cylinder surface has a peak at an optimum axis ratio which is practically independent of the Prandtl number, while may either increase or decrease with increasing the Rayleigh number depending on whether the orientation angle of the tube is above or below a critical value of approximately 67.5°. Dimensionless correlating equations are proposed both for the optimum axis ratio for maximum heat transfer and for the heat transfer rate from the cylinder surface to the undisturbed surrounding fluid reservoir.     

Buoyant heat transport in fluids across tilted square cavities discretely heated at one side

Laminar natural convection heat transfer inside fluid-filled, tilted square cavities cooled at one side and partially heated at the opposite side, is studied numerically. A computational code based on the SIMPLE-C algorithm is used for the solution of the system of mass, momentum, and energy transfer equations. Simulations are performed for a complete range of heater sizes and locations, Rayleigh numbers based on the side of the cavity from 10³ to 10⁷, Prandtl numbers from 0.7 to 700, and tilting angles of the enclosure from ?75° to +75°, where negative angles correspond to configurations with the heater facing downwards. It is found that the heat transfer rate increases with increasing the Rayleigh and Prandtl numbers, and the size of the heater. In addition, for negative inclinations of the enclosure the amount of heat exchanged decreases with increasing the tilting angle, while for positive inclinations the heat transfer rate either increases or decreases according as the heater is located toward the top or the bottom of the cavity. Finally, as far as the heater location is specifically concerned, the heat transfer performance has a peak for intermediate positions, the higher are the Rayleigh and Prandtl numbers, as well as the tilting angle for positive inclinations, the closer to the bottom of the cavity is the optimum heater location for maximum heat removal.     

Low computational cost CFD analysis of thermoacoustic oscillations

The numerical analysis of thermoacoustic oscillation phenomena by means of time-dependent CFD simulations usually requires a great computational effort, which may not be reasonable in industrial design. On the other hand, CFD tools provide the only approach that includes all the physical and chemical aspects involved in the thermoacoustic coupling between flame heat release and the acoustic modes of the burner/combustion chamber system. This paper presents some guidelines to reduce the computational effort required to perform a CFD analysis of the thermoacoustic oscillations with commercial codes. These guidelines are organized in a procedure that can be followed to analyze thermoacoustic coupling conditions that actually lead to unstable oscillations or are identified as potentially critical in the design phase. This procedure is also illustrated by an example of application, the partially-premixed flame type burner of a real 10 MW industrial boiler which shows noisy pressure fluctuations at a low frequency.     

Correlating equations for free convection heat transfer from horizontal isothermal cylinders set in a vertical array

Steady laminar free convection from flat vertical arrays of equally-spaced, horizontal isothermal cylinders set in free air, is studied numerically. A specifically developed computer-code based on the SIMPLE-C algorithm is used for the solution of the mass, momentum and energy transfer governing equations. Simulations are performed for arrays of 2-6 circular cylinders, for center-to-center separation distances from 2 up to more than 50 cylinder-diameters, and for values of the Rayleigh number based on the cylinder-diameter in the range between 5 × 10² and 5 × 10⁵. It is found that the heat transfer rate at the bottom cylinder remains the same as a single cylinder. In contrast, the downstream cylinders may exhibit either enhanced or reduced Nusselt numbers depending on their location in the array and on the geometry of the array. Heat transfer dimensionless correlating equations are proposed both for any individual cylinder in the array and for the whole tube-array. New correlation-equations for the calculation of the heat transfer rate from a single cylinder to the surrounding air are also proposed and compared to those available in the open literature.     

Open-loop groundwater heat pumps development for large buildings: A case study

A study of the feasibility of providing the heating and cooling needs of the new, large commercial building near Turin, Italy, by means of an open-loop indirect groundwater heat pump (GWHP) system is described. A finite element subsurface flow and transport simulator (FEFLOW) was used to investigate possible configurations of extraction and injection wells for five different scenarios. Modelling results confirmed the hydrogeological capacity of the site to provide the necessary amount of groundwater and associated energy with limited environmental impact. Injection of warmer (or cooler) water in the aquifer creates a thermal plume whose dimensions and geometry depend on the properties of the subsurface formations, particularly their thermal dispersivity values. The study suggests that there are several possible well configurations that could support the GWHP system without adversely affecting the aquifer.