Investigations on the migration mode method (MMM) for reactor calculations

Current calculation codes for reactor analysis are based on the multi-group method to evaluate energy distribution of neutron flux. Usually a two energy group diffusion equation is adopted. This choice is adequate for PWRs associated to cross sections libraries tabulated versus fuel exposure and other state parameters as moderator density, fuel temperature, boron concentration. An improvement of this approach is represented by the migration mode method (MMM) by which the neutron spectrum is expanded in terms of base functions corresponding to the different modes of migration of the neutrons in the energy dimension. For a thermal reactor, three such functions may be easily identified: the Maxwellian distribution of the neutrons at thermal equilibrium with the moderator, the 1/E slowing down distribution (corrected to take into account resonance absorption effects) and the fission neutron spectrum. The (space-dependent) coefficients of the expansion are calculated by solving a differential equation which results having a structure similar to the one relevant to multi-group theory. The method can therefore be easily implemented adopting existing diffusion theory codes.     

Hypoxia Enhances the Expression of RNASET2 in Human Monocyte-Derived Dendritic Cells: Role of PI3K/AKT Pathway

Hypoxia is a key component of the tumor microenvironment (TME) and promotes not only tumor growth and metastasis, but also negatively affects infiltrating immune cells by impairing host immunity. Dendritic cells (DCs) are the most potent antigen-presenting cells and their biology is weakened in the TME in many ways, including the modulation of their viability. RNASET2 belongs to the T2 family of extracellular ribonucleases and, besides its nuclease activity, it exerts many additional functions. Indeed, RNASET2 is involved in several human pathologies, including cancer, and it is functionally relevant in the TME. RNASET2 functions are not restricted to cancer cells and its expression could be relevant also in other cell types which are important players in the TME, including DCs. Therefore, this study aimed to unravel the effect of hypoxia (2% O₂) on the expression of RNASET2 in DCs. Here, we showed that hypoxia enhanced the expression and secretion of RNASET2 in human monocyte-derived DCs. This paralleled the HIF-1α accumulation and HIF-dependent and -independent signaling, which are associated with DCs’ survival/autophagy/apoptosis. RNASET2 expression, under hypoxia, was regulated by the PI3K/AKT pathway and was almost completely abolished by TLR4 ligand, LPS. Taken together, these results highlight how hypoxia- dependent and -independent pathways shape RNASET2 expression in DCs, with new perspectives on its implication for TME and, therefore, in anti-tumor immunity.     

Selective Inhibition of Helicobacter pylori Carbonic Anhydrases by Carvacrol and Thymol Could Impair Biofilm Production and the Release of Outer Membrane Vesicles

Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative enzymes or essential pathways such as carbonic anhydrases (CAs), we assessed the anti-H. pylori activity of thymol and carvacrol in terms of CA inhibition, isoform selectivity, growth impairment, biofilm production, and release of associated outer membrane vesicles-eDNA. The microbiological results were correlated by the evaluation in vitro of H. pylori CA inhibition, in silico analysis of the structural requirements to display such isoform selectivity, and the assessment of their limited toxicity against three probiotic species with respect to amoxicillin. Carvacrol and thymol could thus be considered as new lead compounds as alternative H. pylori CA inhibitors or to be used in association with current drugs for the management of H. pylori infection and limiting the spread of antibiotic resistance.     

Congenital diarrheal disorders: an updated diagnostic approach

Congenital diarrheal disorders (CDDs) are a group of inherited enteropathies with a typical onset early in the life. Infants with these disorders have frequently chronic diarrhea of sufficient severity to require parenteral nutrition. For most CDDs the disease-gene is known and molecular analysis may contribute to an unequivocal diagnosis. We review CDDs on the basis of the genetic defect, focusing on the significant contribution of molecular analysis in the complex, multistep diagnostic work-up.     

Blue fish burgers: nutritional characterisation and sensory optimisation

In order to reduce waste of marine resources, valorise fishing discards and move towards fish consumption, a new ready-to-cook seafood product was developed. In particular, a chemical investigation on chub mackerel and hake was conducted to the aim of mixing the two fish species to produce nutritionally balanced fish burgers. In addition, to evaluate consumer opinion about these new fresh products and best acceptability of different proportions of mackerel and hake, focus group interviews and consumer test were also performed. The results of the chemical analyses achieved on both selected fish species gave rise to minimally processed fish products with a high amount of chub mackerel, therefore providing the desired nutritional properties and low level of hake in order to obtain firmer and wetter burgers. By means of focus group interviews, the novelty and high level of convenience of the developed fresh commodity was highlighted. Consumer test declared that the most successful sample was that with 70% chub mackerel and 30% hake.     

MS-275 (Entinostat) Promotes Radio-Sensitivity in PAX3-FOXO1 Rhabdomyosarcoma Cells

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. About 25% of RMS expresses fusion oncoproteins such as PAX3/PAX7-FOXO1 (fusion-positive, FP) while fusion-negative (FN)-RMS harbors RAS mutations. Radiotherapy (RT) plays a crucial role in local control but metastatic RMS is often radio-resistant. HDAC inhibitors (HDACi) radio-sensitize different cancer cells types. Thus, we evaluated MS-275 (Entinostat), a Class I and IV HDACi, in combination with RT on RMS cells in vitro and in vivo. MS-275 reversibly hampered cell survival in vitro in FN-RMS RD (RASmut) and irreversibly in FP-RMS RH30 cell lines down-regulating cyclin A, B, and D1, up-regulating p21 and p27 and reducing ERKs activity, and c-Myc expression in RD and PI3K/Akt/mTOR activity and N-Myc expression in RH30 cells. Further, MS-275 and RT combination reduced colony formation ability of RH30 cells. In both cell lines, co-treatment increased DNA damage repair inhibition and reactive oxygen species formation, down-regulated NRF2, SOD, CAT and GPx4 anti-oxidant genes and improved RT ability to induce G2 growth arrest. MS-275 inhibited in vivo growth of RH30 cells and completely prevented the growth of RT-unresponsive RH30 xenografts when combined with radiation. Thus, MS-275 could be considered as a radio-sensitizing agent for the treatment of intrinsically radio-resistant PAX3-FOXO1 RMS.     

Tobramycin Nanoantibiotics and Their Advantages: A Minireview

Nowadays, antimicrobial resistance (AMR) represents a challenge for antibiotic therapy, mostly involving Gram-negative bacteria. Among the strategies activated to overcome AMR, the repurposing of already available antimicrobial molecules by encapsulating them in drug delivery systems, such as nanoparticles (NPs) and also engineered NPs, seems to be promising. Tobramycin is a powerful and effective aminoglycoside, approved for complicated infections and reinfections and indicated mainly against Gram-negative bacteria, such as Pseudomonas aeruginosa, Escherichia coli, Proteus, Klebsiella, Enterobacter, Serratia, Providencia, and Citrobacter species. However, the drug presents several side effects, mostly due to dose frequency, and for this reason, it is a good candidate for nanomedicine formulation. This review paper is focused on what has been conducted in the last 20 years for the development of Tobramycin nanosized delivery systems (nanoantibiotics), with critical discussion and comparison. Tobramycin was selected as the antimicrobial drug because it is a wide-spectrum antibiotic that is effective against both Gram-positive and Gram-negative aerobic bacteria, and it is characterized by a fast bactericidal effect, even against multidrug-resistant microorganisms (MDR).     

A General Approach to L(h, k)-Label Interconnection Networks

Given two non-negative integers h and k,an L(h,k)-labeling of a graph G=(V,E) is a function from the set V to a set of colors,such that adjacent nodes take colors at distance at least h,and nodes at distance 2 take colors at distance at least k.The aim of the L(h,k)-labeling problem is to minimize the greatest used color.Since the decisional version of this problem is NP-complete,it is important to investigate particular classes of graphs for which the problem can be efficiently solved.It is well known that the most common interconnection topologies,such as Butterfly-like,Bene(?),CCC,Trivalent Cayley networks,are all characterized by a similar structure:they have nodes organized as a matrix and connections are divided into layers.So we naturally introduce a new class of graphs,called (1×n)-multistage graphs,containing the most common interconnection topologies,on which we study the L(h,k)-labeling.A general algorithm for L(h,k)-labeling these graphs is presented,and from this method an efficient L(2,1)-labeling for Butterfly and CCC networks is derived.Finally we describe a possible generalization of our approach.