Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia

The C-terminal aminoacidic sequence from NPM1-mutated protein, absent in normal human tissues, may serve as a leukemia-specific antigen and can be considered an ideal target for NPM1-mutated acute myeloid leukemia (AML) immunotherapy. Different in silico instruments and in vitro/ex vivo immunological platforms have identified the most immunogenic epitopes from NPM1-mutated protein. Spontaneous development of endogenous NPM1-mutated-specific cytotoxic T cells has been observed in patients, potentially contributing to remission maintenance and prolonged survival. Genetically engineered T cells, namely CAR-T or TCR-transduced T cells, directed against NPM1-mutated peptides bound to HLA could prospectively represent a promising therapeutic approach. Although either adoptive or vaccine-based immunotherapies are unlikely to be highly effective in patients with full-blown leukemia, these strategies, potentially in combination with immune-checkpoint inhibitors, could be promising in maintaining remission or preemptively eradicating persistent measurable residual disease, mainly in patients ineligible for allogeneic hematopoietic stem cell transplant (HSCT). Alternatively, neoantigen-specific donor lymphocyte infusion derived from healthy donors and targeting NPM1-mutated protein to selectively elicit graft-versus-leukemia effect may represent an attractive option in subjects experiencing post-HSCT relapse. Future studies are warranted to further investigate dynamics of NPM1-mutated-specific immunity and explore whether novel individualized immunotherapies may have potential clinical utility in NPM1-mutated AML patients.     

Shell-and-Tube Minichannel Condenser for Low Refrigerant Charge

The design of an innovative shell-and-tube heat pump condenser using 2 mm ID minichannels is presented. This condenser has been designed aiming at the minimization of the charge, which can be required by safety or environmental restrictions. Nevertheless, minichannels represent also a solution to the high-pressure challenge when using carbon dioxide as a refrigerant. The present prototype was realized for the use with propane in the framework of the European project SHERHPA, concerning the development of heat pumps working with natural fluids. Experimental data for heat transfer and pressure drop are reported in the present paper. The measurements have been obtained using refrigerant R22, which displays a temperature versus pressure saturation curve pretty close to the one of propane. The data have also been compared against a computational procedure for shell-and-tube heat exchangers design. The refrigerant charge has been computed by means of different void fraction correlations, showing that the expected charge is less than half the quantity required by a brazed plate condenser giving the same capacity.     

The territorial and landscape impacts of photovoltaic systems: Definition of impacts and assessment of the glare risk

The installation and operation of systems that exploit solar energy through photovoltaic conversion, recently promoted in some European countries by new sell-back tariffs, is a relevant transformation of the territory for various reasons (land use, elimination of the existing vegetation, visual impact on the components of the landscape, microclimate change, glare from the reflection of the direct sunlight). The weak energy intensity of the solar source coupled with the low conversion efficiency of the photovoltaic cells, make the physical dimensions of such systems relevant and, with them, also the environmental, territorial and landscape impacts that basically depend on the physical extent of the system. If it is well known that an incentive to the exploitation of renewable sources is one of the features of the policy of land conservation, including the one of the protected areas, at the same time the concerns of local communities and governments about the environmental, territorial and landscape impacts of this technology are increasing rapidly.Given this picture, this work is intended to clarify the territorial impacts of the ground mounted photovoltaic systems. Later, the paper concentrates on a specific impact, which is the assessment of the risk of glare by reflection of direct sunlight from the surfaces of photovoltaic modules. The methodologies that can be used to assess this impact and the outcomes of an evaluation carried out for a 5000 m² PV system currently designed on a hilly territory in Italy are presented.     

Nuclear reactor dynamics on-line estimation by Locally Recurrent Neural Networks

In this paper, the Causal Recursive Back-Propagation (CRBP) algorithm is employed to train on-line an Infinite Impulse Response–Locally Recurrent Neural Network (IIR–LRNN) for modelling the dynamics of a next-generation nuclear reactor. The results demonstrate the advantages of the on-line training over the batch-mode learning in the reconstruction of complex nonlinear dynamic relationships.     

Crystallisation of high density polyethylene from dilute solution: Heterogeneous nucleation

The self-seeding crystallisation technique is applied to a dilute solution of polyethylene in xylene containing, in suspension, foreign particles; data concerning some pigments usually employed for colouring the plastics are reported. It is shown that this method allows easy demonstration of the interactions existing between the dissolved polymer and the pigment; at the same time, it is possible to study the morphology which is evolved as a consequence of these interactions under particularly simple conditions as only a small amount of polymer crystallises on the pigment particles. The behaviour of several pigments is consistent with the results obtained by crystallising the bulk polyethylene coloured with the same pigments. Some unusual morphologies are made evident.     

Mode II intersonic crack propagation in poroelastic media

A crack is steadily running in an elastic isotropic fluid-saturated porous solid at an intersonic constant speed c. The crack tip speeds of interest are bounded below by the slower between the slow longitudinal wave-speed and the shear wave-speed, and above by the fast longitudinal wave-speed. Biot’s theory of poroelasticity with inertia forces governs the motion of the mixture. The poroelastic moduli depend on the porosity, and the complete range of porosities n ∈ [0, 1] is investigated. Solids are obtained as the limit case n = 0, and the continuity of the energy release rate as the porosity vanishes is addressed. Three characteristic regions in the plane (n, c) are delineated, depending on the relative order of the body wave-speeds. Mode II loading conditions are considered, with a permeable crack surface. Cracks with and without process zones are envisaged. In each region, the analytical solution to a Riemann–Hilbert problem provides the stress, pore pressure and velocity fields near the tip of the crack. For subsonic propagation, the asymptotic crack tip fields are known to be continuous in the body [Loret and Radi (2001) J Mech Phys Solids 49(5):995–1020]. In contrast, for intersonic crack propagation without a process zone, the asymptotic stress and pore pressure might display a discontinuity across two or four symmetric rays emanating from the moving crack tip. Under Mode II loading condition, the singularity exponent for energetically admissible tip speeds turns out to be weaker than 1/2, except at a special point and along special curves of the (n, c)-plane. The introduction of a finite length process zone is required so that 1. the energy release rate at the crack tip is strictly positive and finite; 2. the relative sliding of the crack surfaces has the same direction as the applied loading. The presence of the process zone is shown to wipe out possible first order discontinuities.     

A support vector machine integrated system for the classification of operation anomalies in nuclear components and systems

A support vector machine (SVM) approach to the classification of transients in nuclear power plants is presented. SVM is a machine-learning algorithm that has been successfully used in pattern recognition for cluster analysis. In the present work, single- and multiclass SVM are combined into a hierarchical structure for distinguishing among transients in nuclear systems on the basis of measured data. An example of application of the approach is presented with respect to the classification of anomalies and malfunctions occurring in the feedwater system of a boiling water reactor. The data used in the example are provided by the HAMBO simulator of the Halden Reactor Project.     

Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting

In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna® subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna® (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen’s kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna® Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna® testing classified as Prosigna® Luminal A at high / intermediate risk or upgraded to Prosigna® Luminal B.