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Parkinson's disease (PD) is a neurodegenerative condition characterized by the progressive and selective loss of dopaminergic (DAergic) neurons in the midbrain. The replacement of neuromelanin (NM)–containing DAergic neurons in the substantia nigra and the enhancement of NM concentration could offer a promising and safe approach to treating PD symptoms. The objective of this study was to investigate and compare the potential of human periapical-cysts mesenchymal stem cells (hPCy-MSCs) and dental pulp stem cells (DPSCs) to differentiate into DAergic NM-producing neurons and to generate functional 3-dimensional (3D) midbrain-like organoids in vitro. We assessed the changes in morphology and behavior of neuron-like cells (NLCs) as well as the expression of molecular markers characterizing the DAergic neurons. Furthermore, we observed electrically active and functionally mature DAergic neurons by means of electrophysiological assays, NM dosage assays, and the quantification of dopamine release by high-performance liquid chromatography. Our results demonstrate for the first time that both hPCy-MSCs and DPSCs are capable of differentiating into NLCs, further confirmed by the increase in lactate levels in the medium of cells exposed to neurogenic conditions. Importantly, we have induced such NLCs to further differentiate into functional DAergic NM-producing neurons. Finally, 3D midbrain-like organoids have been produced from oral stem cells: they appear as neurosphere-like structures diffusely expressing the neural marker β-III tubulin and containing NM-like granules. Our findings open up a novel and fascinating opportunity to rethink oral stem cells, and the derived 3D disease models, as a strategic and reliable tool for unveiling the neurodegenerative alterations. [ABSTRACT FROM AUTHOR]

A subset of bacterial species that holds genes encoding for β-glucuronidase and β-galactosidase, enzymes involved in the metabolism of conjugated estrogens, is called the "estrobolome." There is an emerging interest embracing this concept, as it may exert a selective impact on a number of pathologies, including oral cancer. Although the estrobolome bacteria are typically part of the gut microbiota, recent experimental pieces of evidence have suggested a crosstalk among oral and gut microbiota. In fact, several oral bacterial species are well represented also in the gut microbiota, and these microbes can effectively induce the estrobolome activation. The main pathways used for activating the estrobolome are based on the induction of the expression patterns for 2 bacterial enzymes: β-glucuronidase and aromatase, both involved in the increase of estrogen released in the bloodstream and consequently in the salivary compartment. Mechanistically, high estrogen availability in saliva is responsible for an increase in oral cancer risk for different reasons: briefly, 1) estrogens directly exert biological and metabolic effects on oral mucosa cells; 2) they can modulate the pathological profile of some bacteria, somewhere associated with neoplastic processes (i.e., Fusobacterium spp., Parvimonas ssp.); and 3) some oral bacteria are able to convert estrogens into carcinogenic metabolites, such as 4-hydroxyestrone and 16α-hydroxyestrone (16α-OHE), and can also promote local and systemic inflammation. Nowadays, only a small number of scientific studies have taken into consideration the potential correlations among oral dysbiosis, alterations of the gut estrobolome, and some hormone-dependent cancers: this lack of attention on such a promising topic could be a bias affecting the full understanding of the pathogenesis of several estrogen-related oral pathologies. In our article, we have speculated on the activity of an oral–gut–estrobolome axis, capable of synergizing these 2 important microbiotas, shedding light on a pilot hypothesis requiring further research. [ABSTRACT FROM AUTHOR]

Distributed maximum power point tracking (DMPPT) is one of the most promising solutions to overcome the drawbacks associated with mismatching phenomena in photovoltaic (PV) applications. DMPPT is based on the adoption of a dc/dc converter dedicated to each PV module. The design of the power stage of such a converter is a challenging task because of the very high efficiency requirements and of the continuous changes of the operating point during the day, depending on the sun irradiation conditions. In this paper the guidelines for the design of dc-dc converters for DMPPT applications are presented and discussed. [DOI: 10.1115/1.4001465]

A worst case robust design approach based on a suitable application of interval arithmetic (IA) is proposed. The use of IA leads to a definition of the interval extension of the Taylor series named interval Taylor extension (ITE). The width of the ITE (WITE) has been shown to be a valuable robustness index in the case of polynomial performance functions (PFs). In this paper, the method is extended to nonpolynomial PFs, as those ones obtained by multiquadric interpolation in computer assisted electromagnetic design (by FEM, BEM, etc.). In particular, it is shown that the ITE of a multiquadric function furnishes a rigorous overbounding of the PF and the WITE gives an overestimation of the PF range in presence of an assigned uncertainty of the design parameters, both in an analytical monodimensional case study and in the benchmark TEAM 22 optimization problem. Moreover, the most robust stationary solution can be achieved by looking at the minimum of WITE. Index Terms--Interval analysis, inverse problems, optimization, worst case design.

The perturb and observe (P&O) best operation conditions are investigated in order to identify the edge efficiency performances of this most popular maximum power point tracking (MPPT) technique for photovoltaic (PV) applications. It is shown that P&O may guarantee top-level efficiency, provided that a proper predictive (by means of a parabolic interpolation of the last three operating points) and adaptive (based on the measure of the actual power) hill climbing strategy is adopted. The approach proposed is aimed at realizing, in addition to absolute best tracking performances, high robustness and promptness both in sunny and cloudy weather conditions. The power gain with respect to standard P&O technique is proved by means of simulation results and experimental measurements performed on a low power system. Besides the performance improvements, it is shown that the proposed approach allows possible reduction of hardware costs of analog-to-digital (A/D) converters used in the MPPT control circuitry.

The use of one-cycle control (OCC) for maximum power point tracking (MPPT) and power factor correction (PFC) in grid connected photovoltaic (PV) applications is discussed. Circuit and operating parameters of the one cycle-based controller of a cost-effective single-stage inverter are optimized in order to obtain the best performances of the system under different irradiance levels. Firstly, design constraints are formulated which allow to get a very efficient OCC operation in terms of power extracted from the PV array, stability, and PFC. Afterwards, such constraints are used to perform the parametric optimization of the one cycle controller by means of suitable heuristic approaches. Various selection criteria of the best parameters set under different conditions are discussed and applied. Finally, a customized perturb and observe (P&O) control is applied to the optimized one cycle controlled single-stage inverter in order to perform a real MPPT in presence of varying irradiance conditions. Subjects described here are covered by the Italian Patent Application SA2005A000014-13.07.2005 and PCT Application PCT/IT2005/000747-20.12.2005.

This paper introduces an evolutionary approach to worst case tolerance analysis of static field problems ruled by the Poisson equation, over suitable spatial domains and with given boundary conditions. The approach ensures a better estimation of the true worst case with respect to classical stochastic methods, especially if parameters are affected by large uncertainties and whenever the performance function of interest is nonlinear or, even worse, nonmonotonical with respect to parameters. Index Terms--Static fields, tolerance, worst case analysis.

This study aimed at evaluating the cytotoxicity of experimental fluoride-doped hydroxy-calcium-phosphates and their bioactivity in converting them into hydroxy/fluoro‐apatite. Experimental fluoride-doped hydroxy-calcium-phosphates were formulated by using a 1:1 molar ratio of beta-tricalcium phosphate (α-TCP) and monocalcium phosphate monohydrate (MCPM), doped with calcium hydroxide (10 wt%) and calcium and sodium fluoride salts (1:1 molar ratio) at different concentration of (VSG5F%; VSG10F%; VSG20F%) (Patent: WO2019243592). A fluoride-free (VSG) hydroxy-calcium-phosphate was also formulated and used as a control material. Each powder was immersion in SBF (24 h, 2 and 4 weeks) and submitted to the following analysis to evaluate their bioactivity in inducing apatite-like formation: a) vibrational analysis FTRI-ATR; b) X-ray diffraction; c) TEM-EDX-XRD. Cumulative fluoride release (ppm) was performed for up to 2 months. Each powder was immersed in SBF for 24 h and placed into a hDPSCs (200 mg/mL) medium (ISO/EN 10993-12). Serial dilutions of extracts were prepared (1:1-to-1:200) and their cytotoxicity was analyzed using a MTT [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay (initial density of 5 ×103), (incubation 24 h, 48 h, 72 h). Cells on tissue culture plates with a medium were used as a control. The results were statistically analyzed by means of analysis of variance (ANOVA) and Tukey's multiple comparison test (α= 0.05). After 2 weeks of storage in SBF, VSG10F and VSG20F were totally converted into crystals of hydroxy/fluoro-apatite. VSG20F still presented unreacted fluoride after 4 weeks of storage, which was continuously released and accumulated in the media. All the powders showed a significant toxicity at all time points at dilution of 1:1. VSG0F and VSG20F showed a significant toxicity after 24 h (dilutions 1:5), but after 72 h a significant increase in cell proliferation was observed in all the SVGF powders. At 1:10, VSG20F showed the greatest toxicity, while at 1:20, VSG10F and VSG20F showed a reduction of cell viability of only 3% and 13% respectively (48 h). At lower dilutions (1:20, 1:100 and 1:200) no powders showed significant toxicity compared to the control, but an increase in cell proliferation was observed at 72 h with VSG5F and VSG10F. The experimental fluoride-doped hydroxy-calcium-phosphates tested in this study may be potentially used for the remineralization of dentine and enamel thanks to their ability to convert into hydroxy/fluoro‐apatite crystals. As a result of their remarkable biocompatibility and to their ability to induce cell proliferation in some specific conditions, the experimental fluoride-doped hydroxy-calcium-phosphates tested in this study could also be employed for the formulation of pulp-protection materials. [ABSTRACT FROM AUTHOR]

The temperature effect on photovoltaic modules is usually quantified by means of some coefficients relating the variations of the open‐circuit voltage, of the short‐circuit current, and of the maximum power to temperature changes. In this paper, comprehensive experimental guidelines to estimate the temperature coefficients when measurements are performed outdoors are given. In addition, a correction procedure is applied to the short‐circuit current to cancel out the influence of the fluctuations in the irradiance level. The experimental results shown in this paper refer to several single‐crystalline silicon modules that have been operating for 21 years. Consequently, the estimated values of the temperature coefficients also account for module ageing processes. The coefficients of determination achieved in the case of the temperature coefficients of the open‐circuit voltage and the maximum power are very close to one. Results concerning the temperature coefficients of the short‐circuit current are also suitable if they are previously corrected. A comprehensive experiment guideline is to estimate the temperature coefficients outdoors. A novel correction procedure is applied to the short‐circuit current to cancel out the influence of the fluctuation in the irradiance level. The experiment result refers to several single‐crystalline silicon modules that have been operating for 21 years; hence, the estimated values account for module ageing processes. [ABSTRACT FROM AUTHOR]

The wide range of requirements and constraints involved in the design of nuclear components for fusion reactors makes the development of multi-physics analysis procedures of utmost importance. In the framework of the European DEMO project, the Karlsruhe Institute of Technology (KIT) is dedicating several efforts to the development of a multi-physics analysis tool allowing the characterization of breeding blanket design points which are consistent from the neutronic, thermal-hydraulic and thermal-mechanical points of view. In particular, a procedure developed at KIT is characterized by the implementation of analysis software only. A preliminary step for the validation of such a procedure has been accomplished using a dedicated model of the DEMO Helium Cooled Pebble Bed Blanket 4th outboard module. A global model representative of nuclear irradiation in DEMO and two local models have been set up. Nuclear power deposition and the spatial distribution of its volumetric density have been calculated using Monte Carlo N-Particle transport code for the aforementioned models and compared in order to validate the procedure set up. The outcomes of this comparative study are herein presented and critically discussed. [ABSTRACT FROM AUTHOR]

Although, the studies about the genotoxic and cytotoxic effects of methacrylate resins have increased considerably, the understanding of molecular regulatory basis is still poorly understood. HOTAIR is a non-coding RNA related to several diseases; originally, it was found in colorectal, gastric cancer and hepatoma. Moreover, HOTAIR is one of the most important regulator of the Epithelial-Mesenchymal Transition process. The aim of this paper was to investigate the ability of three commercial acid resins (Unifast, JetKit and Duralay) to control the HOTAIR gene expression. The cytotoxic activity in HGFs, measured by MTT assay, was always conditioned by high concentrations of the resins. On the other hand, the proliferation rate does not change in HGFs treated with Unifast and Duralay, while Jet Kit is a negative regulator of the cell proliferation. The HOTAIR gene expression was regulated in HGFs treated with Unifast and Duralay, while JetKit did not induce change in charge of HOTAIR expression. In this study, the ability of different commercial polyacrylic acid resins to regulate lncHOTAIR gene has been demonstrated for the first time. Moreover, no data have previously been reported about the HOTAIR gene expression in HGFs. Several experimental evidences identify HOTAIR as a crucial regulator of EMT; pathologically, any alteration of EMT process leads to several diseases. Particularly, overgrowth of gingival epithelium is due to the deregulation of EMT specific markers. In conclusion, our results could lead to better understanding the role of HOTAIR in different gingival pathologies related to the EMT deregulation. [ABSTRACT FROM AUTHOR]

The osteogenesis is a complex process that involves an accurate control of bone development, growth as well as remodeling during postnatal life. In particular, osteoblasts arise from mesenchymal stem cells through a process regulated in several steps that leads to the osteogenic differentiation. Class I homeobox genes (HOX in human and Hox in mice), are 39 transcription factors, mainly involved in the regulation of embryonic development. It has been shown that HOXA10 was able to activate several osteoblast related genes like Osx. The HOXA10 gene was considered a key factor able to control osteogenesis. In the last decade, several non-coding RNAs (ncRNAs), have been identified like crucial factors during osteogenesis. HOTAIR is an lncRNA related to Osteosarcoma and able to induce the Epithelial Mesenchymal Transition. The aim of this paper was understood the role of HOTAIR and HOXC locus in the control of Osteoblasts development in MSCs treated with adipose tissue obtained with Lipogems method. [ABSTRACT FROM AUTHOR]