Pulsed Electromagnetic Field Stimulation in Osteogenesis and Chondrogenesis: Signaling Pathways and Therapeutic Implications

Mesenchymal stem cells (MSCs) are the main cell players in tissue repair and thanks to their self-renewal and multi-lineage differentiation capabilities, they gained significant attention as cell source for tissue engineering (TE) approaches aimed at restoring bone and cartilage defects. Despite significant progress, their therapeutic application remains debated: the TE construct often fails to completely restore the biomechanical properties of the native tissue, leading to poor clinical outcomes in the long term. Pulsed electromagnetic fields (PEMFs) are currently used as a safe and non-invasive treatment to enhance bone healing and to provide joint protection. PEMFs enhance both osteogenic and chondrogenic differentiation of MSCs. Here, we provide extensive review of the signaling pathways modulated by PEMFs during MSCs osteogenic and chondrogenic differentiation. Particular attention has been given to the PEMF-mediated activation of the adenosine signaling and their regulation of the inflammatory response as key player in TE approaches. Overall, the application of PEMFs in tissue repair is foreseen: (1) in vitro: to improve the functional and mechanical properties of the engineered construct; (2) in vivo: (i) to favor graft integration, (ii) to control the local inflammatory response, and (iii) to foster tissue repair from both implanted and resident MSCs cells.     

DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review

DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions.     

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.     

Study of the effect of noble metal promotion in Ni-based catalyst for the Sabatier reaction

This paper reports the preparation and the evaluation of the performance of Ni-based powder catalysts with low nickel loading on the CO2 methanation reaction, that is an integral part of the power-to-gas (PtG) technology. CeO₂, CeZrO₄ and CeO₂/SiO₂ were selected as possible supports, and the results of this first screening pointed out that 10%Ni/CeO₂ catalyst could offer the best reaction performances because of ceria's peculiar characteristics. Moreover, the promotion of this promising formulation with the addition of a small amount of noble metals (Pt, Ru, Rh) was investigated, showing that platinum in particular can enhance the catalyst performances. A further study related to the noble metal loading pointed out that platinum and ruthenium have a different optimum loading condition: this result, together with the activity tests performed on monometallic formulations with only the noble metal, suggested that the two metals are able to catalyse two different reactions, thus promoting two different reaction mechanisms.     

To treat or not to treat: comparison of different criteria used to determine whether weight loss is to be recommended

Background  

Excess body fat is a major risk factor for disease primarily due to its endocrine activity. In recent years several criteria have been introduced to evaluate this factor. Nevertheless, treatment need is currently assessed only on the basis of an individual's Body Mass Index (BMI), calculated as body weight (in kg) divided by height in m². The aim of our study was to determine whether application of the BMI, compared to adiposity-based criteria, results in underestimation of the number of subjects needing lifestyle intervention.     

The Influence of the Amount of Fluoride Catalyst on the Morphological Properties of the Anilinepropylsilica Xerogel Prepared in Basic Medium

Anilinepropylsilica hybrid powder was synthesized by a sol-gel route in basic medium using HF as catalyst. The effect of the amount of HF catalyst on the morphologies and on organic content was studied. The xerogels were characterized using FTIR, SEM and N₂ adsorption-desorption isotherms. The increase in the HF quantity results in an slight increase in organic content and changes in the particle size, surface area and pore structure.     

Fundamental Limitations of Continuous-Time Delta–Sigma Modulators Due to Clock Jitter

We examine noise due to clock jitter in single-loop low-pass continuous-time delta-sigma (Delta Sigma) modulators (CT-DSMs) employing nonreturn to zero (NRZ) feedback digital-to-analog converters (DACs). Using the discrete-time version of the Bode sensitivity integral, we derive a lower bound on jitter noise and its relationship to the noise transfer function (NTF) of the modulator. We show that NTFs with optimized zeros result in lower jitter noise than those with all zeros at the origin. We give intuition to a recent observation (arrived through numerical optimization) that NTFs with peaking in their passbands have lower jitter noise than maximally flat NTFs. We propose a design procedure that minimizes the sum of the quantization and jitter noise. The arguments regarding Delta Sigma analog-to-digital converters are extended to Delta Sigma DACs and measurement results are presented.     

Supporting real-time and multimedia applications on the Mercuritestbed

This paper describes the distributed system, network and software architecture, the application development environment, the performance, and the early lessons learned on the ATM LAN testbed Mercuri established at the Honeywell Technology Center, to develop distributed multimedia technologies for real-time control applications. We have developed a client-server-based software architecture on Sun Sparcstation-2s connected by a Fore Systems' ASX-100 ATM switch, with video processing handled by Parallax's X Video cards. The architecture enables network-transparent applications and provides simple primitives for multimedia capture, display, transmission, storage, and retrieval. A real-time multimedia-in-the-loop control application was developed as the vehicle for testing the capabilities and performance of the network. Our test measurements focus on the end-user-level performance metrics such as message throughput and round-trip delay as well as video-frame jitter under no-load and load conditions. Our results show that the maximum burst throughput that can be supported at the user level is 48 Mb/s using AAL 5, while round-trip delays for 4-kbyte messages are about 3 ms. Our experience reveals a number of performance bottlenecks and open issues in using commercial ATM switches for practical applications. Our conclusions are outlined     

Influence of impact-ionization-induced base current reversal onbipolar transistor parameters

In this paper we describe a set of measurements representing a complete characterization of impact-ionization effects in bipolar transistors. We demonstrate that impact-ionization significantly influences the dependence of base resistance on current and voltages applied to the device. A dc method for the simultaneous extraction of all parasitic resistances in bipolar transistors is presented. The method can separate the influence of current-crowding on the base resistance from that of base width and conductivity modulation; the collector parasitic resistance is measured in the active region. Starting from the parameters extracted by means of these techniques, a complete and accurate circuit-model of impact-ionization effects can be defined