Glutathione participates in the modulation of starvation-induced autophagy in carcinoma cells

Glutathione (γ-L-glutamyl-L-cysteinyl-glycine, GSH) is the most abundant low molecular weight, thiol-containing compound within the cells and has a primary role in the antioxidant defense and intracellular signaling. Here we demonstrated that nutrient deprivation led to a significant decrease of intracellular GSH levels in three different carcinoma cell lines. This phenomenon was dependent on ABCC1-mediated GSH extrusion, along with GCL inhibition and, to a minor extent, the formation of GSH-protein mixed disulfides that synergistically contributed to the modulation of autophagy by shifting the intracellular redox state toward more oxidizing conditions. Modulation of intracellular GSH by inhibiting its de novo synthesis through incubation with buthionine sulfoximine, or by maintaining its levels through GSH ethyl ester, affected the oxidation of protein thiols, such as PRDXs and consequently the kinetics of autophagy activation. We also demonstrated that thiol-oxidizing or -alkylating agents, such as diamide and diethyl maleate activated autophagy, corroborating the evidence that changes in thiol redox state contributed to the occurrence of autophagy

Multi-criteria investigation of a pumped thermal electricity storage (PTES) system with thermal integration and sensible heat storage

In the present paper a multicriteria analysis of a Rankine Pumped Thermal Electricity Storage (PTES) system with low-grade thermal energy integration is performed. The system is composed by an ORC for the discharging phase and a high-temperature heat pump for the charging phase. As previously demonstrated, the low-grade thermal energy can be provided at the heat pump evaporator to boost the PTES performances. As it regards the multi-criteria analysis, a tradeoff is required when electric-to-electric energy ratio ηrt, total exergy exploitation efficiency ψut and energy density ρen, are maximized concurrently. By means of multi-objective optimization, theoretical performances of the system are derived in two different layouts, which are differentiated by the presence, or not, of internal regeneration in charge and discharge subsystems. Results showed that regeneration can be very effective, as it relaxes the tradeoff between the objectives, thus yielding better global performances. Pareto fronts are built and explored to characterize the PTES system. Configurations of interest are proposed, and PTES performances are compared with other storage technologies. Theoretical results showed that, by exploiting thermal energy at temperature lower than 80 °C, ηrt ≈ 0.55 and ρen ≈ 15 kWh/m3 can be concurrently achieved. This can be done at the cost of an inefficient exploitation of the thermal source, as ψut ≈ 0.05. If higher total exergy utilization efficiency is required, storage density can still be maintained high, but ηrt must drop down to 0.4

Rankine carnot batteries with the integration of thermal energy sources: A review

This paper provides an overview of a novel electric energy storage technology. The Thermally Integrated Pumped Thermal Electricity Storage (TI-PTES) stores electric energy as thermal exergy. Compared to standard PTES, TI-PTES takes advantage of both electric and low-temperature heat inputs. Therefore, TI-PTES is a hybrid technology between storage and electric production from low-temperature heat. TI-PTES belongs to a technology group informally referred to as Carnot Batteries (CBs). As the TI-PTES grows in popularity, several configurations have been proposed, with different claimed performances, but no standard has emerged to date. The study provides an overview of the component and operating fluid selection, and it describes the configurations proposed in the literature. Some issues regarding the performance, the ratio between thermal and electrical inputs, and the actual TI-PTES utilisation in realistic scenarios are discussed. As a result, some guidelines are defined. The configurations that utilise high-temperature thermal reservoirs are more extensively studied, due to their superior thermodynamic performance. However, low-temperature TI-PTES may achieve similar performance and have easier access to latent heat storage in the form of water ice. Finally, to achieve satisfactory performance, TI-PTES must absorb a thermal input several times larger than the electric one. This limits TI-PTES to small-scale applications

Influence of emitter-receiver number on measurement accuracy in acoustic pyrometry

Acoustic pyrometry is an interesting technique that may find several useful applications in turbomachinery. As the speed of sound is directly related a medium temperature, this measurement technique estimates the temperature of a gas by considering the time of flight of an acoustic wave moving through it. If only an acoustic emitter-receiver couple is used, only the average temperature along the acoustic path can be determined. If multiple emitter-receiver couples laying on the same plane are used, a reconstruction of the temperature map in the section is possible. This estimation is performed by considering that multiple acoustic paths travel across the same sub-portions of the section and, therefore, the temperature of each sub-portion affects the time of flight along several sound paths. Many parameters affect the accuracy of the measurement, and they are related to the physic of the phenomena involved in the measurement, the accuracy of the instrumentation used, the interaction between the acoustic wave and the flow velocity and the hardware set-up. In this study, the impact of some set-up parameters on the accuracy of the measurement was investigated and, in particular, the number of sound emitter-receiver couples and the number of investigation sub-portions in which the section is divided. A reference temperature map has been considered as a benchmark. This study, which is a preliminary investigation on this technique, was useful to assess the capability of this methodology to correctly describe a temperature distribution in an ideal condition. Therefore, it represents a first step in the set-up of an experimental investigation with an acoustic pyrometer.

SOFC Micro-CHP integration in residential buildings

SOFC technology has reached many of the performance goals that where indicated by scientific society and is providing several application that permits market penetration. One of the main targets is related to Micro Cogeneration Heat and Power (μ-CHP) for residential application. The integration of this system with a residential house has to be deeply investigated to individuate market targets in terms of costs and efficiency. This study evaluates the Italian market condition and analyzes the integration possibility with both thermal and electrical systems. Different solutions are investigated evaluating thermal and electrical driven logic for μ-CHP SOFC based unit and the opportunity of integration with local electrical grid. Evaluation on heat and electricity storage was also considered as integration strategy. The study is based on electrical and thermal loads in typical residential users and the evaluation is based on Italian technical standards and guidelines. Several operating conditions were evaluated and compared to obtain an optimized size and integration of μHP SOFC based solution

Under the ROS…thiol network is the principal suspect for autophagy commitment.

Low molecular weight and protein sulphydryls undergo reactive oxygen species (ROS)-mediated oxidation. However, in contrast to the irreversible damages that oxidative conditions yield on biomolecules, the oxidation of reactive cysteines frequently results in reversible modifications, which represent the prototype of the molecular mechanisms underlying redox signaling. Many proteins involved in a wide range of cellular processes have been classified as “redoxsensitive,” thereby modulating their function/activity dependent on the redox state of their critical thiols. Growing evidence from the past few years supports the idea that ROS production also correlates with the occurrence of autophagy. Nonetheless, the cysteine protease Atg4 remains the sole example of a protein whose redox regulation has been completely characterized and demonstrated to be necessary for the progression of autophagy. The principal aim of this commentary is to draw attention to the remarkable number of proteins that can fit the double role of: (i) being involved in autophagy, especially in autophagosome formation and (ii) sensing alterations of the cellular redox state by means of reactive cysteine residues. We will also attempt to provide a hypothetical model to explain the possible functional role of thiols in the occurrence of autophagy and outline a network of redox reactions likely concurring to allow the correct initiation and completion of autophagosomes

impact of consumption profile discontinuities on the feasibility of a pv plant

Abstract The revenues of a grid-connected photovoltaic plant are strongly related to the local climatic conditions. In addition, since self-consumed electricity is much more valuable than that traded with the main power grid, also consumption profile plays a key role in the profitability of a PV system. Self-consumption to total PV production ratio depends on the temporal mismatch between energy generation and demand. The amount of energy that is not self-consumed may be very high in the case of a consumption profile with several discontinuities. This study is focused on the analysis of a grid-connected PV system serving a compressed natural gas (CNG) fueling station. These facilities are energy-intensive users, characterized by high variability of electricity demand due to intermittent operation of gas compressors: in a few seconds the total load may change from 100% to 5% and vice versa very frequently during the day. The analysis was based on data acquired on the field for the compression station and those already present in the literature for solar irradiation. The influence on plant design of the time step used for the analysis was studied in detail. The outcomes showed that the typical and well-assessed design approaches of a PV pant may lead to errors when used for the design of systems with several consumption profile discontinuities

poly generation capability of a biogas plant with upgrading system

Abstract Biomass, together with other renewable sources, is increasingly used to provide energy to minigrids and distributed generation systems. Particularly, biogas production seems an interesting solution as it can be used to produce electricity, heat and bio-methane (through an upgrading system). In addition, biogas can be relatively easily stored in gasometers to compensate for small request variations. On the other hand, the amounts of heat, electricity and bio-methane produced are strictly dependent one on the others. A poly-generation scenario was considered starting from an existing case study made up of a digester, a 600kWel micro gas turbine and an upgrading system for bio-methane production. An off-design system simulation was carried out to analyze the energy and mass fluxes between plant components as a function of the fraction of the biogas sent to the upgrader. The constraints and relations between heat, electricity and bio-methane production were extensively analyzed. Results show that this system can be a versatile poly-generation unit

TLR3 engagement induces IRF-3-dependent apoptosis in androgen-sensitive prostate cancer cells and inhibits tumour growth in vivo

Toll-like receptors (TLRs) are a family of highly conserved transmembrane proteins expressed in epithelial and immune cells that recognize pathogen associated molecular patterns. Besides their role in immune response against infections, numerous studies have shown an important role of different TLRs in cancer, indicating these receptors as potential targets for cancer therapy. We previously demonstrated that the activation of TLR3 by the synthetic double-stranded RNA analogue poly I:C induces apoptosis of androgen-sensitive prostate cancer (PCa) LNCaP cells and, much less efficiently, of the more aggressive PC3 cell line. Therefore, in this study we selected LNCaP cells to investigate the mechanism of TLR3-mediated apoptosis and the in vivo efficacy of poly I:C-based therapy. We show that interferon regulatory factor-3 (IRF-3) signalling plays an essential role in TLR3-mediated apoptosis in LNCaP cells through the activation of the intrinsic and extrinsic apoptotic pathways. Interestingly, hardly any apoptosis was induced by poly I:C in normal prostate epithelial cells RWPE-1. We also demonstrate for the first time the direct anticancer effect of poly I:C as a single therapeutic agent in a well-established human androgen-sensitive PCa xenograft model, by showing that tumour growth is highly impaired in poly I:C-treated immunodeficient mice. Immunohistochemical analysis of PCa xenografts highlights the antitumour role of poly I:C in vivo both on cancer cells and, indirectly, on endothelial cells. Notably, we show the presence of TLR3 and IRF-3 in both human normal and PCa clinical samples, potentially envisaging poly I:C-based therapy for PCa