Understanding the cellular constituents of the prostate is essential for identifying the cell of origin for prostate adenocarcinoma. Here, we describe a comprehensive single-cell atlas of the adult ...mouse prostate epithelium, which displays extensive heterogeneity. We observe distal lobe-specific luminal epithelial populations (LumA, LumD, LumL, and LumV), a proximally enriched luminal population (LumP) that is not lobe-specific, and a periurethral population (PrU) that shares both basal and luminal features. Functional analyses suggest that LumP and PrU cells have multipotent progenitor activity in organoid formation and tissue reconstitution assays. Furthermore, we show that mouse distal and proximal luminal cells are most similar to human acinar and ductal populations, that a PrU-like population is conserved between species, and that the mouse lateral prostate is most similar to the human peripheral zone. Our findings elucidate new prostate epithelial progenitors, and help resolve long-standing questions about anatomical relationships between the mouse and human prostate.
Therapy resistance is a major roadblock in oncology. Exacerbation of molecular dysfunctions typical of cancer cells have proven effective in twisting oncogenic mechanisms to lethal conditions, thus ...offering new therapeutic avenues for cancer treatment. Here, we demonstrate that selective agonists of Transient Receptor Potential cation channel subfamily M member 8 (TRPM8), a cation channel characteristic of the prostate epithelium frequently overexpressed in advanced stage III/IV prostate cancers (PCa), sensitize therapy refractory models of PCa to radio, chemo or hormonal treatment. Overall, our study demonstrates that pharmacological-induced Ca
cytotoxicity is an actionable strategy to sensitize cancer cells to standard therapies.
An experimental investigation of the local flow field in a Wells turbine has been conducted, in order to produce a detailed analysis of the aerodynamic characteristics of the rotor and support the ...search for optimized solutions. The measurements were conducted with a hot-wire anemometer (HWA) probe, reconstructing the local three-dimensional flow field both upstream and downstream of a small-scale Wells turbine. The multi-rotation technique has been applied to measure the three velocity components of the flow field for a fixed operating condition. The results of the investigation show the local flow structures along a blade pitch, highlighting the location and radial extension of the vortices which interact with the clean flow, thus degrading the turbine’s overall performance. Some peculiarities of this turbine have also been shown, and need to be considered in order to propose modified solutions to improve its performance.
One of the most promising technologies for sea-wave energy conversion is the one based on the Oscillating Water Column (OWC) principle. The system is composed of two units, an open chamber that ...converts the sea water motion into an alternating air-flow, and a turbine driven by the latter. The alternating flow of air requires a turbine capable of maintaining the same direction of rotation. The Wells turbine represents the simplest and most reliable device for this purpose. It is a self-rectifying axial turbine characterized by a rotor with symmetric blades staggered at 90 degrees relative to the axis of rotation. The vast majority of experimental works on Wells turbines and OWC devices analyzed their performance from a global point of view, often under steady conditions, in order to evaluate the pressure drop through the rotor, the torque produced and thus the turbine efficiency. This paper presents an experimental analysis of the three-dimensional flow inside a Wells turbine which operates in a facility capable of reproducing the alternating air-flow typical of an OWC system. The investigation is based on local flow measurements using several probes in order to describe the non-stationary air-flow, both up- and down-stream of the rotor at different heights, along the span of the blade. The investigation, conducted on a high-solidity turbine, details the behavior of the flow field inside the machine, aiming to provide a detailed description that can guide the aerodynamic optimization of the entire system (chamber and turbine) for a better energy conversion.
This discussion is based on the paper by Mamouri et al. (2019) (hereafter identified as “the original authors” or “the original paper”). The original authors employed computational fluid dynamics to ...calculate the flow field around several wind turbine airfoils, and combined this with an evaluation of the entropy generation to estimate the second law efficiency. It came to our attention that the equations used to estimate the entropy generation, and in particular the term that is used to estimate the entropy generated by turbulent fluctuations, are incorrect. In addition, the original authors claim that one of the main contributions of their work is the identification of a relation between entropy generation and drag, probably ignoring that the same relation has been known and used by several authors in the past, and examples can be found from at least 60 years ago.
This discussion is based on the paper by Cui et al. (2019) (hereafter identified as “the original authors” or “the original paper”). The original authors present a review on the application of CFD in ...the analysis of self-rectifying turbines for OWC wave energy conversion devices. We feel that this review is incomplete, as it overlooks a number of papers published in recent years that gave a new explanation for a phenomenon largely studied in the last two decades and discussed in the original paper: the hysteresis in Wells turbine performance. In addition, the original authors, in their conclusions, envisage a larger use of CFD in the coming years, especially for the unsteady analysis of the chamber-turbine interaction, probably ignoring that several CFD studies focusing on this aspect have already been published. In fact, it is through three-dimensional time-dependent CFD studies of the unsteady interaction between chamber and turbine that the explanation of the cause of the hysteresis was found. The objective of this discussion is to clarify two important aspects: the chamber-turbine interaction and the turbine hysteresis, that in our opinion were not correctly analyzed in the original review paper by Cui et al.
Among the various solutions suggested for wave energy harvesting, the ones based on the oscillating water column (OWC) principle are considered as the most promising, due to their constructive ...simplicity and reliability. These systems convert sea wave energy into pneumatic energy in the form of a bi-directional airflow that can conveniently turned into mechanical energy by a Wells turbine. Since their introduction, Wells turbines have been studied extensively in order to characterize their performance. Most of the experimental studies have focused on global machine performance analyses, while the studies focusing on local performance analyses are limited. This work presents a detailed experimental investigation of a small-scale Wells turbine coupled to an OWC simulator. The turbine aerodynamic characteristic has been identified with global measurements, while a miniaturized aerodynamic probe has been used to evaluate local performance, by reconstructing the three-dimensional flow field upstream and downstream of the turbine during a complete regular wave period. Local analyses aid to explain global turbine performance, highlighting the main differences between inflow and outflow phases. Moreover, they allow to describe the variation in loading along the blade radius, and to evaluate the blade design law, which justifies the limited Wells turbine aerodynamic performance.
•A Wells turbine is tested coupled to an OWC simulator.•Experimental investigation of the local 3D flow field in a Wells turbine.•Flow field reconstruction during the inflow and outflow phases.•Different performance for the two phases are due to a swirl flow inside the chamber.•Rotor losses for the two phases are different due to a larger exhaust kinetic energy.•Constant chord blade design results in a reduction of the work in the tip region.
One of the most promising technologies for sea-wave energy conversion is the one based on the OWC principle. In a system of this type, the oscillatory motion of the sea waves is converted into a ...bi-directional air flow which is commonly exploited by means of a self-rectifying turbine such as the Wells turbine, the simplest and most reliable device for this purpose. The vast majority of experiments on Wells turbines and OWC devices has analyzed their performance from a global point of view, often in experimental facilities where the turbine was operated under stationary flow conditions.
This paper presents the results of the experimental investigation carried out on a Wells turbine, by measuring the flow field both upstream and downstream of the rotor, in a laboratory set-up capable to reproduce the bi-directional airflow typical of an OWC system. The investigation aims to evaluate the local performance of the Wells turbine under unsteady flow conditions.
The experimental measurements allow the identification of the loss components that affect the performance of the turbine. Viscous losses, due to the aerodynamic of the rotor cascade, represent the main contribution to the total losses, and appear larger than kinetic energy losses at the machine exhaust.
•Measurements of the local performance of a Wells turbine under bi-directional flow.•Loss components and turbine efficiency are calculated.•Most of losses are due to the aerodynamic behavior of the rotor.•Non-stationary operating conditions strongly affect the performance of the turbine.•Rotor solidity at the hub and tip leakage are main responsible of turbine losses.
A Wells turbine, when coupled with an oscillating water column, allows the generation of power from the energy in waves on the surface of the ocean. In the present work, a tabu search is used to ...control the process of optimising the blade profile in the Wells turbine for greater performance, by maximising the torque coefficient. A free form deformation method is used as an efficient means of manipulating the blade profile and computational fluid dynamics in OpenFOAM are used to assess each profile in both two and three dimensions. Investigations into both the flow coefficient at which the optimization is performed and the number of control variables in the free form deformation tool are performed before optimisations are done on a two-dimensional blade at the hub and tip solidities. This results in increases to the torque coefficient of 34% and 32% at the tip and hub solidities, respectively. These results are then applied to the three-dimensional turbine, giving a 14% increase in the torque coefficient. The results are assessed and an improved method of optimising the blade in two dimensions is proposed.
Nitric oxide (NO) exerts its function in several cell and organ compartments. Recently, several lines of evidence have been accrued showing that NO can play a critical role in oncogenesis. Here we ...summarize some of these findings and highlight the role of NO as a possible target for antineoplastic drugs. Specifically, NO appears to affect some aspects of neuronal tumour progression, particularly the chemoresistance phenotype, through inhibition of MYC activity and expression of a large set of ATP binding cassette transporters. Here we provide lines of evidence supporting the view that MYCN can alter expression of several members of the ABC transporter family thus influencing the chemoresistance phenotype of neuroblastoma cells. Furthermore, we show that increased intracellular NO concentration either through addition of NO donors to culture medium or through forced expression of nNOS in neuroblastoma cells leads to decreased expression of MYCN and ABC drug transporter genes. Overall, data reviewed here and novel results presented, unveil a NO-MYCN-ABC transporters axis with important implication on development and control of the chemoresistance phenotype in neuronal tumours.
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