MS-275 (Entinostat) Promotes Radio-Sensitivity in PAX3-FOXO1 Rhabdomyosarcoma Cells

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. About 25% of RMS expresses fusion oncoproteins such as PAX3/PAX7-FOXO1 (fusion-positive, FP) while fusion-negative (FN)-RMS harbors RAS mutations. Radiotherapy (RT) plays a crucial role in local control but metastatic RMS is often radio-resistant. HDAC inhibitors (HDACi) radio-sensitize different cancer cells types. Thus, we evaluated MS-275 (Entinostat), a Class I and IV HDACi, in combination with RT on RMS cells in vitro and in vivo. MS-275 reversibly hampered cell survival in vitro in FN-RMS RD (RASmut) and irreversibly in FP-RMS RH30 cell lines down-regulating cyclin A, B, and D1, up-regulating p21 and p27 and reducing ERKs activity, and c-Myc expression in RD and PI3K/Akt/mTOR activity and N-Myc expression in RH30 cells. Further, MS-275 and RT combination reduced colony formation ability of RH30 cells. In both cell lines, co-treatment increased DNA damage repair inhibition and reactive oxygen species formation, down-regulated NRF2, SOD, CAT and GPx4 anti-oxidant genes and improved RT ability to induce G2 growth arrest. MS-275 inhibited in vivo growth of RH30 cells and completely prevented the growth of RT-unresponsive RH30 xenografts when combined with radiation. Thus, MS-275 could be considered as a radio-sensitizing agent for the treatment of intrinsically radio-resistant PAX3-FOXO1 RMS.     

Salmonella Typhimurium and Pseudomonas aeruginosa Respond Differently to the Fe Chelator Deferiprone and to Some Novel Deferiprone Derivatives

The ability to obtain Fe is critical for pathogens to multiply in their host. For this reason, there is significant interest in the identification of compounds that might interfere with Fe management in bacteria. Here we have tested the response of two Gram-negative pathogens, Salmonella enterica serovar Typhimurium (STM) and Pseudomonas aeruginosa (PAO1), to deferiprone (DFP), a chelating agent already in use for the treatment of thalassemia, and to some DFP derivatives designed to increase its lipophilicity. Our results indicate that DFP effectively inhibits the growth of PAO1, but not STM. Similarly, Fe-dependent genes of the two microorganisms respond differently to this agent. DFP is, however, capable of inhibiting an STM strain unable to synthesize enterochelin, while its effect on PAO1 is not related to the capability to produce siderophores. Using a fluorescent derivative of DFP we have shown that this chelator can penetrate very quickly into PAO1, but not into STM, suggesting that a selective receptor exists in Pseudomonas. Some of the tested derivatives have shown a greater ability to interfere with Fe homeostasis in STM compared to DFP, whereas most, although not all, were less active than DFP against PAO1, possibly due to interference of the added chemical tails with the receptor-mediated recognition process. The results reported in this work indicate that DFP can have different effects on distinct microorganisms, but that it is possible to obtain derivatives with a broader antimicrobial action.     

Relationships between local and structural stress in the evaluation of the weld toe stress distribution

This paper deals with the problem of determining, by proper stress analyses, the stress fields near arc-welded joint toes and the use of such distributions in fatigue strength predictions. In particular, the relationships between the local stress field and the structural (geometrical) stress field are investigated under the hypothesis that highly stressed zones remain under linear elastic conditions.

The local stress distribution is given for different joints in terms of the relevant notch stress intensity factors (NSIFs), having modelled their weld beads like re-entrant sharp corners. The structural stress distribution is, in contrast, the stress field linearly distributed through the thickness of the welded plates (and sometimes on the plate surfaces), beyond the zone affected by local effects due to the beads. The aim of the proposed methodology is to provide an explicit link between NSIF values and structural stress at a well-defined distance from the weld toe. Such a distance is chosen equal to the main plate thickness.

The expressions obtained allow a direct comparison with the well-known “hot-spot stress” approach; it is demonstrated that there are circumstances of practical interest in which the usual hot-spot stress (which is the simple linear extrapolation at the weld root of the structural field) is not able to predict accurately the fatigue behaviour of the joints, whereas the combination of structural field and NSIF-based field is more advantageous.

The complete methodology can be simplified for rapid calculations involving weldments of different types. Some examples are also reported and discussed.     

Residual steam to energy: a project for Los Azufres geothermal field, Mexico

More than 500 t/h of residual steam are discharged into the atmosphere at Los Azufres geothermal field. Steam comes from nine back-pressure turbines that are at present generating 45 MW. A significant increase in output can be obtained if low pressure turbines are installed to expand residual steam from atmospheric pressure up to a vacuum pressure in condensing cycles. A net output optimization process for each unit in the condensing cycle is presented here. The exergy concept is also applied to compare efficiencies of back pressure cycles with new condensing schemes that include low pressure turbines. Results show that 27.8 MW of additional net output can be generated with the new schemes at competitive production costs and higher conversion efficiencies.     

High temperature metal hydrides for energy systems Part A: Numerical model validation and calibration

Metal hydrides have become more and more significant both as hydrogen storage devices and as basic elements in energy conversion systems. Magnesium hydride (MgH₂) shows very interesting characteristics – i.e. high enthalpy of reaction and hydrogen gravimetric density – making it capable of being employed in the field of energy production. So there is interest in investigating the behaviour of this kind of hydride, placed in an energy system. In order to examine MgH₂ in depth, its main kinetic parameters must be found and this can be accomplished by means of the calibration of a model previously realised by author Marco Gambini in his 1989–1994 works.In the light of this, an assessment of the activation energies (E_a = 72,200 kJ/kmol, E_d = 89,000 kJ/kmol) and kinetic constants (k_0a = 15,000 s^?1, k_0d = 198,500 s^?1) in both absorption and desorption phase of magnesium hydride has been provided. Thanks to these values, the behaviour of MgH₂ can be modelled, making the performance of a magnesium hydride-based energy system estimable.     

Energy demand in solar home systems: the case of the communities in Ribeira Valley in the state of São Paulo,Brazil

An account is given of research on energy demand with solar home systems (SHSs) and the analysis of results of a field survey of 18 families located in 4 communities in the Ribeira Valley, on the southern coast of the State of São Paulo, Brazil. These families' energy consumption was measured over a one‐year period and, in order to do so, equipment that could determine the daily energy requirements in Ampere hour units was developed. The measurement instrument was coupled to existing (SHSs) in these communities and the data collection involved direct user participation. Data collection was done by hand and was intended to provide an interrelationship among the system, the user, and the researcher. The data provided social and cultural information related to the energy use in addition to essentially technical data. Through this methodology it was confirmed that energy demand is related to a number of factors which were not predicted before the survey. It was also confirmed that the people's behavior is reflected in the operation of the photovoltaic system as a whole. The results show that 55% of the SHSs researched showed consumption below 3 kW h/month. Copyright © 2001 John Wiley & Sons, Ltd.     

Cellular and Molecular Mechanism of Pulmonary Fibrosis Post-COVID-19: Focus on Galectin-1, -3, -8, -9

Pulmonary fibrosis is a consequence of the pathological accumulation of extracellular matrix (ECM), which finally leads to lung scarring. Although the pulmonary fibrogenesis is almost known, the last two years of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its post effects added new particularities which need to be explored. Many questions remain about how pulmonary fibrotic changes occur within the lungs of COVID-19 patients, and whether the changes will persist long term or are capable of resolving. This review brings together existing knowledge on both COVID-19 and pulmonary fibrosis, starting with the main key players in promoting pulmonary fibrosis, such as alveolar and endothelial cells, fibroblasts, lipofibroblasts, and macrophages. Further, we provide an overview of the main molecular mechanisms driving the fibrotic process in connection with Galactin-1, -3, -8, and -9, together with the currently approved and newly proposed clinical therapeutic solutions given for the treatment of fibrosis, based on their inhibition. The work underlines the particular pathways and processes that may be implicated in pulmonary fibrosis pathogenesis post-SARS-CoV-2 viral infection. The recent data suggest that galectin-1, -3, -8, and -9 could become valuable biomarkers for the diagnosis and prognosis of lung fibrosis post-COVID-19 and promising molecular targets for the development of new and original therapeutic tools to treat the disease.     

Friendships of older men and women: Exchange patterns and satisfaction.

Investigated the relation between perceived equity of exchanges and friendship satisfaction for 58 female and 58 male 64–91 yr old individuals. Attempts were made to determine whether (a) older men and women differ in the extent to which they view themselves as being involved in equitable vs inequitable friendships, (b) the individuals who perceive themselves to be in equitable friendships report greater satisfaction with the relationship than older persons who perceive themselves to be in nonequitable friendships, and (c) there are gender differences in the relation between equity and friendship satisfaction. Ss were interviewed concerning their relationship with their best friend and 1 other friend in their support network. Perceived equity was a significant predictor of friendship satisfaction only in the case of the other friend. In addition, results show that men were involved in more equitable friendships than were women. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of Surface Morphology on the Wear and Corrosion Resistance of Post-Treated Nitrided and Nitrocarburized 42CrMo4 Steel

The surface of alloyed carbon steel was subjected to thermochemical modification by nitrocarburizing and nitriding with or without postoxidation in order to improve its mechanical properties, corrosion, and wear resistance. Treated samples were characterized by testing their basic properties (compound layer thickness, nitriding, nitrocarburizing depth, and surface hardness) according to standards. Detailed estimation of the modified metal surface was performed by additional testing: X-ray diffraction, microstructure, surface roughness and topography, and wear and corrosion resistance. The surface layer obtained after nitrocarburizing treatment consists mainly of ε-Fe_2-3(N,C) and γ’-Fe₄(N,C); similarly, the nitrided surface is formed by ε-Fe_2-3N and γ’-Fe₄N iron nitrides. The surface layer after postoxidation contains additionally Fe₃O₄. The results obtained show that nitrocarburization, nitridation, and postoxidation result in better mechanical, wear, and corrosion resistance of 42CrMo4 steel, and postoxidized sample properties are influenced by surface morphology.