MTOR cross-talk in cancer and potential for combination therapy

The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understanding of how mTOR dysfunction contributes to several diseases, including cancer. Single-agent mTOR targeting, mostly using rapalogs, has so far met limited clinical success; however, due to the extensive cross-talk between mTOR and other pathways, combined approaches are the most promising avenues to improve clinical efficacy of available therapeutics and overcome drug resistance. This review provides a brief and up-to-date narrative on the regulation of mTOR function, the relative contributions of mTORC1 and mTORC2 complexes to cancer development and progression, and prospects for mTOR inhibition as a therapeutic strategy

Role of mTOR signaling in tumor microenvironment. An overview

The mammalian target of rapamycin (mTOR) pathway regulates major processes by integrating a variety of exogenous cues, including diverse environmental inputs in the tumor microenvironment (TME). In recent years, it has been well recognized that cancer cells co-exist and co-evolve with their TME, which is often involved in drug resistance. The mTOR pathway modulates the interactions between the stroma and the tumor, thereby affecting both the tumor immunity and angiogenesis. The activation of mTOR signaling is associated with these pro-oncogenic cellular processes, making mTOR a promising target for new combination therapies. This review highlights the role of mTOR signaling in the characterization and the activity of the TME’s elements and their implications in cancer immunotherapy

Fully-automated Runtime Enforcement of Component-based Systems with Formal and Sound Recovery

International audienceWe introduce runtime enforcement of specifications on component-based systems (CBS) modeled in the BIP (Behavior, Interaction and Priority) framework. Runtime enforcement is an increasingly popular and effective dynamic validation technique aiming to ensure the correct runtime behavior (w.r.t. a formal specification) of a system using a so-called enforcement monitor. BIP is a powerful and expressive component-based framework for the formal construction of heterogeneous systems. Because of BIP expressiveness however , it is difficult to enforce complex behavioral properties at design-time. We first introduce a theoretical runtime enforcement framework for component-based systems where we delineate a hierarchy of enforceable properties (i.e., properties that can be enforced) according to the number of observational steps a system is allowed to deviate from the property (i.e., the notion of k-step enforceability). To ensure the observational equivalence between the correct executions of the initial system and the monitored system, we show that i) only stutter-invariant properties should be enforced on CBS with our monitors, and ii) safety properties are 1-step enforceable. Second, given an abstract enforcement monitor for some 1-step enforceable property, we define a series of formal transformations to instrument (at relevant locations) a CBS described in the BIP framework to integrate the monitor. At runtime, the monitor observes and automatically avoids any error in the behavior of the system w.r.t. the property. Third, our approach is fully implemented in RE-BIP, an available tool integrated in the BIP tool suite. Fourth, to validate our approach, we use RE-BIP to i) enforce deadlock-freedom on a dining philosophers benchmark, and ii) ensure the correct placement of robots on a map

Survey data for assessing the socio-economic performance of End of Life options of a bio-based product based on expert knowledge

This data article aims at providing a data description about the manuscript entitled “A socio-economic indicator for EoL strategies for bio-based products” [1]. Data regarding the socio-economic assessment of End of Life (EoL) options for the specific case of PLA-based film for food packaging are presented, with a special emphasis on policy recommendations and actions for the EoL practices in the bioeconomy sectors. A new framework, based on data gathering and validation through experts involvement, is proposed in order to calculate a new indicator to measure the socio-economic performance of EoL practices (SEI-EoL) for bio-based products. Experts were identified from the Horizon 2020 LIFE-funded projects and/or Scopus databases. Two rounds of survey were carried out to determine the weights of socio-economic criteria for bio-based products and the values for the selected case study. The aggregation of these data enabled us to obtain a final ranking of different EoL alternatives. Finally, a third round of survey was conducted to further deepen our understanding of actions and recommendations needed to improve EoL practices in bio-based sectors. Resulting data have a mix of quantitative and qualitative characterization. A potential reuse of these data can allow future estimations, empirical analyses or a direct comparison with the use of experimental observations

A sustainable revolution: Let's go sustainable to get our globe cleaner

The concept of sustainability is a clear blue sea, a snowy mountain, a flowery meadow, in which there is resource sharing that allows us to satisfy human needs without damaging natural resources. The challenge is complex, and we hope to support the decarbonization of our society and mitigate climate changes. This Special Issue aims to outline different approaches in several sectors with a common point of view: seeing our world with a green perception and encouraging a sustainable revolution to provide a cleaner world

Decarbonising heating and cooling using temperature setback and geothermal energy

\ua9 2023 Institute of Physics Publishing. All rights reserved. The lion’s share of buildings’ energy consumption is used for maintaining a thermally comfortable indoor environment. Strategies of reducing heating and cooling demand can thus be crucial for buildings to achieve net zero. This research aims to investigate the extent to which an occupancy-based temperature setback strategy and geothermal energy supply can decarbonise an office building. The objectives include: 1) exploring the optimal setback temperature for maximum energy savings, both in present time and under the future climate scenarios, and 2) evaluating the extent to which a geothermal borehole can meet the building’s energy demand. The outcome shows that a temperature setback strategy coupled with geothermal energy supply can decarbonise heating and cooling by around half. As for overall building energy demand, temperature setback can make demand reduction by over a tenth while the geothermal energy can meet the demand by a minimum of a fifth

Meson Correlation Function and Screening Mass in Thermal QCD

Analytical results for the spatial dependence of the correlation functions for all meson excitations in perturbative Quantum Chromodynamics, the lowest order, are calculated. The meson screening mass is obtained as a large distance limit of the correlation function. Our analysis leads to a better understanding of the excitations of Quark Gluon Plasma at sufficiently large temperatures and may be of relevance for future numerical calculations with fully interacting Quantum Chromodynamics.Comment: 11 page

Use of Agro-Waste as a Source of Crop Nutrients in Intensive Horticulture System

The inadequate management of agro-waste in intensive agriculture has a severe negative impact on the environment. The valorization of crop residue as a source of crop nutrients is a valid alternative to close the nutrient cycle and reduce the use of external input. In this study, plant material was incorporated into the soil as fresh crop residue, after either composting and vermicomposting processes, to evaluate their effects on tomato yield and nutritional status (petiole sap analysis: NO3 and K+ concentration) over three crop cycles. A control treatment with mineral fertigation and an organic control treatment with goat manure were also included. Enzymatic activity and microbial population in the soil were evaluated. Although no differences between treatments were observed in the first cycle, in the second and third cycles, the yield obtained with the application of organic amendments derived from agro-waste was comparable to the yield obtained with mineral fertilizers. Overall, the sap analysis did not reveal a clear relationship with yield performances. The compost treatment resulted in higher microorganism presence in the soil. Soil dehydrogenase activity (DHA), acid phosphatase activity (ACP), and β-glucosidase activity (β-GLU) were generally more stimulated when organic amendments were used. The study confirms the applicability of soil fertilizers derived from agro-waste as a good alternative to mineral fertilizers

pre treatment egfr t790m subclones in lung adenocarcinoma harboring activating mutation of egfr a positive prognostic factor for survival

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