Non-destructive monitoring of 3D cell cultures: new technologies and applications

3D cell cultures are becoming the new standard for cell-based in vitro research, due to their higher transferrability toward in vivo biology. The lack of established techniques for the non-destructive quantification of relevant variables, however, constitutes a major barrier to the adoption of these technologies, as it increases the resources needed for the experimentation and reduces its accuracy. In this review, we aim at addressing this limitation by providing an overview of different non-destructive approaches for the evaluation of biological features commonly quantified in a number of studies and applications. In this regard, we will cover cell viability, gene expression, population distribution, cell morphology and interactions between the cells and the environment. This analysis is expected to promote the use of the showcased technologies, together with the further development of these and other monitoring methods for 3D cell cultures. Overall, an extensive technology shift is required, in order for monolayer cultures to be superseded, but the potential benefit derived from an increased accuracy of in vitro studies, justifies the effort and the investment

Unraveling firms: Demand, productivity and markups heterogeneity. National Bank of Belgium Working Paper No. 293

We develop a new econometric framework that simultaneously allows recovering heterogeneity in demand, TFP and markups across firms while leaving the correlation among the three unrestricted. We do this by systematically exploiting assumptions that are implicit in previous firm-level productivity estimation approaches. We use Belgian firms production data to quantify TFP, demand and markups and show how they are correlated among them, across time and with measures obtained from other approaches. We also show to what extent our three dimensions of heterogeneity allow us to gain deeper and sharper insights on two key firm-level outcomes: export status and size

Unraveling firms: demand, productivity and markupsheterogeneity

We develop a new econometric framework that simultaneously allows recovering heterogeneity in demand, TFP and markups across firms while leaving the correlation among the three unrestricted. We do this by systematically exploiting assumptions that are implicit in previous firm-level productivity estimation approaches. We use Belgian firms production data to quantify TFP, demand and markups and show how they are correlated among them, across time and with measures obtained from other approaches. We also show to what extent our three dimensions of heterogeneity allow us to gain deeper and sharper insights on two key firm-level outcomes: export status and size

Rational design of modular circuits for gene transcription: A test of the bottom-up approach

<p>Abstract</p> <p>Background</p> <p>Most of synthetic circuits developed so far have been designed by an ad hoc approach, using a small number of components (i.e. LacI, TetR) and a trial and error strategy. We are at the point where an increasing number of modular, inter-changeable and well-characterized components is needed to expand the construction of synthetic devices and to allow a rational approach to the design.</p> <p>Results</p> <p>We used interchangeable modular biological parts to create a set of novel synthetic devices for controlling gene transcription, and we developed a mathematical model of the modular circuits. Model parameters were identified by experimental measurements from a subset of modular combinations. The model revealed an unexpected feature of the lactose repressor system, i.e. a residual binding affinity for the operator site by induced lactose repressor molecules. Once this residual affinity was taken into account, the model properly reproduced the experimental data from the training set. The parameters identified in the training set allowed the prediction of the behavior of networks not included in the identification procedure.</p> <p>Conclusions</p> <p>This study provides new quantitative evidences that the use of independent and well-characterized biological parts and mathematical modeling, what is called a bottom-up approach to the construction of gene networks, can allow the design of new and different devices re-using the same modular parts.</p

Le rôle de l’espace public dans le développement de la vie nocturne (Montpellier-Lisbonne)

The development of the night-time economy has been linked to the chan- ging regulation of commercial activities, as well as broader social and cultural trans- formations. However, the role played by urban planning and design remains scarcely addressed. Based on the cases of Montpellier and Lisbon, this article shows how conflicts associated with the development of nocturnal leisure activities arise from a lack of consideration for urban practices and their temporality in the production and management of public spaces. The article further shows how the night can be a privile- ged space-time to analyze some of the ambiguities and contradictions that characterize the policies of revitalization of the historic centers of European cities.L’évolution des loisirs nocturnes a été explorée dans sa relation avec les processus de déréglementation des activités commerciales et avec des évolutions des modes de vie. Cependant, le rôle joué par les transformations dans la production de la matérialité de la ville, et en particulier de l’espace public, reste relativement peu interrogé. À partir des cas de Montpellier et de Lisbonne, cet article montre que les conflictualités associées au développement des loisirs nocturnes relèvent de plusieurs impensés et ambiguïtés dans la prise en compte des usages et de leurs temporalités dans la production urbaine, notamment des espaces publics. Ce faisant, l’article montre comment la nuit peut être un espace-temps privilégié pour analyser certaines des ambi- guïtés et contradictions qui caractérisent les politiques de revitalisation des centres historiques des villes européennes

La nuit urbaine, un espace-temps complexe entre opportunités et inégalités

The appropriation of the urban night by economic, social and cultural activi- ties has experienced an unprecedented acceleration in the 20th century. The growing interest of the social sciences in this research object has produced a vast knowledge on the dynamics that characterize the evolution of the nighttime in different parts of the globe. This introduction highlights the need to continue exploring this complex space- time. This issue brings together contributions from different disciplines and focus on various geographic regions, thus making it possible to explore global trends and local specificities which (re)configure the urban night in the contemporary city. These contri- butions are presented and articulated in four axes: differentiated places and uses of nocturnal practices, attractiveness and conflicts, nocturnal inequalities, methodology of night surveys.L’appropriation de la nuit urbaine par des activités économiques, sociales et culturelles a connu au XXe siècle une accélération sans précédent. L’intérêt croissant des sciences sociales pour cet objet de recherche a permis de mieux connaître les dyna- miques caractérisant l’évolution de l’espace-temps nocturne dans les différentes parties du globe. Cette introduction souligne la nécessité de poursuivre l’exploration de cet espace-temps complexe. Ce numéro, en réunissant des contributions de différentes disciplines et sur des régions géographiques variées, propose de lier tendances globales et spécificités locales qui (re)configurent la nuit urbaine dans la ville contemporaine. Les apports de ces contributions sont présentés et articulés autour de quatre axes : lieux et usages différenciés des pratiques nocturnes, attractivité et conflits, inégalités nocturnes, méthodologies des enquêtes sur la nuit

Integration of Quantum Chemistry, Statistical Mechanics, and Artificial Intelligence for Computational Spectroscopy: The UV-Vis Spectrum of TEMPO Radical in Different Solvents

The ongoing integration of quantum chemistry, statistical mechanics, and artificial intelligence is paving the route toward more effective and accurate strategies for the investigation of the spectroscopic properties of medium-to-large size chromo-phores in condensed phases. In this context we are developing a novel workflow aimed at improving the generality, reliability, and ease of use of the available computational tools. In this paper we report our latest developments with specific reference to unsupervised atomistic simulations employing non periodic boundary conditions (NPBC) followed by clustering of the trajectories employing optimized feature spaces. Next accurate variational computations are performed for a representative point of each cluster, whereas intracluster fluctuations are taken into account by a cheap yet reliable perturbative approach. A number of methodological improvements have been introduced including, e.g., more realistic reaction field effects at the outer boundary of the simulation sphere, automatic definition of the feature space by continuous perception of solute-sol v e n t interactions, full account of polarization and charge transfer in the first solvation shell, and inclusion of vibronic contributions. After its validation, this new approach has been applied to the challenging case of solvatochromic effects on the UV-vis spectra of a prototypical nitroxide radical (TEMPO) in different solvents. The reliability, effectiveness, and robustness of the new platform is demonstrated by the remarkable agreement with experiment of the results obtained through an unsupervised approach characterized by a strongly reduced computational cost as compared to that of conventional quantum mechanics and molecular mechanics models without any accuracy reduction

Nutritional support in cancer patients: A position paper from the Italian Society of Medical Oncology (AIOM) and the Italian Society of Artificial Nutrition and Metabolism (SINPE)

Malnutrition is a frequent problem in cancer patients, which leads to prolonged hospitalization, a higher degree of treatment-related toxicity, reduced response to cancer treatment, impaired quality of life and a worse overall prognosis. The attitude towards this issue varies considerably and many malnourished patients receive inadequate nutritional support. We reviewed available data present in the literature, together with the guidelines issued by scientific societies and health authorities, on the nutritional management of patients with cancer, in order to make suitable and concise practical recommendations for appropriate nutritional support in this patient population. Evidence from the literature suggests that nutritional screening should be performed using validated tools (the Nutritional Risk Screening 2002 [NRS 2002], the Malnutrition Universal Screening Tool [MUST], the Malnutrition Screening Tool [MST] and the Mini Nutritional Assessment [MNA]), both at diagnosis and at regular time points during the course of disease according to tumor type, stage and treatment. Patients at nutritional risk should be promptly referred for comprehensive nutritional assessment and support to clinical nutrition services or medical personnel with documented skills in clinical nutrition, specifically for cancer patients. Nutritional intervention should be actively managed and targeted for each patient; it should comprise personalized dietary counseling and/or artificial nutrition according to spontaneous food intake, tolerance and effectiveness. Nutritional support may be integrated into palliative care programs. "Alternative hypocaloric anti-cancer diets" (e.g. macrobiotic or vegan diets) should not be recommended as they may worsen nutritional status. Well-designed clinical trials are needed to further our knowledge of the nutritional support required in different care settings for cancer patients

Specific Biomarkers Are Associated with Docetaxeland Gemcitabine-Resistant NSCLC Cell Lines

AbstractFive-year survival rate for lung cancer is limited to 10% to 15%. Therefore, the identification of novel therapeutic prognostic factors is an urgent requirement. The aim of this study is thus to highlight specific biomarkers in chemoresistant non-small cell lung cancer cell lines. Therefore, we checked—in the control condition as well as after short-term pharmacological treatment with either docetaxel or gemcitabine—the expression of genes such as tumor suppressor genes (CDKN2A, DAPK, FHIT, GSTP1, MGMT, RARβ2, RASSF1A, and TIMP3), genes associated with drug resistance (BRCA1, COX2, ERCC1, IGFBP3, RRM1, and TUBB3), and stemness-related genes (CD133, OCT4, and SLUG) in two cellular models of squamous carcinoma (CAEP) and adenocarcinoma (RAL) of the lung originally established. Their promoter methylation profile was also evaluated. Drug-related genes were upregulated. Cisplatin resistance matched with high levels of BRCA1 and ERCC1 in both cell lines; docetaxel sensitivity of CAEP cells was associated to levels of TUBB3 lower than RAL cells. Although CAEP cells were more sensitive to gemcitabine, both cell lines showed high levels of RRM1. Stemness-related genes were downregulated in the control condition but became upregulated in docetaxel-resistant cells, indicating the selection of a population with stemness features. We did not find an unequivocal correspondence between gene expression and respective DNA promoter methylation status, suggesting the involvement of additional mechanisms of gene expression regulation. These results highlight specific biomarkers consistent with the different responses of the two cell lines to standard pharmacological treatments and indicate specific molecular traits for their chemoresistance