reply to the letter to the editor by C.Nicolazzo et al.: "circulating cell-free DNA and circulating tumor cells as prognostic and predictive biomarkers in advanced non-small cell lung cancer patients treated with first-line chemotherapy"

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Retinoic acid-induced differentiation sensitizes myeloid progenitors cells to ER stress

The clonal expansion of hematopoietic myeloid precursors blocked at different stages of differentiation characterizes the acute myeloid leukemia (AML) phenotype. A subtype of AML, acute promyelocytic leukemia (APL), characterized by the chimeric protein PML-RARα is considered a paradigm of differentiation therapy. In this leukemia subtype the all-trans-retinoic acid (RA)-based treatments are able to induce PML-RARα degradation and leukemic blast terminal differentiation [1-2]. Granulocytic differentiation of APL cells driven by RA triggers a physiological Unfolded Protein Response (UPR), a series of pathways emanating from the ER in case of ER stress, which ensues when higher protein folding activity is required as during differentiation. We show here that, although mild, the ER stress induced by RA is sufficient to render human APL cell lines and primary blasts very sensitive to low doses of Tunicamycin (Tm), an ER stress inducing drug, at doses that are not toxic in the absence of RA. Importantly only human progenitors cells derived from APL patients resulted sensitive to the combined treatment with RA and Tm whereas those obtained from healthy donors were not affected. We also show that the UPR pathway downstream of PERK plays a major protective role against ER stress in differentiating cells and, by using a specific PERK inhibitor, we potentiated the toxic effect of the combination of RA and Tm. In conclusion, our findings identify the ER stress-related pathways as potential targets in the search for novel therapeutic strategies in AML

ka band phase locked loop oscillator dielectric resonator oscillator for satellite ehf band receiver

This paper describes the design and fabrication of a Ka Band PLL DRO having a fundamental oscillation frequency of 19.250 GHz, used as local oscillator in the low-noise block of a down converter (LNB) for an EHF band receiver. Apposite circuital models have been created to describe the behaviour of the dielectric resonator and of the active component used in the oscillator core. The DRO characterization and measurements have shown very good agreement with simulation results. A good phase noise performance is obtained by using a very highQdielectric resonator

Double invisibility: The effects of hidden unemployment on vulnerable populations in Southern European countries during the COVID-19 pandemic

La crisis de la COVID-19 se ha caracterizado por una mayor fragilidad del mercado laboral, especialmente en los países del sur de Europa. Sin embargo, los datos oficiales no reflejan con exactitud las transformaciones reales de sus mercados de trabajo. En este contexto, este trabajo compara el comportamiento del mercado laboral de los colectivos vulnerables de población (jóvenes, mujeres e inmigrantes) en tres países del sur de Europa con un análisis cruzado de datos a lo largo del tiempo. Para ello, hemos desarrollado un indicador alternativo de paro oculto que recupera e incluye a los desempleados de las categorías de subempleo involuntario e inactividad. Nuestros análisis incluyen datos de España, Portugal e Italia, y toman como base la encuesta European Union-Labour Force Survey (EU-LFS). Nuestros resultados muestran que el impacto del desempleo en el sur de Europa se mide mejor cuando se utiliza un indicador ampliado, especialmente cuando se analizan los casos de colectivos vulnerables. Esta herramienta muestra un gran potencial analítico para desvelar el desempleo oculto en el contexto de la pandemia COVID-19

Dynamical changes of the polar cap potential structure: an information theory approach

Some features, such as vortex structures often observed through a wide spread of spatial scales, suggest that ionospheric convection is turbulent and complex in nature. Here, applying concepts from information theory and complex system physics, we firstly evaluate a pseudo Shannon entropy, <i>H</i>, associated with the polar cap potential obtained from the Super Dual Auroral Radar Network (SuperDARN) and, then, estimate the degree of disorder and the degree of complexity of ionospheric convection under different Interplanetary Magnetic Field (IMF) conditions. The aforementioned quantities are computed starting from time series of the coefficients of the 4th order spherical harmonics expansion of the polar cap potential for three periods, characterised by: (i) steady IMF <i>B<sub>z</sub></i> > 0, (ii) steady IMF <i>B<sub>z</sub></i> < 0 and (iii) a double rotation from negative to positive and then positive to negative <i>B<sub>z</sub></i>. A neat dynamical topological transition is observed when the IMF <i>B<sub>z</sub></i> turns from negative to positive and vice versa, pointing toward the possible occurrence of an order/disorder phase transition, which is the counterpart of the large scale convection rearrangement and of the increase of the global coherence. This result has been confirmed by applying the same analysis to a larger data base of about twenty days of SuperDARN data, allowing to investigate the role of IMF <i>B<sub>y</sub></i> too

Dynamical changes of the polar cap potential structure: an information theory approach

Abstract. Some features, such as vortex structures often observed through a wide spread of spatial scales, suggest that ionospheric convection is turbulent and complex in nature. Here, applying concepts from information theory and complex system physics, we firstly evaluate a pseudo Shannon entropy, H, associated with the polar cap potential obtained from the Super Dual Auroral Radar Network (SuperDARN) and, then, estimate the degree of disorder and the degree of complexity of ionospheric convection under different Interplanetary Magnetic Field (IMF) conditions. The aforementioned quantities are computed starting from time series of the coefficients of the 4th order spherical harmonics expansion of the polar cap potential for three periods, characterised by: (i) steady IMF Bz > 0, (ii) steady IMF Bz < 0 and (iii) a double rotation from negative to positive and then positive to negative Bz. A neat dynamical topological transition is observed when the IMF Bz turns from negative to positive and vice versa, pointing toward the possible occurrence of an order/disorder phase transition, which is the counterpart of the large scale convection rearrangement and of the increase of the global coherence. This result has been confirmed by applying the same analysis to a larger data base of about twenty days of SuperDARN data, allowing to investigate the role of IMF By too

Locations of objects are better remembered than their identities in naturalistic scenes:An eye-tracking experiment in mild cognitive impairment

Objective: Retaining the identity or location of decontextualized objects in visual short-term working memory (VWM) is impaired by healthy and pathological ageing, but research remains inconclusive on whether these two features are equally impacted by it. Moreover, it is unclear whether similar impairments would manifest in naturalistic visual contexts. Method: 30 people with mild cognitive impairment (MCI) and 32 age-matched control participants (CPs) were eye-tracked within a change detection paradigm. They viewed 120 naturalistic scenes, and after a retention interval (1 s) asked whether a critical object in the scene had (or not) changed on either: identity (became a different object), location (same object but changed location), or both (changed in location and identity). Results: MCIs performed worse than CP but there was no interaction with the type of change. Changes in both were easiest while changes in identity alone were hardest. The latency to first fixation and first-pass duration to the critical object during successful recognition was not different between MCIs and CPs. Objects that changed in both features took longer to be fixated for the first time but required a shorter first pass compared to changes in identity alone which displayed the opposite pattern. Conclusions: Locations of objects are better remembered than their identities; memory for changes is best when involving both features. These mechanisms are spared by pathological ageing as indicated by the similarity between groups besides trivial differences in overall performance. These findings demonstrate that VWM mechanisms in the context of naturalistic scene information are preserved in people with MCI.info:eu-repo/semantics/acceptedVersio

Unidimensional and Multidimensional Methods for Recurrence Quantification Analysis with crqa

Recurrence quantification analysis is a widely used method for characterizing patterns in time series. This article presents a comprehensive survey for conducting a wide range of recurrence-based analyses to quantify the dynamical structure of single and multivariate time series, and to capture coupling properties underlying leader-follower relationships. The basics of recurrence quantification analysis (RQA) and all its variants are formally introduced step-by-step from the simplest auto-recurrence to the most advanced multivariate case. Importantly, we show how such RQA methods can be deployed under a single computational framework in R using a substantially renewed version our crqa 2.0 package. This package includes implementations of several recent advances in recurrence-based analysis, among them applications to multivariate data, and improved entropy calculations for categorical data. We show concrete applications of our package to example data, together with a detailed description of its functions and some guidelines on their usage.Comment: Describes R package crqa v. 2.0: https://cran.r-project.org/web/packages/crqa