PSY30 Cost-Consequence Analysis of a Treatment Strategy Including Ponatinib Compared to a Treatment Strategy Including Only the 2nd Generation Tyrosine Kinase Inhibitors (2g TKIs), Dasatinib or Nilotinib, in Resistant Patients with Philadelphia Chromosome-Positive (Ph+) Leukemia, in Italy

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Magnetization dynamics of elastically strained nanostructures studied by coupled micromagnetic-mechanical simulations

Elastically strained ferromagnetic objects have been studied by coupled micromagnetic-mechanical numerical simulations. Both temporal evolution of the magnetization and modal frequency analysis of ferromagnetic thin films and arrays of nanostructures are presented. For this purpose, we have numerically coupled the micromagnetic equations (including magnetoelastic effects) to the ones of solid mechanics by including periodic boundary conditions. Our approach has been evaluated first on an elastically strained thin film and validated by performing in situ ferromagnetic resonance experiments. We have undertaken simulations on nanostructured arrays (modulated arrays of nanowires) and show that the heterogeneity of the strain fields and magnetic mode profiles of those strained nanostructures induce significative disparities in the magnetic mode energies, allowing applications to be foreseen where one could control in a differentiated way the spin-wave energies as a function of the applied elastic strains

Using multi-criteria analysis for smart city assessment

Urban centers have been under a new concept of city. Smart Cities are, in a nutshell, organized communities that feature high communication technology and conscious investments in sustainability, providing dynamic and safe environments. This paper presents a methodology to assess and rank Smart Cities based on a multi-criteria decision-making process. Methodologies that do not consider a pondered approach and filter for specific goals are commonly found in the literature, once there is a great number of criteria involved in these analyses. This work proposes filtering the criteria, considering each specific evaluation and its objectives. Our methodology is based on a multi-criteria analysis and uses AHP (Analytic Hierarchy Process) to support the process of weights definition and MACBAC (Multi-Attributive Border Approximation Area Comparison) in an application with compensatory characteristics. Through this study, it is possible to conduct the assessment of Smart Cities according to its multiple contexts, viz. its location, decision-makers and the objectives of the analysis. All in all, this research presents novelty related to the organization of the evaluation in accord to the expected resolution and a pondered approach with reduced number of criteria, making the analysis very straightforward.publicad

Dynamic model to predict the association between air quality, COVID-19 cases, and level of lockdown

Studies have reported significant reductions in air pollutant levels due to the COVID-19 outbreak worldwide due to global lockdowns. Nevertheless, all of the reports are limited compared to data from the same period over the past few years, providing mainly an overview of past events, with no future predictions. Lockdown level can be directly related to the number of new COVID-19 cases, air pollution, and economic restriction. As lockdown status varies considerably across the globe, there is a window for mega-cities to determine the optimum lockdown flexibility. To that end, firstly, we employed four different Artificial Neural Networks (ANN) to examine the compatibility to the original levels of CO, O3, NO2, NO, PM2.5, and PM10, for São Paulo City, the current Pandemic epicenter in South America. After checking compatibility, we simulated four hypothetical scenarios: 10%, 30%, 70%, and 90% lockdown to predict air pollution levels. To our knowledge, ANN have not been applied to air pollution prediction by lockdown level. Using a limited database, the Multilayer Perceptron neural network has proven to be robust (with Mean Absolute Percentage Error ∼ 30%), with acceptable predictive power to estimate air pollution changes. We illustrate that air pollutant levels can effectively be controlled and predicted when flexible lockdown measures are implemented. The models will be a useful tool for governments to manage the delicate balance among lockdown, number of COVID-19 cases, and air pollution

Budding Yeast Dma Proteins Control Septin Dynamics and the Spindle Position Checkpoint by Promoting the Recruitment of the Elm1 Kinase to the Bud Neck

The first step towards cytokinesis in budding yeast is the assembly of a septin ring at the future site of bud emergence. Integrity of this ring is crucial for cytokinesis, proper spindle positioning, and the spindle position checkpoint (SPOC). This checkpoint delays mitotic exit and cytokinesis as long as the anaphase spindle does not properly align with the division axis. SPOC signalling requires the Kin4 protein kinase and the Kin4-regulating Elm1 kinase, which also controls septin dynamics. Here, we show that the two redundant ubiquitin-ligases Dma1 and Dma2 control septin dynamics and the SPOC by promoting the efficient recruitment of Elm1 to the bud neck. Indeed, dma1 dma2 mutant cells show reduced levels of Elm1 at the bud neck and Elm1-dependent activation of Kin4. Artificial recruitment of Elm1 to the bud neck of the same cells is sufficient to re-establish a normal septin ring, proper spindle positioning, and a proficient SPOC response in dma1 dma2 cells. Altogether, our data indicate that septin dynamics and SPOC function are intimately linked and support the idea that integrity of the bud neck is crucial for SPOC signalling

Zds2p Regulates Swe1p-dependent Polarized Cell Growth in Saccharomyces cerevisiae via a Novel Cdc55p Interaction Domain

A C-terminal region in Zds2p (ZH4) is required for regulation of Swe1p-dependent polarized cell growth and this region is necessary and sufficient for interaction with protein phosphatase 2A regulatory subunit, Cdc55p. Our results indicate that the Zds proteins regulate the Swe1p-dependent G2/M checkpoint in a CDC55-dependent manner

Polo kinase recruitment via the constitutive centromere-associated network at the kinetochore elevates centromeric RNA

The kinetochore, a multi-protein complex assembled on centromeres, is essential to segregate chromosomes during cell division. Deficiencies in kinetochore function can lead to chromosomal instability and aneuploidy-a hallmark of cancer cells. Kinetochore function is controlled by recruitment of regulatory proteins, many of which have been documented, however their function often remains uncharacterized and many are yet to be identified. To identify candidates of kinetochore regulation we used a proteome-wide protein association strategy in budding yeast and detected many proteins that are involved in post-translational modifications such as kinases, phosphatases and histone modifiers. We focused on the Polo-like kinase, Cdc5, and interrogated which cellular components were sensitive to constitutive Cdc5 localization. The kinetochore is particularly sensitive to constitutive Cdc5 kinase activity. Targeting Cdc5 to different kinetochore subcomplexes produced diverse phenotypes, consistent with multiple distinct functions at the kinetochore. We show that targeting Cdc5 to the inner kinetochore, the constitutive centromere-associated network (CCAN), increases the levels of centromeric RNA via an SPT4 dependent mechanism