Bayesian functional emulation of CO2 emissions on future climate change scenarios

We propose a statistical emulator for a climate-economy deterministic integrated assessmentmodel ensemble, based on a functional regression framework. Inference on the unknown parameters is carried out through a mixed effects hierarchical model using a fully Bayesian framework with a prior distribution on the vector of all parameters. We also suggest an autoregressive parameterization of the covariance matrix of the error, with matching marginal prior. In this way, we allow for a functional framework for the discretized output of the simulators that allows their time continuous evaluation

A Wif1 mediated feedback loop suppresses premature Wnt signaling in nascent habenular neurons

Precise temporal and spatial control of cell signaling processes is pivotal for embryonic development. A vast number of secreted signaling molecules such as Wnt ligands travel between cells and tissues and influence their fate. If they are to induce a signaling cascade depends on various control mechanisms of potential target cells. These can include the temporal expression control of pathway components or the generation of signaling agonisers or antagonisers. Control of Wnt/beta-catenin signaling is important for the establishment of left- rigt (l-r) neuronal asymmetries of the evolutionarily conserved habenulae in the vertebrate dorsal diencephalon. During neurogenesis, this pathway is activated only when habenular precursor cells become post-mitotic, although Wnt ligands secreted by the adjacent mid-diencephalic organizer (MDO) surround these cells much earlier. The underlying control mechanism and its purpose have remained unexplored. We find that Wnt signaling is indeed initially inhibited in habenular precursors and that this is required for habenular neurons to subsequently adopt different neuronal fates. Indeed, premature induction of the pathway critically delays neuronal differentiation which ultimately lead to precursor differentiation into only one out of two neuron types of the habenulae on both sides of the brain. We further show that the early activation of Wnt signaling is naturally prevented by Wnt inhibitor factor 1 (Wif1), which is specifically expressed in the habenulae until precursors become post-mitotic. Suppression of wif1 phenocopies the effect of early Wnt induction. Furthermore, wif1 expression is positively regulated by Wnt signaling showing that wif1 is functioning within a negative feedback loop. Our data are consistent with a model by which Wif1 dynamically shields early multipotent habenular precursor cells from incoming Wnt ligands secreted by the MDO and possibly other the sources until they become post-mitotic and differentiate into neurons. wif1 and different Wnt ligands are overlappingly expressed in a number of developing structures including both the habenulae the downstream target the interpenduncular nucleus (IPN). This suggests that the Wnt/Wif1 buffering system may serve as a general mechanism for temporally tuning neurogenesis across the different nuclei of the brain

Susceptibility and Severity of Viral Infections in Obesity: Lessons from Influenza to COVID-19. Does Leptin Play a Role?

The recent pandemic Sars-CoV2 infection and studies on previous influenza epidemic have drawn attention to the association between the obesity and infectious diseases susceptibility and worse outcome. Metabolic complications, nutritional aspects, physical inactivity, and a chronic unbalance in the hormonal and adipocytokine microenvironment are major determinants in the severity of viral infections in obesity. By these pleiotropic mechanisms obesity impairs immune surveillance and the higher leptin concentrations produced by adipose tissue and that characterize obesity substantially contribute to such immune response dysregulation. Indeed, leptin not only controls energy balance and body weight, but also plays a regulatory role in the interplay between energy metabolism and immune system. Since leptin receptor is expressed throughout the immune system, leptin may exert effects on cells of both innate and adaptive immune system. Chronic inflammatory states due to metabolic (i.e., obesity) as well as infectious diseases increase leptin concentrations and consequently lead to leptin resistance further fueling inflammation. Multiple factors, including inflammation and ER stress, contribute to leptin resistance. Thus, if leptin is recognized as one of the adipokines responsible for the low grade inflammation found in obesity, on the other hand, impairments of leptin signaling due to leptin resistance appear to blunt the immunologic effects of leptin and possibly contribute to impaired vaccine-induced immune responses. However, many aspects concerning leptin interactions with inflammation and immune system as well as the therapeutical approaches to overcome leptin resistance and reduced vaccine effectiveness in obesity remain a challenge for future research

Ketogenic Diet for Preoperative Weight Reduction in Bariatric Surgery: A Narrative Review

Bariatric surgery (BS) is the most effective treatment in reducing weight and the burden of comorbidities in patients with severe obesity. Despite the overall low mortality rate, intra- and post-operative complications remains quite common. Weight loss before BS reduces surgical risk, but studies are inconclusive regarding which is the best approach to apply. In this review, we summarize the current evidence on the effect of a ketogenic diet (KD) before BS. All studies agree that KD leads to considerable weight loss and important improvements in terms of surgical risk, but populations, interventions and outcomes are very heterogeneous. KD appears to be a safe and effective approach to induce weight loss before BS. However, randomized controlled trials with better-defined dietary protocols and homogeneous outcomes are necessary in order to draw firm conclusions

"Charge while driving" for electric vehicles: road traffic modeling and energy assessment

The aim of this research study is to present a method for analyzing the performance of the wireless inductive charge-while-driving (CWD) electric vehicles, from both traffic and energy points of view. To accurately quantify the electric power required from an energy supplier for the proper management of the charging system, a traffic simulation model is implemented. This model is based on a mesoscopic approach, and it is applied to a freight distribution scenario. Lane changing and positioning are managed according to a cooperative system among vehicles and supported by advanced driver assistance systems (ADAS). From the energy point of view, the analyses indicate that the traffic may have the following effects on the energy of the system: in a low traffic level scenario, the maximum power that should be supplied for the entire road is simulated at approximately 9 MW; and in a high level traffic scenario with lower average speeds, the maximum power required by the vehicles in the charging lane increases by more than 50 %

Electromagnetic two-body problem: recurrent dynamics in the presence of state-dependent delay

We study the electromagnetic two-body problem of classical electrodynamics as a prototype dynamical system with state-dependent delays. The equations of motion are analysed with reference to motion along a straight line in the presence of an electrostatic field. We consider the general electromagnetic equations of motion for point charges with advanced and retarded interactions and study two limits, (a) retarded-only interactions (Dirac electrodynamics) and (b) half-retarded plus half-advanced interactions (Wheeler-Feynman electrodynamics). A fixed point is created where the electrostatic field balances the Coulombian attraction, and we use local analysis near this fixed point to derive necessary conditions for a Hopf bifurcation. In case (a), we study a Hopf bifurcation about an unphysical fixed point and find that it is subcritical. In case (b), there is a Hopf bifurcation about a physical fixed point and we study several families of periodic orbits near this point. The bifurcating periodic orbits are illustrated and simulated numerically, by introducing a surrogate dynamical system into the numerical analysis which transforms future data into past data by exploiting the periodicity, thus obtaining systems with only delays

Staphylococcal scalded skin syndrome in adults with obesity and type 2 diabetes: A case series

: Staphylococcal scalded skin syndrome (SSSS) primarily affects children and rarely adults with immunodepression. We describe two cases of adults diagnosed with SSSS with no additional cause of immunological compromise other than obesity and uncontrolled diabetes. An increased risk of infection should be considered in cases of obesity and diabetes

An improved Erk biosensor reveals oscillatory Erk dynamics driven by mitotic erasure during early development

Erk signaling dynamics elicit distinct cellular responses in a variety of contexts. The early zebrafish embryo is an ideal model to explore the role of Erk signaling dynamics in vivo, as a gradient of activated diphosphorylated Erk (P-Erk) is induced by Fgf signaling at the blastula embryonic margin. Here we describe an improved Erk-specific biosensor which we term modified Erk Kinase Translocation Reporter (modErk-KTR). We demonstrate the utility of this biosensor in vitro and in developing zebrafish and Drosophila embryos. Moreover, we show that Fgf/Erk signaling is dynamic and coupled to tissue growth during both early zebrafish and Drosophila development. Signaling is rapidly extinguished just prior to mitosis, which we refer to as mitotic erasure, inducing periods of inactivity, thus providing a source of heterogeneity in an asynchronously dividing tissue. Our modified reporter and transgenic lines represent an important resource for interrogating the role of Erk signaling dynamics in vivo

An improved Erk biosensor detects oscillatory Erk dynamics driven by mitotic erasure during early development

Extracellular signal-regulated kinase (Erk) signaling dynamics elicit distinct cellular responses in a variety of contexts. The early zebrafish embryo is an ideal model to explore the role of Erk signaling dynamics in vivo, as a gradient of activated diphosphorylated Erk (P-Erk) is induced by fibroblast growth factor (Fgf) signaling at the blastula margin. Here, we describe an improved Erk-specific biosensor, which we term modified Erk kinase translocation reporter (modErk-KTR). We demonstrate the utility of this biosensor in vitro and in developing zebrafish and Drosophila embryos. Moreover, we show that Fgf/Erk signaling is dynamic and coupled to tissue growth during both early zebrafish and Drosophila development. Erk activity is rapidly extinguished just prior to mitosis, which we refer to as mitotic erasure, inducing periods of inactivity, thus providing a source of heterogeneity in an asynchronously dividing tissue. Our modified reporter and transgenic lines represent an important resource for interrogating the role of Erk signaling dynamics in vivo