Reference Tissue Models for FDG-PET Data: Identifiability and Solvability

A reference tissue model (RTM) is a compartmental approach to the estimation of the kinetic parameters of the tracer flow in a given two-compartment target tissue (TT) without explicit knowledge of the time activity curve (TAC) of tracer concentration in the arterial blood. An \u201cindirect\u201d measure of arterial concentration is provided by the TAC of a suitably chosen one-compartment reference tissue (RT). The RTM is formed by the RT and the TT. In this paper, it is shown that the RTM is identifiable, i.e., the rate constants are uniquely retrievable, provided that a selection criterion for one of the coefficients, which is based on the Logan plot of the RT, is introduced. The exchange coefficients are then evaluated by the application of a Gauss-Newton method, with a regularizing term, accounting for the ill-posedness of the problem. The reliability of the method is validated against synthetic data generated according to realistic conditions, and compared with the full two-compartment model for the TT, here used as \u201cgold standard.\u201d Finally, the RTM is applied to the estimate of the rate constants in the case of animal models with murine cancer cell lines CT26 inoculated

EphrinB1/EphB3b Coordinate Bidirectional Epithelial-Mesenchymal Interactions Controlling Liver Morphogenesis and Laterality

Positioning organs in the body often requires the movement of multiple tissues, yet the molecular and cellular mechanisms coordinating such movements are largely unknown. Here, we show that bidirectional signaling between EphrinB1 and EphB3b coordinates the movements of the hepatic endoderm and adjacent lateral plate mesoderm (LPM), resulting in asymmetric positioning of the zebrafish liver. EphrinB1 in hepatoblasts regulates directional migration and mediates interactions with the LPM, where EphB3b controls polarity and movement of the LPM. EphB3b in the LPM concomitantly repels hepatoblasts to move leftward into the liver bud. Cellular protrusions controlled by Eph/Ephrin signaling mediate hepatoblast motility and long-distance cell-cell contacts with the LPM beyond immediate tissue interfaces. Mechanistically, intracellular EphrinB1 domains mediate EphB3b-independent hepatoblast extension formation, while EpB3b interactions cause their destabilization. We propose that bidirectional short- and long-distance cell interactions between epithelial and mesenchyme-like tissues coordinate liver bud formation and laterality via cell repulsion. Copyright © 2016. Published by Elsevier Inc

In-silico modelling of the mitogen-activated protein kinase (MAPK) pathway in colorectal cancer: mutations and targeted therapy

Introduction: Chemical reaction networks (CRNs) are powerful tools for describing the complex nature of cancer’s onset, progression, and therapy. The main reason for their effectiveness is in the fact that these networks can be rather naturally encoded as a dynamical system whose asymptotic solution mimics the proteins' concentration profile at equilibrium.Methods and Results: This paper relies on a complex CRN previously designed for modeling colorectal cells in their G1-S transition phase and presents a mathematical method to investigate global and local effects triggered on the network by partial and complete mutations occurring mainly in its mitogen-activated protein kinase (MAPK) pathway. Further, this same approach allowed the in-silico modeling and dosage of a multi-target therapeutic intervention that utilizes MAPK as its molecular target.Discussion: Overall the results shown in this paper demonstrate how the proposed approach can be exploited as a tool for the in-silico comparison and evaluation of different targeted therapies. Future effort will be devoted to refine the model so to incorporate more biologically sound partial mutations and drug combinations

Digital competence across boundaries - beyond a common Nordic model of the digitalisation of K-12 schools?

This paper explores policy related to digital competence and the digitalisation of Nordic K-12 schools. Anchored in some key transnational policies on digital competence, it describes some current Nordic movements in the national policies of Denmark, Finland, Norway and Sweden. The concept of boundary objects is used as an analytical lens, for understanding digital competence as a plastic and temporal concept that can be used to discuss the multi-dimensional translation of this concept in these Nordic countries. The paper ends with a discussion of the potential to view digital competence as a unifying boundary object that, with its plasticity, temporality and n-dimensionality, can show signs of common Nordic efforts in the K-12 school policy.Peer reviewe

Working Memory abilities, attachment relationships and learning process in children of primary school age: an empirical research

Several studies underline a definite link between “working memory†(WM) and the learning process (deficit and learning disorder in children). WM abi-lities mainly affect written language learning and arithmetic learning. According to studies related to the Attachment Theory, it is possible to rationalize that child with a secure attachment to the caregiver and/or to the teacher have higher skills in school adaptability. In this study—based on previous pilot study (Del Villano, Ce-cere, Sapuppo, & Caviglia., 2011)—the relationship between: cognitive test (WM measurement test), learning test and the student’s attachment style (both with his caregivers and his teacher) have been empirically evaluated. This pilot study was performed in several of the primary schools in Campania Italy between 2009 and 2011. The selected sample was composed of 80 children 6-7 years old (38 Female and 42 Male) who, after parental and school consent, were tested by the tools de-scribed in the main body of this research paper. The pilot study shows an absence of linguistic deficit, and a relationship between cognitive abilities and the learning le-vel achieved in reading and mathematical calculation, furthermore it has shown a modulation effect of the attachment on the relationship between the WM ability and MT calculation and reading tests. This modulation effect is more evident if we consider the unsecure or disorganized attachment, especially if we consider the data accumulated with reference to the attachment to the teacher. Our research was conducted with the sole intention to widen the sample and make the outcomes more valid and reliable. The recruited sample was composed of 130 children age 6-7 who, after parenentalt and school consent, were tested with the TVL -Linguistic As-sessment Test , the short version of AWMA (Automated Working Memory As-sessment), the SAT-Separation Anxiety Test, both family and school versions, and the Reading Trials MT -AC-MT 6-11- Calculation Ability Assessment Test. The re-sults underline the absence of deficit or malfunctions in the subjects’ linguistic de-velopment, a significant connection between the learning performances and the verbal and visual-spatial trials assessed with the AWMA, and a moderating effect of the attachment style upon the connection itself

Faecal miRNA profiles associated with age, sex, BMI, and lifestyle habits in healthy individuals

Abstract For their stability and detectability faecal microRNAs represent promising molecules with potential clinical interest as non-invasive diagnostic and prognostic biomarkers. However, there is no evidence on how stool miRNA profiles change according to an individual’s age, sex, and body mass index (BMI) or how lifestyle habits influence the expression levels of these molecules. We explored the relationship between the stool miRNA levels and common traits (sex, age, BMI, and menopausal status) or lifestyle habits (physical activity, smoking status, coffee, and alcohol consumption) as derived by a self-reported questionnaire, using small RNA-sequencing data of samples from 335 healthy subjects. We detected 151 differentially expressed miRNAs associated with one variable and 52 associated with at least two. Differences in miR-638 levels were associated with age, sex, BMI, and smoking status. The highest number of differentially expressed miRNAs was associated with BMI (n = 92) and smoking status (n = 84), with several miRNAs shared between them. Functional enrichment analyses revealed the involvement of the miRNA target genes in pathways coherent with the analysed variables. Our findings suggest that miRNA profiles in stool may reflect common traits and lifestyle habits and should be considered in relation to disease and association studies based on faecal miRNA expression