Search results for "agile"

OMiLAB: A Smart Innovation Environment for Digital Engineers

2020

This position paper introduces a Smart Innovation Environment for experimentation related to digital transformation projects, for the consolidation of a proposed "Digital Engineer" skill profile (with a business-oriented facet labelled as "Digital Innovator"). In the Internet of Things era, this profile implies the ability to perform both digital design and engineering activities, to semantically bridge multiple layers of abstraction and specificity - from business analysis down to cyber-physical engineering. In the paper's proposal, this integration is enabled by conceptual modelling methods and interoperable modelling tools, tailored to support the creation of Digital Twins for innovative…

Exploring Virtual Reality as an Integrated Development Environment for Cyber-Physical Systems

2019

Cyber Physical Systems (CPS) development approaches tend to start from the physical (hardware) perspective, and the software is the final element in the process. However, this approach is unfit for the more software-intensive world that is increasingly iterative, connected, and constantly online. Many constraints prevent the application of iterative, incremental, and agile development methodologies, which now are the norm for many other fields of software. Time-consuming system validation can only start when both hardware and software components are ready, which implies that the software delivery and quality is almost always the final bottleneck in the CPS development and integration. Also …

FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability

2021

Common fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability involves transcription- and replication-dependent mechanisms. Here, we uncover a role for the mitochondrial stress response pathway in the regulation of CFS stability in human cells. We show that FANCD2, a master regulator of CFS stability, dampens the activation of the mitochondrial stress response and prevents mitochondrial dysfunction. Genetic or pharmacological activation of mitochondrial stress signaling induces CFS gene expression and concomitant relocalization to CFSs of FANCD2. FANCD2 attenuates CFS gene transcription and pr…

Dicer prevents genome instability in response to replication stress

2019

Dicer, an endoribonuclease best-known for its role in microRNA biogenesis and RNA interference pathway, has been shown to play a role in the DNA damage response and repair of double-stranded DNA breaks (DSBs) in mammalian cells. However, it remains unknown whether Dicer is also important to preserve genome integrity upon replication stress. To address this question, we focused our study on common fragile sites (CFSs), which are susceptible to breakage after replication stress. We show that inhibition of the Dicer pathway leads to an increase in CFS expression upon induction of replication stress and to an accumulation of 53BP1 nuclear bodies, indicating transmission of replication-associate…

Dysregulated Prefrontal Cortex Inhibition in Prepubescent and Adolescent Fragile X Mouse Model

2020

Changes in excitation and inhibition are associated with the pathobiology of neurodevelopmental disorders of intellectual disability and autism and are widely described in Fragile X syndrome (FXS). In the prefrontal cortex (PFC), essential for cognitive processing, excitatory connectivity and plasticity are found altered in the FXS mouse model, however, little is known about the state of inhibition. To that end, we investigated GABAergic signaling in the Fragile X Mental Retardation 1 (FMR1) knock out (Fmr1-KO) mouse medial PFC (mPFC). We report changes at the molecular, and functional levels of inhibition at three (prepubescence) and six (adolescence) postnatal weeks. Functional changes we…

Neuroactive Steroids Reverse Tonic Inhibitory Deficits in Fragile X Syndrome Mouse Model

2018

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. A reduction in neuronal inhibition mediated by γ-aminobutyric acid type A receptors (GABAARs) has been implicated in the pathophysiology of FXS. Neuroactive steroids (NASs) are known allosteric modulators of GABAAR channel function, but recent studies from our laboratory have revealed that NASs also exert persistent metabotropic effects on the efficacy of tonic inhibition by increasing the protein kinase C (PKC)-mediated phosphorylation of the α4 and β3 subunits which increase the membrane expression and boosts tonic inhibition. We have assessed the GABAergic signaling in the hippocampus of fragile X ment…

How to Write Ethical User Stories? : Impacts of the ECCOLA Method

2021

AbstractArtificial Intelligence (AI) systems are increasing in significance within software services. Unfortunately, these systems are not flawless. Their faults, failures and other systemic issues have emphasized the urgency for consideration of ethical standards and practices in AI engineering. Despite the growing number of studies in AI ethics, comparatively little attention has been placed on how ethical issues can be mitigated in software engineering (SE) practice. Currently understanding is lacking regarding the provision of useful tools that can help companies transform high-level ethical guidelines for AI ethics into the actual workflow of developers. In this paper, we explore the i…

Ethical Requirements Stack : A framework for implementing ethical requirements of AI in software engineering practices

2023

Fragile-X carrier females: evidence for a distinct psychopathological phenotype?

1996

The present study examined 35 mothers (29 premutation carriers) of children with fragile-X syndrome in measures of intelligence and psychiatric disorders by comparing them with two control groups: a) 30 mothers of children in the general population and b) 17 mothers of non-fra-X retarded children with autism. Premutation carriers had a higher frequency of affective disorders than mothers from the general population. Preliminary data indicate that normally intelligent premutation carriers of the fra-X genetic abnormality have a similar frequency of affective disorders (DSM-III-R criteria [APA, 1987]) than mothers of autistic children. Neither carriers of the premutation nor carriers of the f…

Sleep phenotypes of intellectual disability: a polysomnographic evaluation in subjects with Down syndrome and Fragile X syndrome

2008

Abstract Objective To analyze sleep architecture and NREM sleep alterations by means of the Cyclic Alternating Pattern (CAP) in children with Down syndrome (DS) and Fragile-X syndrome (fraX), the two most common causes of inherited mental retardation, in order to find out eventual alterations of their sleep microstructure related to their mental retardation phenotypes. Methods Fourteen patients affected by fraX (mean age 13.1 years) and 9 affected by Down syndrome (mean age 13.8 years) and 26 age-matched normal controls were included. All subjects underwent overnight polysomnography in the sleep laboratory, after one adaptation night and their sleep architecture and CAP were visually scored…