Bridging The Gap: Defining the Molecular Mechanisms of Cep290 Disease Pathogenesis

Mutations in the gene CEP290 cause an array of debilitating and phenotypically distinct human diseases, ranging in severity from the devastating blinding disease Leber congenital amaurosis (LCA) to Senior Løken Syndrome, Joubert syndrome, and the embryonically lethal Meckel-Grüber syndrome. The pathology observed in these diseases is thought to be due to CEP290\u27s essential role in the development and maintenance of the primary cilium, but despite its critical role in biology and disease we know only little about CEP290\u27s function. Here we identify four novel functional domains of the protein, showing that CEP290 directly binds to cellular membranes through an N-terminal domain that includes a highly conserved amphipathic helix motif, and to microtubules through a domain located within its myosin-tail homology domain. Furthermore, CEP290 activity was found to be regulated by two novel autoinhibitory domains within its N- and C-termini, both of which were also found to play critical roles in regulating ciliogenesis. Disruption of the microtubule-binding domain in the rd16 mouse LCA model was found to be sufficient to induce significant deficits in cilium formation leading to retinal degeneration. Taking these findings into account, we developed a novel model that accurately predicts patient CEP290 protein levels in a mutation-specific fashion. Predicted CEP290 protein levels were found to robustly correlate with disease severity for all reported CEP290 patients. All these data implicate CEP290 as an integral structural and regulatory component of the primary cilium and provide insight into the pathological mechanisms of LCA and related ciliopathies. Our findings also suggest novel strategies for therapeutic intervention in the treatment of CEP290-based disease that, if fully realized, would be the first treatment available for the many patients suffering the devastating effects of CEP290 dysfunction

A NIS Directive compliant Cybersecurity Maturity Model

The EU NIS Directive introduces obligations related to the security of the network and information systems for Operators of Essential Services and for Digital Service Providers. Moreover, National Competent Authorities for cybersecurity are required to assess compliance with these obligations. This paper describes a novel Cybersecurity Maturity Assessment Framework (CMAF) that is tailored to the NIS Directive requirements. CMAF can be used either as a self-assessment tool from Operators of Essential Services and Digital Service Providers or as an audit tool from the National Competent Authorities for cybersecurity

Pattern of Smoking Habit among Greek Blue and White Collar Workers

The aim of our study was to investigate the prevalence of smoking in a Greek working population. A questionnaire regarding smoking habit was collected from 1,005 out of 1,200 blue and white-collar employees (response rate: 84%). The overall smoking prevalence was 48.4% and did not differ by sex, age, education, and occupation. The mean cigarette consumption per day was 25.54, with no difference observed by occupation. The above-mentioned findings, if confirmed by further research, are alarming and inconsistent with the prevalent pattern of smoking habits in the West

PHOENI2X -- A European Cyber Resilience Framework With Artificial-Intelligence-Assisted Orchestration, Automation and Response Capabilities for Business Continuity and Recovery, Incident Response, and Information Exchange

As digital technologies become more pervasive in society and the economy, cybersecurity incidents become more frequent and impactful. According to the NIS and NIS2 Directives, EU Member States and their Operators of Essential Services must establish a minimum baseline set of cybersecurity capabilities and engage in cross-border coordination and cooperation. However, this is only a small step towards European cyber resilience. In this landscape, preparedness, shared situational awareness, and coordinated incident response are essential for effective cyber crisis management and resilience. Motivated by the above, this paper presents PHOENI2X, an EU-funded project aiming to design, develop, and deliver a Cyber Resilience Framework providing Artificial-Intelligence-assisted orchestration, automation and response capabilities for business continuity and recovery, incident response, and information exchange, tailored to the needs of Operators of Essential Services and the EU Member State authorities entrusted with cybersecurity

Measurement and interpretation of same-sign W boson pair production in association with two jets in pp collisions at s = 13 TeV with the ATLAS detector

This paper presents the measurement of fducial and diferential cross sections for both the inclusive and electroweak production of a same-sign W-boson pair in association with two jets (W±W±jj) using 139 fb−1 of proton-proton collision data recorded at a centre-of-mass energy of √s = 13 TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed by selecting two same-charge leptons, electron or muon, and at least two jets with large invariant mass and a large rapidity diference. The measured fducial cross sections for electroweak and inclusive W±W±jj production are 2.92 ± 0.22 (stat.) ± 0.19 (syst.)fb and 3.38±0.22 (stat.)±0.19 (syst.)fb, respectively, in agreement with Standard Model predictions. The measurements are used to constrain anomalous quartic gauge couplings by extracting 95% confdence level intervals on dimension-8 operators. A search for doubly charged Higgs bosons H±± that are produced in vector-boson fusion processes and decay into a same-sign W boson pair is performed. The largest deviation from the Standard Model occurs for an H±± mass near 450 GeV, with a global signifcance of 2.5 standard deviations

Studies of new Higgs boson interactions through nonresonant HH production in the b¯bγγ fnal state in pp collisions at √s = 13 TeV with the ATLAS detector

A search for nonresonant Higgs boson pair production in the b ¯bγγ fnal state is performed using 140 fb−1 of proton-proton collisions at a centre-of-mass energy of 13 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. This analysis supersedes and expands upon the previous nonresonant ATLAS results in this fnal state based on the same data sample. The analysis strategy is optimised to probe anomalous values not only of the Higgs (H) boson self-coupling modifer κλ but also of the quartic HHV V (V = W, Z) coupling modifer κ2V . No signifcant excess above the expected background from Standard Model processes is observed. An observed upper limit µHH < 4.0 is set at 95% confdence level on the Higgs boson pair production cross-section normalised to its Standard Model prediction. The 95% confdence intervals for the coupling modifers are −1.4 < κλ < 6.9 and −0.5 < κ2V < 2.7, assuming all other Higgs boson couplings except the one under study are fxed to the Standard Model predictions. The results are interpreted in the Standard Model efective feld theory and Higgs efective feld theory frameworks in terms of constraints on the couplings of anomalous Higgs boson (self-)interactions

Model-independent search for the presence of new physics in events including H → γγ with s \sqrt{s} = 13 TeV pp data recorded by the ATLAS detector at the LHC

Abstract A model-independent search for new physics leading to final states containing a Higgs boson, with a mass of 125.09 GeV, decaying to a pair of photons is performed with 139 fb−1 of s $$\sqrt{s}$$ = 13 TeV pp collision data recorded by the ATLAS detector at the Large Hadron Collider at CERN. This search examines 22 final states categorized by the objects that are produced in association with the Higgs boson. These objects include isolated electrons or muons, hadronically decaying τ-leptons, additional photons, missing transverse momentum, and hadronic jets, as well as jets that are tagged as containing a b-hadron. No significant excesses above Standard Model expectations are observed and limits on the production cross section at 95% confidence level are set. Detector efficiencies are reported for all 22 signal regions, which can be used to convert detector-level cross-section limits reported in this paper to particle-level cross-section constraints