Novel loss-of-function mutation in HERC2 is associated with severe developmental delay and paediatric lethality

Background: The HERC2 gene encodes a 527 kDa E3 ubiquitin protein ligase that has key roles in cell cycle regulation, spindle formation during mitosis, mitochondrial functions and DNA damage responses. It has essential roles during embryonic development, particularly for neuronal and muscular functions. To date, missense mutations in HERC2 have been associated with an autosomal recessive neurodevelopmental disorder with some phenotypical similarities to Angelman syndrome, and a homozygous deletion spanning HERC2 and OCA2 causing a more severe neurodevelopmental phenotype. Methods and results: We ascertained a consanguineous family with a presumed autosomal recessive severe neurodevelopmental disorder that leads to paediatric lethality. In affected individuals, we identified a homozygous HERC2 frameshift variant that results in a premature stop codon and complete loss of HERC2 protein. Functional characterisation of this variant in fibroblasts, from one living affected individual, revealed impaired mitochondrial network and function as well as disrupted levels of known interacting proteins such as XPA. Conclusion: This study extends the genotype–phenotype correlation for HERC2 variants to include a distinct lethal neurodevelopmental disorder, highlighting the importance of further characterisation for HERC2-related disorders

To Trust or Not to Trust? Developing Trusted Digital Spaces through Timely Reliable and Personalized Provenance

Organizations are increasingly dependent on data stored and processed by distributed, heterogeneous services to make critical, high-value decisions. However, these service-oriented computing environments are dynamic in nature and are becoming ever more complex systems of systems. In such evolving and dynamic eco-system infrastructures, knowing how data was derived is of significant importance in determining its validity and reliability. To address this, a number of advocates and theorists postulate that provenance is critical to building trust in data and the services that generated it as it provides evidence for data consumers to judge the integrity of the results. This paper presents a summary of the STRAPP (trusted digital Spaces through Timely Reliable And Personalised Provenance) project, which is designing and engineering mechanisms to achieve a holistic solution to a number of real-world service-based decision-support systems

Psychometric properties of the Bergen Social Media Addiction Scale: an analysis using item response theory

Background: Social media use has become an everyday behavior in contemporary life resulting in increased participation. A minority of individuals, especially younger adults, may engage excessively with the medium, resulting in the emergence of problematic social media use (PSMU). One way of assessing PSMU is by administering the Bergen Social Media Addiction Scale (BSMAS). The present study investigated the psychometric properties and prevalence of the BSMAS using Item Response Theory (IRT). Additionally, it evaluated risk factors such as gender and age. Methods: A relatively large community sample (N = 968, Mage = 29.5 years, SD = 9.36, 32.5% women) completed the BSMAS online. Results: IRT analyses showed differences regarding the BSMAS items’ discrimination, difficulty, and reliability capacities, with a raw score exceeding 26 (out of 30) indicating a higher risk of PSMU (n = 11; 1.1%). Females and younger participants were at greater risk of developing PSMU. Conclusion: The BSMAS functions as a reliable measure of PSMU, particularly between average to high levels of the trait. Additionally, younger participants were shown to be at higher risk of PSMU suggesting that prevention and intervention protocols should focus on this group

Plasmon oscillations in ellipsoid nanoparticles: beyond dipole approximation

The plasmon oscillations of a metallic triaxial ellipsoid nanoparticle have been studied within the framework of the quasistatic approximation. A general method has been proposed for finding the analytical expressions describing the potential and frequencies of the plasmon oscillations of an arbitrary multipolarity order. The analytical expressions have been derived for an electric potential and plasmon oscillation frequencies of the first 24 modes. Other higher orders plasmon modes are investigated numerically.Comment: 33 pages, 12 figure

Linearized f(R) Gravity: Gravitational Radiation & Solar System Tests

We investigate the linearized form of metric f(R)-gravity, assuming that f(R) is analytic about R = 0 so it may be expanded as f(R) = R + a_2 R^2/2 + ... . Gravitational radiation is modified, admitting an extra mode of oscillation, that of the Ricci scalar. We derive an effective energy-momentum tensor for the radiation. We also present weak-field metrics for simple sources. These are distinct from the equivalent Kerr (or Schwarzschild) forms. We apply the metrics to tests that could constrain f(R). We show that light deflection experiments cannot distinguish f(R)-gravity from general relativity as both have an effective post-Newtonian parameter \gamma = 1. We find that planetary precession rates are enhanced relative to general relativity; from the orbit of Mercury we derive the bound |a_2| < 1.2 \times 10^18 m^2. Gravitational wave astronomy may be more useful: considering the phase of a gravitational waveform we estimate deviations from general relativity could be measurable for an extreme-mass-ratio inspiral about a 10^6 M_sol black hole if |a_2| > 10^17 m^2, assuming that the weak-field metric of the black hole coincides with that of a point mass. However Eot-Wash experiments provide the strictest bound |a_2| < 2 \times 10^-9 m^2. Although the astronomical bounds are weaker, they are still of interest in the case that the effective form of f(R) is modified in different regions, perhaps through the chameleon mechanism. Assuming the laboratory bound is universal, we conclude that the propagating Ricci scalar mode cannot be excited by astrophysical sources.Comment: 19 pages, 1 figure; typos in Sec. VIII. A. correcte

Particle motion in the field of a five-dimensional charged black hole

In this paper, we have investigated the geodesics of neutral particles near a five-dimensional charged black hole using a comparative approach. The effective potential method is used to determine the location of the horizons and to study radial and circular trajectories. This also helps us to analyze the stability of radial and circular orbits. The radius of the innermost stable circular orbits have also been determined. Contrary to the case of massive particles for which, the circular orbits may have up to eight possible values of specific radius, we find that the photons will only have two distinct values for the specific radii of circular trajectories. Finally we have used the dynamical systems analysis to determine the critical points and the nature of the trajectories for the timelike and null geodesics.Comment: 15 pages, accepted for publication in Astrophysics and Space Scienc

The Quantum-Classical Correspondence in Polygonal Billiards

We show that wave functions in planar rational polygonal billiards (all angles rationally related to Pi) can be expanded in a basis of quasi-stationary and spatially regular states. Unlike the energy eigenstates, these states are directly related to the classical invariant surfaces in the semiclassical limit. This is illustrated for the barrier billiard. We expect that these states are also present in integrable billiards with point scatterers or magnetic flux lines.Comment: 8 pages, 9 figures (in reduced quality), to appear in PR

A spectral method for elliptic equations: the Dirichlet problem

An elliptic partial differential equation Lu=f with a zero Dirichlet boundary condition is converted to an equivalent elliptic equation on the unit ball. A spectral Galerkin method is applied to the reformulated problem, using multivariate polynomials as the approximants. For a smooth boundary and smooth problem parameter functions, the method is proven to converge faster than any power of 1/n with n the degree of the approximate Galerkin solution. Examples in two and three variables are given as numerical illustrations. Empirically, the condition number of the associated linear system increases like O(N), with N the order of the linear system.Comment: This is latex with the standard article style, produced using Scientific Workplace in a portable format. The paper is 22 pages in length with 8 figure