A 22-Week-Old Fetus with Nager Syndrome and Congenital Diaphragmatic Hernia due to a Novel SF3B4 Mutation.

Nager syndrome, or acrofacial dysostosis type 1 (AFD1), is a rare multiple malformation syndrome characterized by hypoplasia of first and second branchial arches derivatives and appendicular anomalies with variable involvement of the radial/axial ray. In 2012, AFD1 has been associated with dominant mutations in SF3B4. We report a 22-week-old fetus with AFD1 associated with diaphragmatic hernia due to a previously unreported SF3B4 mutation (c.35-2A>G). Defective diaphragmatic development is a rare manifestation in AFD1 as it is described in only 2 previous cases, with molecular confirmation in 1 of them. Our molecular finding adds a novel pathogenic splicing variant to the SF3B4 mutational spectrum and contributes to defining its prenatal/fetal phenotype

On the Parity Problem in One-Dimensional Cellular Automata

We consider the parity problem in one-dimensional, binary, circular cellular automata: if the initial configuration contains an odd number of 1s, the lattice should converge to all 1s; otherwise, it should converge to all 0s. It is easy to see that the problem is ill-defined for even-sized lattices (which, by definition, would never be able to converge to 1). We then consider only odd lattices. We are interested in determining the minimal neighbourhood that allows the problem to be solvable for any initial configuration. On the one hand, we show that radius 2 is not sufficient, proving that there exists no radius 2 rule that can possibly solve the parity problem from arbitrary initial configurations. On the other hand, we design a radius 4 rule that converges correctly for any initial configuration and we formally prove its correctness. Whether or not there exists a radius 3 rule that solves the parity problem remains an open problem.Comment: In Proceedings AUTOMATA&JAC 2012, arXiv:1208.249

Molecular analysis of sarcomeric and non-sarcomeric genes in patients with hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is a common genetic heart disorder characterized by unexplained left ventricle hypertrophy associated with non-dilated ventricular chambers. Several genes encoding heart sarcomeric proteins have been associated to HCM, but a small proportion of HCM patients harbor alterations in other non-sarcomeric loci. The variable expression of HCM seems influenced by genetic modifier factors and new sequencing technologies are redefining the understanding of genotype–phenotype relationships, even if the interpretations of the numerous identified variants pose several challenges. Methods and results: We investigated 62 sarcomeric and non-sarcomeric genes in 41 HCM cases and in 3 HCM-related disorders patients. We employed an integrated approach that combines multiple tools for the prediction, annotation and visualization of functional variants. Genotype–phenotype correlations were carried out for inspecting the involvement of each gene in age onset and clinical variability of HCM. The 80% of the non-syndromic patients showed at least one rare non-synonymous variant (nsSNV) and among them, 58% carried alterations in sarcomeric loci, 14% in desmosomal and 7% in other non-sarcomeric ones without any sarcomere change. Statistical analyses revealed an inverse correlation between the number of nsSNVs and age at onset, and a relationship between the clinical variability and number and type of variants. Conclusions: Our results extend the mutational spectrum of HCM and contribute in defining the molecular pathogenesis and inheritance pattern(s) of this condition. Besides, we delineate a specific procedure for the identification of the most likely pathogenetic variants for a next generation sequencing approach embodied in a clinical context

From spinning to non-spinning cosmic string spacetimes

We analyse the properties of a fluid generating a spinning cosmic string spacetime with flat limiting cases corresponding to a constant angular momentum in the infinite past and static configuration in the infinite future. The spontaneous loss of angular momentum of a spinning cosmic string due to particle emission is discussed. The rate of particle production between the spinning and non-spinning cosmic string spacetimes is calculated.Comment: 11 pages, 1 figure, LaTeX To appear in Class. Quantum Gra

Accelerated detectors in Dirac vacuum: the effects of horizon fluctuations

We consider an Unruh-DeWitt detector interacting with a massless Dirac field. Assuming that the detector is moving along an hyperbolic trajectory, we modeled the effects of fluctuations in the event horizon using a Dirac equation with random coefficients. First, we develop the perturbation theory for the fermionic field in a random media. Further we evaluate corrections due to the randomness in the response function associated to different model detectors.Comment: 19 pages, 1 figur

Modelling fluid flow in complex natural fault zones. Implications for natural and human-induced earthquake nucleation

Pore fluid overpressures in active fault systems can drive fluid flow and cause fault weakening and seismicity. In return, deformation accommodated by different modes of failure (e.g. brittle vs. ductile) also affects fault zone permeability and, hence, fluid flow and pore fluid pressure distribution. Current numerical simulation techniques model how fluid flow controls fault reactivation and associated seismicity. However, the control exerted by pore fluid pressure on the transition from slow aseismic fault sliding to fast seismic sliding, during the earthquake nucleation phase, is still poorly understood. Here, we model overpressured, supercritical CO2 fluid flow in natural faults, where non-linear, complex feedback between fluid flow, fluid pressure and fault deformation controls the length of the nucleation phase of an earthquake and the duration of the interseismic period. The model setup is an analogue for recent seismic source events in the Northern Apennines of Italy (e.g. Mw 6.0 1997-98 Colfiorito and Mw 6.5 2016 Norcia earthquakes). Our modelling results of Darcy fluid flow show that the duration of the nucleation phase can be reduced by orders of magnitude, when realistic models of fault zone architecture and pore pressure- and deformation-dependent permeability are considered. In particular, earthquake nucleation phase duration can drop from more than 10 years to a few days/minutes, while the seismic moment can decrease by a factor of 6. Notably, the moment of aseismic slip (M0=109Nm) obtained during the nucleation phase modelled in our study is of the same order as the detection limit of local strain measurements using strain meters. These findings have significant implications for earthquake early warning systems, as the duration and moment of the nucleation phase will affect the likelihood of timely precursory signal detection. Interestingly, aseismic slip has been measured up to a few months before some recent large earthquakes, although in a different tectonic context than the model developed here, rekindling interest in the nucleation phase of earthquakes. In addition, our results have important implications for short and long term earthquake forecasting, as crustal fluid migration during the interseismic period may control fault strength and earthquake recurrence intervals