PRRT2 gene variant in a child with dysmorphic features, congenital microcephaly, and severe epileptic seizures: genotype-phenotype correlation?

BACKGROUND: Mutations in Proline-rich Transmembrane Protein 2 (PRRT2) have been primarily associated with individuals presenting with infantile epilepsy, including benign familial infantile epilepsy, benign infantile epilepsy, and benign myoclonus of early infancy, and/or with dyskinetic paroxysms such as paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, and exercise-induced dyskinesia. However, the clinical manifestations of this disorder vary widely. PRRT2 encodes a protein expressed in the central nervous system that is mainly localized in the pre-synaptic neurons and is involved in the modulation of synaptic neurotransmitter release. The anomalous function of this gene has been proposed to cause dysregulation of neuronal excitability and cerebral disorders. CASE PRESENTATION: We hereby report on a young child followed-up for three years who presents with a spectrum of clinical manifestations such as congenital microcephaly, dysmorphic features, severe intellectual disability, and drug-resistant epileptic encephalopathy in association with a synonymous variant in PRRT2 gene (c.501C > T; p.Thr167Ile) of unknown clinical significance variant (VUS) revealed by diagnostic exome sequencing. CONCLUSION: Several hypotheses have been advanced on the specific role that PRRT2 gene mutations play to cause the clinical features of affected patients. To our knowledge, the severe phenotype seen in this case has never been reported in association with any clinically actionable variant, as the missense substitution detected in PRRT2 gene. Intriguingly, the same mutation was reported in the healthy father: the action of modifying factors in the affected child may be hypothesized. The report of similar observations could extend the spectrum of clinical manifestations linked to this mutation

Motion Deblurring in the Wild

The task of image deblurring is a very ill-posed problem as both the image and the blur are unknown. Moreover, when pictures are taken in the wild, this task becomes even more challenging due to the blur varying spatially and the occlusions between the object. Due to the complexity of the general image model we propose a novel convolutional network architecture which directly generates the sharp image.This network is built in three stages, and exploits the benefits of pyramid schemes often used in blind deconvolution. One of the main difficulties in training such a network is to design a suitable dataset. While useful data can be obtained by synthetically blurring a collection of images, more realistic data must be collected in the wild. To obtain such data we use a high frame rate video camera and keep one frame as the sharp image and frame average as the corresponding blurred image. We show that this realistic dataset is key in achieving state-of-the-art performance and dealing with occlusions

Multi-step self-guided pathways for shape-changing metamaterials

Multi-step pathways, constituted of a sequence of reconfigurations, are central to a wide variety of natural and man-made systems. Such pathways autonomously execute in self-guided processes such as protein folding and self-assembly, but require external control in macroscopic mechanical systems, provided by, e.g., actuators in robotics or manual folding in origami. Here we introduce shape-changing mechanical metamaterials, that exhibit self-guided multi-step pathways in response to global uniform compression. Their design combines strongly nonlinear mechanical elements with a multimodal architecture that allows for a sequence of topological reconfigurations, i.e., modifications of the topology caused by the formation of internal self-contacts. We realized such metamaterials by digital manufacturing, and show that the pathway and final configuration can be controlled by rational design of the nonlinear mechanical elements. We furthermore demonstrate that self-contacts suppress pathway errors. Finally, we demonstrate how hierarchical architectures allow to extend the number of distinct reconfiguration steps. Our work establishes general principles for designing mechanical pathways, opening new avenues for self-folding media, pluripotent materials, and pliable devices in, e.g., stretchable electronics and soft robotics.Comment: 16 pages, 3 main figures, 10 extended data figures. See https://youtu.be/8m1QfkMFL0I for an explanatory vide

Probing anomalous tbW couplings in single-top production using top polarization at the Large Hadron Collider

We study the sensitivity of the Large Hadron Collider (LHC) to anomalous tbW couplings in single-top production in association with a W^- boson followed by semileptonic decay of the top. We calculate top polarization and the effects of these anomalous couplings to it at two centre-of-mass (cm) energies of 7 TeV and 14 TeV. As a measure of top polarization, we look at various laboratory frame distributions of its decay products, viz., lepton angular and energy distributions and b-quark angular distributions, without requiring reconstruction of the rest frame of the top, and study the effect of anomalous couplings on these distributions. We construct certain asymmetries to study the sensitivity of these distributions to anomalous tbW couplings. We find that 1\sigma limits on real and imaginary parts of the dominant anomalous coupling Ref_{2R} which may be obtained by utilizing these asymmetries at the LHC with cm energy of 14 TeV and an integrated luminosity of 10 fb^{-1} will be significantly better than the expectations from direct measurements of cross sections and some other variables at the LHC and over an order of magnitude better than the indirect limits.Comment: 25 pages, 34 figure

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures

Search for the Decays B^0 -> D^{(*)+} D^{(*)-}

Using the CLEO-II data set we have searched for the Cabibbo-suppressed decays B^0 -> D^{(*)+} D^{(*)-}. For the decay B^0 -> D^{*+} D^{*-}, we observe one candidate signal event, with an expected background of 0.022 +/- 0.011 events. This yield corresponds to a branching fraction of Br(B^0 -> D^{*+} D^{*-}) = (5.3^{+7.1}_{-3.7}(stat) +/- 1.0(syst)) x 10^{-4} and an upper limit of Br(B^0 -> D^{*+} D^{*-}) D^{*\pm} D^\mp and B^0 -> D^+ D^-, no significant excess of signal above the expected background level is seen, and we calculate the 90% CL upper limits on the branching fractions to be Br(B^0 -> D^{*\pm} D^\mp) D^+ D^-) < 1.2 x 10^{-3}.Comment: 12 page postscript file also available through http://w4.lns.cornell.edu/public/CLNS, submitted to Physical Review Letter

State-space Manifold and Rotating Black Holes

We study a class of fluctuating higher dimensional black hole configurations obtained in string theory/ $M$-theory compactifications. We explore the intrinsic Riemannian geometric nature of Gaussian fluctuations arising from the Hessian of the coarse graining entropy, defined over an ensemble of brane microstates. It has been shown that the state-space geometry spanned by the set of invariant parameters is non-degenerate, regular and has a negative scalar curvature for the rotating Myers-Perry black holes, Kaluza-Klein black holes, supersymmetric $AdS_5$ black holes, $D_1$-$D_5$ configurations and the associated BMPV black holes. Interestingly, these solutions demonstrate that the principal components of the state-space metric tensor admit a positive definite form, while the off diagonal components do not. Furthermore, the ratio of diagonal components weakens relatively faster than the off diagonal components, and thus they swiftly come into an equilibrium statistical configuration. Novel aspects of the scaling property suggest that the brane-brane statistical pair correlation functions divulge an asymmetric nature, in comparison with the others. This approach indicates that all above configurations are effectively attractive and stable, on an arbitrary hyper-surface of the state-space manifolds. It is nevertheless noticed that there exists an intriguing relationship between non-ideal inter-brane statistical interactions and phase transitions. The ramifications thus described are consistent with the existing picture of the microscopic CFTs. We conclude with an extended discussion of the implications of this work for the physics of black holes in string theory.Comment: 44 pages, Keywords: Rotating Black Holes; State-space Geometry; Statistical Configurations, String Theory, M-Theory. PACS numbers: 04.70.-s Physics of black holes; 04.70.Bw Classical black holes; 04.70.Dy Quantum aspects of black holes, evaporation, thermodynamics; 04.50.Gh Higher-dimensional black holes, black strings, and related objects. Edited the bibliograph

Development of microspheres for biomedical applications: a review

An overview of microspheres manufactured for use in biomedical applications based on recent literature is presented in this review. Different types of glasses (i.e. silicate, borate, and phosphates), ceramics and polymer-based microspheres (both natural and synthetic) in the form of porous , non-porous and hollow structures that are either already in use or are currently being investigated within the biomedical area are discussed. The advantages of using microspheres in applications such as drug delivery, bone tissue engineering and regeneration, absorption and desorption of substances, kinetic release of the loaded drug components are also presented. This review also reports on the preparation and characterisation methodologies used for the manufacture of these microspheres. Finally, a brief summary of the existing challenges associated with processing these microspheres which requires further research and development are presented