Impaired intracortical inhibition demonstrated in vivo in people with Dravet syndrome

OBJECTIVE: Dravet syndrome is a rare neurodevelopmental disorder characterized by seizures and other neurologic problems. SCN1A mutations account for ∼80% of cases. Animal studies have implicated mutation-related dysregulated cortical inhibitory networks in its pathophysiology. We investigated such networks in people with the condition. METHODS: Transcranial magnetic stimulation using single and paired pulse paradigms was applied to people with Dravet syndrome and to 2 control groups to study motor cortex excitability. RESULTS: Short interval intracortical inhibition (SICI), which measures GABAergic inhibitory network behavior, was undetectable in Dravet syndrome, but detectable in all controls. Other paradigms, including those testing excitatory networks, showed no difference between Dravet and control groups. CONCLUSIONS: There were marked differences in inhibitory networks, detected using SICI paradigms, while other inhibitory and excitatory paradigms yielded normal results. These human data showing reduced GABAergic inhibition in vivo in people with Dravet syndrome support established animal models

Modelling of an aza-Michael reaction from crystalline naphthalene derivatives containing peri–peri interactions: very long N–C bonds?

The separation between a pair of peri-located dimethylamino and ethene-2,2-dinitrile groups in a naphthalene molecule, which models the progress of a Michael reaction, can be controlled by the installation of a short ethylene bridge or the introduction of repulsive interactions at the opposite set of peri positions. Introduction of a dimethylammonium substituent produced a hydrated chloride salt in which the Me2N⋯C(H)[double bond, length as m-dash]C(CN)2 separation between reactive groups decreases, reversibly, from 2.167 Å at 200 K to 1.749 Å at 100 K, with the maximum rate of change in the range 128–140 K, which was studied by variable temperature X-ray crystallography and solid state NMR. From these and other crystallographic data a correlation between Me2N⋯C bond formation and alkene bond breaking was constructed for the first step of an aza-Michael reaction

Topological modes bound to dislocations in mechanical metamaterials

Mechanical metamaterials are artificial structures with unusual properties, such as negative Poisson ratio, bistability or tunable vibrational properties, that originate in the geometry of their unit cell. At the heart of such unusual behaviour is often a soft mode: a motion that does not significantly stretch or compress the links between constituent elements. When activated by motors or external fields, soft modes become the building blocks of robots and smart materials. Here, we demonstrate the existence of topological soft modes that can be positioned at desired locations in a metamaterial while being robust against a wide range of structural deformations or changes in material parameters. These protected modes, localized at dislocations, are the mechanical analogue of topological states bound to defects in electronic systems. We create physical realizations of the topological modes in prototypes of kagome lattices built out of rigid triangular plates. We show mathematically that they originate from the interplay between two Berry phases: the Burgers vector of the dislocation and the topological polarization of the lattice. Our work paves the way towards engineering topologically protected nano-mechanical structures for molecular robotics or information storage and read-out.Comment: 13 pages, 6 figures; changes to text and figures and added analysis on mode localization; see http://www.lorentz.leidenuniv.nl/~paulose/dislocation-modes/ for accompanying video

How South Pacific mangroves may respond to predicted climate change and sea level rise

In the Pacific islands the total mangrove area is about 343,735 ha, with largest areas in Papua New Guinea, Solomon Islands, Fiji and New Caledonia. A total of 34 species of mangroves occur, as well as 3 hybrids. These are of the Indo-Malayan assemblage (with one exception), and decline in diversity from west to east across the Pacific, reaching a limit at American Samoa. Mangrove resources are traditionally exploited in the Pacific islands, for construction and fuel wood, herbal medicines, and the gathering of crabs and fish. There are two main environmental settings for mangroves in the Pacific, deltaic and estuarine mangroves of high islands, and embayment, lagoon and reef flat mangroves of low islands. It is indicated from past analogues that their close relationship with sea-level height renders these mangrove swamps particularly vulnerable to disruption by sea-level rise. Stratigraphic records of Pacific island mangrove ecosystems during sea-level changes of the Holocene Period demonstrate that low islands mangroves can keep up with a sea-level rise of up to 12 cm per 100 years. Mangroves of high islands can keep up with rates of sea-level rates of up to 45 cm per 100 years, according to the supply of fluvial sediment. When the rate of sea-level rise exceeds the rate of accretion, mangroves experience problems of substrate erosion, inundation stress and increased salinity. Rise in temperature and the direct effects of increased CO2 levels are likely to increase mangrove productivity, change phenological patterns (such as the timing of flowering and fruiting), and expand the ranges of mangroves into higher latitudes. Pacific island mangroves are expected to demonstrate a sensitive response to the predicted rise in sea-level. A regional monitoring system is needed to provide data on ecosystem changes in productivity, species composition and sedimentation. This has been the intention of a number of programs, but none has yet been implemented

An atypical presentation of cystic fibrosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>The presentation of cystic fibrosis is dependant upon which organs are affected. Common presentations include chronic respiratory infections and malabsorption. Patients with atypical disease tend to present late in childhood or as adults. Eye manifestations of cystic fibrosis are less well known.</p> <p>Case presentation</p> <p>A 14-year-old Caucasian boy presented with tiredness and difficulty seeing at night, over a period of 6 months. Good vision was only described in bright conditions. There was no history of jaundice, steatorrhea or diarrhoea.</p> <p>Conclusion</p> <p>This is the first reported case of newly diagnosed cystic fibrosis-related liver disease in a teenage boy, whose presenting symptom was night blindness secondary to vitamin A deficiency.</p

BRS "Symmetry", prehistory and history

Prehistory - Starting from 't Hooft's (1971) we have a short look at Taylor's and Slavnov's works (1971-72) and at the lectures given by Rouet and Stora in Lausanne-1973 which determine the transition from pre-history to history. History - We give a brief account of the main analyses and results of the BRS collaboration concerning the renormalized gauge theories, in particular the method of the regularization independent, algebraic renormalization, the algebraic proof of S-matrix unitarity and that of gauge choice independence of the renormalized physics. We conclude this report with a suggestion to the crucial question: what could remain of BRS invariance beyond perturbation theory.Comment: Talk given at: A Special day in honour of Raymond Stora, Annecy, July 8, 201

Molecular Characterization of the Gastrula in the Turtle Emys orbicularis: An Evolutionary Perspective on Gastrulation

Due to the presence of a blastopore as in amphibians, the turtle has been suggested to exemplify a transition form from an amphibian- to an avian-type gastrulation pattern. In order to test this hypothesis and gain insight into the emergence of the unique characteristics of amniotes during gastrulation, we have performed the first molecular characterization of the gastrula in a reptile, the turtle Emys orbicularis. The study of Brachyury, Lim1, Otx2 and Otx5 expression patterns points to a highly conserved dynamic of expression with amniote model organisms and makes it possible to identify the site of mesoderm internalization, which is a long-standing issue in reptiles. Analysis of Brachyury expression also highlights the presence of two distinct phases, less easily recognizable in model organisms and respectively characterized by an early ring-shaped and a later bilateral symmetrical territory. Systematic comparisons with tetrapod model organisms lead to new insights into the relationships of the blastopore/blastoporal plate system shared by all reptiles, with the blastopore of amphibians and the primitive streak of birds and mammals. The biphasic Brachyury expression pattern is also consistent with recent models of emergence of bilateral symmetry, which raises the question of its evolutionary significance

Counting all dyons in N =4 string theory

For dyons in heterotic string theory compactified on a six-torus, with electric charge vector Q and magnetic charge vector P, the positive integer I = g.c.d.(Q \wedge P) is an invariant of the U-duality group. We propose the microscopic theory for computing the spectrum of all dyons for all values of I, generalizing earlier results that exist only for the simplest case of I=1. Our derivation uses a combination of arguments from duality, 4d-5d lift, and a careful analysis of fermionic zero modes. The resulting degeneracy agrees with the black hole degeneracy for large charges and with the degeneracy of field-theory dyons for small charges. It naturally satisfies several physical requirements including integrality and duality invariance. As a byproduct, we also derive the microscopic (0,4) superconformal field theory relevant for computing the spectrum of five-dimensional Strominger-Vafa black holes in ALE backgrounds and count the resulting degeneracies

Invited Editorial: Health as a crucial driver for climate policy

Health impacts of climate change and the need to prevent them should be at centre stage of the ongoing debate on climate policies (1). We have specifically prepared this series of papers to be available for the COP151 conference in Copenhagen, to which the world looks to agree on targets and procedures to reduce greenhouse gas (GHG) emissions on the basis of fair burden-sharing between high and low-income countries