Mutations in SLC1A4, encoding the brain serine transporter, are associated with developmental delay, microcephaly and hypomyelination

BACKGROUND L-serine plays an essential role in neuronal development and function. Although a non-essential amino acid, L-serine must be synthesised within the brain because of its poor permeability by the blood-brain barrier. Within the brain, its synthesis is confined to astrocytes, and its shuttle to neuronal cells is performed by a dedicated neutral amino acid transporter, ASCT1. METHODS AND RESULTS Using exome analysis we identified the recessive mutations, p.E256K, p.L315fs, and p.R457W, in SLC1A4, the gene encoding ASCT1, in patients with developmental delay, microcephaly and hypomyelination; seizure disorder was variably present. When expressed in a heterologous system, the mutations did not affect the protein level at the plasma membrane but abolished or markedly reduced L-serine transport for p.R457W and p.E256K mutations, respectively. Interestingly, p.E256K mutation displayed a lower L-serine and alanine affinity but the same substrate selectivity as wild-type ASCT1. CONCLUSIONS The clinical phenotype of ASCT1 deficiency is reminiscent of defects in L-serine biosynthesis. The data underscore that ASCT1 is essential in brain serine transport. The SLC1A4 p.E256K mutation has a carrier frequency of 0.7% in the Ashkenazi-Jewish population and should be added to the carrier screening panel in this community.

Family Court Judges' Training, Background, and Child Development Knowledge: Associations with Child Custody Decision Making

Family court judges are often asked to make inferences about - or directly interview children to ascertain - children's custody preferences and their maturity to express such preferences. These estimates of children's developmental maturity are important to the judges' considerations of children's "best interests" in custody cases. The research literature describing family court judges' background, education, training, and knowledge about child development is scant. With appropriate child development knowledge, judges should be better able to identify the developmental stages at which children have the cognitive and social capabilities to communicate directly their placement wishes or concerns. The current study is the first to examine judges' estimates of - and actual tests of - their child development knowledge, their training/education, and their application of this knowledge to their decisions to involve children as participants in contested custody cases.

The rose of Castille : opera in three acts ; ... and performed in the presence of Her Majesty and the Court (by Royal command) on the occasion of the festival performances at Her Majesty's Theatre, in honor of the nuptials of The Princess Royal and The Prince of Prussia, January 21, 1858

the music (composed expressly for the Pyne and Harrison English opera Company) by M. W. Balfe. [Text] by A. Harris and E. Falconer

How health care delay and avoidance decisions are affected by finances and health insurance

Objective. To identify how an individual's finances and health insurance coverage affects their decision whether to avoid or delay medical care. Methods. Secondary data analysis of The Effects of Financial and Insurance Considerations on Health Care Utilization 2007 telephone survey data. Study inclusion criteria. 18 years old, Harris County resident, and had a need for medical care within the past year. Post weighing was done to correct for non-response bias. Results. Survey decision makers were predominately minorities (60%), Female (70%), and insured (71%). Ninety-two percent of participants sought care when needed, however, of this population 39% delayed medical care. Fifty-six percent of participants who delayed medical care sought care in the Doctor's office. For those who replied "Yes" to considering health insurance and finances in deciding to avoid medical care, 61% stated that they were confused about their insurance coverage as the explanation why. Fifty-five percent of Respondents indicated that delaying medical care was due to not knowing whether medical care was necessary. Conclusion. Additional research needs to be conducted to examine the relationship between onset of medical symptoms and final medical diagnosis to identify whether survey participants who delayed or avoided medical care actions were appropriate responses to their initial medical symptoms and final diagnosis. ^

Broadband Channel Long Delay Cluster Measurements and Analysis at 2.4GHz in Subway Tunnels

The delay caused by the reflected ray in broadband communication has a great influence on the communications in subway tunnel. This paper presents measurements taken in subway tunnels at 2.4 GHz, with 5 MHz bandwidth. According to propagation characteristics of tunnel, the measurements were carried out with a frequency domain channel sounding technique, in three typical scenarios: line of sight (LOS), Non-line-of-sight (NLOS) and far line of sight (FLOS), which lead to different delay distributions. Firstly IFFT was chosen to get channel impulse response (CIR) h(t) from measured three-dimensional transfer functions. Power delay profile (PDP) was investigated to give an overview of broadband channel model. Thereafter, a long delay caused by the obturation of tunnel is observed and investigated in all the scenarios. The measurements show that the reflection can be greatly remained by the tunnel, which leads to long delay cluster where the reflection, but direct ray, makes the main contribution for radio wave propagation. Four important parameters: distribution of whole PDP power, first peak arriving time, reflection cluster duration and PDP power distribution of reflection cluster were studied to give a detailed description of long delay characteristic in tunnel. This can be used to ensure high capacity communication in tunnels

Optical Multistability and Oscillations in Hybrid Optical Bistable Systems with Short Delay Times

Optical instabilities in the output light from a bistable optical device (BOD) with a delayed feedback was predicted by Ikeda [1]. Gibbs et al. [2] gave the first experimental verification of this type of instabilities. From that time several groups have studied the instabilities of the BOD for different relations between the delay time tR and the time constant ح of the system. In a previous paper [3] an empirical and analytical study of instabilities in hybrid BOD was reported by us. The employed set up is shown in Fig. 1.

Integration of congestion pricing and intertemporal preference rate in social welfare function

Assessing social benefits in transport policy implementation has been studied by many researchers using theoretical or empirical measures. However, few of them measure social benefit using different discount rates including the inter-temporal preferences rate of users, the private investment discount rate and the inter-temporal preferences rate of the government. In general, the social discount rate used is the same for all social actors. Therefore, this paper aims to assess a new method by integrating different types of discount rate belonging to different social actors in order to measure the real benefits of each actor in the short, medium and long term. A dynamic simulation is provided by a strategic Land-Use and Transport Interaction (LUTI) model. The method is tested by optimizing a cordon toll scheme in Madrid considering socio- economic efficiency and environmental criteria. Based on the modified social welfare function (WF), the effects on the measure of social benefits are estimated and compared with the classical WF results as well. The results of this research could be a key issue to understanding the relationship between transport system policies and social actors' benefits distribution in a metropolitan context. The results show that the use of more suitable discount rates for each social actor had an effect on the selection and definition of optimal strategy of congestion pricing. The usefulness of the measure of congestion toll declines more quickly overtime.

Integration of congestion pricing and intertemporal preferences rate integration in social welfare function

Many researchers have used theoretical or empirical measures to assess social benefits in transport policy implementation. However, few have measured social benefits by using discount rates, including the intertemporal preference rate of users, the private investment discount rate, and the intertemporal preference rate of the government. In general, the social discount rate used is the same for all social actors. This paper aims to assess a new method by integrating different types of discount rates belonging to different social actors to measure the real benefits of each actor in the short term, medium term, and long term. A dynamic simulation is provided by a strategic land use and transport interaction model. The method was tested by optimizing a cordon toll scheme in Madrid, Spain. Socioeconomic efficiency and environmental criteria were considered. On the basis of the modified social welfare function, the effects on the measure of social benefits were estimated and compared with the classical welfare function measures. The results show that the use of more suitable discount rates for each social actor had an effect on the selection and definition of optimal strategy of congestion pricing. The usefulness of the measure of congestion toll declines more quickly over time. This result could be the key to understanding the relationship between transport system policies and the distribution of social actors? benefits in a metropolitan context.

A framework for the analysis and optimization of delay in multiview video coding schemes

Esta tesis presenta un novedoso marco de referencia para el análisis y optimización del retardo de codificación y descodificación para vídeo multivista. El objetivo de este marco de referencia es proporcionar una metodología sistemática para el análisis del retardo en codificadores y descodificadores multivista y herramientas útiles en el diseño de codificadores/descodificadores para aplicaciones con requisitos de bajo retardo. El marco de referencia propuesto caracteriza primero los elementos que tienen influencia en el comportamiento del retardo: i) la estructura de predicción multivista, ii) el modelo hardware del codificador/descodificador y iii) los tiempos de proceso de cuadro. En segundo lugar, proporciona algoritmos para el cálculo del retardo de codificación/ descodificación de cualquier estructura arbitraria de predicción multivista. El núcleo de este marco de referencia consiste en una metodología para el análisis del retardo de codificación/descodificación multivista que es independiente de la arquitectura hardware del codificador/descodificador, completada con un conjunto de modelos que particularizan este análisis del retardo con las características de la arquitectura hardware del codificador/descodificador. Entre estos modelos, aquellos basados en teoría de grafos adquieren especial relevancia debido a su capacidad de desacoplar la influencia de los diferentes elementos en el comportamiento del retardo en el codificador/ descodificador, mediante una abstracción de su capacidad de proceso. Para revelar las posibles aplicaciones de este marco de referencia, esta tesis presenta algunos ejemplos de su utilización en problemas de diseño que afectan a codificadores y descodificadores multivista. Este escenario de aplicación cubre los siguientes casos: estrategias para el diseño de estructuras de predicción que tengan en consideración requisitos de retardo además del comportamiento tasa-distorsión; diseño del número de procesadores y análisis de los requisitos de velocidad de proceso en codificadores/ descodificadores multivista dado un retardo objetivo; y el análisis comparativo del comportamiento del retardo en codificadores multivista con diferentes capacidades de proceso e implementaciones hardware. ABSTRACT This thesis presents a novel framework for the analysis and optimization of the encoding and decoding delay for multiview video. The objective of this framework is to provide a systematic methodology for the analysis of the delay in multiview encoders and decoders and useful tools in the design of multiview encoders/decoders for applications with low delay requirements. The proposed framework characterizes firstly the elements that have an influence in the delay performance: i) the multiview prediction structure ii) the hardware model of the encoder/decoder and iii) frame processing times. Secondly, it provides algorithms for the computation of the encoding/decoding delay of any arbitrary multiview prediction structure. The core of this framework consists in a methodology for the analysis of the multiview encoding/decoding delay that is independent of the hardware architecture of the encoder/decoder, which is completed with a set of models that particularize this delay analysis with the characteristics of the hardware architecture of the encoder/decoder. Among these models, the ones based in graph theory acquire special relevance due to their capacity to detach the influence of the different elements in the delay performance of the encoder/decoder, by means of an abstraction of its processing capacity. To reveal possible applications of this framework, this thesis presents some examples of its utilization in design problems that affect multiview encoders and decoders. This application scenario covers the following cases: strategies for the design of prediction structures that take into consideration delay requirements in addition to the rate-distortion performance; design of number of processors and analysis of processor speed requirements in multiview encoders/decoders given a target delay; and comparative analysis of the encoding delay performance of multiview encoders with different processing capabilities and hardware implementations.

A Modified Positive Velocity and Position Feedback scheme with delay compensation for improved nanopositioning performance

Acknowledgments This paper was sponsored by the Spanish FPU12/00984 Program (Ministerio de Educacion, Cultura y Deporte). It was also sponsored by the Spanish Government Research Program with the Project DPI2012-37062-CO2-01 (Ministerio de Economia y Competitividad) and by the European Social Fund.

Continuous and lurching traveling pulses in neuronal networks with delay and spatially decaying connectivity

Propagation of discharges in cortical and thalamic systems, which is used as a probe for examining network circuitry, is studied by constructing a one-dimensional model of integrate-and-fire neurons that are coupled by excitatory synapses with delay. Each neuron fires only one spike. The velocity and stability of propagating continuous pulses are calculated analytically. Above a certain critical value of the constant delay, these pulses lose stability. Instead, lurching pulses propagate with discontinuous and periodic spatio-temporal characteristics. The parameter regime for which lurching occurs is strongly affected by the footprint (connectivity) shape; bistability may occur with a square footprint shape but not with an exponential footprint shape. For strong synaptic coupling, the velocity of both continuous and lurching pulses increases logarithmically with the synaptic coupling strength gsyn for an exponential footprint shape, and it is bounded for a step footprint shape. We conclude that the differences in velocity and shape between the front of thalamic spindle waves in vitro and cortical paroxysmal discharges stem from their different effective delay; in thalamic networks, large effective delay between inhibitory neurons arises from their effective interaction via the excitatory cells which display postinhibitory rebound.

Residual delay maps unveil global patterns of atmospheric nonlinearity and produce improved local forecasts

We use residual-delay maps of observational field data for barometric pressure to demonstrate the structure of latitudinal gradients in nonlinearity in the atmosphere. Nonlinearity is weak and largely lacking in tropical and subtropical sites and increases rapidly into the temperate regions where the time series also appear to be much noisier. The degree of nonlinearity closely follows the meridional variation of midlatitude storm track frequency. We extract the specific functional form of this nonlinearity, a V shape in the lagged residuals that appears to be a basic feature of midlatitude synoptic weather systems associated with frontal passages. We present evidence that this form arises from the relative time scales of high-pressure versus low-pressure events. Finally, we show that this nonlinear feature is weaker in a well regarded numerical forecast model (European Centre for Medium-Range Forecasts) because small-scale temporal and spatial variation is smoothed out in the grided inputs. This is significant, in that it allows us to demonstrate how application of statistical corrections based on the residual-delay map may provide marked increases in local forecast accuracy, especially for severe weather systems.