Whole Exome Sequencing Identifies a Heterozygous Variant in the Cav1.3 Gene CACNA1D Associated with Familial Sinus Node Dysfunction and Focal Idiopathic Epilepsy

Cav1.3 voltage-gated L-type calcium channels (LTCCs) are involved in cardiac pacemaking, hearing and hormone secretion, but are also expressed postsynaptically in neurons. So far, homozygous loss of function mutations in CACNA1D encoding the Cav1.3 α₁-subunit are described in congenital sinus node dysfunction and deafness. In addition, germline mutations in CACNA1D have been linked to neurodevelopmental syndromes including epileptic seizures, autism, intellectual disability and primary hyperaldosteronism. Here, a three-generation family with a syndromal phenotype of sinus node dysfunction, idiopathic epilepsy and attention deficit hyperactivity disorder (ADHD) is investigated. Whole genome sequencing and functional heterologous expression studies were used to identify the disease-causing mechanisms in this novel syndromal disorder. We identified a heterozygous non-synonymous variant (p.Arg930His) in the CACNA1D gene that cosegregated with the combined clinical phenotype in an autosomal dominant manner. Functional heterologous expression studies showed that the CACNA1D variant induces isoform-specific alterations of Cav1.3 channel gating: a gain of ion channel function was observed in the brain-specific short CACNA1D isoform (Cav1.3_S), whereas a loss of ion channel function was seen in the long (Cav1.3_L) isoform. The combined gain-of-function (GOF) and loss-of-function (LOF) induced by the R930H variant are likely to be associated with the rare combined clinical and syndromal phenotypes in the family. The GOF in the Cav1.3_S variant with high neuronal expression is likely to result in epilepsy, whereas the LOF in the long Cav1.3_L variant results in sinus node dysfunction.     

The Chloroplast Import Receptor Toc90 Partially Restores the Accumulation of Toc159 Client Proteins in the Arabidopsis thaliana ppi2 Mutant

Successful import of hundreds of nucleus-encoded proteins is essential for chloroplast biogenesis. The import of cytosolic precursor proteins relies on the Toc- (translocon at the outer chloroplast membrane) and Tic- (translocon at the inner chloroplast membrane) complexes. In Arabidopsis thaliana,precursor recognition is mainly mediated by outer membrane receptors belonging to two gene families: Toc34/33 and Toc159/132/120/90. The role in import and precursor selectivity of these receptors has been intensively studied,but the function of Toc90 still remains unclear. Here,we report the ability of Toc90 to support the import of Toc159 client proteins. We show that the overexpression of Toc90 partially complements the albino knockout of Toc159 and restores photoautotrophic growth. Several lines of evidence including proteome profiling demonstrate the import and accumulation of proteins essential for chloroplast biogenesis and functionality.     

Non-invasive 3-D patient registration for image-guided skull base surgery

Image-guided, computer-assisted surgery systems require a common reference between the preoperative image data and the corresponding patient pathology. Therefore, the problem of an accurate and reliable 3-D patient registration and referencing has to be solved. Considering that during image data acquisition patient misalignment and movement can arise in three dimensions, an automatic image registration method must be based on a three-dimensional approach. The method presented in this paper provides accurate 3-D patient registration for correction of these movement errors during data acquisition and active patient referencing to update the position of the head during surgery. Experimental data concerning the accuracy of repeated positionings of our patient registration and reference system demonstrated a high degree of accuracy with mean spatial errors of 0.82 mm ± 0.31 mm in a plastic skull and 1.56 ± 0.76 mm in patients, respectively. Results suggest that non-invasive 3-D patient registration for image-guided surgery may be a precise and useful method for computer-assisted identification of anatomical structures.     

European classes for the reaction to fire performance of wood products

The new classification system for the reaction to fire performance of building products in Europe has been applied to five different product families of wood: Wood-based panels, Structural timber, Glued laminated timber, Solid wood panelling and cladding and Wood flooring as being ‘products with known and stable fire performance’. The European classification system includes two sub-systems, one main system for all construction products except floorings and the other for flooring products. Wood properties such as density, thickness, joints and types of end use application including different substrates have been studied thoroughly and are included in the classification. Most wood products fall in classes D-s2, d0 or D_fl-s1 (for floorings). Testing has been performed according to EN 13823 (2002) SBI- Single Burning Item test, EN ISO 9239-1 (2002) Radiant panel test, and EN ISO 11925-2 (2002) Small flame test. In all, more than one hundred wood products in different end use applications have been studied. Clear relationships between the main Euroclass fire performance parameters and product parameters (such as density and thickness) have been demonstrated. Tables with reaction to fire classification of different wood products and end use applications have been developed, approved by the European Commission and published in their Official Journal. This procedure is ongoing with further official decisions to be published.     

Diminished cooperativeness of psychopaths in a prisoner's dilemma game yields higher rewards.

Maladaptive social behavior is one of the defining characteristics of psychopathic personality disorder. Nevertheless, maladaptive social behavior has only rarely been observed among psychopaths in experimentally controlled situations. The authors assessed the behavior of criminal psychopaths from high-security psychiatric hospitals in a computer simulation of a social dilemma situation. The psychopaths showed a markedly higher proneness to competitive (i.e., noncooperative) behavior than did healthy adults from the general population. The odds ratio between defection and being a psychopath was estimated at 7.86 in the sample. The probability to choose selfish instead of cooperative behavior was significantly linked to the following subscales of the Psychopathy Personality Inventory-Revised (S. O. Lilienfeld & M. R. Widows, 2005): rebellious nonconformity, Machiavellian egocentricity, and the total score. On average, the psychopathic participants accumulated higher gain and more strongly exploited their counterpart than did the healthy participants. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

CD-R产品检测:高的品质来自成熟的工艺

根据最新的市场调查显示：在2004年，CD-R产品的市场需求将小于之前的2年。这源于在2003年期间，CD-R产品的生产能力以非常迅速的速度同市场的需求之间达到平衡。特别是在印度、中东和远东地区，新的风险企业家在偶然情况下发现可记录光盘领域的市场需求，从而大量进入来填补这个空白。     

Smoke data from the Cone Calorimeter for comparison with the room fire test

Smoke production in the full–scale room fire test ISO 9705 (Commonly referred to as the Room Corner Test) and in the Cone Calorimeter ISO 5660 has been analysed for three sets of building products comprising a total of 28 products. The smoke production may be critical for the fire classification of surface products since some products produce large amounts of smoke in the room fire test even if they do not reach flashover within 20 min. Several smoke parameters in the Cone Calorimeter and the room fire test have been analysed. Good correlations have been obtained when the products are divided into two groups: products with more than 10 min to flashover in the room fire test and those with less than 10 min. These two time categories correspond to the two heat output levels in the room fire test: 100 kW for the first 10 min and then 300 kW up to 20 min. For products with more than 10 min to flashover the average rate of smoke production and the total smoke production seem to be useful parameters for predictions of smoke release in the room fire test. Both parameters have good correlations between data from the Cone Calorimeter and the room fire test. For products with less than 10 min to flashover no parameter seems to give useful predictions. For all products evaluated together, the correlations are not so good, but the same regression lines as for products with more than 10 min might be used as a first rough estimate. In this case the total smoke production in the Cone Calorimeter could be used to estimate the total smoke production in the room fire test for different building products, independent of their estimated time to flashover. It is suggested that the average rate of smoke production and the total smoke production from the Cone Calorimeter is reported in addition to the mass-based specific extinction area. This will be helpful in predicting smoke release in the room fire test and will also make the data on smoke release analogous to those on heat release.     

Rate of heat release by oxygen consumption in an open test arrangement

Equipment has been developed for measuring the rate of heat release from building materials in an open test arrangement. The method is based on an oxygen consumption technique. A vertical sample is placed under an open hood in which the combustion gases and a certain amount of air are collected. The decrease in oxygen concentration and the mass flow of the gases are measured in the exhaust duct. The rate of heat release is then calculated. The equipment has been calibrated with good agreement between input and measured effects. The total response time for the system is 10s. The method has been used for testing building materials at radiation intensities up to 5W Cm^?2. It is able to distinguish between different board materials, and the repeatability is good, The paper describes the equipment, including the weighing of a burning sample and the selection of test condition. Smoke and gas analysis can be added when desirable. Some test results with building materials are also presented.