Functional Characterization of Two Novel Mutations in SCN5A Associated with Brugada Syndrome Identified in Italian Patients

Background. Brugada syndrome (BrS) is an autosomal dominantly inherited cardiac disease characterized by “coved type” ST-segment elevation in the right precordial leads, high susceptibility to ventricular arrhythmia and a family history of sudden cardiac death. The SCN5A gene, encoding for the cardiac voltage-gated sodium channel Nav1.5, accounts for ~20–30% of BrS cases and is considered clinically relevant. Methods. Here, we describe the clinical findings of two Italian families affected by BrS and provide the functional characterization of two novel SCN5A mutations, the missense variant Pro1310Leu and the in-frame insertion Gly1687_Ile1688insGlyArg. Results. Despite being clinically different, both patients have a family history of sudden cardiac death and had history of arrhythmic events. The Pro1310Leu mutation significantly reduced peak sodium current density without affecting channel membrane localization. Changes in the gating properties of expressed Pro1310Leu channel likely account for the loss-of-function phenotype. On the other hand, Gly1687_Ile1688insGlyArg channel, identified in a female patient, yielded a nearly undetectable sodium current. Following mexiletine incubation, the Gly1687_Ile1688insGlyArg channel showed detectable, albeit very small, currents and biophysical properties similar to those of the Nav1.5 wild-type channel. Conclusions. Overall, our results suggest that the degree of loss-of-function shown by the two Nav1.5 mutant channels correlates with the aggressive clinical phenotype of the two probands. This genotype-phenotype correlation is fundamental to set out appropriate therapeutical intervention.     

High-pressure structural stability and elasticity of supercrystals self-assembled from nanocrystals

We report here combined quasi-hydrostatic high-pressure small-angle X-ray scattering (SAXS) and X-ray diffraction (XRD) studies on faceted 3D supercrystals (SCs) self-assembled from colloidal 7.0 nm spherical PbS nanocrystals (NCs). Diamond anvil cell (DAC) SAXS experiments in the pressure range from ambient to 12.5 GPa revealed nearly perfect structural stability of the SCs, with face-centered cubic organization of the NCs. Pressure-induced ordering (annealing effect) of the superstructure was observed. The ambient pressure bulk modulus of the SCs was calculated to be ～5 GPa for compression and ～14.5 GPa for decompression from fitting of Vinet and Birch-Murnaghan equations of state. XRD measurements revealed strong preferential crystallographic orientation of the NCs through all phase transformations to as high as 55 GPa without any indication of NC sintering. The first phase transition pressure of the NCs was found between 8.1 and 9.2 GPa and proceeds through homogeneous nucleation. Bulk modulus of PbS NCs was calculated to be ～51 GPa based on fitting to the equations of state (K(PbS,bulk) ～ 51-57 GPa). Closest surface-to-surface distance between the NCs in the SCs was calculated based on combined XRD and SAXS data, to reversibly tune from ～1.56 nm to ～0.9-0.92 nm and back to ～1.36 nm in the ambient-12.5 GPa-ambient pressure cycle. The bulk modulus of the ligand matrix was extrapolated to be ～2.2-2.95 GPa. These results show a general method of tuning NC interactions in packed nanoparticle solids.     

Gas phase synthesis and field emission properties of 3D aligned double walled carbon nanotube/anatase hybrid architectures

A 3D hybrid architecture composed of macroscopic, vertically aligned CNT blocks which are formed via a metal catalyzed CVD process followed by deposition of TiO(2) on the CNT side walls in nanocrystalline or amorphous form is presented. The morphology of the deposited TiO(2) can be tailored by the deposition method employed. Depositing TiO(2) from the gas phase by employing the organometallic precursor Ti[OCH(CH(3))(2)](4) leads to formation of nanocrystalline anatase or rutile particles with a dense coverage on the surface and within the 3D CNT scaffold. Phase pure TiO(2) (anatase) is formed between 500 and 700 °C, while higher temperatures resulted in rutile modification of TiO(2). Below 500 °C, TiO(2) forms an amorphous oxide layer. At higher temperatures such initially formed TiO(2) layers segregate into particles which tend to crystallize. In contrast, when generating TiO(2) by oxidation of Ti metal which is deposited by vaporization onto the 3D CNT block array, and subsequently oxidized in air or controlled O(2) atmosphere this leads to a porous layer with a particular nanostructure on top of the CNT blocks. First studies of the fabrication and field emission of the new 3D CNT/TiO(2) hybrid cathodes display good and stable FE characteristics with onset fields for current density of 1 μA cm(-2) of 1.7 to 1.9 V μm(-1), while the average field enhancement factor is in the range between 2000 and 2500 depending on the O(2) base pressure during the measurements.     

Seasonal pattern of mortality and relationships between mortality and temperature-humidity index in dairy cows

The 2 studies described investigated seasonal variations of mortality and temperature-humidity index (THI)-mortality relationships in dairy cows. Mortality data were extracted from the Italian Bovine Spongiform Encephalopathy databases, which contain records on cows older than 24 mo that died on a farm from all causes (98% of total records), were slaughtered in an emergency state, or were sent for normal slaughter but were sick in the preslaughter inspection (2% of total records). Both studies evaluated mortality data during a 6-yr period (2002 to 2007). The seasonal pattern study was conducted throughout Italy and was based on 320,120 deaths. An association between season and deaths was found for all 6 yr. Summer and spring were the seasons with the highest and lowest frequency of deaths (15,773.3 ± 2,861 and 11,619.3 ± 792.3), respectively, and within summer months, the number of deaths in July and August (5,435 ± 284 and 5,756 ± 676.2, respectively) was higher than in June (4,839 ± 344.8). The THI-mortality relationships study was carried out only for deaths (51,240) reported for the Lombardia and Emilia Romagna regions. For this study, the mortality databases were integrated with THI data, which were calculated by using data from 73 weather stations. Each farm where deaths were recorded was assigned the THI values (maximum and minimum) calculated at the closest weather station for each day the events (deaths) were reported. Analysis of data indicated that approximate THI values of 80 and 70 were the maximum and minimum THI, respectively, above which the number of deaths in dairy farms starts to increase. Maximum and minimum THI values of 87 and 77 were the upper critical THI above which the risk of death for dairy cows becomes maximum. This study defined quantitative relationships between mortality risk and THI in dairy cows and may help to provide emergency interventions and mitigation measures, which may ensure survival of dairy cows and reduce replacement costs associated with heat stress-related mortality.     

Estimate of European 129I releases supported by 129I analysis in an Alpine ice core

129I in the European environment originates predominantly from the industrial nuclear fuel reprocessing plants Sellafield (Great Britain), Marcoule, and La Hague (both France). While reliable data on 129I releases from La Hague exist for the whole period of operation, less is known about the contributions from Sellafield and Marcoule. For those periods where no data are available, i.e., for the first 16 years of the Sellafield operation and for the first 3 decades of the Marcoule operation, we estimated releases into the atmosphere of 118 GBq and 825 GBq, respectively. Hence, Marcoule was the major European source of airborne 129I, contributing about 45% to the total airborne 129I releases from all the European reprocessing facilities, until it was decommissioned in 1997. The estimated total emissions were compared with 129I deposition fluxes for the time period 1970-2002, obtained from the analysis of an ice core from Fiescherhorn glacier, Swiss Alps (46 degrees 33'N, 08 degrees 04'E; 3900 m asl). The temporal evolution of the 129I deposition agrees well with the total 129I releases into the atmosphere from the European reprocessing facilities and from atmospheric nuclear weapons tests, supporting our estimated release rates. However,the 129I concentrations and deposition fluxes at Fiescherhorn glacier were a factor of 6 lower than values obtained from the analysis of rainwater collected near Zurich (408 m asl) in Switzerland in the years 1994-97. This suggests a strong vertical concentration gradient of 129I, typical for water-soluble atmospheric trace species which are removed from the atmosphere in the course of days by precipitation scavenging, and must be taken into account if glaciers are used as an archive for a retrospective quantification of 129I deposition fluxes. In addition, the temporal evolution of the contribution of 129I re-emitted from the ocean's surface for the 129I inventory in the atmosphere was quantified for the first time. Although the annual amount of 129I released this way was very low until the early 1990s, it is similar to the airborne 129I releases from Sellafield and La Hague in the present time.     

Parole outcome as predicted from the CPI, the MMPI, and a Base Expectancy table.

Parole outcomes for 183 violators and 261 nonviolators (initial sample), and 130 violators and 165 nonviolators (cross-validating sample) were forecast from demographic and personality inventory data. The best single source of prediction in the cross-validating sample was a demographic Base Expectancy index. The best combination was given by an equation including this index, the socialization, selfcontrol, and communality scales of the CPI with positive weightings, and the social presence scale of the CPI with a negative weighting. Conceptual analysis of the equation from the CPI, MMPI, and CPI + MMPI revealed a clear dimension of psychological meaning, having significance for normal as well as for deviant behavior. (44 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multi-fidelity design of stiffened composite panel with a crack

Crack propagation is an important concern in the design of aircraft composite fuselage and wing panels. However, numerical simulation of crack propagation is computationally expensive. This work proposes combining high-fidelity analysis model with low-fidelity model to calculate the crack propagation constraint in the design optimization process. Correction response surfaces are employed to relate the high-fidelity models to the low-fidelity models. Four different forms of correction response surface methods are explored and their prediction capabilities are compared. The multi-fidelity approach is found to be more accurate than single-fidelity response surface method at the same computational cost.