Electronic excitation of transition metal nitrides by light ions with keV energies

We investigated the specific electronic energy deposition by protons and He ions with keV energies in different transition metal nitrides of technological interest. Data were obtained from two different time-of-flight ion scattering setups and show excellent agreement. For protons interacting with light nitrides, i.e. TiN, VN and CrN, very similar stopping cross sections per atom were found, which coincide with literature data of N2 gas for primary energies <= 25 keV. In case of the chemically rather similar nitrides with metal constituents from the 5th and 6th period, i.e. ZrN and HfN, the electronic stopping cross sections were measured to exceed what has been observed for molecular N2 gas. For He ions, electronic energy loss in all nitrides was found to be significantly higher compared to the equivalent data of N2 gas. Additionally, deviations from velocity proportionality of the observed specific electronic energy loss are observed. A comparison with predictions from density functional theory for protons and He ions yields a high apparent efficiency of electronic excitations of the target for the latter projectile. These findings are considered to indicate the contributions of additional mechanisms besides electron hole pair excitations, such as electron capture and loss processes of the projectile or promotion of target electrons in atomic collisions

Anisotropic electrical resistivity during annealing of oriented columnar titanium films

International audienceWe report on the evolution of anisotropic electrical resistivity versus temperature of titanium thin films. An oriented titanium film (1 μm thick) is sputter deposited by GLancing Angle Deposition (GLAD) using an incident angle α = 80° of the particle flux. Two parallel Ti electrodes cover this GLAD film. We measure the components of the conductivity tensor by the van der Pauw method during an annealing treatment in air ranging from 298 to 873 K. The average DC electrical resistivity ρ changes from 6.03×10-6 to more than 2.40×10-1 Ωm with the increasing temperature. The anisotropy ratio is A = 1.39 before annealing and reaches 12.4 for the highest temperatures. This enhanced anisotropy is interpreted assuming the oxidation of the porous GLAD titanium film

Individual Exposure to NO2 in Relation to Spatial and Temporal Exposure Indices in Stockholm, Sweden: The INDEX Study

Epidemiology studies of health effects from air pollution, as well as impact assessments, typically rely on ambient monitoring data or modelled residential levels. The relationship between these and personal exposure is not clear. To investigate personal exposure to NO2 and its relationship with other exposure metrics and time-activity patterns in a randomly selected sample of healthy working adults (20–59 years) living and working in Stockholm. Personal exposure to NO2 was measured with diffusive samplers in sample of 247 individuals. The 7-day average personal exposure was 14.3 µg/m3 and 12.5 µg/m3 for the study population and the inhabitants of Stockholm County, respectively. The personal exposure was significantly lower than the urban background level (20.3 µg/m3). In the univariate analyses the most influential determinants of individual exposure were long-term high-resolution dispersion-modelled levels of NO2 outdoors at home and work, and concurrent NO2 levels measured at a rural location, difference between those measured at an urban background and rural location and difference between those measured in busy street and at an urban background location, explaining 20, 16, 1, 2 and 4% (R2) of the 7-day personal NO2 variation, respectively. A regression model including these variables explained 38% of the variation in personal NO2 exposure. We found a small improvement by adding time-activity variables to the latter model (R2 = 0.44). The results adds credibility primarily to long-term epidemiology studies that utilise long-term indices of NO2 exposure at home or work, but also indicates that such studies may still suffer from exposure misclassification and dilution of any true effects. In contrast, urban background levels of NO2 are poorly related to individual exposure

Auxilin is a novel susceptibility gene for congenital heart block which directly impacts fetal heart function

Objective: Neonatal lupus erythematosus (NLE) may develop after transplacental transfer of maternal autoantibodies with cardiac manifestations (congenital heart block, CHB) including atrioventricular block, atrial and ventricular arrhythmias, and cardiomyopathies. The association with anti-Ro/SSA antibodies is well established, but a recurrence rate of only 12%–16% despite persisting maternal autoantibodies suggests that additional factors are required for CHB development. Here, we identify fetal genetic variants conferring risk of CHB and elucidate their effects on cardiac function. Methods: A genome-wide association study was performed in families with at least one case of CHB. Gene expression was analysed by microarrays, RNA sequencing and PCR and protein expression by western blot, immunohistochemistry, immunofluorescence and flow cytometry. Calcium regulation and connectivity were analysed in primary cardiomyocytes and cells induced from pleuripotent stem cells. Fetal heart performance was analysed by Doppler/echocardiography. Results: We identified DNAJC6 as a novel fetal susceptibility gene, with decreased cardiac expression of DNAJC6 associated with the disease risk genotype. We further demonstrate that fetal cardiomyocytes deficient in auxilin, the protein encoded by DNAJC6, have abnormal connectivity and Ca2+ homoeostasis in culture, as well as decreased cell surface expression of the Cav1.3 calcium channel. Doppler echocardiography of auxilin-deficient fetal mice revealed cardiac NLE abnormalities in utero, including abnormal heart rhythm with atrial and ventricular ectopias, as well as a prolonged atrioventricular time intervals. Conclusions: Our study identifies auxilin as the first genetic susceptibility factor in NLE modulating cardiac function, opening new avenues for the development of screening and therapeutic strategies in CHB.publishedVersio

Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P &lt; 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10-6, 1.7 × 10-9, 3.5 × 10-12 and 1.0 × 10-4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes

Beyond the Global Brain Differences:Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

BACKGROUND: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and globalbrain differences compared with noncarriers. However, interpreting regional differences is challenging if a globaldifference drives the regional brain differences. Intraindividual variability measures can be used to test for regionaldifferences beyond global differences in brain structure.METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n =30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matchednoncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual’sregional difference and global difference, were used to test for regional differences that diverge from the globaldifference.RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differedmore than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thicknessin regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal andsomatosensory cortex differed more than the global difference in cortical thickness.CONCLUSIONS: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distaland 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distaland 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanismsinvolved in altered neurodevelopment

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease