Combined neutron reflectometry and rheology

We have combined neutron reflectometry with rheology in order to investigate the solid boundary of liquids and polymers under shear deformation. Our approach allows one to apply a controlled stress to a material while resolving the structural arrangements on the sub nanometer length scale with neutron reflectivity, off-specular and small angle scattering at the same time. The specularly reflected neutron intensity of a 20 % by weight solution of the Pluronic F127 in deuterated water is evaluated. We find pronounced changes in the near interface structure under applied deformation for surfaces with different surface energies, which are correlated with changes in the storage and loss modulus

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Understanding Domestic Saving in Latin America and the Caribbean: The Case of Mexico

This study addresses why Mexico continues to show below-average economic growth rates in spite of displaying systematically higher domestic savings than other countries in the region. Using the wealth of relevant databases available for the country, the paper finds that a possible explanation is that household savings account for a majority of domestic savings, and that the main instrument used for savings is durable goods, which implies that savings are not directly injected into the financial system for fueling productive investment. The construction of a synthetic panel from household survey data shows that household savings in Mexico have a clear age-increasing trend and have been growing across generations during the past 30 years; it is thus probable that rates will increase in years to come. However, if those savings continue to elude the financial system, their influence on economic growth may remain limited

Bi-allelic loss-of-function CACNA1B mutations in progressive epilepsy-dyskinesia

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment

Depletion at solid/liquid interfaces: Flowing hexadecane on functionalized surfaces

We present a neutron reflectivity study on interfaces in contact with flowing hexadecane, which is known to exhibit surface slip on functionalized solid surfaces. The single crystalline silicon substrates were either chemically cleaned Si(100) or Si(100) coated by octadecyl-trichlorosilane (OTS), which resulted in different interfacial energies. The liquid was sheared in situ and changes in reflectivity profiles were compared to the static case. For the OTS surface, the temperature dependence was also recorded. For both types of interfaces, density depletion of the liquid at the interface was observed. In the case of the bare Si substrate, shear load altered the structure of the depletion layer, whereas for the OTS covered surface no effect of shear was observed. Possible links between the depletion layer and surface slip are discussed. The results show that, in contrast to water, for hexadecane the enhancement of the depletion layer with temperature and interfacial energy reduces the amount of slip. Thus a density depletion cannot be the origin of surface slip in this system

Depletion at solid/liquid interfaces: Flowing hexadecane on functionalized surfaces

We present a neutron reflectivity study on interfaces in contact with flowing hexadecane, which is known to exhibit surface slip on functionalized solid surfaces. The single crystalline silicon substrates were either chemically cleaned Si(100) or Si(100) coated by octadecyl-trichlorosilane (OTS), which resulted in different interfacial energies. The liquid was sheared in situ and changes in reflectivity profiles were compared to the static case. For the OTS surface, the temperature dependence was also recorded. For both types of interfaces, density depletion of the liquid at the interface was observed. In the case of the bare Si substrate, shear load altered the structure of the depletion layer, whereas for the OTS covered surface no effect of shear was observed. Possible links between the depletion layer and surface slip are discussed. The results show that, in contrast to water, for hexadecane the enhancement of the depletion layer with temperature and interfacial energy reduces the amount of slip. Thus a density depletion cannot be the origin of surface slip in this system

Supplementary Figures 1-5, Supplementary Tables 1-3, Full List of Authors and Affiliations from Saliva-Derived DNA Performs Well in Large-Scale, High-Density Single-Nucleotide Polymorphism Microarray Studies

Supplementary Figures 1-5, Supplementary Tables 1-3, Full List of Authors and Affiliations from Saliva-Derived DNA Performs Well in Large-Scale, High-Density Single-Nucleotide Polymorphism Microarray Studie

Identity-by-descent mapping to detect rare variants conferring susceptibility to Multiple Sclerosis

Genome-wide association studies (GWAS) have identified around 60 common variants associated with multiple sclerosis (MS), but these loci only explain a fraction of the heritability of MS. Some missing heritability may be caused by rare variants that have been suggested to play an important role in the aetiology of complex diseases such as MS. However current genetic and statistical methods for detecting rare variants are expensive and time consuming. 'Population-based linkage analysis' (PBLA) or so called identity-by-descent (IBD) mapping is a novel way to detect rare variants in extant GWAS datasets. We employed BEAGLE fastIBD to search for rare MS variants utilising IBD mapping in a large GWAS dataset of 3,543 cases and 5,898 controls. We identified a genome-wide significant linkage signal on chromosome 19 (LOD = 4.65; p = 1.9×10). Network analysis of cases and controls sharing haplotypes on chromosome 19 further strengthened the association as there are more large networks of cases sharing haplotypes than controls. This linkage region includes a cluster of zinc finger genes of unknown function. Analysis of genome wide transcriptome data suggests that genes in this zinc finger cluster may be involved in very early developmental regulation of the CNS. Our study also indicates that BEAGLE fastIBD allowed identification of rare variants in large unrelated population with moderate computational intensity. Even with the development of whole-genome sequencing, IBD mapping still may be a promising way to narrow down the region of interest for sequencing priority