Angular distribution of N-doped carbon nanotubes in alumina membrane channels : A high-energy X-ray diffraction study

An alignment study of multi-wall N-doped carbon nanotubes prepared by a template pyrolytic carbon deposition method inside channels of an alumina membrane has been performed using high-energy X-ray diffraction on the ID15B beamline at the European Synchrotron Radiation Facility (ESRF, Grenoble). The two-dimensional diffraction pattern of the deposited carbon nanotubes, recorded directly, within the alumina membrane, using an image plate detector, exhibits two non-continuous arcs corresponding to the 002 graphitic reflection. The following values of the angle between the axis of the carbon nanotubes lying along the membrane channels and the incident beam were taken for five positions: 0±, 30±, 45±, 60± and 90±. The anisotropic scattering distribution of the two-dimensional patterns indicates an orientational alignment of the nanotubes. The one-dimensional intensity patterns obtained by scanning around the circumference of the (0 0 2) ring have allowed an estimation of the angular distribution of the nanotubes axes

Response of CsI(Tl) scintillators over a large range in energy and atomic number of ions (Part I): recombination and delta -- electrons

A simple formalism describing the light response of CsI(Tl) to heavy ions, which quantifies the luminescence and the quenching in terms of the competition between radiative transitions following the carrier trapping at the Tl activator sites and the electron-hole recombination, is proposed. The effect of the delta rays on the scintillation efficiency is for the first time quantitatively included in a fully consistent way. The light output expression depends on four parameters determined by a procedure of global fit to experimental data.Comment: 28 pages, 6 figures, submitted to Nucl. Inst. Meth.

Controlling the dissociation of ligands from the adenosine A(2A) receptor through modulation of salt bridge strength

Controlling the Dissociation of Ligands from the Adenosine A2A Receptor through Modulation of Salt Bridge StrengthElena Segala, Dong Guo, Robert K. Y. Cheng, Andrea Bortolato, Francesca Deflorian, Andrew S. Doré, James C. Errey, Laura H. Heitman, Adriaan P. IJzerman, Fiona H. Marshall, and Robert M. CookeHeptares Therapeutics Ltd, Biopark Broadwater Road, Welwyn Garden City AL7 3AX, U.K.Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research (LACDR), Leiden University P.O. Box 9502, 2300 RA Leiden, the NetherlandsAbstractThe association and dissociation kinetics of ligands binding to proteins vary considerably, but the mechanisms behind this variability are poorly understood, limiting their utilization for drug discovery. This is particularly so for G protein-coupled receptors (GPCRs) where high resolution structural information is only beginning to emerge. Engineering the human A2A adenosine receptor has allowed structures to be solved in complex with the reference compound ZM241385 and four related ligands at high resolution. Differences between the structures are limited, with the most pronounced being the interaction of each ligand with a salt bridge on the extracellular side of the receptor. Mutagenesis experiments confirm the role of this salt bridge in controlling the dissociation kinetics of the ligands from the receptor, while molecular dynamics simulations demonstrate the ability of ligands to modulate salt bridge stability. These results shed light on a structural determinant of ligand dissociation kinetics and identify a means by which this property may be optimized.Medicinal Chemistr

Multifragmentation process for different mass asymmetry in the entrance channel around the Fermi energy

The influence of the entrance channel asymmetry upon the fragmentation process is addressed by studying heavy-ion induced reactions around the Fermi energy. The data have been recorded with the INDRA 4pi array. An event selection method called the Principal Component Analysis is presented and discussed. It is applied for the selection of central events and furthermore to multifragmentation of single source events. The selected subsets of data are compared to the Statistical Multifragmentation Model (SMM) to check the equilibrium hypothesis and get the source characteristics. Experimental comparisons show the evidence of a decoupling between thermal and compresional (radial flow) degrees of freedom in such nuclear systems.Comment: 28 pages, 15 figures, article sumitted to Nuclear Physics

Towards standards for human fecal sample processing in metagenomic studies

Technical variation in metagenomic analysis must be minimized to confidently assess the contributions of microbiota to human health. Here we tested 21 representative DNA extraction protocols on the same fecal samples and quantified differences in observed microbial community composition. We compared them with differences due to library preparation and sample storage, which we contrasted with observed biological variation within the same specimen or within an individual over time. We found that DNA extraction had the largest effect on the outcome of metagenomic analysis. To rank DNA extraction protocols, we considered resulting DNA quantity and quality, and we ascertained biases in estimates of community diversity and the ratio between Gram-positive and Gram-negative bacteria. We recommend a standardized DNA extraction method for human fecal samples, for which transferability across labs was established and which was further benchmarked using a mock community of known composition. Its adoption will improve comparability of human gut microbiome studies and facilitate meta-analyses

Age at symptom onset and death and disease duration in genetic frontotemporal dementia : an international retrospective cohort study

Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. Methods: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. Findings: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49\ub75 years (SD 10\ub70; onset) and 58\ub75 years (11\ub73; death) in the MAPT group, 58\ub72 years (9\ub78; onset) and 65\ub73 years (10\ub79; death) in the C9orf72 group, and 61\ub73 years (8\ub78; onset) and 68\ub78 years (9\ub77; death) in the GRN group. Mean disease duration was 6\ub74 years (SD 4\ub79) in the C9orf72 group, 7\ub71 years (3\ub79) in the GRN group, and 9\ub73 years (6\ub74) in the MAPT group. Individual age at onset and at death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0\ub745 between individual and parental age at onset, r=0\ub763 between individual and mean family age at onset, r=0\ub758 between individual and parental age at death, and r=0\ub769 between individual and mean family age at death) than in either the C9orf72 group (r=0\ub732 individual and parental age at onset, r=0\ub736 individual and mean family age at onset, r=0\ub738 individual and parental age at death, and r=0\ub740 individual and mean family age at death) or the GRN group (r=0\ub722 individual and parental age at onset, r=0\ub718 individual and mean family age at onset, r=0\ub722 individual and parental age at death, and r=0\ub732 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35\u201362, for age at onset; 61%, 47\u201373, for age at death), and even more by family membership (66%, 56\u201375, for age at onset; 74%, 65\u201382, for age at death). In the GRN group, only 2% (0\u201310) of the variability of age at onset and 9% (3\u201321) of that of age of death was explained by the specific mutation, whereas 14% (9\u201322) of the variability of age at onset and 20% (12\u201330) of that of age at death was explained by family membership. In the C9orf72 group, family membership explained 17% (11\u201326) of the variability of age at onset and 19% (12\u201329) of that of age at death. Interpretation: Our study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership. Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, our study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates. Funding: UK Medical Research Council, National Institute for Health Research, and Alzheimer's Society

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Independence of fragment charge distributions of the size of heavy multifragmenting sources

International audienceCharged product multiplicities and Z distributions were measured for single multifragmenting sources produced in collisions between Full-size image (<1 K) and Full-size image (<1 K) at the same available energy per nucleon. Z distributions are found identical for both reactions while fragment multiplicities scale as the charge of the total systems. A complete dynamical simulation, in which multifragmentation originates in the spinodal decomposition of a finite piece of nuclear matter resulting from an incomplete fusion of projectile and target, well accounts for this experimental observation

Change and continuity in Japanese compensation practices: the case of occupational pensions since the early 2000s

This article analyses changes in the provision of Japanese occupational pensions since the early 2000s. It shows how Japanese companies have followed strategies of cost and risk reduction by creating multi-layered benefit systems that offer a combination of defined benefit (DB) and defined contribution (DC) plans whose benefits are becoming increasingly performance-oriented. Analysing the reasons behind the resilience of DB schemes in Japan, the article concludes that enterprise union behaviour has had less influence than regulatory issues and continued corporate commitment to long-standing employment practices for regular workers. These findings highlight the embeddedness of Japanese employment practices in their institutional context