Chaotic Diffusion on Periodic Orbits: The Perturbed Arnol'd Cat Map

Chaotic diffusion on periodic orbits (POs) is studied for the perturbed Arnol'd cat map on a cylinder, in a range of perturbation parameters corresponding to an extended structural-stability regime of the system on the torus. The diffusion coefficient is calculated using the following PO formulas: (a) The curvature expansion of the Ruelle zeta function. (b) The average of the PO winding-number squared, $w^{2}$, weighted by a stability factor. (c) The uniform (nonweighted) average of $w^{2}$. The results from formulas (a) and (b) agree very well with those obtained by standard methods, for all the perturbation parameters considered. Formula (c) gives reasonably accurate results for sufficiently small parameters corresponding also to cases of a considerably nonuniform hyperbolicity. This is due to {\em uniformity sum rules} satisfied by the PO Lyapunov eigenvalues at {\em fixed} $w$. These sum rules follow from general arguments and are supported by much numerical evidence.Comment: 6 Tables, 2 Figures (postscript); To appear in Physical Review

Atmospheric composition and thermodynamic retrievals from the ARIES airborne TIR-FTS system--Part 2: Validation and results from aircraft campaigns

This study validates trace gas and thermodynamic retrievals from nadir infrared spectroscopic measurements recorded by the UK Met Office Airborne Research Interferometer Evaluation System (ARIES) – a thermal infrared, Fourier transform spectrometer (TIR-FTS) on the UK Facility for Airborne Atmospheric Measurements (FAAM) BAe-146 aircraft.Trace-gas-concentration and thermodynamic profiles have been retrieved and validated for this study throughout the troposphere and planetary boundary layer (PBL) over a range of environmental variability using data from aircraft campaigns over and around London, the US Gulf Coast, and the Arctic Circle during the Clear air for London (ClearfLo), Joint Airborne IASI (Infrared Atmospheric Sounding Interferometer) Validation Experiment (JAIVEx), and Measurements, process studies, and Modelling (MAMM) aircraft campaigns, respectively. Vertically resolved retrievals of temperature and water vapour (H2O), and partial-column retrievals of methane (CH4), carbon monoxide (CO), and ozone (O3) (over both land and sea) were compared to corresponding measurements from high-precision in situ analysers and dropsondes operated on the FAAM aircraft. Average degrees of freedom for signal (DOFS) over a 0–9 km column range were found to be 4.97, 3.11, 0.91, 1.10, and 1.62 for temperature, H2O, CH4, CO, and O3, respectively, when retrieved on 10 vertical levels. Partial-column mean biases (and bias standard error) between the surface and ~ 9 km, when averaged across all flight campaigns, were found to be −0.7(±0.3) K, −479(±56) ppm, −11(±2) ppb, −3.3(±1.0) ppb, and +3.5(±1.0) ppb, respectively, whilst the typical a posteriori (total) uncertainties for individually retrieved profiles were 0.4, 9.5, 5.0, 21.2, and 15.0 %, respectively.Averaging kernels (AKs) derived for progressively lower altitudes show improving sensitivity to lower atmospheric layers when flying at lower altitudes. Temperature and H2O display significant vertically resolved sensitivity throughout the column, whilst trace gases are usefully retrieved only as partial-column quantities, with maximal sensitivity for trace gases other than H2O within a layer 1 and 2 km below the aircraft. This study demonstrates the valuable atmospheric composition information content that can be obtained by ARIES nadir TIR remote sensing for atmospheric process studies

The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism

Although multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P≤2.40E-09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P≤3.83E-23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P≤4.16E-04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Altres ajuts: Max Planck Society (Germany).The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes