Free Water in White Matter Differentiates Mci and ad From Control Subjects

Recent evidence shows that neuroinflammation plays a role in many neurological diseases including mild cognitive impairment (MCI) and Alzheimer\u27s disease (AD), and that free water (FW) modeling from clinically acquired diffusion MRI (DTI-like acquisitions) can be sensitive to this phenomenon. This FW index measures the fraction of the diffusion signal explained by isotropically unconstrained water, as estimated from a bi-tensor model. In this study, we developed a simple but powerful whole-brain FW measure designed for easy translation to clinical settings and potential use as a priori outcome measure in clinical trials. These simple FW measures use a safe white matter (WM) mask without gray matter (GM)/CSF partial volume contamination

Decay of Classical Chaotic Systems - the Case of the Bunimovich Stadium

The escape of an ensemble of particles from the Bunimovich stadium via a small hole has been studied numerically. The decay probability starts out exponentially but has an algebraic tail. The weight of the algebraic decay tends to zero for vanishing hole size. This behaviour is explained by the slow transport of the particles close to the marginally stable bouncing ball orbits. It is contrasted with the decay function of the corresponding quantum system.Comment: 16 pages, RevTex, 3 figures are available upon request from [email protected], to be published in Phys.Rev.

Gas-phase dehydration of glycerol over thermally-stable SAPO-40 catalyst

SAPO-40 was used as catalyst for the gas-phase dehydration of glycerol towards acrolein. At 350 ºC the catalyst attained full conversion of glycerol with a negligible deactivation in the first 48 h, a glycerol conversion above 50 % after 120 h on stream and a nearly constant selectivity to acrolein above 70%. This catalyst proved to be highly resistant under the experimental conditions used and can be regenerated without loss of activity or significant structural damage. The comparison of SAPO-40 with SAPO-34 and SAPO-11 illustrates the importance of the porous structure and emphasizes the good catalytic performance of this material

Locus-Specific Decoupling of Base Composition Evolution at Synonymous Sites and Introns along the Drosophila melanogaster and Drosophila sechellia Lineages

Selection is thought to be partially responsible for patterns of molecular evolution at synonymous sites within numerous Drosophila species. Recently, “per-site” and likelihood methods have been developed to detect loci for which positive selection is a major component of synonymous site evolution. An underlying assumption of these methods, however, is a homogeneous mutation process. To address this potential shortcoming, we perform a complementary analysis making gene-by-gene comparisons of paired synonymous site and intron substitution rates toward and away from the nucleotides G and C because preferred codons are G or C ending in Drosophila. This comparison may reduce both the false-positive rate (due to broadscale heterogeneity in mutation) and false-negative rate (due to lack of power comparing small numbers of sites) of the per-site and likelihood methods. We detect loci with patterns of evolution suggestive of synonymous site selection pressures predominately favoring unpreferred and preferred codons along the Drosophila melanogaster and Drosophila sechellia lineages, respectively. Intron selection pressures do not appear sufficient to explain all these results as the magnitude of the difference in synonymous and intron evolution is dependent on recombination environment and chromosomal location in a direction supporting the hypothesis of selectively driven synonymous fixations. This comparison identifies 101 loci with an apparent switch in codon preference between D. melanogaster and D. sechellia, a pattern previously only observed at the Notch locus

Transmission time of wave packets through tunneling barriers

The transmission of wave packets through tunneling barriers is studied in detail by the method of quantum molecular dynamics. The distribution function of the times describing the arrival of a tunneling packet in front of and behind a barrier and the momentum distribution function of the packet are calculated. The behavior of the average coordinate of a packet, the average momentum, and their variances is investigated. It is found that under the barrier a part of the packet is reflected and a Gaussian barrier increases the average momentum of the transmitted packet and its variance in momentum space.Comment: 23 pages, 5 figure

PKCε-CREB-Nrf2 signalling induces HO-1 in the vascular endothelium and enhances resistance to inflammation and apoptosis

Aims Vascular injury leading to endothelial dysfunction is a characteristic feature of chronic renal disease, diabetes mellitus, and systemic inflammatory conditions, and predisposes to apoptosis and atherogenesis. Thus, endothelial dysfunction represents a potential therapeutic target for atherosclerosis prevention. The observation that activity of either protein kinase C epsilon (PKCε) or haem oxygenase-1 (HO-1) enhances endothelial cell (EC) resistance to inflammation and apoptosis led us to test the hypothesis that HO-1 is a downstream target of PKCε. Methods and results Expression of constitutively active PKCε in human EC significantly increased HO-1 mRNA and protein, whereas conversely aortas or cardiac EC from PKCε-deficient mice exhibited reduced HO-1 when compared with wild-type littermates. Angiotensin II activated PKCε and induced HO-1 via a PKCε-dependent pathway. PKCε activation significantly attenuated TNFα-induced intercellular adhesion molecule-1, and increased resistance to serum starvation-induced apoptosis. These responses were reversed by the HO antagonist zinc protoporphyrin IX. Phosphokinase antibody array analysis identified CREB1(Ser133) phosphorylation as a PKCε signalling intermediary, and cAMP response element-binding protein 1 (CREB1) siRNA abrogated PKCε-induced HO-1 up-regulation. Likewise, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) was identified as a PKCε target using nuclear translocation and DNA-binding assays, and Nrf2 siRNA prevented PKCε-mediated HO-1 induction. Moreover, depletion of CREB1 inhibited PKCε-induced Nrf2 DNA binding, suggestive of transcriptional co-operation between CREB1 and Nrf2. Conclusions PKCε activity in the vascular endothelium regulates HO-1 via a pathway requiring CREB1 and Nrf2. Given the potent protective actions of HO-1, we propose that this mechanism is an important contributor to the emerging role of PKCε in the maintenance of endothelial homeostasis and resistance to injury

On Reconciling Single and Recurrent Hitchhiking Models

A major focus of modern population genetics involves using polymorphism data in order to identify regions impacted by recent positive selection (so-called genomic scans). Recently, methodology has been proposed not to identify individual loci, but rather to quantify genomic recurrent hitchhiking (RHH) parameters using this same type of polymorphism data. I here examine to what extent genomic scans for adaptively important loci may be informed by recently estimated RHH parameters (and vice versa). I find that published results are largely incompatible with one another, with approximately an order of magnitude more sweeps being empirically identified than would be predicted under RHH estimates. Results demonstrate that making this connection between SHH and RHH models is crucial for a more complete and accurate characterization of adaptive evolution

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder

Molecular transformation and degradation of refractory dissolved organic matter in the Atlantic and Southern Ocean

More than 90% of the global ocean dissolved organic carbon (DOC) is refractory, has an average age of 4,000–6,000 years and a lifespan from months to millennia. The fraction of dissolved organic matter (DOM) that is resistant to degradation is a long-term buffer in the global carbon cycle but its chemical composition, structure, and biochemical formation and degradation mechanisms are still unresolved. We have compiled the most comprehensive molecular data set of 197 Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) analyses from solid-phase extracted marine DOM covering two major oceans, the Atlantic sector of the Southern Ocean and the East Atlantic Ocean (ranging from 50° N to 70° S). Molecular trends and radiocarbon dating of 34 DOM samples (comprising Δ14C values from -229 to -495‰) were combined to model an integrated degradation rate for bulk DOC resulting in a predicted age of >24 ka for the most persistent DOM fraction. First order kinetic degradation rates for 1,557 mass peaks indicate that numerous DOM molecules cycle on timescales much longer than the turnover of the bulk DOC pool (estimated residence times of >100 ka) and the range of validity of radiocarbon dating. Changes in elemental composition were determined by assigning molecular formulae to the detected mass peaks. The combination of residence times with molecular information enabled modelling of the average elemental composition of the slowest degrading fraction of the DOM pool. In our dataset, a group of 361 molecular formulae represented the most stable composition in the oceanic environment (“island of stability”). These most persistent compounds encompass only a narrow range of the elemental ratios H/C (average of 1.17 ± 0.13), and O/C (average of 0.52 ± 0.10) and molecular masses (360 ± 28 and 497 ± 51 Da). In the Weddell Sea DOC concentrations in the surface waters were low (46.3 ± 3.3 μM) while the organic radiocarbon was significantly more depleted than that of the East Atlantic, indicating average surface water DOM ages of 4,920 ± 180 a. These results are in accordance with a highly degraded DOM in the Weddell Sea surface water as also shown by the molecular degradation index IDEG obtained from FT-ICR MS data. Further, we identified 339 molecular formulae which probably contribute to an increased DOC concentration in the Southern Ocean and potentially reflect an accumulation or enhanced sequestration of refractory DOC in the Weddell Sea. These results will contribute to a better understanding of the persistent nature of marine DOM and its role as an oceanic carbon buffer in a changing climate