Apolipoprotein E4 effects on topological brain network organization in mild cognitive impairment.

The Apolipoprotein E isoform E4 (ApoE4) is consistently associated with an elevated risk of developing late-onset Alzheimer's Disease (AD); however, less is known about the potential genetic modulation of the brain networks organization during prodromal stages like Mild Cognitive Impairment (MCI). To investigate this issue during this critical stage, we used a dataset with a cross-sectional sample of 253 MCI patients divided into ApoE4-positive (‛Carriers') and ApoE4-negative ('non-Carriers'). We estimated the cortical thickness (CT) from high-resolution T1-weighted structural magnetic images to calculate the correlation among anatomical regions across subjects and build the CT covariance networks (CT-Nets). The topological properties of CT-Nets were described through the graph theory approach. Specifically, our results showed a significant decrease in characteristic path length, clustering-index, local efficiency, global connectivity, modularity, and increased global efficiency for Carriers compared to non-Carriers. Overall, we found that ApoE4 in MCI shaped the topological organization of CT-Nets. Our results suggest that in the MCI stage, the ApoE4 disrupting the CT correlation between regions may be due to adaptive mechanisms to sustain the information transmission across distant brain regions to maintain the cognitive and behavioral abilities before the occurrence of the most severe symptoms

Apolipoprotein E allele 4 effects on Single-Subject Gray Matter Networks in Mild Cognitive Impairment.

There is evidence that gray matter networks are disrupted in Mild Cognitive Impairment (MCI) and associated with cognitive impairment and faster disease progression. However, it remains unknown how these alterations are related to the presence of Apolipoprotein E isoform E4 (ApoE4), the most prominent genetic risk factor for late-onset Alzheimer's disease (AD). To investigate this topic at the individual level, we explore the impact of ApoE4 and the disease progression on the Single-Subject Gray Matter Networks (SSGMNets) using the graph theory approach. Our data sample comprised 200 MCI patients selected from the ADNI database, classified as non-Converters and Converters (will progress into AD). Each group included 50 ApoE4-positive ('Carriers', ApoE4 + ) and 50 ApoE4-negative ('non-Carriers', ApoE4-). The SSGMNets were estimated from structural MRIs at two-time points: baseline and conversion. We investigated whether altered network topological measures at baseline and their rate of change (RoC) between baseline and conversion time points were associated with ApoE4 and disease progression. We also explored the correlation of SSGMNets attributes with general cognition score (MMSE), memory (ADNI-MEM), and CSF-derived biomarkers of AD (Aβ42, T-tau, and P-tau). Our results showed that ApoE4 and the disease progression modulated the global topological network properties independently but not in their RoC. MCI converters showed a lower clustering index in several regions associated with neurodegeneration in AD. The SSGMNets' topological organization was revealed to be able to predict cognitive and memory measures. The findings presented here suggest that SSGMNets could indeed be used to identify MCI ApoE4 Carriers with a high risk for AD progression

H^+ -> W^+ l_i^- l_j^+$ decay in the two Higgs doublet model

We study the lepton flavor violating H^+ -> W^+ l_i^- l_j^+ and the lepton flavor conserving $H^+ -> W^+ l_i^- l_i^+ (l_i=\tau, l_j=\mu) decays in the general 2HDM, so called model III. We estimate the decay width \Gamma for LFV (LFC) at the order of the magnitude of (10^{-11}-10^{-5}) GeV ((10^{-9}-10^{-4}) GeV), for 200 GeV\leq m_{H^\pm}\leq 400 GeV, and the intermediate values of the coupling \bar{\xi}^{E}_{N,\tau \mu}\sim 5 GeV (\bar{\xi}^{E}_{N,\tau \tau}\sim 30 GeV). We observe that the experimental result of the process under consideration can give comprehensive information about the physics beyond the standard model and the existing free parameters.Comment: 8 pages, 7 Figure

On the recurrence and robust properties of Lorenz'63 model

Lie-Poisson structure of the Lorenz'63 system gives a physical insight on its dynamical and statistical behavior considering the evolution of the associated Casimir functions. We study the invariant density and other recurrence features of a Markov expanding Lorenz-like map of the interval arising in the analysis of the predictability of the extreme values reached by particular physical observables evolving in time under the Lorenz'63 dynamics with the classical set of parameters. Moreover, we prove the statistical stability of such an invariant measure. This will allow us to further characterize the SRB measure of the system.Comment: 44 pages, 7 figures, revised version accepted for pubblicatio

Reconstructing Neutrino Properties from Collider Experiments in a Higgs Triplet Neutrino Mass Model

We extend the minimal supersymmetric standard model with bilinear R-parity violation to include a pair of Higgs triplet superfields. The neutral components of the Higgs triplets develop small vacuum expectation values (VEVs) quadratic in the bilinear R-parity breaking parameters. In this scheme the atmospheric neutrino mass scale arises from bilinear R-parity breaking while for reasonable values of parameters the solar neutrino mass scale is generated from the small Higgs triplet VEVs. We calculate neutrino masses and mixing angles in this model and show how the model can be tested at future colliders. The branching ratios of the doubly charged triplet decays are related to the solar neutrino angle via a simple formula.Comment: 19 pages, 4 figures; one formula corrected, two author's names corrected; some explanatory comments adde

Electroweak Corrections to the Charged Higgs Boson Decay into Chargino and Neutralino

The electroweak corrections to the partial widths of the $H^+ \to \tilde{\chi}^+_i \tilde{\chi}_j^0 (i=1,j=1,2)$ decays including one-loop diagrams of the third generation quarks and squarks, are investigated within the Supersymmetric Standard Model. The relative corrections can reach the values about 10%, therefore they should be taken into account for the precise experimental measurement at future colliders.Comment: 21 pages, 6 eps figures, 1 Latex fil

A CD36 ectodomain mediates insect pheromone detection via a putative tunnelling mechanism.

CD36 transmembrane proteins have diverse roles in lipid uptake, cell adhesion and pathogen sensing. Despite numerous in vitro studies, how they act in native cellular contexts is poorly understood. A Drosophila CD36 homologue, sensory neuron membrane protein 1 (SNMP1), was previously shown to facilitate detection of lipid-derived pheromones by their cognate receptors in olfactory cilia. Here we investigate how SNMP1 functions in vivo. Structure-activity dissection demonstrates that SNMP1's ectodomain is essential, but intracellular and transmembrane domains dispensable, for cilia localization and pheromone-evoked responses. SNMP1 can be substituted by mammalian CD36, whose ectodomain can interact with insect pheromones. Homology modelling, using the mammalian LIMP-2 structure as template, reveals a putative tunnel in the SNMP1 ectodomain that is sufficiently large to accommodate pheromone molecules. Amino-acid substitutions predicted to block this tunnel diminish pheromone sensitivity. We propose a model in which SNMP1 funnels hydrophobic pheromones from the extracellular fluid to integral membrane receptors

Constraint methods for determining pathways and free energy of activated processes

Activated processes from chemical reactions up to conformational transitions of large biomolecules are hampered by barriers which are overcome only by the input of some free energy of activation. Hence, the characteristic and rate-determining barrier regions are not sufficiently sampled by usual simulation techniques. Constraints on a reaction coordinate r have turned out to be a suitable means to explore difficult pathways without changing potential function, energy or temperature. For a dense sequence of values of r, the corresponding sequence of simulations provides a pathway for the process. As only one coordinate among thousands is fixed during each simulation, the pathway essentially reflects the system's internal dynamics. From mean forces the free energy profile can be calculated to obtain reaction rates and insight in the reaction mechanism. In the last decade, theoretical tools and computing capacity have been developed to a degree where simulations give impressive qualitative insight in the processes at quantitative agreement with experiments. Here, we give an introduction to reaction pathways and coordinates, and develop the theory of free energy as the potential of mean force. We clarify the connection between mean force and constraint force which is the central quantity evaluated, and discuss the mass metric tensor correction. Well-behaved coordinates without tensor correction are considered. We discuss the theoretical background and practical implementation on the example of the reaction coordinate of targeted molecular dynamics simulation. Finally, we compare applications of constraint methods and other techniques developed for the same purpose, and discuss the limits of the approach

Supersymmetric predictions for the inclusive b→sγb\to s\gamma decay

We study the penguin induced transition $b\to s\ \gamma$ in the minimal N=1 supersymmetric extension of the Standard Model with radiative breaking of the electroweak group. We include the effects of one-loop corrections to the Higgs potential and scalar masses. We show that the present upper and lower experimental limits on the inclusive decay sharply constrain the parameter space of the model in a wide range of $\tan\beta$ values. The implications of the recently advocated relation $|B|\ge 2$ for the bilinear SUSY soft breaking parameter in grand unified theories are also analyzed.Comment: 23 pages + 12 figures (hardcopies available on request), LATEX, SISSA 40/94/E