White matter integrity in physically fit older adults

Background: White matter (WM) integrity declines with normal aging. Physical activity may attenuate age-related WM integrity changes and improve cognitive function. This study examined brain WM integrity in Masters athletes who have engaged in life-long aerobic exercise training. We tested the hypothesis that life-long aerobic training is associated with improved brain WM integrity in older adults. Methods: Ten Masters athletes (3 females, age = 72.2 ± 5.3 years, endurance training \u3e15 years) and 10 sedentary older adults similar in age and educational level (2 females, age = 74.5 ± 4.3 years) participated. MRI fluid-attenuated-inversion-recovery (FLAIR) images were acquired to assess white matter hyperintensities (WMH) volume. Diffusion tensor imaging (DTI) was performed to evaluate the WM microstructural integrity with a DTI-derived metric, fractional anisotropy (FA) and mean diffusivity (MD). Results: After normalization to whole-brain volume, Masters athletes showed an 83% reduction in deep WMH volume relative to their sedentary counterparts (0.05 ± 0.05% vs. 0.29 ± 0.29%, p b 0.05). In addition, we found an inverse relationship between aerobic fitness (VO2max) and deep WMH volume (r = −0.78, p \u3c 0.001). Using TBSS, Masters athletes showed higher FA values in the right superior corona radiata (SCR), both sides of superior longitudinal fasciculus (SLF), right inferior fronto-occipital fasciculus (IFO), and left inferior longitudinal fasciculus (ILF). In addition, Masters athletes also showed lower MD values in the left posterior thalamic radiation (PTR) and left cingulum hippocampus. Conclusions: These findings suggest that life-long exercise is associated with reducedWMH and may preserveWM fiber microstructural integrity related to motor control and coordination in older adults

White matter integrity in physically fit older adults

Background: White matter (WM) integrity declines with normal aging. Physical activity may attenuate age-related WM integrity changes and improve cognitive function. This study examined brain WM integrity in Masters athletes who have engaged in life-long aerobic exercise training. We tested the hypothesis that life-long aerobic training is associated with improved brain WM integrity in older adults. Methods: Ten Masters athletes (3 females, age = 72.2 ± 5.3 years, endurance training \u3e15 years) and 10 sedentary older adults similar in age and educational level (2 females, age = 74.5 ± 4.3 years) participated. MRI fluid-attenuated-inversion-recovery (FLAIR) images were acquired to assess white matter hyperintensities (WMH) volume. Diffusion tensor imaging (DTI) was performed to evaluate the WM microstructural integrity with a DTI-derived metric, fractional anisotropy (FA) and mean diffusivity (MD). Results: After normalization to whole-brain volume, Masters athletes showed an 83% reduction in deep WMH volume relative to their sedentary counterparts (0.05 ± 0.05% vs. 0.29 ± 0.29%, p b 0.05). In addition, we found an inverse relationship between aerobic fitness (VO2max) and deep WMH volume (r = −0.78, p \u3c 0.001). Using TBSS, Masters athletes showed higher FA values in the right superior corona radiata (SCR), both sides of superior longitudinal fasciculus (SLF), right inferior fronto-occipital fasciculus (IFO), and left inferior longitudinal fasciculus (ILF). In addition, Masters athletes also showed lower MD values in the left posterior thalamic radiation (PTR) and left cingulum hippocampus. Conclusions: These findings suggest that life-long exercise is associated with reducedWMH and may preserveWM fiber microstructural integrity related to motor control and coordination in older adults

The Effect of Tamoxifen and Raloxifene on Estrogen Metabolism and Endometrial Cancer Risk

Selective estrogen receptor modulators (SERMs) demonstrate differential endometrial cancer (EC) risk. While tamoxifen (TAM) use increases the risk of endometrial hyperplasia and malignancy, raloxifene (RAL) has neutral effects on the uterus. How TAM increases the risk of EC and why TAM and RAL differentially modulate the risk for EC, however, remain elusive. Here, we tested the hypothesis that TAM increases the risk for EC, at least in part, by enhancing the local estrogen biosynthesis and directing estrogen metabolism towards the formation of genotoxic and hormonally active estrogen metabolites. In addition, the differential effects of TAM and RAL in EC risk are attributed to their differential effect on estrogen metabolism/metabolites. The endometrial cancer cell line (Ishikawa cells) and the nonmalignant immortalized human endometrial glandular cell line (EM1) were used for the study. The profile of estrogen/estrogen metabolites (EM), depurinating estrogen-DNA adducts, and the expression of estrogen-metabolizing enzymes in cells treated with 17β-estradiol (E2) alone or in combination with TAM or RAL were investigated using high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS(2)), ultraperformance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS), and Western blot analysis, respectively. TAM significantly increased the total EM and enhanced the formation of hormonally active and carcinogenic estrogen metabolites, 4-hydroxestrone (4-OHE1) and 16α-hydroxyestrone, with concomitant reduction in the formation of antiestrogenic and anticarcinogenic 2-hydroxyestradiol and 2-methoxyestradiol. Furthermore, TAM increased the formation of depurinating estrogen-DNA adducts 4-OHE1 [2]-1-N7Guanine and 4-OHE1 [2]-1-N3 Adenine. TAM-induced alteration in EM and depurinating DNA adduct formation is associated with altered expression of estrogen metabolizing enzymes CYP1A1, CYP1B1, COMT, NQO1, and SF-1 as revealed by Western blot analysis. In contrast to TAM, RAL has minimal effect on EM, estrogen-DNA adduct formation, or estrogen-metabolizing enzymes expression. These data show that TAM perturbs the balance of estrogen-metabolizing enzymes and alters the disposition of estrogen metabolites, which can explain, at least in part, the mechanism for TAM-induced EC. These results also implicate the differential effect of TAM and RAL on estrogen metabolism/metabolites as a potential mechanism for their disparate effects on the endometrium

Thermalization from gauge/gravity duality: Evolution of singularities in unequal time correlators

We consider a gauge/gravity dual model of thermalization which consists of a collapsing thin matter shell in asymptotically Anti-de Sitter space. A central aspect of our model is to consider a shell moving at finite velocity as determined by its equation of motion, rather than a quasi-static approximation as considered previously in the literature. By applying a divergence matching method, we obtain the evolution of singularities in the retarded unequal time correlator $G^R(t,t')$, which probes different stages of the thermalization. We find that the number of singularities decreases from a finite number to zero as the gauge theory thermalizes. This may be interpreted as a sign of decoherence. Moreover, in a second part of the paper, we show explicitly that the thermal correlator is characterized by the existence of singularities in the complex time plane. By studying a quasi-static state, we show the singularities at real times originate from contributions of normal modes. We also investigate the possibility of obtaining complex singularities from contributions of quasi-normal modes.Comment: 35 pages, 4 figure

Time singularities of correlators from Dirichlet conditions in AdS/CFT

Within AdS/CFT, we establish a general procedure for obtaining the leading singularity of two-point correlators involving operator insertions at different times. The procedure obtained is applied to operators dual to a scalar field which satisfies Dirichlet boundary conditions on an arbitrary time-like surface in the bulk. We determine how the Dirichlet boundary conditions influence the singularity structure of the field theory correlation functions. New singularities appear at boundary points connected by null geodesics bouncing between the Dirichlet surface and the boundary. We propose that their appearance can be interpreted as due to a non-local double trace deformation of the dual field theory, in which the two insertions of the operator are separated in time. The procedure developed in this paper provides a technical tool which may prove useful in view of describing holographic thermalization using gravitational collapse in AdS space.Comment: 30 pages, 3 figures. Version as in JHE

Plasma photoemission from string theory

Leading 't Hooft coupling corrections to the photoemission rate of the planar limit of a strongly-coupled {\cal {N}}=4 SYM plasma are investigated using the gauge/string duality. We consider the full order \alpha'^3 type IIB string theory corrections to the supergravity action, including higher order terms with the Ramond-Ramond five-form field strength. We extend our previous results presented in arXiv:1110.0526. Photoemission rates depend on the 't Hooft coupling, and their curves suggest an interpolating behaviour from strong towards weak coupling regimes. Their slopes at zero light-like momentum give the electrical conductivity as a function of the 't Hooft coupling, in full agreement with our previous results of arXiv:1108.6306. Furthermore, we also study the effect of corrections beyond the large N limit.Comment: 36 pages, 5 figures, paragraph added in the conclusions, references added, typos correcte

Fast Scramblers, Horizons and Expander Graphs

We propose that local quantum systems defined on expander graphs provide a simple microscopic model for thermalization on quantum horizons. Such systems are automatically fast scramblers and are motivated from the membrane paradigm by a conformal transformation to the so-called optical metric.Comment: 22 pages, 2 figures. Added further discussion in section 3. Added reference

Thermal quenches in N=2* plasmas

We exploit gauge/gravity duality to study `thermal quenches' in a plasma of the strongly coupled N=2* gauge theory. Specifically, we consider the response of an initial thermal equilibrium state of the theory under variations of the bosonic or fermionic mass, to leading order in m/T<<1. When the masses are made to vary in time, novel new counterterms must be introduced to renormalize the boundary theory. We consider transitions the conformal super-Yang-Mills theory to the mass deformed gauge theory and also the reverse transitions. By construction, these transitions are controlled by a characteristic time scale \calt and we show how the response of the system depends on the ratio of this time scale to the thermal time scale 1/T. The response shows interesting scaling behaviour both in the limit of fast quenches with T\calt<<1 and slow quenches with T\calt>>1. In the limit that T\calt\to\infty, we observe the expected adiabatic response. For fast quenches, the relaxation to the final equilibrium is controlled by the lowest quasinormal mode of the bulk scalar dual to the quenched operator. For slow quenches, the system relaxes with a (nearly) adiabatic response that is governed entirely by the late time profile of the mass. We describe new renormalization scheme ambiguities in defining gauge invariant observables for the theory with time dependant couplings.Comment: 78 pages, 17 figure