Applications of High Resolution High Sensitivity Observations of the CMB

With WMAP putting the phenomenological standard model of cosmology on a strong footing, one can look forward to mining the cosmic microwave background (CMB) for fundamental physics with higher sensitivity and on smaller scales. Future CMB observations have the potential to measure absolute neutrino masses, test for cosmic acceleration independent of supernova Ia observations, probe for the presence of dark energy at redshifts of 2 and larger, illuminate the end of the dark ages, measure the scale--dependence of the primordial power spectrum and detect gravitational waves generated by inflation.Comment: To be published in the proceedings of the workshop on "The Cosmic Microwave Background and its Polarization", New Astronomy Reviews, (eds. S. Hanany and K.A. Olive

Cardiac Specific Overexpression of Mitochondrial Omi/HtrA2 Induces Myocardial Apoptosis and Cardiac Dysfunction.

Myocardial apoptosis is a significant problem underlying ischemic heart disease. We previously reported significantly elevated expression of cytoplasmic Omi/HtrA2, triggers cardiomyocytes apoptosis. However, whether increased Omi/HtrA2 within mitochondria itself influences myocardial survival in vivo is unknown. We aim to observe the effects of mitochondria-specific, not cytoplasmic, Omi/HtrA2 on myocardial apoptosis and cardiac function. Transgenic mice overexpressing cardiac-specific mitochondrial Omi/HtrA2 were generated and they had increased myocardial apoptosis, decreased systolic and diastolic function, and decreased left ventricular remodeling. Transiently or stably overexpression of mitochondria Omi/HtrA2 in H9C2 cells enhance apoptosis as evidenced by elevated caspase-3, -9 activity and TUNEL staining, which was completely blocked by Ucf-101, a specific Omi/HtrA2 inhibitor. Mechanistic studies revealed mitochondrial Omi/HtrA2 overexpression degraded the mitochondrial anti-apoptotic protein HAX-1, an effect attenuated by Ucf-101. Additionally, transfected cells overexpressing mitochondrial Omi/HtrA2 were more sensitive to hypoxia and reoxygenation (H/R) induced apoptosis. Cyclosporine A (CsA), a mitochondrial permeability transition inhibitor, blocked translocation of Omi/HtrA2 from mitochondrial to cytoplasm, and protected transfected cells incompletely against H/R-induced caspase-3 activation. We report in vitro and in vivo overexpression of mitochondrial Omi/HtrA2 induces cardiac apoptosis and dysfunction. Thus, strategies to directly inhibit Omi/HtrA2 or its cytosolic translocation from mitochondria may protect against heart injury

T-cadherin deficiency increases vascular vulnerability in T2DM through impaired NO bioactivity.

BACKGROUND: Endothelial dysfunction plays a critical role in the development of type 2 diabetes (T2DM). T-cadherin (T-cad) has gained recognition as a regulator of endothelial cell (EC) function. The present study examined whether T-cad deficiency increases vascular vulnerability in T2DM. METHODS: Vascular segments were isolated from WT or T-cad knockout mice. Endothelial function, total NO accumulation, and the expression of T-cad related proteins were determined. RESULTS: Ach and acidified NaNO2 induced similar vasorelaxation in WT groups. T-cad KO mice exhibited normal response to acidified NaNO2, but manifested markedly reduced response to Ach. NO accumulation was also decreased in T-cad KO group. T-cad expression was reduced in WT mice fed 8 weeks of high fat diet (HFD). Furthermore, exacerbated reduction of vasorelaxation was observed in T-cad KO mice fed 8 weeks of HFD. CONCLUSIONS: In the current study, we provide the first in vivo evidence that T-cadherin deficiency causes endothelial dysfunction in T2DM vascular segments, suggesting the involvement of T-cad deficiency in T2DM pathogenesis

Halo bias in the excursion set approach with correlated steps

In the Excursion Set approach, halo abundances and clustering are closely related. This relation is exploited in many modern methods which seek to constrain cosmological parameters on the basis of the observed spatial distribution of clusters. However, to obtain analytic expressions for these quantities, most Excursion Set based predictions ignore the fact that, although different k-modes in the initial Gaussian field are uncorrelated, this is not true in real space: the values of the density field at a given spatial position, when smoothed on different real-space scales, are correlated in a nontrivial way. We show that when the excursion set approach is extended to include such correlations, then one must be careful to account for the fact that the associated prediction for halo bias is explicitly a real-space quantity. Therefore, care must be taken when comparing the predictions of this approach with measurements in simulations, which are typically made in Fourier-space. We show how to correct for this effect, and demonstrate that ignorance of this effect in recent analyses of halo bias has led to incorrect conclusions and biased constraints.Comment: 7 pages, 3 figures; v2 -- minor clarifications, accepted in MNRA

alpha - HgS Nanocrystals: Synthesis, Structure and Optical Properties

Well-separated mercury sulfide (HgS) nanocrystals are synthesized by a wet chemical route. Transmission electron microscopy studies show that nanocrystals are nearly spherical in shape with average size of 9 nm. Grazing angle X-ray diffraction confirms that HgS nanocrystals are in cinnabar phase. Particle induced X-ray emission and Rutherford back scattering spectrometry analysis reveal HgS nanocrystals are stoichiometric and free from foreign impurities. The optical absorption measurements show two excitonic peaks corresponding to electron-heavy hole and electron-light hole transitions, which are blue shifted by 0.1 and 0.2 eV, respectively, from its bulk value, due to quantum size effect. The experimental data obtained by optical absorption measurement is simulated with a theoretical model considering the particle size distribution as Gaussian

Noisy weak-lensing convergence peak statistics near clusters of galaxies and beyond

Taking into account noise from intrinsic ellipticities of source galaxies, in this paper, we study the peak statistics in weak-lensing convergence maps around clusters of galaxies and beyond. We emphasize how the noise peak statistics is affected by the density distribution of nearby clusters, and also how cluster-peak signals are changed by the existence of noise. These are the important aspects to be understood thoroughly in weak-lensing analyses for individual clusters as well as in cosmological applications of weak-lensing cluster statistics. We adopt Gaussian smoothing with the smoothing scale $\theta_G=0.5\hbox{ arcmin}$ in our analyses. It is found that the noise peak distribution near a cluster of galaxies depends sensitively on the density profile of the cluster. For a cored isothermal cluster with the core radius $R_c$, the inner region with $R\le R_c$ appears noisy containing on average $\sim 2.4$ peaks with $\nu\ge 5$ for $R_c= 1.7\hbox{ arcmin}$ and the true peak height of the cluster $\nu=5.6$, where $\nu$ denotes the convergence signal to noise ratio. For a NFW cluster of the same mass and the same central $\nu$, the average number of peaks with $\nu\ge 5$ within $R\le R_c$ is $\sim 1.6$. Thus a high peak corresponding to the main cluster can be identified more cleanly in the NFW case. In the outer region with $R_c<R\le 5R_c$, the number of high noise peaks is considerably enhanced in comparison with that of the pure noise case without the nearby cluster. (abridged)Comment: 10 figures, ApJ in pres

Systemic adiponectin malfunction as a risk factor for cardiovascular disease.

Adiponectin (Ad) is an abundant protein hormone regulatory of numerous metabolic processes. The 30 kDa protein originates from adipose tissue, with full-length and globular domain circulatory forms. A collagenous domain within Ad leads to spontaneous self-assemblage into various oligomeric isoforms, including trimers, hexamers, and high-molecular-weight multimers. Two membrane-spanning receptors for Ad have been identified, with differing concentration distribution in various body tissues. The major intracellular pathway activated by Ad includes phosphorylation of AMP-activated protein kinase, which is responsible for many of Ad\u27s metabolic regulatory, anti-inflammatory, vascular protective, and anti-ischemic properties. Additionally, several AMP-activated protein kinase-independent mechanisms responsible for Ad\u27s anti-inflammatory and anti-ischemic (resulting in cardioprotective) effects have also been discovered. Since its 1995 discovery, Ad has garnered considerable attention for its role in diabetic and cardiovascular pathology. Clinical observations have demonstrated the association of hypoadiponectinemia in patients with obesity, cardiovascular disease, and insulin resistance. In this review, we elaborate currently known information about Ad malfunction and deficiency pertaining to cardiovascular disease risk (including atherosclerosis, endothelial dysfunction, and cardiac injury), as well as review evidence supporting Ad resistance as a novel risk factor for cardiovascular injury, providing insight about the future of Ad research and the protein\u27s potential therapeutic benefits

Sevoflurane Pre-conditioning Ameliorates Diabetic Myocardial Ischemia/Reperfusion Injury Via Differential Regulation of p38 and ERK.

Diabetes mellitus (DM) significantly increases myocardial ischemia/reperfusion (MI/R) injury. During DM, cardioprotection induced by conventional pre-conditioning (PreCon) is decreased due to impaired AMP-activated protein kinase (AMPK) signaling. The current study investigated whether PreCon with inhaled anesthetic sevoflurane (SF-PreCon) remains cardioprotective during DM, and identified the involved mechanisms. Normal diet (ND) and high-fat diet (HFD)-induced DM mice were randomized into control and SF-PreCon (3 cycles of 15-minute period exposures to 2% sevoflurane) groups before MI/R. SF-PreCon markedly reduced MI/R injury in DM mice, as evidenced by improved cardiac function (increased LVEF and ±Dp/dt), decreased infarct size, and decreased apoptosis. To determine the relevant role of AMPK, the effect of SF-PreCon was determined in cardiac-specific AMPKα2 dominant negative expressing mice (AMPK-DN). SF-PreCon decreased MI/R injury in AMPK-DN mice. To explore the molecular mechanisms responsible for SF-PreCon mediated cardioprotection in DM mice, cell survival molecules were screened. Interestingly, in ND mice, SF-PreCon significantly reduced MI/R-induced activation of p38, a pro-death MAPK, without altering ERK and JNK. In DM and AMPK-DN mice, the inhibitory effect of SF-PreCon upon p38 activation was significantly blunted. However, SF-PreCon significantly increased phosphorylation of ERK1/2, a pro-survival MAPK in DM and AMPK-DN mice. We demonstrate that SF-PreCon protects the heart via AMPK-dependent inhibition of pro-death MAPK in ND mice. However, SF-PreCon exerts cardioprotective action via AMPK-independent activation of a pro-survival MAPK member in DM mice. SF-PreCon may be beneficial compared to conventional PreCon in diabetes or clinical scenarios in which AMPK signaling is impaired

Implications of C1q/TNF-related protein superfamily in patients with coronary artery disease.

The C1q complement/TNF-related protein superfamily (CTRPs) displays differential effects on the regulation of metabolic homeostasis, governing cardiovascular function. However, whether and how they may serve as predictor/pro-diagnosis factors for assessing the risks of coronary artery disease (CAD) remains controversial. Therefore, we performed a clinical study to elaborate on the implication of CTRPs (CTRP1, CTRP5, CTRP7, and CTRP15) in CAD. CTRP1 were significantly increased, whereas CTRP7 and CTRP15 levels were decreased in CAD patients compared to the non-CAD group. Significant differences in CTRP1 levels were discovered between the single- and triple-vascular-vessel lesion groups. ROC analysis revealed that CTRP7 and CTRP15 may serve as CAD markers, while CTRP1 may serve as a marker for the single-vessel lesion of CAD. CTRP1 and CTRP5 can serve as markers for the triple-vessel lesion. CTRP1 may serve as an independent risk predictor for triple-vessel lesion, whereas CTRP15 alteration may serve for a single-vessel lesion of CAD. CTRP1 may serve as a novel superior biomarker for diagnosis of severity of vessel-lesion of CAD patients. CTRP7, CTRP15 may serve as more suitable biomarker for the diagnosis of CAD patients, whereas CTRP5 may serve as an independent predictor for CAD. These findings suggest CTRPs may be the superior predictive factors for the vascular lesion of CAD and represent novel therapeutic targets against CAD

Small-scale CMB Temperature and Polarization Anisotropies due to Patchy Reionization

We study contributions from inhomogeneous (patchy) reionization to arcminute scale ($1000 < \ell < 10,000$) cosmic microwave background (CMB) anisotropies. We show that inhomogeneities in the ionization fraction, rather than in the mean density, dominate both the temperature and the polarization power spectra. Depending on the ionization history and the clustering bias of the ionizing sources, we find that rms temperature fluctuations range from 2 $\mu$K to 8 $\mu$K and the corresponding values for polarization are over two orders of magnitude smaller. Reionization can significantly bias cosmological parameter estimates and degrade gravitational lensing potential reconstruction from temperature maps but not from polarization maps. We demonstrate that a simple modeling of the reionization temperature power spectrum may be sufficient to remove the parameter bias. The high-$\ell$ temperature power spectrum will contain some limited information about the sources of reionization.Comment: 11 pages, 8 figures. Minor changes to match version accepted by Ap