Epigenomes in Cardiovascular Disease.

If unifying principles could be revealed for how the same genome encodes different eukaryotic cells and for how genetic variability and environmental input are integrated to impact cardiovascular health, grand challenges in basic cell biology and translational medicine may succumb to experimental dissection. A rich body of work in model systems has implicated chromatin-modifying enzymes, DNA methylation, noncoding RNAs, and other transcriptome-shaping factors in adult health and in the development, progression, and mitigation of cardiovascular disease. Meanwhile, deployment of epigenomic tools, powered by next-generation sequencing technologies in cardiovascular models and human populations, has enabled description of epigenomic landscapes underpinning cellular function in the cardiovascular system. This essay aims to unpack the conceptual framework in which epigenomes are studied and to stimulate discussion on how principles of chromatin function may inform investigations of cardiovascular disease and the development of new therapies

Topologies on unparameterised path space

The signature of a path, introduced by K.T. Chen [10] in 1954, has been extensively studied in recent years. The fundamental 2010 paper [20] of Hambly and Lyons showed that the signature is an injective function on the space of continuous, finite-variation paths up to a general notion of reparameterisation called tree-like equivalence. This result has been extended to geometric rough paths by Boedihardjo et al. [5]. More recently, the approximation theory of the signature has been widely used in the literature in applications. The archetypal instance of these results, see e.g. [24], guarantees uniform approximation, on compact sets, of a continuous function by a linear functional on the (extended) tensor algebra acting on the signature. In this paper we study in detail, and for the first time, the properties of three natural candidate topologies on the set of unparameterised paths, i.e. the tree-like equivalence classes. These are obtained by privileging different properties of the signature and are: (1) the product topology, obtained by equipping the range of the signature with the (subspace topology of the) product topology in the extended tensor algebra and then requiring S to be an embedding, (2) the quotient topology derived from the 1-variation topology on the underlyind path space, and (3) the metric topology associated to ([γ], [σ]) := ||γ* - σ*||₁ using the (constant-speed) tree-reduced representatives γ* and σ* of the respective equivalence classes. We evaluate these spaces from the point of view of their suitability when it comes to studying (probability) measures on them. We prove that the respective collections of open sets are ordered by strict inclusion, (1) being the weakest and (3) the strongest. Our other conclusions can be summarised as follows. All three topological spaces are separable and Hausdorff, (1) being both metrisable and σ-compact, but not a Baire space and hence being neither Polish nor locally compact. The completion of (1), in any metric inducing the product topology, is the subspace G* of group-like elements. The quotient topology (2) is not metrisable and the metric d is not complete. We also discuss some open problems related to these spaces. We consider finally the implications of the selection of the topology for uniform approximation results involving the signature. A stereotypical model for a continuous function on (unparameterised) path space is the solution of a controlled differential equation. We thus prove, for a broad class of these equations, well-definedness and measurability of the (fixed-time) solution map with respect to the Borel sigma-algebra of each topology. Under stronger regularity assumptions, we further show continuity of this same map on explicit compact subsets of the product topology (1). We relate these results to the expected signature model of [24]

The use of satellites in non-goestationary orbits for unloading geostationary communication satellite traffic peaks. Volume 2: Technical report

The part of the geostationary (GEO) orbital arc used for United States domestic fixed, communications service is rapidly becoming filled with satellites. One of the factors currently limiting its utilization is that communications satellites must be designed to have sufficient capacity to handle peak traffic leads, and thus are under utilized most of the time. A solution is to use satellites in suitable non-geostationary orbits to unload the traffic peaks. Three different designs for a non-geostationary orbit communications satellite system are presented for the 1995 time frame. The economic performance is analyzed and compared with geostationary satellites for two classes of service, trunking and customer premise service. The result is that the larger payload of the non-geostationary satellite offsets the burdens of increased complexity and worse radiation environment to give improved economic performance. Depending on ground terminal configuration, the improved economic performance of the space segment may be offset by increased ground terminal expenses

A Chandra ACIS view of the Thermal Composite Supernova Remnant 3C391

We present a 60 ks Chandra ACIS-S observation of the thermal composite supernova remnant 3C391. The southeast-northwest elongated morphology is similar to that previously found in radio and X-ray studies. This observation unveils a highly clumpy structure of the remnant. Detailed spatially resolved spectral analysis for the small-scale features reveals that the interior gas is generally of normal metal abundance and has approached or basically reached ionization equilibrium. The hydrogen column density increases from southeast to northwest. Three mechanisms, radiative rim, thermal conduction, and cloudlet evaporation, may all play roles in the X-ray appearance of 3C391 as a "thermal composite" remnant, but there are difficulties with each of them in explaining some physical properties. Comparatively, the cloudlet evaporation model is favored by the main characteristics such as the highly clumpy structure and the uniform temperature and density distribution over most of the remnant. The directly measured postshock temperature also implies a young age, about 4 kyr, for the remnant. The postshock gas pressure derived from the NE and SW rims, which harbor maser spots, is consistent with the estimate for the maser regions. An unresolved X-ray source is observed on the northwest border and its spectrum is best fitted by a power-law.Comment: aastex, 27 pages (including 4 figures), to appear in the ApJ 1 Dec. 2004, v616 issu

Stratospheric dynamics and transport studies

A three dimensional General Circulation Model/Transport Model is used to simulate stratospheric circulation and constituent distributions. Model simulations are analyzed to interpret radiative, chemical, and dynamical processes and their mutual interactions. Concurrent complementary studies are conducted using both global satellite data and other appropriate data. Comparisons of model simulations and data analysis studies are used to aid in understanding stratospheric dynamics and transport processes and to assess the validity of current theory and models

An extreme, blueshifted iron line profile in the Narrow Line Seyfert 1 PG 1402+261; an edge-on accretion disk or highly ionized absorption?

We report on a short XMM-Newton observation of the radio-quiet Narrow Line Seyfert 1 PG 1402+261. The EPIC X-ray spectrum of PG 1402+261 shows a strong excess of counts between 6-9 keV in the rest frame. This feature can be modeled by an unusually strong (equivalent width 2 keV) and very broad (FWHM velocity of 110000 km/s) iron K-shell emission line. The line centroid energy at 7.3 keV appears blue-shifted with respect to the iron Kalpha emission band between 6.4-6.97 keV, while the blue-wing of the line extends to 9 keV in the quasar rest frame. The line profile can be fitted by reflection from the inner accretion disk, but an inclination angle of >60 deg is required to model the extreme blue-wing of the line. Furthermore the extreme strength of the line requires a geometry whereby the hard X-ray emission from PG 1402+261 above 2 keV is dominated by the pure-reflection component from the disk, while little or none of the direct hard power-law is observed. Alternatively the spectrum above 2 keV may instead be explained by an ionized absorber, if the column density is sufficiently high (N_H > 3 x 10^23 cm^-2) and if the matter is ionized enough to produce a deep (tau~1) iron K-shell absorption edge at 9 keV. This absorber could originate in a large column density, high velocity outflow, perhaps similar to those which appear to be observed in several other high accretion rate AGN. Further observations, especially at higher spectral resolution, are required to distinguish between the accretion disk reflection or outflow scenarios.Comment: Accepted for publication in ApJ (18 pages, 5 figures, 1 table

NGC 2992 in an X-ray high state observed by XMM: Response of the Relativistic Fe Kα\alpha Line to the Continuum

We present the analysis of an XMM observation of the Seyfert galaxy NGC 2992. The source was found in its highest level of X-ray activity yet detected, a factor $\sim 23.5$ higher in 2--10 keV flux than the historical minimum. NGC 2992 is known to exhibit X-ray flaring activity on timescales of days to weeks, and the XMM data provide at least factor of $\sim 3$ better spectral resolution in the Fe K band than any previously measured flaring X-ray state. We find that there is a broad feature in the \sim 5-7 keV band which could be interpreted as a relativistic Fe K$\alpha$ emission line. Its flux appears to have increased in tandem with the 2--10 keV continuum when compared to a previous Suzaku observation when the continuum was a factor of $\sim 8$ lower than that during the XMM observation. The XMM data are consistent with the general picture that increased X-ray activity and corresponding changes in the Fe K$\alpha$ line emission occur in the innermost regions of the putative accretion disk. This behavior contrasts with the behavior of other AGN in which the Fe K$\alpha$ line does not respond to variability in the X-ray.Comment: 30 pages, 6 figures, Accepted to Ap

The 1 keV to 200 keV X-ray Spectrum of NGC 2992 and NGC 3081

The Seyfert 2 galaxies NGC 2992 and NGC 3081 have been observed by INTEGRAL and Swift. We report about the results and the comparison of the spectrum above 10 keV based on INTEGRAL IBIS/ISGRI, Swift/BAT, and BeppoSAX/PDS. A spectrum can be extracted in the X-ray energy band ranging from 1 keV up to 200 keV. Although NGC 2992 shows a complex spectrum below 10 keV, the hard tail observed by various missions exhibits a slope with photon index = 2, independent on the flux level during the observation. No cut-off is detectable up to the detection limit around 200 keV. In addition, NGC 3081 is detected in the INTEGRAL and Swift observation and also shows an unbroken Gamma = 1.8 spectrum up to 150 keV. These two Seyfert galaxies give further evidence that a high-energy cut-off in the hard X-ray spectra is often located at energies E_C >> 100 keV. In NGC 2992 a constant spectral shape is observed over a hard X-ray luminosity variation by a factor of 11. This might indicate that the physical conditions of the emitting hot plasma are constant, while the amount of plasma varies, due to long-term flaring activity.Comment: 8 pages, 4 figures, accepted for publication in Ap

An assessment of the histidine-loading (Figlu) test in infancy

No Abstract

Planck-Scale Effects on Global Symmetries: Cosmology of Pseudo-Goldstone Bosons

We consider a model with a small explicit breaking of a global symmetry, as suggested by gravitational arguments. Our model has one scalar field transforming under a non-anomalous U(1) symmetry, and coupled lo matter and to gauge bosons. The spontaneous breaking of the explicitly broken symmetry gives rise to a massive pseudo-Goldstone boson. We analyze thermal and non-thermal production of this particle in the early universe, and perform a systematic study of astrophysical and cosmological constraints on its properties. We find that for very suppressed explicit breaking the pseudo-Goldstone boson is a cold dark matter candidate.Comment: 31 pages, 9 figures, Latex file; sections 3 and 4 merged; sections 5 and 6 merged; appendix B removed; to be published in Phys Rev