Distant X-ray Galaxies: Insights from the Local Population

A full understanding of the origin of the hard X-ray background requires a complete and accurate census of the distant galaxies that produce it. Unfortunately, distant X-ray galaxies tend to be very faint at all wavelengths, which hinders efforts to perform this census. This chapter discusses the insights that can be obtained through comparison of the distant population to local X-ray galaxies, whose properties are well characterized. Such comparisons will ultimately aid investigations into the cosmic evolution of supermassive black holes and their environments.Comment: 19 pages, 10 figures, to appear as Chapter 7 in "Supermassive Black Holes in the Distant Universe" (2004), ed. A. J. Barger, Kluwer Academic Publishers, in pres

Volcanism in Antarctica: An assessment of the present state of research and future directions

Over the past decades, significant efforts have been made to understand the nature, dynamics and evolution of volcanic systems. In parallel, the continuous demographic expansion and extensive urbanization of volcanic areas have increased the exposure of our society to these natural phenomena. This increases the need to improve our capacities to accurately assess projected volcanic hazards and their potential socioeconomic and environmental impact, and Antarctica and the sub-Antarctic islands are no exception. More than a hundred volcanoes have been identified in Antarctica, some of which are entirely buried beneath the ice sheet and others as submarine volcanoes. Of these, at least eight large (basal diameters > c. 20-30 km) volcanoes are known to be active and pose a considerable threat to scientific and ever-increasing tourism activities being carried out in the region. Despite the scientific and socioeconomic interest, many aspects of the past volcanic activity and magmatic processes in Antarctica, and current volcanic hazards and risks, remain unknown. Moreover, many of Antarctica's volcanoes preserve a remarkable history of the eruptive environment, from which multiple parameters of past configurations of the Antarctic ice sheet (AIS) can be deduced. Given the critical role that the AIS plays in regulating Earth's climate, Antarctica's volcanoes therefore can be regarded as the ground truth for current models of past climates derived from modelling and studies of marine sediments. Here, we provide a succinct overview of the evolution of volcanism and magmatism in Antarctica and the sub-Antarctic region over the past 200 million years. Then, we briefly review the current state of knowledge of the most crucial aspects regarding Antarctica's volcanic and magmatic processes, and the contributions volcanic studies have made to our understanding of ice sheet history and evolution, geothermal heat flow, as well as present-day and future volcanic hazard and risk. A principal objective is to highlight the problems and critical limitations of the current state of knowledge and to provide suggestions for future potential directions of volcanic-driven investigations in Antarctica. Finally, we also discuss and assess the importance and scope of education and outreach activities specifically relating to Antarctic volcanism, and within the context of broader polar sciences

An inhomogeneous fractal cosmological model

We present a cosmological model in which the metric allows for an inhomogeneous Universe with no intrinsic symmetries (Stephani models), providing the ideal features to describe a fractal distribution of matter. Constraints on the metric functions are derived using the expansion and redshift relations and allowing for scaling number counts, as expected in a fractal set. The main characteristics of such a cosmological model are discussed.Comment: 11 pages, no figures, accepted for publication on Classical and Quantum Gravit

Inhomogeneous cosmologies, the Copernican principle and the cosmic microwave background: More on the EGS theorem

We discuss inhomogeneous cosmological models which satisfy the Copernican principle. We construct some inhomogeneous cosmological models starting from the ansatz that the all the observers in the models view an isotropic cosmic microwave background. We discuss multi-fluid models, and illustrate how more general inhomogeneous models may be derived, both in General Relativity and in scalar-tensor theories of gravity. Thus we illustrate that the cosmological principle, the assumption that the Universe we live in is spatially homogeneous, does not necessarily follow from the Copernican principle and the high isotropy of the cosmic microwave background.Comment: 17 pages; to appear in GR

Intimal aortic sarcoma mimicking ruptured thoracoabdominal type IV aneurysm. a rare case report and review of the literature

Primary intimal aortic sarcoma represents a very rare and highly lethal medical entity. Diagnosis is made either by embolic events caused by the tumor or by surrounding tissue symptoms such as pain. Herein we report an extremely rare case of a 51-year-old man previously operated for ascending aortic aneurysm, who presented with clinical and radiological findings suggestive of a ruptured thoracoabdominal type IV aneurysm. The patient underwent radical resection of the aorta and surrounding tissue with placement of a composite 4-branched graft. The diagnosis was made by frozen section and regular histopathologic examination of the specimen and the patient received adjuvant chemotherapy. Nine months after surgery the patient is still alive and has no signs of recurrence. We review the literature and discuss the option of postoperative chemotherapy

Exploring digenic inheritance in arrhythmogenic cardiomyopathy

Background: Arrhythmogenic cardiomyopathy (ACM) is an inherited genetic disorder, characterized by the substitution of heart muscle with fibro-fatty tissue and severe ventricular arrhythmias, often leading to heart failure and sudden cardiac death. ACM is considered a monogenic disorder, but the low penetrance of mutations identified in patients suggests the involvement of additional genetic or environmental factors. Methods: We used whole exome sequencing to investigate digenic inheritance in two ACM families where previous diagnostic tests have revealed a PKP2 mutation in all affected and some healthy individuals. In family members with PKP2 mutations we determined all genes that harbor variants in affected but not in healthy carriers or vice versa. We computationally prioritized the most likely candidates, focusing on known ACM genes and genes related to PKP2 through protein interactions, functional relationships, or shared biological processes. Results: We identified four candidate genes in family 1, namely DAG1, DAB2IP, CTBP2 and TCF25, and eleven candidate genes in family 2. The most promising gene in the second family is TTN, a gene previously associated with ACM, in which the affected individual harbors two rare deleterious-predicted missense variants, one of which is located in the protein's only serine kinase domain. Conclusions: In this study we report genes that might act as digenic players in ACM pathogenesis, on the basis of co-segregation with PKP2 mutations. Validation in larger cohorts is still required to prove the utility of this model

Cosmological Evolution of the Hard X-ray AGN Luminosity Function and the Origin of the Hard X-ray Background

We investigate the cosmological evolution of the hard X-ray luminosity function (HXLF) of Active Galactic Nuclei (AGN) in the 2-10 keV luminosity range of 10^{41.5} - 10^{46.5} erg s^-1 as a function of redshift up to 3. From a combination of surveys conducted at photon energies above 2 keV with HEAO1, ASCA, and Chandra, we construct a highly complete (>96%) sample consisting of 247 AGNs over the wide flux range of 10^{-10} - 3.8*10^{-15} erg cm^-2 s^-1 (2-10 keV). For our purpose, we develop an extensive method of calculating the intrinsic (before-absorption) HXLF and the absorption (N_H) function. This utilizes the maximum likelihood method fully correcting for observational biases with consideration of the X-ray spectrum of each source. We find that (i) the fraction of X-ray absorbed AGNs decreases with the intrinsic luminosity and (ii) the evolution of the HXLF of all AGNs (including both type-I and type-II AGNs) is best described with a luminosity dependent density evolution (LDDE) where the cutoff redshift increases with the luminosity. Our results directly constrain the evolution of AGNs that produce a major part of the hard X-ray background, thus solving its origin quantitatively. A combination of the HXLF and the NH function enables us to construct a purely "observation based" population synthesis model. We present basic consequences of this model, and discuss the contribution of Compton-thick AGNs to the rest of the hard X-ray background.Comment: 62 pages, 26 figures (13 colour figures included). Accepted for publication in ApJ. Minor corrections. References are update

In vitro epigenetic reprogramming of human cardiac mesenchymal stromal cells into functionally competent cardiovascular precursors

Adult human cardiac mesenchymal-like stromal cells (CStC) represent a relatively accessible cell type useful for therapy. In this light, their conversion into cardiovascular precursors represents a potential successful strategy for cardiac repair. The aim of the present work was to reprogram CStC into functionally competent cardiovascular precursors using epigenetically active small molecules. CStC were exposed to low serum (5% FBS) in the presence of 5 \ub5M all-trans Retinoic Acid (ATRA), 5 \ub5M Phenyl Butyrate (PB), and 200 \ub5M diethylenetriamine/nitric oxide (DETA/NO), to create a novel epigenetically active cocktail (EpiC). Upon treatment the expression of markers typical of cardiac resident stem cells such as c-Kit and MDR-1 were up-regulated, together with the expression of a number of cardiovascular-associated genes including KDR, GATA6, Nkx2.5, GATA4, HCN4, NaV1.5, and \u3b1-MHC. In addition, profiling analysis revealed that a significant number of microRNA involved in cardiomyocyte biology and cell differentiation/proliferation, including miR 133a, 210 and 34a, were up-regulated. Remarkably, almost 45% of EpiC-treated cells exhibited a TTX-sensitive sodium current and, to a lower extent in a few cells, also the pacemaker I(f) current. Mechanistically, the exposure to EpiC treatment introduced global histone modifications, characterized by increased levels of H3K4Me3 and H4K16Ac, as well as reduced H4K20Me3 and H3s10P, a pattern compatible with reduced proliferation and chromatin relaxation. Consistently, ChIP experiments performed with H3K4me3 or H3s10P histone modifications revealed the presence of a specific EpiC-dependent pattern in c-Kit, MDR-1, and Nkx2.5 promoter regions, possibly contributing to their modified expression. Taken together, these data indicate that CStC may be epigenetically reprogrammed to acquire molecular and biological properties associated with competent cardiovascular precursors

HMGB1 Attenuates Cardiac Remodelling in the Failing Heart via Enhanced Cardiac Regeneration and miR-206-Mediated Inhibition of TIMP-3

Aims: HMGB1 injection into the mouse heart, acutely after myocardial infarction (MI), improves left ventricular (LV) function and prevents remodeling. Here, we examined the effect of HMGB1 in chronically failing hearts. Methods and Results: Adult C57 BL16 female mice underwent coronary artery ligation; three weeks later 200 ng HMGB1 or denatured HMGB1 (control) were injected in the peri-infarcted region of mouse failing hearts. Four weeks after treatment, both echocardiography and hemodynamics demonstrated a significant improvement in LV function in HMGB1-treated mice. Further, HMGB1-treated mice exhibited a,23 % reduction in LV volume, a,48 % increase in infarcted wall thickness and a,14 % reduction in collagen deposition. HMGB1 induced cardiac regeneration and, within the infarcted region, it was found a,2-fold increase in c-kit + cell number, a,13-fold increase in newly formed myocytes and a,2-fold increase in arteriole length density. HMGB1 also enhanced MMP2 and MMP9 activity and decreased TIMP-3 levels. Importantly, miR-206 expression 3 days after HMGB1 treatment was 4-5-fold higher than in control hearts and 20–25 fold higher that in sham operated hearts. HMGB1 ability to increase miR-206 was confirmed in vitro, in cardiac fibroblasts. TIMP3 was identified as a potential miR-206 target by TargetScan prediction analysis; further, in cultured cardiac fibroblasts, miR-206 gain- and loss-offunction studies and luciferase reporter assays showed that TIMP3 is a direct target of miR-206. Conclusions: HMGB1 injected into chronically failing hearts enhanced LV function and attenuated LV remodelling; thes

An in vitro collagen perfusion wound biofilm model; with applications for antimicrobial studies and microbial metabolomics

BackgroundThe majority of in vitro studies of medically relevant biofilms involve the development of biofilm on an inanimate solid surface. However, infection in vivo consists of biofilm growth on, or suspended within, the semi-solid matrix of the tissue, whereby current models do not effectively simulate the nature of the in vivo environment. This paper describes development of an in vitro method for culturing wound associated microorganisms in a system that combines a semi-solid collagen gel matrix with continuous flow of simulated wound fluid. This enables culture of wound associated reproducible steady state biofilms under conditions that more closely simulate the dynamic wound environment. To demonstrate the use of this model the antimicrobial kinetics of ceftazidime, against both mature and developing Pseudomonas aeruginosa biofilms, was assessed. In addition, we have shown the potential application of this model system for investigating microbial metabolomics by employing selected ion flow tube mass spectrometry (SIFT-MS) to monitor ammonia and hydrogen cyanide production by Pseudomonas aeruginosa biofilms in real-time. ResultsThe collagen wound biofilm model facilitates growth of steady-state reproducible Pseudomonas aeruginosa biofilms under wound like conditions. A maximum biofilm density of 1010 cfu slide-1 was achieved by 30 hours of continuous culture and maintained throughout the remainder of the experiment. Treatment with ceftazidime at a clinically relevant dose resulted in a 1.2 – 1.6 log reduction in biofilm density at 72 hours compared to untreated controls. Treatment resulted in loss of complex biofilm architecture and morphological changes to bacterial cells, visualised using confocal microscopy. When monitoring the biofilms using SIFT-MS, ammonia and hydrogen cyanide levels peaked at 12 hours at 2273 ppb (±826.4) and 138 ppb (±49.1) respectively and were detectable throughout experimentation. ConclusionsThe collagen wound biofilm model has been developed to facilitate growth of reproducible biofilms under wound-like conditions. We have successfully used this method to: (1) evaluate antimicrobial efficacy and kinetics, clearly demonstrating the development of antimicrobial tolerance in biofilm cultures; (2) characterise volatile metabolite production by P. aeruginosa biofilms, demonstrating the potential use of this method in metabolomics studies