Ultraviolet observations of LMC nova 1988

The IUE obtained ultraviolet spectra of a nova in an external galaxy. The spectral features do not seem unusual for a nova at maximum but it is hoped to be able to follow it for a long enough time to be able to study the high ionization lines that appear when the density drops to lower values (the nebular stage). A high dispersion spectrum was also obtained to assist in the line identification and to study the line of sight to the LMC 1 deg of arc away from SN 1987A

Hubble Space Telescope Far Ultraviolet Spectroscopy of the Recurrent Nova T Pyxidis

With six recorded nova outbursts, the prototypical recurrent nova T Pyxidis is the ideal cataclysmic variable system to assess the net change of the white dwarf mass within a nova cycle. Recent estimates of the mass ejected in the 2011 outburst ranged from a few 1.E-5 sollar mass to 3.3E-4 sollar mass, and assuming a mass accretion rate of 1.E-8 to 1.E-7 Sollar mass/yr for 44yrs, it has been concluded that the white dwaf in T Pyx is actually losing mass. Using NLTE disk modeling spectra to fit our recently obtained Hubble Space Telescope (HST) COS and STIS spectra, we find a mass accretion rate of up to two orders of magnitude larger than previously estimated. Our larger mass accretion rate is due mainly to the newly derived distance of T Pyx (4.8kpc; Sokoloski et al. 2013, larger than the previous 3.5kpc estimate), our derived reddening of E(B-V)=0.35 (based on combined IUE and GALEX spectra) and NLTE disk modeling (compared to black body and raw flux estimates in earlier works). We find that for most values of the reddening (0.25 < E(B-V) < 0.50) and white dwaf mass (0.70 to 1.35 Sollar mass) the accreted mass is larger than the ejected mass. Only for a low reddening (0.25 and smaller) combined with a large white dwaf mass (0.9 sollar mass and larger) is the ejected mass larger than the accreted one. However, the best spectral fitting results are obtained for a larger value of the reddening.Comment: The Astrophysical Journal Letter, in pres

MitoTALENs: A general approach to reduce mutant mtDNA loads and restore oxidative phosphorylation function in mitochondrial diseases

We have designed mitochondrially targeted Transcription Activator-Like Effector Nucleases or mitoTALENs to cleave specific sequences in the mitochondrial DNA (mtDNA) with the goal of eliminating mtDNA carrying pathogenic point mutations. To test the generality of the approach we designed mitoTALENs to target two relatively common pathogenic mtDNA point mutations associated with mitochondrial diseases: the m.8344A>G tRNA^(Lys) gene mutation associated with Myoclonic Epilepsy with Ragged-Red Fibers (MERRF) and the m.13513G>A ND5 mutation associated with MELAS/Leigh Syndrome. Transmitochondrial cybrid cells harbouring the respective heteroplasmic mtDNA mutations were transfected with the respective mitoTALEN and analysed after different time periods. MitoTALENs efficiently reduced the levels of the targeted pathogenic mtDNAs in the respective cell lines. Functional assays showed that cells with heteroplasmic mutant mtDNA were able to recover respiratory capacity and oxidative phosphorylation enzymes activity after transfection with the mitoTALEN. To improve the design in the context of the low complexity of mtDNA, we designed shorter versions of the mitoTALEN specific for the MERRF m.8344A>G mutation. These shorter mitoTALENs also eliminated the mutant mtDNA. These reductions in size improve our ability to package these large sequences into viral vectors, bringing the use of these genetic tools closer to clinical trials

RNA-sequencing analysis of a multistep and hit-and-run cell and animal model of KSHV tumorigenesis reveal the roles of mutations, CpG methylation, and viral-infection footprints in oncogenesis

Human viral oncogenesis is the consequence of cell transformation mediated by virally encoded oncogenes in combination with host oncogenic alterations. Kaposi’s sarcoma (KS), caused by the Kaposi’s sarcoma-associated herpes virus (KSHV), is an AIDS-associated cancer characterized by angiogenesis and spindle-cells proliferation. KSHV-infected KS lesions are composed of latently-infected cells, as well as cells expressing lytic genes that have been implicated in the development of the KS angioproliferative phenotype. The existence of KS lesions with varying levels of KSHV-infected cells suggests also the existence of virus-independent “hit-and-run” mechanisms of sarcomagenesis, whereby viral infection irreversibly induce genetic or epigenetic oncogenic alterations in host cells. We have integrated genetic mutations, changes in expression signatures and methylation analysis to dissect genetic and epigenetic signaling pathways in an unbiased manner in the mECK36 mouse model of KSHV tumorigenesis. Pathway analysis of differential expressed genes (DEGs) showed KSHV lytic switch, DNA methylation and Epigenetic as the most regulated pathways during KSHV-dependent in vivo tumorigenesis. Methylation analysis data indicates that during the development of KSHV-infected tumors the most changes were towards hypo-methylation of tissues specific genes and oncogenic signature pathways, on the other hand during viral loss and development of KSHV-negative tumors changes are towards hyper-methylation. Mutational analysis of KSHV-infected cells and tumors revealed a set of mutations, including mutations in three inflammasome-related IFN response genes, that were absent in KSHV-infected cells but present in all KSHV-infected tumors in the same loci pointing to clonal selection “in vivo”. This result suggests that in the context of in vivo tumorigenesis both these mutations and the virus may determine tumor growth. On the other hand, clustering analysis of mutations driving KSHV-negative tumors reveal a network comprising PDGFRA D842V, Pak1 and Nucleolin mutations implicated in cell proliferation. Our results have uncovered novel specific aspects of the interplay between host oncogenic alterations and virus-induced transcriptional effects as well as the epigenetic changes induced by KSHV infection and tumorigenesis. The existence virally-induced irreversible genetic and epigenetic oncogenic alterations support the possibility for hit-and-run KSHV sarcomagenesis which is consistent with pathological and clinical findings. AUTHOR SUMMARY We performed whole genome RNA sequencing and CpG DNA methylation analysis in a mouse bone-marrow endothelial-lineage cells (mEC) transfected with the KSHVBac36 (mECK36 cells), that are able to form KSHV-infected tumors in nude mice, which were thoroughly characterized as KS-like tumors. This unique model allowed us to dissect genetic and epigenetic mechanisms of KSHV dependent and hit-and-run sarcomagenesis. We found that during KSHV in vivo lytic switch and KSHV-dependent tumorigenesis DNA methylation and Epigenetic regulation are among the most host-regulated pathways. CpG DNA methylation analysis during transformation supports the notion that loss of methylation (hypo-methylation) is the major epigenetic change during this process. Sequence analysis of KSHV-positive tumors revealed that KSHV tumorigenesis not only selects for the presence of the virus but also pre-existing host mutations that allow the KSHV oncovirus to express the oncogenic lytic program and creates a permissive environment of inflammation and viral tumorigenesis providing a selective advantage in vivo.Centro de Investigaciones Inmunológicas Básicas y Aplicada

In vivo methylation of mtDNA reveals the dynamics of protein–mtDNA interactions

To characterize the organization of mtDNA–protein complexes (known as nucleoids) in vivo, we have probed the mtDNA surface exposure using site-specific DNA methyltransferases targeted to the mitochondria. We have observed that DNA methyltransferases have different accessibility to different sites on the mtDNA based on the levels of protein occupancy. We focused our studies on selected regions of mtDNA that are believed to be major regulatory regions involved in transcription and replication. The transcription termination region (TERM) within the tRNALeu(UUR) gene was consistently and strongly protected from methylation, suggesting frequent and high affinity binding of mitochondrial transcription termination factor 1 (mTERF1) to the site. Protection from methylation was also observed in other regions of the mtDNA, including the light and heavy strand promoters (LSP, HSP) and the origin of replication of the light strand (OL). Manipulations aiming at increasing or decreasing the levels of the mitochondrial transcription factor A (TFAM) led to decreased in vivo methylation, whereas manipulations that stimulated mtDNA replication led to increased methylation. We also analyzed the effect of ATAD3 and oxidative stress in mtDNA exposure. Our data provide a map of human mtDNA accessibility and demonstrate that nucleoids are dynamically associated with proteins

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Inflows, Outflows, and a Giant Donor in the Remarkable Recurrent Nova M31N 2008-12a? - Hubble Space Telescope Photometry of the 2015 Eruption

The recurrent nova M31N 2008-12a experiences annual eruptions, contains a near-Chandrasekhar mass white dwarf, and has the largest mass accretion rate in any nova system. In this paper, we present Hubble Space Telescope (HST) WFC3/UVIS photometry of the late decline of the 2015 eruption. We couple these new data with archival HST observations of the quiescent system and Keck spectroscopy of the 2014 eruption. The late-time photometry reveals a rapid decline to a minimum luminosity state, before a possible recovery / re-brightening in the run-up to the next eruption. Comparison with accretion disk models supports the survival of the accretion disk during the eruptions, and uncovers a quiescent disk mass accretion rate of the order of $10^{-6}\,M_\odot\,\mathrm{yr}^{-1}$, which may rise beyond $10^{-5}\,M_\odot\,\mathrm{yr}^{-1}$ during the super-soft source phase - both of which could be problematic for a number of well-established nova eruption models. Such large accretion rates, close to the Eddington limit, might be expected to be accompanied by additional mass loss from the disk through a wind and even collimated outflows. The archival HST observations, combined with the disk modeling, provide the first constraints on the mass donor; $L_\mathrm{donor}=103^{+12}_{-11}\,L_\odot$, $R_\mathrm{donor}=14.14^{+0.46}_{-0.47}\,R_\odot$, and $T_\mathrm{eff, donor}=4890\pm110$ K, which may be consistent with an irradiated M31 red-clump star. Such a donor would require a system orbital period $\gtrsim5$ days. Our updated analysis predicts that the M31N 2008-12a WD could reach the Chandrasekhar mass in < 20 kyr

M31N 2008-12a - the remarkable recurrent nova in M31: Pan-chromatic observations of the 2015 eruption

The Andromeda Galaxy recurrent nova M31N 2008-12a had been observed in eruption ten times, including yearly eruptions from 2008-2014. With a measured recurrence period of $P_\mathrm{rec}=351\pm13$ days (we believe the true value to be half of this) and a white dwarf very close to the Chandrasekhar limit, M31N 2008-12a has become the leading pre-explosion supernova type Ia progenitor candidate. Following multi-wavelength follow-up observations of the 2013 and 2014 eruptions, we initiated a campaign to ensure early detection of the predicted 2015 eruption, which triggered ambitious ground and space-based follow-up programs. In this paper we present the 2015 detection; visible to near-infrared photometry and visible spectroscopy; and ultraviolet and X-ray observations from the Swift observatory. The LCOGT 2m (Hawaii) discovered the 2015 eruption, estimated to have commenced at Aug. $28.28\pm0.12$ UT. The 2013-2015 eruptions are remarkably similar at all wavelengths. New early spectroscopic observations reveal short-lived emission from material with velocities $\sim13000$ km s$^{-1}$, possibly collimated outflows. Photometric and spectroscopic observations of the eruption provide strong evidence supporting a red giant donor. An apparently stochastic variability during the early super-soft X-ray phase was comparable in amplitude and duration to past eruptions, but the 2013 and 2015 eruptions show evidence of a brief flux dip during this phase. The multi-eruption Swift/XRT spectra show tentative evidence of high-ionization emission lines above a high-temperature continuum. Following Henze et al. (2015a), the updated recurrence period based on all known eruptions is $P_\mathrm{rec}=174\pm10$ d, and we expect the next eruption of M31N 2008-12a to occur around mid-Sep. 2016

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET

Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate