Large Highly-Ionized Nebulae Around Ultra-luminous X-ray Sources

We present the results of deep optical spectroscopic observations using the LRIS spectrograph on the Keck I 10-m telescope of three ultra-luminous X-ray sources (ULXs), Ho IX X-1; M81 X-6; and Ho II X-1. Our observations reveal the existence of large (100 - 200 pc diameter) highly-ionized nebulae, identified by diffuse He II (4686 Angstrom) emission, surrounding these sources. Our results are the first to find highly-ionized nebulae of this extent, and the detection in all three objects indicates this may be a common feature of ULXs. In addition to the extended emission, Ho IX X-1 has an unresolved central component containing about one-third of the total He II flux, with a significant velocity dispersion of ~ 370 km/s, suggestive of the existence of a photo-ionized accretion disk or an extremely hot early-type stellar counterpart. Most of the He II emission appears to be surrounded by significantly more extended Hbeta emission, and the intensity ratios between the two lines, which range from 0.12 - 0.33, indicate that photo-ionization is the origin of the He II emission. Sustaining these extended nebulae requires substantial X-ray emission, in the range ~ 10^{39} - 10^{40} ergs/s, comparable to the measured X-ray luminosities of the sources. This favors models where the X-ray emission is isotropic, rather than beamed, which includes the interpretation that ULXs harbor intermediate-mass black holes.Comment: Accepted for publication in ApJ Letter

The Chandra ACIS Survey of M33 (ChASeM33): The final source catalog

This study presents the final source catalog of the Chandra ACIS Survey of M33 (ChASeM33). With a total exposure time of 1.4 Ms, ChASeM33 covers ~70% of the D25 isophote (R\approx4kpc) of M33 and provides the deepest, most complete, and detailed look at a spiral galaxy in X-rays. The source catalog includes 662 sources, reaches a limiting unabsorbed luminosity of ~2.4x10^(34) erg/s in the 0.35-8.0keV energy band, and contains source positions, source net counts, fluxes and significances in several energy bands, and information on source variability. The analysis challenges posed by ChASeM33 and the techniques adopted to address these challenges are discussed. To constrain the nature of the detected X-ray source, hardness ratios were constructed and spectra were fit for 254 sources, followup MMT spectra of 116 sources were acquired, and cross-correlations with previous X-ray catalogs and other multi-wavelength data were generated. Based on this effort, 183 of the 662 ChASeM33 sources could be identified. Finally, the luminosity function for the detected point sources as well as the one for the X-ray binaries in M33 is presented. The luminosity functions in the soft band (0.5-2.0 keV) and the hard band (2.0-8.0 keV) have a limiting luminosity at the 90% completeness limit of 4.0x10^(34) erg/s and 1.6x10^(35) erg/s (for D=817kpc), respectively, which is significantly lower than what was reported by previous X-ray binary population studies in galaxies more distant than M33. The resulting distribution is consistent with a dominant population of high mass X-ray binaries as would be expected for M33.Comment: 186 pages, 11 figures, 10 tables. Accepted for publication in the ApJS. For a high resolution version of the paper, see http://hea-www.harvard.edu/vlp_m33_public

Imbibition in Disordered Media

The physics of liquids in porous media gives rise to many interesting phenomena, including imbibition where a viscous fluid displaces a less viscous one. Here we discuss the theoretical and experimental progress made in recent years in this field. The emphasis is on an interfacial description, akin to the focus of a statistical physics approach. Coarse-grained equations of motion have been recently presented in the literature. These contain terms that take into account the pertinent features of imbibition: non-locality and the quenched noise that arises from the random environment, fluctuations of the fluid flow and capillary forces. The theoretical progress has highlighted the presence of intrinsic length-scales that invalidate scale invariance often assumed to be present in kinetic roughening processes such as that of a two-phase boundary in liquid penetration. Another important fact is that the macroscopic fluid flow, the kinetic roughening properties, and the effective noise in the problem are all coupled. Many possible deviations from simple scaling behaviour exist, and we outline the experimental evidence. Finally, prospects for further work, both theoretical and experimental, are discussed.Comment: Review article, to appear in Advances in Physics, 53 pages LaTe

The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

The Two-State Prehensile Tail of the Antibacterial Toxin Colicin N

Intrinsically disordered regions within proteins are critical elements in many biomolecular interactions and signaling pathways. Antibacterial toxins of the colicin family, which could provide new antibiotic functions against resistant bacteria, contain disordered N-terminal translocation domains (T-domains) that are essential for receptor binding and the penetration of the Escherichia coli outer membrane. Here we investigate the conformational behavior of the T-domain of colicin N (ColN-T) to understand why such domains are widespread in toxins that target Gram-negative bacteria. Like some other intrinsically disordered proteins in the solution state of the protein, ColN-T shows dual recognition, initially interacting with other domains of the same colicin N molecule and later, during cell killing, binding to two different receptors, OmpF and TolA, in the target bacterium. ColN-T is invisible in the high-resolution x-ray model and yet accounts for 90 of the toxin’s 387 amino acid residues. To reveal its solution structure that underlies such a dynamic and complex system, we carried out mutagenic, biochemical, hydrodynamic and structural studies using analytical ultracentrifugation, NMR, and small-angle x-ray scattering on full-length ColN and its fragments. The structure was accurately modeled from small-angle x-ray scattering data by treating ColN as a flexible system, namely by the ensemble optimization method, which enables a distribution of conformations to be included in the final model. The results reveal, to our knowledge, for the first time the dynamic structure of a colicin T-domain. ColN-T is in dynamic equilibrium between a compact form, showing specific self-recognition and resistance to proteolysis, and an extended form, which most likely allows for effective receptor binding