Optimization of graded multilayer designs for astronomical x-ray telescopes

We developed a systematic method for optimizing the design of depth-graded multilayers for astronomical hard-x-ray and soft-γ-ray telescopes based on the instrument’s bandpass and the field of view. We apply these methods to the design of the conical-approximation Wolter I optics employed by the balloon-borne High Energy Focusing Telescope, using W/Si as the multilayer materials. In addition, we present optimized performance calculations of mirrors, using other material pairs that are capable of extending performance to photon energies above the W K-absorption edge (69.5 keV), including Pt/C, Ni/C, Cu/Si, and Mo/Si

A signaling visualization toolkit to support rational design of combination therapies and biomarker discovery: SiViT

Targeted cancer therapy aims to disrupt aberrant cellular signalling pathways. Biomarkers are surrogates of pathway state, but there is limited success in translating candidate biomarkers to clinical practice due to the intrinsic complexity of pathway networks. Systems biology approaches afford better understanding of complex, dynamical interactions in signalling pathways targeted by anticancer drugs. However, adoption of dynamical modelling by clinicians and biologists is impeded by model inaccessibility. Drawing on computer games technology, we present a novel visualisation toolkit, SiViT, that converts systems biology models of cancer cell signalling into interactive simulations that can be used without specialist computational expertise. SiViT allows clinicians and biologists to directly introduce for example loss of function mutations and specific inhibitors. SiViT animates the effects of these introductions on pathway dynamics, suggesting further experiments and assessing candidate biomarker effectiveness. In a systems biology model of Her2 signalling we experimentally validated predictions using SiViT, revealing the dynamics of biomarkers of drug resistance and highlighting the role of pathway crosstalk. No model is ever complete: the iteration of real data and simulation facilitates continued evolution of more accurate, useful models. SiViT will make accessible libraries of models to support preclinical research, combinatorial strategy design and biomarker discovery

Identifying prognostic structural features in tissue sections of colon cancer patients using point pattern analysis

Diagnosis and prognosis of cancer is informed by the architecture inherent in cancer patient tissue sections. This architecture is typically identified by pathologists, yet advances in computational image analysis facilitate quantitative assessment of this structure. In this article we develop a spatial point process approach in order to describe patterns in cell distribution within tissue samples taken from colorectal cancer (CRC) patients. In particular, our approach is centered on the Palm intensity function. This leads to taking an approximate-likelihood technique in fitting point processes models. We consider two Neyman-Scott point processes and a void process, fitting these point process models to the CRC patient data. We find that the parameter estimates of these models may be used to quantify the spatial arrangement of cells. Importantly, we observe characteristic differences in the spatial arrangement of cells between patients who died from CRC and those alive at follow-up

Coral community decline at Bonaire, Southern Caribbean

We assessed the status of coral reef benthic communities at Bonaire, Netherlands Antilles, in December 2008 and January 2009 through ∼5 km of photo transects taken at depths of 5, 10, and 20 m at 14 locations around the island. Univariate and multivariate analyses detected significant variation in benthic communities among depths and locations, as well as between leeward and windward sides of the island. Mean percentage cover of scleractinian corals ranged between 0.2% and 43.6% at the study sites and tended to be lowest at 5-m depth. The survey recorded 40 scleractinian coral species from 19 genera, within 10 families. Faviidae were by far the most abundant scleractinian family at all depths (predominantly Montastraea spp.), followed by Agariciidae at 20 and 10 m, and by Astrocoeniidae at 5-m depth. Macroalgal cover exceeded scleractinian coral cover at nearly all sites, averaging 34.9% (all samples pooled), compared with a pooled mean coral cover of 15.4%. Windward reefs were characterized by prolific growth of the brown algae Sargassum spp., and leeward reefs by growth of turf algae, Dictyota spp., Trichogloeopsis pedicellata (Howe) I. A. Abbott & Doty, and Lobophora variegata (Lamouroux) Womersley ex Oliveira. Damage from recent hurricanes was evident from the presence of toppled and fragmented corals, the movement of sand, and exposure of cemented Acropora cervicornis (Lamarck, 1816) rubble on the shallow reef platform. The combination of algal dominance and low to moderate coral cover are symptomatic of partly degraded reef systems, particularly as they coincide with elevated nutrients and reduced herbivory

Development of thermally formed glass optics for astronomical hard x-ray telescopes

The next major observational advance in hard X-ray/soft gamma-ray astrophysics will come with the implementation of telescopes capable of focusing 10-200 keV radiation. Focusing allows high signal-to-noise imaging and spectroscopic observations of many sources in this band for the first time. The recent development of depth-graded multilayer coatings has made the design of telescopes for this bandpass practical, however the ability to manufacture inexpensive substrates with appropriate surface quality and figure to achieve sub-arcminute performance has remained an elusive goal. In this paper, we report on new, thermally-formed glass micro-sheet optics capable of meeting the requirements of the next-generation of astronomical hard X-ray telescopes

The Rich Mid-Infrared Environments of Two Highly-Obscured X-ray Binaries: Spitzer Observations of IGR J16318-4848 and GX 301-2

We present the results of Spitzer mid-infrared spectroscopic observations of two highly-obscured massive X-ray binaries: IGR J16318-4848 and GX301-2. Our observations reveal for the first time the extremely rich mid-infrared environments of this type of source, including multiple continuum emission components (a hot component with T > 700 K and a warm component with T ~ 180 K) with apparent silicate absorption features, numerous HI recombination lines, many forbidden ionic lines of low ionization potentials, and pure rotational H2 lines. This indicates that both sources have hot and warm circumstellar dust, ionized stellar winds, extended low-density ionized regions, and photo-dissociated regions. It appears difficult to attribute the total optical extinction of both sources to the hot and warm dust components, which suggests that there could be an otherwise observable colder dust component responsible for the most of the optical extinction and silicate absorption features. The observed mid-infrared spectra are similar to those from Luminous Blue Variables, indicating that the highly-obscured massive X-ray binaries may represent a previously unknown evolutionary phase of X-ray binaries with early-type optical companions. Our results highlight the importance and utility of mid-infrared spectroscopy to investigate highly-obscured X-ray binaries.Comment: To appear in ApJ Letter

The fast transient sky with Gaia

The ESA Gaia satellite scans the whole sky with a temporal sampling ranging from seconds and hours to months. Each time a source passes within the Gaia field of view, it moves over 10 CCDs in 45 s and a lightcurve with 4.5 s sampling (the crossing time per CCD) is registered. Given that the 4.5 s sampling represents a virtually unexplored parameter space in optical time domain astronomy, this data set potentially provides a unique opportunity to open up the fast transient sky. We present a method to start mining the wealth of information in the per CCD Gaia data. We perform extensive data filtering to eliminate known on-board and data processing artefacts, and present a statistical method to identify sources that show transient brightness variations on ~2 hours timescales. We illustrate that by using the Gaia photometric CCD measurements, we can detect transient brightness variations down to an amplitude of 0.3 mag on timescales ranging from 15 seconds to several hours. We search an area of ~23.5 square degrees on the sky, and find four strong candidate fast transients. Two candidates are tentatively classified as flares on M-dwarf stars, while one is probably a flare on a giant star and one potentially a flare on a solar type star. These classifications are based on archival data and the timescales involved. We argue that the method presented here can be added to the existing Gaia Science Alerts infrastructure for the near real-time public dissemination of fast transient events.Comment: 10 pages, 5 figures and 5 tables; MNRAS in pres

Structural and Functional Dissection of Mif2p, a Conserved DNA-binding Kinetochore Protein

Mif2p is the budding-yeast orthologue of the mammalian centromere-binding protein CENP-C. We have mapped domains of Saccharomyces cerevisiae Mif2p and studied the phenotyptic consequences of their deletion. Using chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays, we have further shown that Mif2p binds in the CDEIII region of the budding-yeast centromere, probably in close spatial association with Ndc10p. Moreover, ChIP experiments show that Mif2p recruits to yeast kinetochores a substantial subset of inner and outer kinetochore proteins, but not the Ndc80 or Spc105 complexes. We have determined the crystal structure of the C-terminal, dimerization domain of Mif2p. It has a "cupin" fold, extremely similar both in polypeptide chain conformation and in dimer geometry to the dimerization domain of a bacterial transcription factor. The Mif2p dimer seems to be part of an enhanceosome-like structure that nucleates kinetochore assembly in budding yeast.Molecular and Cellular Biolog