Calcium Pyrophosphate Crystal Deposition: The Effect of Soluble Iron in a Kinetic Study Using a Gelatin Matrix Model

The kinetics of calcium pyrophosphate dihydrate (CPPD) crystal growth was studied by allowing calcium and pyrophosphate (PPi-4) ions to diffuse through a denatured collagen matrix (biological grade gelatin) in the presence of either ferric or ferrous ions. Ferric and, to some extent, ferrous ions blocked the migration of the PPi-4 diffusion gradient. This retardation in the [PPi-4] gradient led to numerous changes in the patterns of CPPD crystal formation. At the initial stages of crystal growth, the iron ions induced more crystal growth compared to control. At later incubation times, ferrous and ferric ions enhanced crystal growth at the expense of crystal nucleation. The presence of both ferrous and ferric ions resulted in the more rapid formation of the two crystals observed in vivo, triclinic CPPD and monoclinic CPPD. Further, both ferrous and ferric ions also reduced the solubility of the crystalline material in the broad diffuse band which formed when the Ca+2 and PPi-4 gradients first met. In this system, the presence of either ferrous or ferric ions increased the amount of hydroxyproline included in the crystalline precipitates. Iron was also incorporated into the crystals, particularly into the triclinic CPPD and monoclinic CPPD crystals

Calcium Pyrophosphate Crystal Deposition: The Effect of Monosodium Urate and Apatite Crystals in a Kinetic Study Using a Gelatin Matrix Model

The kinetics of calcium pyrophosphate dihydrate (CPPD) crystal growth was studied by allowing calcium and pyrophosphate (PPi-4) ions to diffuse through a denatured collagen matrix (biological grade gelatin) in the presence of either monosodium urate monohydrate (MSU) or hydroxyapatite (HA) crystals. In this in vitro model system, MSU crystals significantly altered the kinetics of PPi-4 ionic diffusion through the gelatin matrix by allowing the [PPi-4] gradient to fall off much more rapidly, suggesting an increased level of scavenging of PPi-4 ions into crystalline materials. Even more significantly, the presence of MSU crystals markedly influenced the crystal growth morphology of triclinic CPPD, producing that observed in vivo. A large number of epitaxially dimensional matches between MSU and triclinic (t) and monoclinic (m) CPPD were identified, suggesting that MSU crystals can epitaxially induce CPPD crystal growth. This finding supports the hypothesis that the association of urate gout and CPPD crystal deposition disease is based on the nucleating potential of MSU crystals for CPPD crystal growth. In contrast, the HA crystal structure did not appear to serve as a nucleating agent for CPPD crystals. However, HA crystals did serve as effective traps for PPi-4 ions and their presence led to more stable CPPD crystal growth

Calcium Pyrophosphate Crystal Deposition: A Kinetic Study Using a Type I Collagen Gel Model

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is characterized by deposits of triclinic (t) and monoclinic (m) CPPD crystals in articular and fibrocartilage. Many investigators have attempted to model CPPD crystal growth using both solution and a variety of gel systems. We have investigated the effect of type I collagen fibrils on CPPD crystal nucleation and growth using an ionic diffusion model. Collagen was isolated from porcine menisci using a pepsin solubilization procedure and gelled in three layers, with one containing 10 mM pyrophosphate (PPi) plus physiologic ions, the middle containing only the ions, while the third contained 25 mM Ca plus physiologic ions. Initially, amorphorous calcium pyrophosphate formed at the Ca-PPi interface. Monoclinic CPPD crystallized in 6 weeks when the [Ca] was between 2 and 3 mM and the [PPi] was between 50 and 75 μM. At 13 weeks, t-CPPD formed when the [Ca] was also between 2 and 3 mM, but the PPi was less than 25 μM. One of the most striking differences between this system and all previous solution and gel model systems is the total absence of orthorhombic calcium pyrophosphate tetrahydrate (o-CPPT) from the gels made of collagen fibrils in near native conformation. Further, crystals of t-CPPD appear as large single crystals with the classic prismatic growth habit observed in vivo, and crystals of m-CPPD also evidence the in vivo rod habit. In contrast, the crystal growth habits of t-CPPD, m-CPPD, and o-CPPT grown in all of the other model systems never matched that observed in vivo. When compared to the previous studies, these results, particularly the crystal growth habit data, suggest that the native collagen fibrils themselves can nucleate CPPD crystal formation

Detection Strategies for Extreme Mass Ratio Inspirals

The capture of compact stellar remnants by galactic black holes provides a unique laboratory for exploring the near horizon geometry of the Kerr spacetime, or possible departures from general relativity if the central cores prove not to be black holes. The gravitational radiation produced by these Extreme Mass Ratio Inspirals (EMRIs) encodes a detailed map of the black hole geometry, and the detection and characterization of these signals is a major scientific goal for the LISA mission. The waveforms produced are very complex, and the signals need to be coherently tracked for hundreds to thousands of cycles to produce a detection, making EMRI signals one of the most challenging data analysis problems in all of gravitational wave astronomy. Estimates for the number of templates required to perform an exhaustive grid-based matched-filter search for these signals are astronomically large, and far out of reach of current computational resources. Here I describe an alternative approach that employs a hybrid between Genetic Algorithms and Markov Chain Monte Carlo techniques, along with several time saving techniques for computing the likelihood function. This approach has proven effective at the blind extraction of relatively weak EMRI signals from simulated LISA data sets.Comment: 10 pages, 4 figures, Updated for LISA 8 Symposium Proceeding

Massive Black Hole Binary Inspirals: Results from the LISA Parameter Estimation Taskforce

The LISA Parameter Estimation (LISAPE) Taskforce was formed in September 2007 to provide the LISA Project with vetted codes, source distribution models, and results related to parameter estimation. The Taskforce's goal is to be able to quickly calculate the impact of any mission design changes on LISA's science capabilities, based on reasonable estimates of the distribution of astrophysical sources in the universe. This paper describes our Taskforce's work on massive black-hole binaries (MBHBs). Given present uncertainties in the formation history of MBHBs, we adopt four different population models, based on (i) whether the initial black-hole seeds are small or large, and (ii) whether accretion is efficient or inefficient at spinning up the holes. We compare four largely independent codes for calculating LISA's parameter-estimation capabilities. All codes are based on the Fisher-matrix approximation, but in the past they used somewhat different signal models, source parametrizations and noise curves. We show that once these differences are removed, the four codes give results in extremely close agreement with each other. Using a code that includes both spin precession and higher harmonics in the gravitational-wave signal, we carry out Monte Carlo simulations and determine the number of events that can be detected and accurately localized in our four population models.Comment: 14 pages, 2 figures, 5 tables, minor changes to match version to be published in the proceedings of the 7th LISA Symposium. For more information see the Taskforce's wiki at http://www.tapir.caltech.edu/dokuwiki/lisape:hom

The Mock LISA Data Challenges: from Challenge 3 to Challenge 4

The Mock LISA Data Challenges are a program to demonstrate LISA data-analysis capabilities and to encourage their development. Each round of challenges consists of one or more datasets containing simulated instrument noise and gravitational waves from sources of undisclosed parameters. Participants analyze the datasets and report best-fit solutions for the source parameters. Here we present the results of the third challenge, issued in Apr 2008, which demonstrated the positive recovery of signals from chirping Galactic binaries, from spinning supermassive--black-hole binaries (with optimal SNRs between ~ 10 and 2000), from simultaneous extreme-mass-ratio inspirals (SNRs of 10-50), from cosmic-string-cusp bursts (SNRs of 10-100), and from a relatively loud isotropic background with Omega_gw(f) ~ 10^-11, slightly below the LISA instrument noise.Comment: 12 pages, 2 figures, proceedings of the 8th Edoardo Amaldi Conference on Gravitational Waves, New York, June 21-26, 200

Supplement: "Going the Distance: Mapping Host Galaxies of LIGO and Virgo Sources in Three Dimensions Using Local Cosmography and Targeted Follow-up" (2016, ApJL, 829, L15)

This is a supplement to the Letter of Singer et al., in which we demonstrated a rapid algorithm for obtaining joint 3D estimates of sky location and luminosity distance from observations of binary neutron star mergers with Advanced LIGO and Virgo. We argued that combining the reconstructed volumes with positions and redshifts of possible host galaxies can provide large-aperture but small field of view instruments with a manageable list of targets to search for optical or infrared emission. In this Supplement, we document the new HEALPix-based file format for 3D localizations of gravitational-wave transients. We include Python sample code to show the reader how to perform simple manipulations of the 3D sky maps and extract ranked lists of likely host galaxies. Finally, we include mathematical details of the rapid volume reconstruction algorithm

The Druze: A Population Genetic Refugium of the Near East

BACKGROUND: Phylogenetic mitochondrial DNA haplogroups are highly partitioned across global geographic regions. A unique exception is the X haplogroup, which has a widespread global distribution without major regions of distinct localization. PRINCIPAL FINDINGS: We have examined mitochondrial DNA sequence variation together with Y-chromosome-based haplogroup structure among the Druze, a religious minority with a unique socio-demographic history residing in the Near East. We observed a striking overall pattern of heterogeneous parental origins, consistent with Druze oral tradition, together with both a high frequency and a high diversity of the mitochondrial DNA (mtDNA) X haplogroup within a confined regional subpopulation. Furthermore demographic modeling indicated low migration rates with nearby populations. CONCLUSIONS: These findings were enabled through the use of a paternal kindred based sampling approach, and suggest that the Galilee Druze represent a population isolate, and that the combination of a high frequency and diversity of the mtDNA X haplogroup signifies a phylogenetic refugium, providing a sample snapshot of the genetic landscape of the Near East prior to the modern age

The Mock LISA Data Challenges: from Challenge 1B to Challenge 3

The Mock LISA Data Challenges are a programme to demonstrate and encourage the development of LISA data-analysis capabilities, tools and techniques. At the time of this workshop, three rounds of challenges had been completed, and the next was about to start. In this article we provide a critical analysis of entries to the latest completed round, Challenge 1B. The entries confirm the consolidation of a range of data-analysis techniques for Galactic and massive--black-hole binaries, and they include the first convincing examples of detection and parameter estimation of extreme--mass-ratio inspiral sources. In this article we also introduce the next round, Challenge 3. Its data sets feature more realistic waveform models (e.g., Galactic binaries may now chirp, and massive--black-hole binaries may precess due to spin interactions), as well as new source classes (bursts from cosmic strings, isotropic stochastic backgrounds) and more complicated nonsymmetric instrument noise.Comment: 20 pages, 3 EPS figures. Proceedings of the 12th Gravitational Wave Data Analysis Workshop, Cambridge MA, 13--16 December 2007. Typos correcte

Interactome Analyses Identify Ties of PrPC and Its Mammalian Paralogs to Oligomannosidic N-Glycans and Endoplasmic Reticulum-Derived Chaperones

The physiological environment which hosts the conformational conversion of the cellular prion protein (PrPC) to disease-associated isoforms has remained enigmatic. A quantitative investigation of the PrPC interactome was conducted in a cell culture model permissive to prion replication. To facilitate recognition of relevant interactors, the study was extended to Doppel (Prnd) and Shadoo (Sprn), two mammalian PrPC paralogs. Interestingly, this work not only established a similar physiological environment for the three prion protein family members in neuroblastoma cells, but also suggested direct interactions amongst them. Furthermore, multiple interactions between PrPC and the neural cell adhesion molecule, the laminin receptor precursor, Na/K ATPases and protein disulfide isomerases (PDI) were confirmed, thereby reconciling previously separate findings. Subsequent validation experiments established that interactions of PrPC with PDIs may extend beyond the endoplasmic reticulum and may play a hitherto unrecognized role in the accumulation of PrPSc. A simple hypothesis is presented which accounts for the majority of interactions observed in uninfected cells and suggests that PrPC organizes its molecular environment on account of its ability to bind to adhesion molecules harboring immunoglobulin-like domains, which in turn recognize oligomannose-bearing membrane proteins