BSSN in Spherical Symmetry

The BSSN (Baumgarte-Shapiro-Shibata-Nakamura) formulation of the Einstein evolution equations is written in spherical symmetry. These equations can be used to address a number of technical and conceptual issues in numerical relativity in the context of a single Schwarzschild black hole. One of the benefits of spherical symmetry is that the numerical grid points can be tracked on a Kruskal--Szekeres diagram. Boundary conditions suitable for puncture evolution of a Schwarzschild black hole are presented. Several results are shown for puncture evolution using a fourth--order finite difference implementation of the equations.Comment: This is the final version to be published in CQG. It contains much more information and detail than the original versio

Relativistic MHD and black hole excision: Formulation and initial tests

A new algorithm for solving the general relativistic MHD equations is described in this paper. We design our scheme to incorporate black hole excision with smooth boundaries, and to simplify solving the combined Einstein and MHD equations with AMR. The fluid equations are solved using a finite difference Convex ENO method. Excision is implemented using overlapping grids. Elliptic and hyperbolic divergence cleaning techniques allow for maximum flexibility in choosing coordinate systems, and we compare both methods for a standard problem. Numerical results of standard test problems are presented in two-dimensional flat space using excision, overlapping grids, and elliptic and hyperbolic divergence cleaning.Comment: 22 pages, 8 figure

Accurate evolutions of unequal-mass neutron-star binaries: properties of the torus and short GRB engines

We present new results from accurate and fully general-relativistic simulations of the coalescence of unmagnetized binary neutron stars with various mass ratios. The evolution of the stars is followed through the inspiral phase, the merger and prompt collapse to a black hole, up until the appearance of a thick accretion disk, which is studied as it enters and remains in a regime of quasi-steady accretion. Although a simple ideal-fluid equation of state with \Gamma=2 is used, this work presents a systematic study within a fully general relativistic framework of the properties of the resulting black-hole--torus system produced by the merger of unequal-mass binaries. More specifically, we show that: (1) The mass of the torus increases considerably with the mass asymmetry and equal-mass binaries do not produce significant tori if they have a total baryonic mass M_tot >~ 3.7 M_sun; (2) Tori with masses M_tor ~ 0.2 M_sun are measured for binaries with M_tot ~ 3.4 M_sun and mass ratios q ~ 0.75-0.85; (3) The mass of the torus can be estimated by the simple expression M_tor(q, M_tot) = [c_1 (1-q) + c_2](M_max-M_tot), involving the maximum mass for the binaries and coefficients constrained from the simulations, and suggesting that the tori can have masses as large as M_tor ~ 0.35 M_sun for M_tot ~ 2.8 M_sun and q ~ 0.75-0.85; (4) Using a novel technique to analyze the evolution of the tori we find no evidence for the onset of non-axisymmetric instabilities and that very little, if any, of their mass is unbound; (5) Finally, for all the binaries considered we compute the complete gravitational waveforms and the recoils imparted to the black holes, discussing the prospects of detection of these sources for a number of present and future detectors.Comment: 35 pages; small changes to match the published versio

The discrete energy method in numerical relativity: Towards long-term stability

The energy method can be used to identify well-posed initial boundary value problems for quasi-linear, symmetric hyperbolic partial differential equations with maximally dissipative boundary conditions. A similar analysis of the discrete system can be used to construct stable finite difference equations for these problems at the linear level. In this paper we apply these techniques to some test problems commonly used in numerical relativity and observe that while we obtain convergent schemes, fast growing modes, or ``artificial instabilities,'' contaminate the solution. We find that these growing modes can partially arise from the lack of a Leibnitz rule for discrete derivatives and discuss ways to limit this spurious growth.Comment: 18 pages, 22 figure

Grazing Collisions of Black Holes via the Excision of Singularities

We present the first simulations of non-headon (grazing) collisions of binary black holes in which the black hole singularities have been excised from the computational domain. Initially two equal mass black holes $m$ are separated a distance $\approx10m$ and with impact parameter $\approx2m$. Initial data are based on superposed, boosted (velocity $\approx0.5c$) solutions of single black holes in Kerr-Schild coordinates. Both rotating and non-rotating black holes are considered. The excised regions containing the singularities are specified by following the dynamics of apparent horizons. Evolutions of up to $t \approx 35m$ are obtained in which two initially separate apparent horizons are present for $t\approx3.8m$. At that time a single enveloping apparent horizon forms, indicating that the holes have merged. Apparent horizon area estimates suggest gravitational radiation of about 2.6% of the total mass. The evolutions end after a moderate amount of time because of instabilities.Comment: 2 References corrected, reference to figure update

The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling

BACKGROUND & AIMS: Chromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer-associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic.METHODS: We performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, gamma-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2'-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients.RESULTS: High expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients.CONCLUSIONS: We found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors

Murine and Bovine γδ T Cells Enhance Innate Immunity against Brucella abortus Infections

γδ T cells have been postulated to act as a first line of defense against infectious agents, particularly intracellular pathogens, representing an important link between the innate and adaptive immune responses. Human γδ T cells expand in the blood of brucellosis patients and are active against Brucella in vitro. However, the role of γδ T cells in vivo during experimental brucellosis has not been studied. Here we report TCRδ−/− mice are more susceptible to B. abortus infection than C57BL/6 mice at one week post-infection as measured by splenic colonization and splenomegaly. An increase in TCRγδ cells was observed in the spleens of B. abortus-infected C57BL/6 mice, which peaked at two weeks post-infection and occurred concomitantly with diminished brucellae. γδ T cells were the major source of IL-17 following infection and also produced IFN-γ. Depletion of γδ T cells from C57BL/6, IL-17Rα−/−, and GMCSF−/− mice enhanced susceptibility to B. abortus infection although this susceptibility was unaltered in the mutant mice; however, when γδ T cells were depleted from IFN-γ−/− mice, enhanced susceptibility was observed. Neutralization of γδ T cells in the absence of TNF-α did not further impair immunity. In the absence of TNF-α or γδ T cells, B. abortus-infected mice showed enhanced IFN-γ, suggesting that they augmented production to compensate for the loss of γδ T cells and/or TNF-α. While the protective role of γδ T cells was TNF-α-dependent, γδ T cells were not the major source of TNF-α and activation of γδ T cells following B. abortus infection was TNF-α-independent. Additionally, bovine TCRγδ cells were found to respond rapidly to B. abortus infection upon co-culture with autologous macrophages and could impair the intramacrophage replication of B. abortus via IFN-γ. Collectively, these results demonstrate γδ T cells are important for early protection to B. abortus infections

Tomato Pathogenesis-related Protein Genes are Expressed in Response to Trialeurodes vaporariorum and Bemisia tabaci Biotype B Feeding

The temporal and spatial expression of tomato wound- and defense-response genes to Bemisia tabaci biotype B (the silverleaf whitefly) and Trialeurodes vaporariorum (the greenhouse whitefly) feeding were characterized. Both species of whiteflies evoked similar changes in tomato gene expression. The levels of RNAs for the methyl jasmonic acid (MeJA)- or ethylene-regulated genes that encode the basic β-1,3-glucanase (GluB), basic chitinase (Chi9), and Pathogenesis-related protein-1 (PR-1) were monitored. GluB and Chi9 RNAs were abundant in infested leaves from the time nymphs initiated feeding (day 5). In addition, GluB RNAs accumulated in apical non-infested leaves. PR-1 RNAs also accumulated after whitefly feeding. In contrast, the ethylene- and salicylic acid (SA)-regulated Chi3 and PR-4 genes had RNAs that accumulated at low levels and GluAC RNAs that were undetectable in whitefly-infested tomato leaves. The changes in Phenylalanine ammonia lyase5 (PAL5) were variable; in some, but not all infestations, PAL5 RNAs increased in response to whitefly feeding. PAL5 RNA levels increased in response to MeJA, ethylene, and abscisic acid, and declined in response to SA. Transcripts from the wound-response genes, leucine aminopeptidase (LapA1) and proteinase inhibitor 2 (pin2), were not detected following whitefly feeding. Furthermore, whitefly infestation of transgenic LapA1:GUS tomato plants showed that whitefly feeding did not activate the LapA1 promoter, although crushing of the leaf lamina increased GUS activity up to 40 fold. These studies indicate that tomato plants perceive B. tabaci and T. vaporariorum in a manner similar to baterical pathogens and distinct from tissue-damaging insects

Whole Genome Sequences of Three Treponema pallidum ssp. pertenue Strains: Yaws and Syphilis Treponemes Differ in Less than 0.2% of the Genome Sequence

Spirochete Treponema pallidum ssp. pertenue (TPE) is the causative agent of yaws while strains of Treponema pallidum ssp. pallidum (TPA) cause syphilis. Both yaws and syphilis are distinguished on the basis of epidemiological characteristics and clinical symptoms. Neither treponeme can reproduce outside the host organism, which precludes the use of standard molecular biology techniques used to study cultivable pathogens. In this study, we determined high quality whole genome sequences of TPE strains and compared them to known genetic information for T. pallidum ssp. pallidum strains. The genome structure was identical in all three TPE strains and also between TPA and TPE strains. The TPE genome length ranged between 1,139,330 bp and 1,139,744 bp. The overall sequence identity between TPA and TPE genomes was 99.8%, indicating that the two pathogens are extremely closely related. A set of 34 TPE genes (3.5%) encoded proteins containing six or more amino acid replacements or other major sequence changes. These genes more often belonged to the group of genes with predicted virulence and unknown functions suggesting their involvement in infection differences between yaws and syphilis