What is the nature of morality? A response to Casebeer, Railton and Ruse

A response to comments by William Casebeer, Peter Railton, and Michael Ruse on "Naturalizing Ethics" (2007)

Intestinal stem cell dynamics: a story of mice and humans

Stem cell dynamics define the probability of accumulating mutations within the intestinal epithelium. In this issue of Cell Stem Cell, Nicholson et al. (2018) report that human intestinal stem cell dynamics differ significantly from those of mice and establish that oncogenic mutations are more likely to expand; therefore, "normal" epithelium may carry multiple mutations

Time-frequency detection algorithm for gravitational wave bursts

An efficient algorithm is presented for the identification of short bursts of gravitational radiation in the data from broad-band interferometric detectors. The algorithm consists of three steps: pixels of the time-frequency representation of the data that have power above a fixed threshold are first identified. Clusters of such pixels that conform to a set of rules on their size and their proximity to other clusters are formed, and a final threshold is applied on the power integrated over all pixels in such clusters. Formal arguments are given to support the conjecture that this algorithm is very efficient for a wide class of signals. A precise model for the false alarm rate of this algorithm is presented, and it is shown using a number of representative numerical simulations to be accurate at the 1% level for most values of the parameters, with maximal error around 10%.Comment: 26 pages, 15 figures, to appear in PR

An excess power statistic for detection of burst sources of gravitational radiation

We examine the properties of an excess power method to detect gravitational waves in interferometric detector data. This method is designed to detect short-duration (< 0.5 s) burst signals of unknown waveform, such as those from supernovae or black hole mergers. If only the bursts' duration and frequency band are known, the method is an optimal detection strategy in both Bayesian and frequentist senses. It consists of summing the data power over the known time interval and frequency band of the burst. If the detector noise is stationary and Gaussian, this sum is distributed as a chi-squared (non-central chi-squared) deviate in the absence (presence) of a signal. One can use these distributions to compute frequentist detection thresholds for the measured power. We derive the method from Bayesian analyses and show how to compute Bayesian thresholds. More generically, when only upper and/or lower bounds on the bursts duration and frequency band are known, one must search for excess power in all concordant durations and bands. Two search schemes are presented and their computational efficiencies are compared. We find that given reasonable constraints on the effective duration and bandwidth of signals, the excess power search can be performed on a single workstation. Furthermore, the method can be almost as efficient as matched filtering when a large template bank is required. Finally, we derive generalizations of the method to a network of several interferometers under the assumption of Gaussian noise.Comment: 22 pages, 6 figure

Detecting gravitational waves from precessing binaries of spinning compact objects: Adiabatic limit

Black-hole (BH) binaries with single-BH masses m=5--20 Msun, moving on quasicircular orbits, are among the most promising sources for first-generation ground-based gravitational-wave (GW) detectors. Until now, the development of data-analysis techniques to detect GWs from these sources has been focused mostly on nonspinning BHs. The data-analysis problem for the spinning case is complicated by the necessity to model the precession-induced modulations of the GW signal, and by the large number of parameters needed to characterize the system, including the initial directions of the spins, and the position and orientation of the binary with respect to the GW detector. In this paper we consider binaries of maximally spinning BHs, and we work in the adiabatic-inspiral regime to build families of modulated detection templates that (i) are functions of very few physical and phenomenological parameters, (ii) model remarkably well the dynamical and precessional effects on the GW signal, with fitting factors on average >~ 0.97, but (iii) might require increasing the detection thresholds, offsetting at least partially the gains in the fitting factors. Our detection-template families are quite promising also for the case of neutron-star--black-hole binaries, with fitting factors on average ~ 0.93. For these binaries we also suggest (but do not test) a further template family, which would produce essentially exact waveforms written directly in terms of the physical spin parameters.Comment: 38 pages, 16 figures, RevTeX4. Final PRD version. Lingering typos corrected. Small corrections to GW flux terms as per Blanchet et al., PRD 71, 129902(E)-129904(E) (2005

Measuring gravitational waves from binary black hole coalescences: II. the waves' information and its extraction, with and without templates

We discuss the extraction of information from detected binary black hole (BBH) coalescence gravitational waves, focusing on the merger phase that occurs after the gradual inspiral and before the ringdown. Our results are: (1) If numerical relativity simulations have not produced template merger waveforms before BBH detections by LIGO/VIRGO, one can band-pass filter the merger waves. For BBHs smaller than about 40 solar masses detected via their inspiral waves, the band pass filtering signal to noise ratio indicates that the merger waves should typically be just barely visible in the noise for initial and advanced LIGO interferometers. (2) We derive an optimized (maximum likelihood) method for extracting a best-fit merger waveform from the noisy detector output; one "perpendicularly projects" this output onto a function space (specified using wavelets) that incorporates our prior knowledge of the waveforms. An extension of the method allows one to extract the BBH's two independent waveforms from outputs of several interferometers. (3) If numerical relativists produce codes for generating merger templates but running the codes is too expensive to allow an extensive survey of the merger parameter space, then a coarse survey of this parameter space, to determine the ranges of the several key parameters and to explore several qualitative issues which we describe, would be useful for data analysis purposes. (4) A complete set of templates could be used to test the nonlinear dynamics of general relativity and to measure some of the binary parameters. We estimate the number of bits of information obtainable from the merger waves (about 10 to 60 for LIGO/VIRGO, up to 200 for LISA), estimate the information loss due to template numerical errors or sparseness in the template grid, and infer approximate requirements on template accuracy and spacing.Comment: 33 pages, Rextex 3.1 macros, no figures, submitted to Phys Rev

Gravitational field and equations of motion of spinning compact binaries to 2.5 post-Newtonian order

We derive spin-orbit coupling effects on the gravitational field and equations of motion of compact binaries in the 2.5 post-Newtonian approximation to general relativity, one PN order beyond where spin effects first appear. Our method is based on that of Blanchet, Faye, and Ponsot, who use a post-Newtonian metric valid for general (continuous) fluids and represent pointlike compact objects with a delta-function stress-energy tensor, regularizing divergent terms by taking the Hadamard finite part. To obtain post-Newtonian spin effects, we use a different delta-function stress-energy tensor introduced by Bailey and Israel. In a future paper we will use the 2.5PN equations of motion for spinning bodies to derive the gravitational-wave luminosity and phase evolution of binary inspirals, which will be useful in constructing matched filters for signal analysis. The gravitational field derived here may help in posing initial data for numerical evolutions of binary black hole mergers.Comment: 18 pages, no figur

Using Markov chain Monte Carlo methods for estimating parameters with gravitational radiation data

We present a Bayesian approach to the problem of determining parameters for coalescing binary systems observed with laser interferometric detectors. By applying a Markov Chain Monte Carlo (MCMC) algorithm, specifically the Gibbs sampler, we demonstrate the potential that MCMC techniques may hold for the computation of posterior distributions of parameters of the binary system that created the gravity radiation signal. We describe the use of the Gibbs sampler method, and present examples whereby signals are detected and analyzed from within noisy data.Comment: 21 pages, 10 figure

Searching for periodic sources with LIGO

We investigate the computational requirements for all-sky, all-frequency searches for gravitational waves from spinning neutron stars, using archived data from interferometric gravitational wave detectors such as LIGO. These sources are expected to be weak, so the optimal strategy involves coherent accumulaton of signal-to-noise using Fourier transforms of long stretches of data (months to years). Earth-motion-induced Doppler shifts, and intrinsic pulsar spindown, will reduce the narrow-band signal-to-noise by spreading power across many frequency bins; therefore, it is necessary to correct for these effects before performing the Fourier transform. The corrections can be implemented by a parametrized model, in which one does a search over a discrete set of parameter values. We define a metric on this parameter space, which can be used to determine the optimal spacing between points in a search; the metric is used to compute the number of independent parameter-space points Np that must be searched, as a function of observation time T. The number Np(T) depends on the maximum gravitational wave frequency and the minimum spindown age tau=f/(df/dt) that the search can detect. The signal-to-noise ratio required, in order to have 99% confidence of a detection, also depends on Np(T). We find that for an all-sky, all-frequency search lasting T=10^7 s, this detection threshhold is at a level of 4 to 5 times h(3/yr), where h(3/yr) is the corresponding 99% confidence threshhold if one knows in advance the pulsar position and spin period.Comment: 18 pages, LaTeX, 12 PostScript figures included using psfig. Submitted to Phys. Rev.

Expression of R-Spondin 1 in Apc(Min/+) Mice Suppresses Growth of Intestinal Adenomas by Altering Wnt and Transforming Growth Factor Beta Signaling

BACKGROUND & AIMS: Mutations in the APC gene and other genes in the Wnt signaling pathway contribute to development of colorectal carcinomas. R-spondins (RSPOs) are secreted proteins that amplify Wnt signaling in intestinal stem cells. Alterations in RSPO genes have been identified in human colorectal tumors. We studied the effects of RSPO1 overexpression in ApcMin/thorn mutant mice. METHODS: An adeno associated viral vector encoding RSPO1-Fc fusion protein, or control vector, was injected into ApcMin/thornmice. Their intestinal crypts were isolated and cultured as organoids. which were incubated with or without RSPO1-Fc and an inhibitor of transforming growth factor beta receptor (TGFBR). Livers were collected from mice and analyzed by immunohistochemistry. Organoids and adenomas were analyzed by quantitative reverse-transcription PCR, single cell RNA sequencing, and immunohistochemistry. RESULTS: Intestines from Apcthorn/thorn mice injected with the vector encoding RSPO1-Fc had significantly deeper crypts, longer villi, with increased EdU labeling, indicating increased proliferation of epithelial cells, in comparison to mice given control vector. AAV-RSPO1-Fctransduced ApcMin/thorn mice also developed fewer and smaller intestinal tumors and had significantly longer survival times. Adenomas of ApcMin/thorn mice injected with the RSPO1-Fc vector showed a rapid increase in apoptosis and in the expression of Wnt target genes, followed by reduced expression of messenger RNAs and proteins regulated by the Wnt pathway, reduced cell proliferation, and less crypt branching than adenomas of mice given the control vector. Addition of RSPO1 reduced the number of adenoma organoids derived from ApcMin/thorn mice and suppressed expression of Wnt target genes but increased phosphorylation of SMAD2 and transcription of genes regulated by SMAD. Inhibition of TGFBR signaling in organoids stimulated with RSPO1-Fc restored organoid formation and expression of genes regulated by Wnt. The TGFBR inhibitor restored apoptosis in adenomas from ApcMin/thorn mice expressing RSPO1Fc back to the same level as in the adenomas from mice given the control vector. CONCLUSIONS: Expression of RSPO1 in ApcMin/thorn mice increases apoptosis and reduces proliferation and Wnt signaling in adenoma cells, resulting in development of fewer and smaller intestinal tumors and longer mouse survival. Addition of RSPO1 to organoids derived from adenomas inhibits their growth and promotes proliferation of intestinal stem cells that retain the APC protein; these effects are reversed by TGFB inhibitor. Strategies to increase the expression of RSPO1 might be developed for the treatment of intestinal adenomas.Peer reviewe