Bayesian meta-analysis for identifying periodically expressed genes in fission yeast cell cycle

The effort to identify genes with periodic expression during the cell cycle from genome-wide microarray time series data has been ongoing for a decade. However, the lack of rigorous modeling of periodic expression as well as the lack of a comprehensive model for integrating information across genes and experiments has impaired the effort for the accurate identification of periodically expressed genes. To address the problem, we introduce a Bayesian model to integrate multiple independent microarray data sets from three recent genome-wide cell cycle studies on fission yeast. A hierarchical model was used for data integration. In order to facilitate an efficient Monte Carlo sampling from the joint posterior distribution, we develop a novel Metropolis--Hastings group move. A surprising finding from our integrated analysis is that more than 40% of the genes in fission yeast are significantly periodically expressed, greatly enhancing the reported 10--15% of the genes in the current literature. It calls for a reconsideration of the periodically expressed gene detection problem.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS300 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Fermat Potentials for Non-Perturbative Gravitational Lensing

The images of many distant galaxies are displaced, distorted and often multiplied by the presence of foreground massive galaxies near the line of sight; the foreground galaxies act as gravitational lenses. Commonly, the lens equation, which relates the placement and distortion of the images to the real source position in the thin-lens scenario, is obtained by extremizing the time of arrival among all the null paths from the source to the observer (Fermat's principle). We show that the construction of envelopes of certain families of null surfaces consitutes an alternative variational principle or version of Fermat's principle that leads naturally to a lens equation in a generic spacetime with any given metric. We illustrate the construction by deriving the lens equation for static asymptotically flat thin lens spacetimes. As an application of the approach, we find the bending angle for moving thin lenses in terms of the bending angle for the same deflector at rest. Finally we apply this construction to cosmological spacetimes (FRW) by using the fact they are all conformally related to Minkowski space.Comment: accepted for publication in Phys. Rev.

Dynamics of Fermat potentials in non-perturbative gravitational lensing

We present a framework, based on the null-surface formulation of general relativity, for discussing the dynamics of Fermat potentials for gravitational lensing in a generic situation without approximations of any kind. Additionally, we derive two lens equations: one for the case of thick compact lenses and the other one for lensing by gravitational waves. These equations in principle generalize the astrophysical scheme for lensing by removing the thin-lens approximation while retaining the weak fields.Comment: Accepted for publication in Phys. Rev.

Self-calibration of weak lensing systematic effects using combined two- and three-point statistics

We investigate the prospects for using the weak lensing bispectrum alongside the power spectrum to control systematic uncertainties in a Euclid-like survey. Three systematic effects are considered: the intrinsic alignment of galaxies, uncertainties in the means of tomographic redshift distributions, and multiplicative bias in the measurement of the shear signal. We find that the bispectrum is very effective in mitigating these systematic errors. Varying all three systematics simultaneously, a joint power spectrum and bispectrum analysis reduces the area of credible regions for the cosmological parameters Ω_{m} and σ_{8} by a factor of 90 and for the two parameters of a time-varying dark energy equation of state by a factor of almost 20, compared with the baseline approach of using the power spectrum alone and of imposing priors consistent with the accuracy requirements specified for Euclid. We also demonstrate that including the bispectrum self-calibrates all three systematic effects to the stringent levels required by the forthcoming generation of weak lensing surveys, thereby reducing the need for external calibration data

Iterative Approach to Gravitational Lensing Theory

We develop an iterative approach to gravitational lensing theory based on approximate solutions of the null geodesic equations. The approach can be employed in any space-time which is ``close'' to a space-time in which the null geodesic equations can be completely integrated, such as Minkowski space-time, Robertson-Walker cosmologies, or Schwarzschild-Kerr geometries. To illustrate the method, we construct the iterative gravitational lens equations and time of arrival equation for a single Schwarzschild lens. This example motivates a discussion of the relationship between the iterative approach, the standard thin lens formulation, and an exact formulation of gravitational lensing.Comment: 27 pages, 2 figures, submitted to Phys.Rev.D, minor revisions, new reference

Synthetic and spectroscopic studies on the structures of uniflorines A and B: structural revision to 1,2,6,7-tetrahydroxy-3-hydroxymethylpyrrolizidine alkaloids

The diastereoselective synthesis of the C-2 epimer and the C-1, C-2 di-epimers of the putative structure of the alkaloid uniflorine A has been achieved. The synthesis of the latter di-epimers employed a novel pyrrolo[1,2-c]oxazin-1-one precursor to allow for the reversal of π-facial diastereoselectivity in an osmium(VIII)-catalyzed syn-dihydroxylation (DH) reaction. The NMR spectral data of these epimeric compounds and that of related isomers did not match that of the natural product. From a comparison of the NMR data of uniflorines A and B with that of casuarine and the known synthetic 1,2,6,7-tetrahydroxy-3-hydroxymethylpyrrolizidine isomers we concluded unequivocally that uniflorine B is the known alkaloid casuarine. Although we cannot unequivocally prove the structure of uniflorine A, without access to the original material and data, the published data suggest that the natural product is also a 1,2,6,7-tetrahydroxy-3-hydroxymethylpyrrolizidine with the same relative C-7–C-7a–C-1–C-2–C-3 stereochemistry as casuarine. We thus suggest that uniflorine A is 6-epi-casuarine

Second Order Perturbations of Flat Dust FLRW Universes with a Cosmological Constant

We summarize recent results concerning the evolution of second order perturbations in flat dust irrotational FLRW models with $\Lambda\ne 0$. We show that asymptotically these perturbations tend to constants in time, in agreement with the cosmic no-hair conjecture. We solve numerically the second order scalar perturbation equation, and very briefly discuss its all time behaviour and some possible implications for the structure formation.Comment: 6 pages, 1 figure. to be published in "Proceedings of the 5th Alexander Friedmann Seminar on Gravitation and Cosmology", Int. Journ. Mod. Phys. A (2002). Macros: ws-ijmpa.cls, ws-p9-75x6-50.cl

Synthesis of mono and Bis[60]fullerene-based dicationic peptoids

Increasing numbers of biological applications of fullerenyl amino acids and their derivatives encouraged us to synthesise [60]fullerenyldihydropyrrole peptides, prepared from the coupling of mono- and bis[60]fullerenyldihydropyrrolecarboxylic acids 4, 5 and 41 with presynthesised peptides 13, 16, 24, 28, 29 and 46. The resulting hydrophobic scaffolded di- and tetra-cationic derivatives were tested against Staphylococcus aureus NCTC 6571 and Escherichia coli NCTC 10418. The synthesis, characterisation and biological results are discussed in this paper

A Mixture of Regressions Model of COVID-19 Death Rates and Population Comorbidities

As the COVID-19 pandemic spread worldwide, it has become clearer that prevalence of certain comorbidities in a given population could make it more vulnerable to serious outcomes of that disease, including fatality. Indeed, it might be insightful from a health policy perspective to identify clusters of populations in terms of the associations between their prevalent comorbidities and the observed COVID-19 specific death rates. In this study, we described a mixture of polynomial time series (MoPTS) model to simultaneously identify (a) three clusters of 86 U.S. cities in terms of their dynamic death rates, and (b) the different associations of those rates with 5 key comorbidities among the populations in the clusters. We also described an EM algorithm for efficient maximum likelihood estimation of the model parameters

Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies

Sphingolipids, such as ceramide, sphingosine and sphingosine 1-phosphate (S1P) are bioactive molecules that have important functions in a variety of cellular processes, which include proliferation, survival, differentiation and cellular responses to stress. Sphingolipids have a major impact on the determination of cell fate by contributing to either cell survival or death. Although ceramide and sphingosine are usually considered to induce cell death, S1P promotes survival of cells. Sphingosine kinases (SPHKs) are the enzymes that catalyze the conversion of sphingosine to S1P. There are two isoforms, SPHK1 and SPHK2, which are encoded by different genes. SPHK1 has recently been implicated in contributing to cell transformation, tumor angiogenesis and metastatic spread, as well as cancer cell multidrug-resistance. More recent findings suggest that SPHK2 also has a role in cancer progression. This review is an overview of our understanding of the role of SPHKs and S1P in hematopoietic malignancies and provides information on the current status of SPHK inhibitors with respect to their therapeutic potential in the treatment of haematological cancers