Recursive Algorithms for Computing the Cramer-Rao Bound

Computation of the Cramer-Rao bound (CRB) on estimator variance requires the inverse or the pseudo-inverse Fisher information matrix (FIM). Direct matrix inversion can be computationally intractable when the number of unknown parameters is large. In this correspondence, we compare several iterative methods for approximating the CRB using matrix splitting and preconditioned conjugate gradient algorithms. For a large class of inverse problems, we show that nonmonotone Gauss-Seidel and preconditioned conjugate gradient algorithms require significantly fewer flops for convergence than monotone “bound preserving” algorithms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85866/1/Fessler94.pd

An argument for the use of Aristotelian method in bioethics

The main claim of this paper is that the method outlined and used in Aristotle's Ethics is an appropriate and credible one to use in bioethics. Here “appropriate” means that the method is capable of establishing claims and developing concepts in bioethics and “credible” that the method has some plausibility, it is not open to obvious and immediate objection. It begins by suggesting why this claim matters and then gives a brief outline of Aristotle's method. The main argument is made in three stages. First, it is argued that Aristotelian method is credible because it compares favourably with alternatives. In this section it is shown that Aristotelian method is not vulnerable to criticisms that are made both of methods that give a primary place to moral theory (such as utilitarianism) and those that eschew moral theory (such as casuistry and social science approaches). As such, it compares favourably with these other approaches that are vulnerable to at least some of these criticisms. Second, the appropriateness of Aristotelian method is indicated through outlining how it would deal with a particular case. Finally, it is argued that the success of Aristotle's philosophy is suggestive of both the credibility and appropriateness of his method.</p

The genus <i>Elaphomyces </i>(<i>Ascomycota</i>, <i>Eurotiales</i>):a ribosomal DNA-based phylogeny and revised systematics of European 'deer truffles'

Elaphomyces (‘deer truffles’) is one of the most important ectomycorrhizal fungal genera in temperate and subarctic forest ecosystems, but also one of the least documented in public databases. The current systematics are mainly based on macromorphology, and is not significantly different from that proposed by Vittadini (1831). Within the 49 species recognised worldwide, 23 were originally described from Europe and 17 of these were described before the 20th century. Moreover, very recent phylogenetic treatments of the genus are mainly based on a few extra-European species and most common European species are still poorly documented. Based on an extensive taxonomic sampling mainly made in the biogeographically rich Cantabrian area (Spain), complemented with collections from France, Greece, Italy, Norway, Portugal and Sweden, all currently recognized species in Europe have been sequenced at the ITS and 28S of the rDNA. Combined phylogenetic analyses yielded molecular support to sections Elaphomyces and Ceratogaster (here emended), while a third, basal lineage encompasses the sections Malacodermei and Ascoscleroderma as well as the tropical genus Pseudotulostoma. Species limits are discussed and some taxa formerly proposed as genuine species based on morphology and biogeography are re-evaluated as varieties or forms. Spore size and ornamentation, features of the peridial surface, structure of the peridium, and the presence of mycelium patches attached to the peridial surface emerge as the most significant systematic characters. Four new species: E. barrioi, E. quercicola, E. roseolus and E. violaceoniger, one new variety: E. papillatus var. sulphureopallidus, and two new forms: E. granulatus forma pallidosporus and E. anthracinus forma talosporus are introduced, as well as four new combinations in the genus: E. muricatus var. reticulatus, E. muricatus var. variegatus, E. papillatus var. striatosporus and E. morettii var. cantabricus. Lectotypes and epitypes are designated for most recognised species. For systematic purposes, new infrageneric taxa are introduced: E. sect. Ascoscleroderma stat. nov., E. subsect. Sclerodermei stat. nov., E. subsect. Maculati subsect. nov., E. subsect. Muricati subsect. nov., and E. subsect. Papillati subsect. nov. Lastly, E. laevigatus, E. sapidus, E. sulphureopallidus and E. trappei are excluded from the genus and referred to Rhizopogon roseolus, Astraeus sapidus comb. nov., Astraeus hygrometricus and Terfezia trappei comb. nov. (syn.: Terfezia cistophila), respectively

Influence of definition based versus pragmatic birth registration on international comparisons of perinatal and infant mortality: population based retrospective study

Objectives To examine variations in the registration of extremely low birthweight and early gestation births and to assess their effect on perinatal and infant mortality rankings of industrialised countries

Acetylation-defective mutant of Pparγ is associated with decreased lipid synthesis in breast cancer cells.

In our prior publications we characterized a conserved acetylation motif (K(R)xxKK) of evolutionarily related nuclear receptors. Recent reports showed that peroxisome proliferator activated receptor gamma (PPARγ) deacetylation by SIRT1 is involved in delaying cellular senescence and maintaining the brown remodeling of white adipose tissue. However, it still remains unknown whether lysyl residues 154 and 155 (K154/155) of the conserved acetylation motif (RIHKK) in Pparγ1 are acetylated. Herein, we demonstrate that Pparγ1 is acetylated and regulated by both endogenous TSA-sensitive and NAD-dependent deacetylases. Acetylation of lysine 154 was identified by mass spectrometry (MS) while deacetylation of lysine 155 by SIRT1 was confirmed by in vitro deacetylation assay. An in vivo labeling assay revealed K154/K155 as bona fide acetylation sites. The conserved acetylation sites of Pparγ1 and the catalytic domain of SIRT1 are both required for the interaction between Pparγ1 and SIRT1. Sirt1 and Pparγ1 converge to govern lipid metabolism in vivo. Acetylation-defective mutants of Pparγ1 were associated with reduced lipid synthesis in ErbB2 overexpressing breast cancer cells. Together, these results suggest that the conserved lysyl residues K154/K155 of Pparγ1 are acetylated and play an important role in lipid synthesis in ErbB2-positive breast cancer cells

Biomarker discovery and redundancy reduction towards classification using a multi-factorial MALDI-TOF MS T2DM mouse model dataset

Diabetes like many diseases and biological processes is not mono-causal. On the one hand multifactorial studies with complex experimental design are required for its comprehensive analysis. On the other hand, the data from these studies often include a substantial amount of redundancy such as proteins that are typically represented by a multitude of peptides. Coping simultaneously with both complexities (experimental and technological) makes data analysis a challenge for Bioinformatics

Detecting small low emission radiating sources

The article addresses the possibility of robust detection of geometrically small, low emission sources on a significantly stronger background. This problem is important for homeland security. A technique of detecting such sources using Compton type cameras is developed, which is shown on numerical examples to have high sensitivity and specificity and also allows to assign confidence probabilities of the detection. 2D case is considered in detail

Harvest: an open-source tool for the validation and improvement of peptide identification metrics and fragmentation exploration

<p>Abstract</p> <p>Background</p> <p>Protein identification using mass spectrometry is an important tool in many areas of the life sciences, and in proteomics research in particular. Increasing the number of proteins correctly identified is dependent on the ability to include new knowledge about the mass spectrometry fragmentation process, into computational algorithms designed to separate true matches of peptides to unidentified mass spectra from spurious matches. This discrimination is achieved by computing a function of the various features of the potential match between the observed and theoretical spectra to give a numerical approximation of their similarity. It is these underlying "metrics" that determine the ability of a protein identification package to maximise correct identifications while limiting false discovery rates. There is currently no software available specifically for the simple implementation and analysis of arbitrary novel metrics for peptide matching and for the exploration of fragmentation patterns for a given dataset.</p> <p>Results</p> <p>We present Harvest: an open source software tool for analysing fragmentation patterns and assessing the power of a new piece of information about the MS/MS fragmentation process to more clearly differentiate between correct and random peptide assignments. We demonstrate this functionality using data metrics derived from the properties of individual datasets in a peptide identification context. Using Harvest, we demonstrate how the development of such metrics may improve correct peptide assignment confidence in the context of a high-throughput proteomics experiment and characterise properties of peptide fragmentation.</p> <p>Conclusions</p> <p>Harvest provides a simple framework in C++ for analysing and prototyping metrics for peptide matching, the core of the protein identification problem. It is not a protein identification package and answers a different research question to packages such as Sequest, Mascot, X!Tandem, and other protein identification packages. It does not aim to maximise the number of assigned peptides from a set of unknown spectra, but instead provides a method by which researchers can explore fragmentation properties and assess the power of novel metrics for peptide matching in the context of a given experiment. Metrics developed using Harvest may then become candidates for later integration into protein identification packages.</p