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

Short Peptides as Inhibitors of Amyloid Aggregation

The misfolding and aggregation of proteins into amyloid has been linked to a variety of age-related diseases. Aggregation of proteins, such as Aβ in Alzheimer\u27s disease and Islet Amyloid Polypeptide (IAPP, amylin) in type 2 diabetes, appears to lead to the formation of toxic assemblies. These assemblies range in size from small oligomers (2-8 proteins) to large fibrils (thousands of proteins). It remains unclear how these amyloidogenic proteins misfold and form toxic species, but growing evidence suggests that inhibiting the aggregation of these proteins could slow, if not prevent altogether, the progression of these diseases. We describe the use of small peptides (\u3c43 amino acids) as inhibitors of amyloid- based aggregation. These peptides, often short complementary segments of the amyloid proteins, can be useful (i) for identifying the aggregation-prone regions of the amyloid proteins (ii) as models for drug discovery and (iii) as potential therapeutic agents themselves

Loss of AP-2delta reduces retinal ganglion cell numbers and axonal projections to the superior colliculus

Background: AP-2 delta is the most divergent member of the Activating Protein-2 (TFAP2) family of transcription factors. AP-2 delta is restricted to specific regions of the CNS, including a subset of ganglion cells in the retina. Retinal ganglion cells (RGCs), the only output neurons of the retina, are responsible for transmitting the visual signal to the brain. Results: AP-2 delta knockout results in loss of Brn3c (Pou4f3) expression in AP-2 delta -positive RGCs. While AP-2 delta-/- mice have morphologically normal retinas at birth, there is a significant reduction in retinal ganglion cell numbers by P21, after eye opening. Chromatin immunoprecipitation indicates that Brn3c is a target of AP-2 delta in the retina. Using fluorochrome-conjugated cholera toxin subunit B to trace ganglion cell axons from the eye to the major visual pathways in the brain, we found 87 % and 32 % decreases in ipsilateral and contralateral projections, respectively, to the superior colliculus in AP-2 delta-/- mice. In agreement with anatomical data, visually evoked responses recorded from the brain confirmed that retinal outputs to the brain are compromised. Conclusions: AP-2 delta is important for the maintenance of ganglion cell numbers in the retina. Loss of AP-2 delta alters retinal axonal projections to visual centers of the brain, with ipsilaterial projections to the superior colliculus being the most dramatically affected. Our results have important implications for integration of the visual signal at the superior colliculus

Tracking the emergence of a pitch hierarchy using an artificial grammar requires extended exposure

Introduction: The tonal hierarchy is a perceived musical structure implicitly learned through exposure. Previous studies have demonstrated that new grammars, for example based on the Bohlen-Pierce scale, can be learned in as little as 20 minutes. Methods: In this study, we created two grammars derived from the Bohlen-Pierce scale similar in complexity to the western tonal hierarchy. Participants rated the goodness-of-fit of all Bohlen-Pierce scale notes in a probe tone paradigm before and after 30 minutes of exposure to one of the two grammars. Participants were then asked about their experience in a short interview. Results: Results do not support the learning of the artificial grammar: correlations between goodness-of-fit ratings and pitch frequency distribution of a grammar were no different before and after exposure to a grammar. Interviews suggest that participants are bad at identifying the strategy they used to complete the task. Testing the strategies reported on the data revealed that ratings decreased with increasing distance of the probe tone from the tonic. Discussion: This is consistent with early brain responses to chromatic pitches of the tonal hierarchy. We suggest that longer exposure time is necessary to learn more complex grammars

Efficiency of the traditional practice of traps to stimulate black truffle production, and its ecological mechanisms

The black truffle Tuber melanosporum was disseminated all over the world, propelled by the development of a wide variety of empirical practices. A widespread practice, called ‘truffle trap’, consists of placing pieces of truffles into excavations dug under host trees, and of collecting truffle in these traps in the next years. This research aims at (1) evaluating the effect of this practice on fruitbody production based on the analysis of 9924 truffle traps installed in 11 orchards across T. melanosporum native area in France and (2) exploring the mechanisms involved in fruitbody emergence using traps where the genotypes of introduced truffles were compared with those of fruitbodies collected in the same traps. We confirmed that truffle traps provide a major and highly variable part of truffle ground production, representing up to 89% of the collected fruitbodies. We evidenced a genetic link between introduced spores and collected fruitbodies, and then demonstrated that truffle growers provide paternal partners for mating with local maternal mycelia. We also highlighted that soil disturbance stimulate the vegetative development of established maternal mycelia. This research supports that a widely used traditional practice enhances fruitbody production by shaping favorable conditions and providing sexual partners required for fruiting.info:eu-repo/semantics/publishedVersio

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

A national survey of antimicrobial stewardship content in Canadian entry-to-practice pharmacy programs

Abstract Objective: To describe the current landscape of antimicrobial stewardship (AMS) instruction in Canadian entry-to-practice pharmacy programs and the perceived barriers and facilitators to optimizing teaching and learning. Design: Electronic survey. Participants: Faculty representatives from the 10 Canadian entry-to-practice pharmacy programs, including content experts and faculty leadership. Methods: A review of international literature pertaining to AMS in pharmacy curricula informed a 24-item survey, which was open for completion from March to May of 2021. Curriculum content questions were developed using AMS topics recommended by pharmacy educators in the United States, and professional roles described by the Association of Faculties of Pharmacy of Canada. Results: All 10 Canadian faculties returned a completed survey. All programs reported teaching AMS principles in their core curricula. Content coverage varied, with programs teaching, on average, 68% of the recommended AMS topics from the United States. Potential gaps were identified within the professional roles of “communicator” and “collaborator.” Didactic methods of content delivery and student assessment, such as lectures and multiple-choice questions, were most frequently used. Three programs offered additional AMS content in their elective curricula. Experiential rotations in AMS were commonly offered, though teaching AMS in formalized interprofessional settings was rare. Curricular time constraints were identified by all programs as a barrier to enhancing AMS instruction. A course to teach AMS, a curriculum framework, and prioritization by the faculty’s curriculum committee were perceived as facilitators. Conclusions: Our findings highlight potential gaps and areas of opportunity within Canadian pharmacy AMS instruction

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