Neural network approximation of optimal controls for stochastic reaction-diffusion equations.

We present a numerical algorithm that allows the approximation of optimal controls for stochastic reaction-diffusion equations with additive noise by first reducing the problem to controls of feedback form and then approximating the feedback function using finitely based approximations. Using structural assumptions on the finitely based approximations, rates for the approximation error of the cost can be obtained. Our algorithm significantly reduces the computational complexity of finding controls with asymptotically optimal cost. Numerical experiments using artificial neural networks as well as radial basis function networks illustrate the performance of our algorithm. Our approach can also be applied to stochastic control problems for high dimensional stochastic differential equations and more general stochastic partial differential equations.

Independent evolution of sexual dimorphism and female-limited mimicry in swallowtail butterflies (Papilio dardanus and Papilio phorcas).

Several species of swallowtail butterflies (genus Papilio) are Batesian mimics that express multiple mimetic female forms, while the males are monomorphic and nonmimetic. The evolution of such sex-limited mimicry may involve sexual dimorphism arising first and mimicry subsequently. Such a stepwise scenario through a nonmimetic, sexually dimorphic stage has been proposed for two closely related sexually dimorphic species: Papilio phorcas, a nonmimetic species with two female forms, and Papilio dardanus, a female-limited polymorphic mimetic species. Their close relationship indicates that female-limited polymorphism could be a shared derived character of the two species. Here, we present a phylogenomic analysis of the dardanus group using 3964 nuclear loci and whole mitochondrial genomes, showing that they are not sister species and thus that the sexually dimorphic state has arisen independently in the two species. Nonhomology of the female polymorphism in both species is supported by population genetic analysis of engrailed, the presumed mimicry switch locus in P. dardanus. McDonald-Kreitman tests performed on SNPs in engrailed showed the signature of balancing selection in a polymorphic population of P. dardanus, but not in monomorphic populations, nor in the nonmimetic P. phorcas. Hence, the wing polymorphism does not balance polymorphisms in engrailed in P. phorcas. Equally, unlike in P. dardanus, none of the SNPs in P. phorcas engrailed were associated with either female morph. We conclude that sexual dimorphism due to female polymorphism evolved independently in both species from monomorphic, nonmimetic states. While sexual selection may drive male-female dimorphism in nonmimetic species, in mimetic Papilios, natural selection for protection from predators in females is an alternative route to sexual dimorphism.

The discovery of Iberobaeniidae (Coleoptera: Elateroidea): a new family of beetles from Spain, with immatures detected by environmental DNA sequencing.

The ongoing exploration of biodiversity and the implementation of new molecular tools continue to unveil hitherto unknown lineages. Here, we report the discovery of three species of neotenic beetles for which we propose the new family Iberobaeniidae. Complete mitochondrial genomes and rRNA genes recovered Iberobaeniidae as a deep branch in Elateroidea, as sister to Lycidae (net-winged beetles). Two species of the new genus Iberobaenia, Iberobaenia minuta sp. nov. and Iberobaenia lencinai sp. nov. were found in the adult stage. In a separate incidence, a related sequence was identified in bulk samples of soil invertebrates subjected to shotgun sequencing and mitogenome assembly, which was traced to a larval voucher specimen of a third species of Iberobaenia Iberobaenia shows characters shared with other elateroid neotenic lineages, including soft-bodiedness, the hypognathous head, reduced mouthparts with reduced labial palpomeres, and extremely small-bodied males without strengthening structures due to miniaturization. Molecular dating shows that Iberobaeniidae represents an ancient relict lineage originating in the Lower Jurassic, which possibly indicates a long history of neoteny, usually considered to be evolutionarily short-lived. The apparent endemism of Iberobaeniidae in the Mediterranean region highlights the importance of this biodiversity hotspot and the need for further species exploration even in the well-studied European continent.

Viability of Yersinia pestis subcultures in agar stabs.

UNLABELLED: Since its identification as the causative agent of plague in 1894, thousands of Yersinia pestis strains have been isolated and stored. Here, we report the ability of Y. pestis to survive up to 47 years in agar stabs, in rubber-stoppered tubes, under refrigeration (+4 to +10°C), although overall subculture recovery rates were poor and inversely related to the length of time stored. Genetic characterization of virulence gene presence among these subcultures was suggestive of significant variation in the genomic stability of Y. pestis subcultures stored under these conditions. Specifically, we found variation in the presence of plasmid and chromosomal virulence markers (genes pla, lcrV, caf1 and irp2) among multiple subcultures of Y. pestis strains in the 'Collection of Yersinia pestis' (Fiocruz-CYP) maintained by the SRP of FIOCRUZ-PE in Brazil. This variation, together with all of the inherent temporal, geographic and other genetic variation represented by all of the recoverable strains in this historical collection was preserved in new frozen culture stocks stored at -70°C as a result of this study. These frozen culture stocks represent a valuable resource for future comparative studies of Y. pestis. SIGNIFICANCE AND IMPACT OF THE STUDY: We report the ability of Yersinia pestis to survive up to 47 years in agar stabs, in rubber-stoppered tubes, under refrigeration (+4 to +10°C), although overall subculture recovery rates were poor and inversely related to the length of time stored. Genetic characterization of virulence gene presence among these subcultures was suggestive of significant variation in the genomic stability of Y. pestis subcultures stored under these conditions. This variation, together with all of the inherent temporal, geographic and other genetic variation represented by all of the recoverable strains in the historical 'Collection of Yersinia pestis' (Fiocruz-CYP) maintained by the SRP of FIOCRUZ-PE in Brazil was preserved in new frozen culture stocks stored at -70°C as a result of this study. These frozen culture stocks represent a valuable resource for future comparative studies of Y. pestis.

[Orbital inflammatory diseases]. / Entzündliche Erkrankungen der Orbita.

CLINICAL/METHODICAL ISSUE: Inflammatory orbital processes on imaging are often misinterpreted as tumors. STANDARD RADIOLOGICAL METHODS: Imaging comprises computed tomography (CT) and magnetic resonance imaging (MRI). ACHIEVEMENTS: Clinical and laboratory data play a crucial role in diagnosing many inflammatory orbital diseases. Radiological imaging provides a supporting but relevant role. PRACTICAL RECOMMENDATIONS: Clinical examination, including specialized ophthalmological examinations, laboratory diagnostics, and MRI are important in the diagnosis of inflammatory orbital diseases.

Controlling the dynamics of an open many-body quantum system with localized dissipation.

We experimentally investigate the action of a localized dissipative potential on a macroscopic matter wave, which we implement by shining an electron beam on an atomic Bose-Einstein condensate (BEC). We measure the losses induced by the dissipative potential as a function of the dissipation strength observing a paradoxical behavior when the strength of the dissipation exceeds a critical limit: for an increase of the dissipation rate the number of atoms lost from the BEC becomes lower. We repeat the experiment for different parameters of the electron beam and we compare our results with a simple theoretical model, finding excellent agreement. By monitoring the dynamics induced by the dissipative defect we identify the mechanisms which are responsible for the observed paradoxical behavior. We finally demonstrate the link between our dissipative dynamics and the measurement of the density distribution of the BEC allowing for a generalized definition of the Zeno effect. Because of the high degree of control on every parameter, our system is a promising candidate for the engineering of fully governable open quantum systems.

Identification and typing of Francisella tularensis with a highly automated genotyping assay.

A PCR assay was developed to genotypically characterize Francisella tularensis and F. novicida. An integrated and partially redundant set of markers was selected to provide positive identification of these species, identify subspecies of F. tularensis and genotype 14 variable number tandem repeat (VNTR) markers. Assay performance was evaluated with 117 Francisella samples. Sample DNA was amplified, and the masses of the PCR products were determined with electrospray ionization/time of flight mass spectrometry (ESI-MS). The base compositions of the PCR amplicons were derived from these high-accuracy mass measurements and contrasted with databased information associated with each of the 25 assay markers. Species and subspecies determinations for all samples were fully concordant with results from established typing methods, and VNTR markers provided additional discrimination among samples. Sequence variants were observed with a number of assay markers, but these did not interfere with sample characterization, and served to increase the genetic diversity detected by the assay.

[Pediatric posterior fossa tumors]. / Infratentorielle Hirntumoren bei Kindern.

CLINICAL ISSUE: Tumors of the posterior fossa account for about 50-55% of brain tumors in childhood. DIAGNOSTIC WORKUP: The most frequent tumor entities are medulloblastomas, pilocytic astrocytomas, ependymomas, diffuse midline gliomas and atypical teratoid-rhabdoid tumors. Neuroradiological differential diagnosis with magnetic resonance imaging (MRI) is of considerable importance for preoperative planning as well as planning of follow-up therapy. PERFORMANCE: Most important findings for differential diagnosis of pediatric posterior fossa tumors are tumor location, patient age and the intratumoral apparent diffusion assessed by diffusion-weighted imaging. ACHIEVEMENTS: Advanced MR techniques like MRI perfusion and MR spectroscopy can be helpful both in the initial differential diagnosis and in tumor surveillance, but exceptional characteristics of certain tumor entities should be kept in mind. PRACTICAL RECOMMENDATIONS: Standard clinical MRI sequences including diffusion-weighted imaging are the main diagnostic tool in evaluating posterior fossa tumors in children. Advanced imaging methods can be helpful, but should never be interpreted separately from conventional MRI sequences.

Why barcode? High-throughput multiplex sequencing of mitochondrial genomes for molecular systematics.

Mitochondrial genome sequences are important markers for phylogenetics but taxon sampling remains sporadic because of the great effort and cost required to acquire full-length sequences. Here, we demonstrate a simple, cost-effective way to sequence the full complement of protein coding mitochondrial genes from pooled samples using the 454/Roche platform. Multiplexing was achieved without the need for expensive indexing tags ('barcodes'). The method was trialled with a set of long-range polymerase chain reaction (PCR) fragments from 30 species of Coleoptera (beetles) sequenced in a 1/16th sector of a sequencing plate. Long contigs were produced from the pooled sequences with sequencing depths ranging from ∼10 to 100× per contig. Species identity of individual contigs was established via three 'bait' sequences matching disparate parts of the mitochondrial genome obtained by conventional PCR and Sanger sequencing. This proved that assembly of contigs from the sequencing pool was correct. Our study produced sequences for 21 nearly complete and seven partial sets of protein coding mitochondrial genes. Combined with existing sequences for 25 taxa, an improved estimate of basal relationships in Coleoptera was obtained. The procedure could be employed routinely for mitochondrial genome sequencing at the species level, to provide improved species 'barcodes' that currently use the cox1 gene only.

Phylogeography of Francisella tularensis ssp. holarctica in France.

AIM: To investigate the phylogeography of French Francisella tularensis ssp. holarctica isolates. METHODS AND RESULTS: Canonical SNPs and MLVA were used to genotype 103 French F. tularensis ssp. holarctica isolates. We confirmed the presence of one subclade, the central and western European group (B.Br.FTNF002-00), and identified four major MLVA genotypes with no obvious geographical differentiation. CONCLUSIONS: The lack of geographical resolution among MLVA genotypes suggests rapid dispersal, convergent evolution or a combination of the two. SIGNIFICANCE AND IMPACT OF THE STUDY: This study expands knowledge of the phylogeography of one of the two dominant European F. tularensis ssp. holarctica subclades and illustrates the need for additional SNP discovery within this subclade.

Morphological and molecular variation in tiger beetles of the Cicindela hybrida complex: is an 'integrative taxonomy' possible?

Current taxon assignments at the species level are frequently discordant with DNA-based analyses. Recent studies on tiger beetles in the Cicindela hybrida complex identified discordance between mtDNA patterns and the entities currently defined by the taxonomic literature. To test the accuracy of morphologically delimited groups, five named taxa (species) from 24 representative sampling sites across Europe were scored for 41 external morphological characters. Three of the named taxa were 'diagnosable', that is, defined by between one and three characters unique to each group. Newly sequenced ITS1 and existing mitochondrial cox1 markers established 20 and 22 different haplotypes, respectively, but only cox1 produced (four) diagnosable units. Phylogenetic analysis and statistical parsimony networks showed poor congruence of character variation with the taxonomic entities (and each other). Variation in morphological characters was therefore tested directly for association with DNA-based nesting groups at various hierarchical levels using permutational contingency analysis. Significant statistical associations of 11 (of 13 variable) morphological characters were observed with nesting groups from ITS1 and mitochondrial DNA markers, predominantly at the 4-step level. The analysis demonstrates the need for formal tests of congruence with morphological variation at the level of individual characters, a step that is omitted from recent studies of 'integrative taxonomy'. In addition, statistical correlation of particular morphological characters with DNA-based nesting groups can identify the lowest hierarchical level at which various character sets show congruence, as a means to define evolutionarily separated entities supported by diverse data sources.

An optimized, multiplexed multi-locus variable-number tandem repeat analysis system for genotyping Francisella tularensis.

We present a truncated, optimized, multiplexed multiple-locus variable-number tandem repeat analysis system for the molecular subtyping of Francisella tularensis that reduces time and cost requirements while retaining high discriminatory power.

Species richness: does flower power explain beetle-mania?

The huge species richness of beetles has been attributed to their colonisation of flowering plants, but a vegetarian diet may not be the sole secret of the beetles' success.

The mitogenome of Hydropsyche pellucidula (Hydropsychidae): first gene arrangement in the insect order Trichoptera.

We describe the mitochondrial genome of Hydropsyche pellucidula Curtis 1834, which is first described for the suborder Annulipalpia and the first in the order Trichoptera to show a non-canonical gene order. The mitogenome was obtained by de novo assembly of shotgun sequenced total genomic DNA using Illumina Miseq technology, which produced an average coverage of 115× and a minimum coverage of 48×. The mitochondrial genome includes 13 protein-coding genes, 2 rRNAs and 22 tRNAs. The genome is characterized by a rearrangement in the relative position of protein-coding and ribosomal genes. This mitogenome sequence will be useful for studying the family Hydropsychidae, which is commonly used for freshwater pollution biomonitoring.

Lessons from genome skimming of arthropod-preserving ethanol.

Field-collected specimens of invertebrates are regularly killed and preserved in ethanol, prior to DNA extraction from the specimens, while the ethanol fraction is usually discarded. However, DNA may be released from the specimens into the ethanol, which can potentially be exploited to study species diversity in the sample without the need for DNA extraction from tissue. We used shallow shotgun sequencing of the total DNA to characterize the preservative ethanol from two pools of insects (from a freshwater habitat and terrestrial habitat) to evaluate the efficiency of DNA transfer from the specimens to the ethanol. In parallel, the specimens themselves were subjected to bulk DNA extraction and shotgun sequencing, followed by assembly of mitochondrial genomes for 39 of 40 species in the two pools. Shotgun sequencing from the ethanol fraction and read-matching to the mitogenomes detected ~40% of the arthropod species in the ethanol, confirming the transfer of DNA whose quantity was correlated to the biomass of specimens. The comparison of diversity profiles of microbiota in specimen and ethanol samples showed that 'closed association' (internal tissue) bacterial species tend to be more abundant in DNA extracted from the specimens, while 'open association' symbionts were enriched in the preservative fluid. The vomiting reflex of many insects also ensures that gut content is released into the ethanol, which provides easy access to DNA from prey items. Shotgun sequencing of DNA from preservative ethanol provides novel opportunities for characterizing the functional or ecological components of an ecosystem and their trophic interactions.

Quantitative Trait Loci Analysis of Resistance to Sclerotinia sclerotiorum in Sunflower.

ABSTRACT A quantitative trait loci (QTL) analysis of resistance to Sclerotinia sclerotiorum was carried out with 283 sunflower (Helianthus annuus) F(2:3) families derived from a cross between a resistant (SWS-B-04) and a highly susceptible sunflower inbred line. For that purpose, a genetic map based on 195 amplified fragment length polymorphism and 20 simple sequence repeat markers was constructed. The map has a size of 2,273.5 centimorgans and comprises 17 linkage groups, 12 of which could be associated to already defined linkage groups. The heads of sunflower F(3) families were artificially inoculated by using sclerotinia mycelium in three field environments. The lesion length was measured in centimeters 1 week postinoculation and head rot was scored according to a 1-to-8 head rot scale 2 weeks postinoculation. Using the composite interval mapping procedure, three QTL for lesion length and two QTL for head rot could be identified. These QTL explain 10.6 to 17.1% of the total phenotypic variance.

Homologues of the engrailed gene from five molluscan classes.

We used the polymerase chain reaction (PCR) to amplify, clone, and sequence 10 engrailed homeodomains from 8 species in the five major molluscan classes, including the serially organized chiton (Polyplacophora) lineage. The Drosophila melanogaster gene engrailed (en) is one of several genes involved in embryonic segment polarity determination. Studies of engrailed sequence and expression in molluscs are of interest due to questions regarding the evolution and homology of segmentation in these taxa. Nucleotide and deduced amino acid sequence comparisons reflect evolutionary conservation within helices of the en homeodomain and ancient divergences in the region 3' to the homeodomain.

Induction and circumvention of nitrate tolerance applying different dosage intervals.

There is increasing evidence that constant nitrate plasma levels, as induced by at least three-times-daily ingestions of isosorbide dinitrate in sustained-release form, lead to an attenuation or even complete loss of the anti-ischemic effects (nitrate tolerance). Therefore, the dependence of tolerance development on dosage intervals according to once-daily and twice-daily ingestions was assessed. Tablets of isosorbide dinitrate (80 mg) in sustained-release form were administered once-daily at 8 A.M. (dosage interval 24 hours) or twice-daily at 8 A.M. and 8 P.M. (dosage interval 12 hours), as well as at 8 A.M. and 2 P.M., respectively (maximal dosage interval 18 hours). A total of 34 patients with angiographically proven coronary artery disease, a history of stable, exercise-dependent angina pectoris, and a reproducible, exercise-induced ST-segment depression of at least 0.15 mV (1.5 mm), who initially showed a response to 80 mg of isosorbide dinitrate, were enrolled. The anti-ischemic effects of isosorbide dinitrate on exercise-induced ischemia were objectively determined by the measurement of exercise-induced ST-segment depression before as well as two, six, and 12 hours after the ingestion at the first and the 15th day of the studies. Since the dosage interval of 12 hours resulted in constant plasma levels, the initially beneficial anti-ischemic effects of isosorbide dinitrate were considerably attenuated after two weeks of treatment. In contrast, the once-daily regimen with its intermittent peaks and valleys of nitrate plasma levels showed identical anti-ischemic effects at the 15th day as compared with the first day. Ingestions at 8 A.M. and 2 P.M. also circumvented the development of nitrate tolerance, however, combined with an even more pronounced anti-ischemic effect after 12 hours as compared with the once-daily regimen. Thus, the circumvention of nitrate tolerance requires a daily "nitrate-poor" interval. The best compromise between a maximal possible anti-ischemic effect and the circumvention of tolerance development was found for the "eccentric" dosage regimen in which the tablets were ingested in the morning and early afternoon.

Discovery of Aspidytidae, a new family of aquatic Coleoptera.

The six extant aquatic families of Hydradephaga (Coleoptera) known so far represent a diverse group of beetles morphologically highly modified for life in the water. We report the discovery of a new genus with two species from South Africa and China, which differ greatly from all extant families, but resemble the Jurassic-Cretaceous dagger Liadytidae (the dagger symbol indicates that the taxa are known only as fossils). Based on a combined phylogenetic analysis of molecular and morphological data we erect a new family, Aspidytidae, which is the sister group of Dytiscidae plus Hygrobiidae. We propose a new scenario for the evolution of swimming behaviour in adephagan beetles, in which the transition into the aquatic environment is followed by complex and repeated changes in lifestyles, including the secondary complete loss of swimming ability in Aspidytidae.

The haemodynamic and anti-ischaemic effects of a single tablet of 80 mg isosorbide dinitrate in slow-release formulation and a review of nitrate tolerance.

There is increasing evidence that relatively constant plasma nitrate concentrations induced by 3-times-daily administration of isosorbide dinitrate can lead to an attenuation or even complete loss of the drug's anti-ischaemic effects (nitrate tolerance). We therefore assessed the dependence of nitrate tolerance development from the haemodynamic and anti-ischaemic effects of a slow-release tablet formulation of isosorbide dinitrate 80 mg, administered according to different daily dosage regimens in patients with angina. It was found that a once-daily regimen, with its consequent peak and trough plasma nitrate concentrations, is capable of protecting against exercise-induced myocardial ischaemia for about 12 hours with the circumvention of nitrate tolerance.