Extraction of Airways with Probabilistic State-space Models and Bayesian Smoothing

Segmenting tree structures is common in several image processing applications. In medical image analysis, reliable segmentations of airways, vessels, neurons and other tree structures can enable important clinical applications. We present a framework for tracking tree structures comprising of elongated branches using probabilistic state-space models and Bayesian smoothing. Unlike most existing methods that proceed with sequential tracking of branches, we present an exploratory method, that is less sensitive to local anomalies in the data due to acquisition noise and/or interfering structures. The evolution of individual branches is modelled using a process model and the observed data is incorporated into the update step of the Bayesian smoother using a measurement model that is based on a multi-scale blob detector. Bayesian smoothing is performed using the RTS (Rauch-Tung-Striebel) smoother, which provides Gaussian density estimates of branch states at each tracking step. We select likely branch seed points automatically based on the response of the blob detection and track from all such seed points using the RTS smoother. We use covariance of the marginal posterior density estimated for each branch to discriminate false positive and true positive branches. The method is evaluated on 3D chest CT scans to track airways. We show that the presented method results in additional branches compared to a baseline method based on region growing on probability images.Comment: 10 pages. Pre-print of the paper accepted at Workshop on Graphs in Biomedical Image Analysis. MICCAI 2017. Quebec Cit

Wake response to an ocean-feedback mechanism: Madeira Island case study

This discussion focused on the numerical study of a wake episode. The Weather Research and Forecasting model was used in a downscale mode. The current literature focuses the discussion on the adiabatic dynamics of atmospheric wakes. Changes in mountain height and consequently on its relation to the atmospheric inversion layer should explain the shift in wake regimes: from a 'strong-wake' to a 'weak-wake' scenario. Nevertheless, changes in SST variability can also induce similar regime shifts. Increase in evaporation, contributes to increase convection and thus to an uplift of the stratified atmospheric layer, above the critical height, with subsequent internal gravity wave activity.Comment: Under review proces

Levetiracetam in spinal cord injury pain: a randomized controlled trial

Udgivelsesdato: 2009-Jun-9Study design:A randomized, double-blind, placebo-controlled, crossover, multicenter trial. A 1-week baseline period was followed by two treatment periods of 5 weeks duration with levetiracetam increased from 500 mg b.i.d. to a maximum of 1500 mg b.i.d. separated by a 1-week washout period.Objectives:The objective of the study was primarily to evaluate the efficacy of the anticonvulsant levetiracetam in patients with spinal cord injury (SCI) at- and below-level pain and secondarily to evaluate the effect on spasm severity.Setting:Outpatients at two spinal cord units and a pain center.Methods:Patients were allowed to continue their usual pain treatment at a constant dose. The primary outcome measure was the change in median daily pain score (on a 0-10 point numeric rating scale) from 1-week baseline period to the last week of each treatment period. Secondary outcome measures included pain relief of at- and below-level pain, allodynia, spasms and spasticity.Results:A total of 36 patients with SCI at- and or below-level pain were enrolled. Of these, 24 patients completed the trial. We found no effect of levetiracetam on the primary (P=0.46) or any of the secondary outcome measures. Only two patients continued levetiracetam treatment following the trial, and one patient was still in levetiracetam treatment at the 6-month follow-up. Levetiracetam was generally well tolerated with no serious adverse events.Conclusions:Levetiracetam does not relieve neuropathic pain or spasm severity following spinal cord injury.Spinal Cord advance online publication, 9 June 2009; doi:10.1038/sc.2009.55

25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression

Age-associated decline in muscle function represents a significant public health burden. Vitamin D-deficiency is also prevalent in aging subjects, and has been linked to loss of muscle mass and strength (sarcopenia), but the precise role of specific vitamin D metabolites in determining muscle phenotype and function is still unclear. To address this we quantified serum concentrations of multiple vitamin D metabolites, and assessed the impact of these metabolites on body composition/muscle function parameters, and muscle biopsy gene expression in a retrospective study of a cohort of healthy volunteers. Active serum 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3), but not inactive 25-hydroxyvitamin D3 (25OHD3), correlated positively with measures of lower limb strength including power (rho = 0.42, p = 0.02), velocity (Vmax, rho = 0.40, p = 0.02) and jump height (rho = 0.36, p = 0.04). Lean mass correlated positively with 1α,25(OH)2D3 (rho = 0.47, p = 0.02), in women. Serum 25OHD3 and inactive 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) had an inverse relationship with body fat (rho = -0.30, p = 0.02 and rho = -0.33, p = 0.01, respectively). Serum 25OHD3 and 24,25(OH)2D3 were also correlated with urinary steroid metabolites, suggesting a link with glucocorticoid metabolism. PCR array analysis of 92 muscle genes identified vitamin D receptor (VDR) mRNA in all muscle biopsies, with this expression being negatively correlated with serum 25OHD3, and Vmax, and positively correlated with fat mass. Of the other 91 muscle genes analysed by PCR array, 24 were positively correlated with 25OHD3, but only 4 were correlated with active 1α,25(OH)2D3. These data show that although 25OHD3 has potent actions on muscle gene expression, the circulating concentrations of this metabolite are more closely linked to body fat mass, suggesting that 25OHD3 can influence muscle function via indirect effects on adipose tissue. By contrast, serum 1α,25(OH)2D3 has limited effects on muscle gene expression, but is associated with increased muscle strength and lean mass in women. These pleiotropic effects of the vitamin D ‘metabolome’ on muscle function indicate that future supplementation studies should not be restricted to conventional analysis of the major circulating form of vitamin D, 25OHD3

Assessing the congruence of thermal niche estimations derived from distribution and physiological data. A test using diving beetles.

A basic aim of ecology is to understand the determinants of organismal distribution, the niche concept and species distribution models providing key frameworks to approach the problem. As temperature is one of the most important factors affecting species distribution, the estimation of thermal limits is crucially important for inferring range constraints. It is expectable that thermal physiology data derived from laboratory experiments and species' occurrences may express different aspects of the species' niche. However, there is no study systematically testing this prediction in a given taxonomic group while controlling by potential phylogenetic inertia. We estimate the thermal niches of twelve Palaearctic diving beetles species using physiological data derived from experimental analyses in order to examine the extent to which these coincided with those estimated from distribution models based on observed occurrences. We found that thermal niche estimates derived from both approaches lack general congruence, and these results were similar before and after controlling by phylogeny. The congruence between potential distributions obtained from the two different procedures was also explored, and we found again that the percentage of agreement were not very high (~60%). We confirm that both thermal niche estimates derived from geographical and physiological data are likely to misrepresent the true range of climatic variation that these diving beetles are able to tolerate, and so these procedures could be considered as incomplete but complementary estimations of an inaccessible reality

A Unified Model of the GABA(A) Receptor Comprising Agonist and Benzodiazepine Binding Sites

We present a full-length α(1)β(2)γ(2) GABA receptor model optimized for agonists and benzodiazepine (BZD) allosteric modulators. We propose binding hypotheses for the agonists GABA, muscimol and THIP and for the allosteric modulator diazepam (DZP). The receptor model is primarily based on the glutamate-gated chloride channel (GluCl) from C. elegans and includes additional structural information from the prokaryotic ligand-gated ion channel ELIC in a few regions. Available mutational data of the binding sites are well explained by the model and the proposed ligand binding poses. We suggest a GABA binding mode similar to the binding mode of glutamate in the GluCl X-ray structure. Key interactions are predicted with residues α(1)R66, β(2)T202, α(1)T129, β(2)E155, β(2)Y205 and the backbone of β(2)S156. Muscimol is predicted to bind similarly, however, with minor differences rationalized with quantum mechanical energy calculations. Muscimol key interactions are predicted to be α(1)R66, β(2)T202, α(1)T129, β(2)E155, β(2)Y205 and β(2)F200. Furthermore, we argue that a water molecule could mediate further interactions between muscimol and the backbone of β(2)S156 and β(2)Y157. DZP is predicted to bind with interactions comparable to those of the agonists in the orthosteric site. The carbonyl group of DZP is predicted to interact with two threonines α(1)T206 and γ(2)T142, similar to the acidic moiety of GABA. The chlorine atom of DZP is placed near the important α(1)H101 and the N-methyl group near α(1)Y159, α(1)T206, and α(1)Y209. We present a binding mode of DZP in which the pending phenyl moiety of DZP is buried in the binding pocket and thus shielded from solvent exposure. Our full length GABA(A) receptor is made available as Model S1

Formation of Sclerotia and Production of Indoloterpenes by Aspergillus niger and Other Species in Section Nigri

Several species in Aspergillus section Nigri have been reported to produce sclerotia on well-known growth media, such as Czapek yeast autolysate (CYA) agar, with sclerotia considered to be an important prerequisite for sexual development. However Aspergillus niger sensu stricto has not been reported to produce sclerotia, and is thought to be a purely asexual organism. Here we report, for the first time, the production of sclerotia by certain strains of Aspergillus niger when grown on CYA agar with raisins, or on other fruits or on rice. Up to 11 apolar indoloterpenes of the aflavinine type were detected by liquid chromatography and diode array and mass spectrometric detection where sclerotia were formed, including 10,23-dihydro-24,25-dehydroaflavinine. Sclerotium induction can thus be a way of inducing the production of new secondary metabolites from previously silent gene clusters. Cultivation of other species of the black aspergilli showed that raisins induced sclerotium formation by A. brasiliensis, A. floridensis A. ibericus, A. luchuensis, A. neoniger, A. trinidadensis and A. saccharolyticus for the first time

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal speciesFilamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence. Here, we examined SM variation in 66 cosmopolitan strains of a single species, the opportunistic human pathogen Aspergillus fumigatus. Investigation of genome-wide within-species variation revealed 5 general types of variation in SM gene clusters: nonfunctional gene polymorphisms; gene gain and loss polymorphisms; whole cluster gain and loss polymorphisms; allelic polymorphisms, in which different alleles corresponded to distinct, nonhomologous clusters; and location polymorphisms, in which a cluster was found to differ in its genomic location across strains. These polymorphisms affect the function of representative A. fumigatus SM gene clusters, such as those involved in the production of gliotoxin, fumigaclavine, and helvolic acid as well as the function of clusters with undefined products. In addition to enabling the identification of polymorphisms, the detection of which requires extensive genome-wide synteny conservation (e.g., mobile gene clusters and nonhomologous cluster alleles), our approach also implicated multiple underlying genetic drivers, including point mutations, recombination, and genomic deletion and insertion events as well as horizontal gene transfer from distant fungi. Finally, most of the variants that we uncover within A. fumigatus have been previously hypothesized to contribute to SM gene cluster diversity across entire fungal classes and phyla. We suggest that the drivers of genetic diversity operating within a fungal species shown here are sufficient to explain SM cluster macroevolutionary patterns.National Science Foundation (grant number DEB-1442113). Received by AR. U.S. National Library of Medicine training grant (grant number 2T15LM007450). Received by ALL. Conselho Nacional de Desenvolvimento Cientı´fico e 573 Tecnológico. Northern Portugal Regional Operational Programme (grant number NORTE-01- 0145-FEDER-000013). Received by FR. Fundação de Amparo à Pesquisa do 572 Estado de São Paulo. Received by GHG. National Institutes of Health (grant number R01 AI065728-01). Received by NPK. National Science Foundation (grant number IOS-1401682). Received by JHW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Redefining the "carrier" state for foot-and-mouth disease from the dynamics of virus persistence in endemically affected cattle populations

The foot-and-mouth disease virus (FMDV) “carrier” state was defined by van Bekkum in 1959. It was based on the recovery of infectious virus 28 days or more post infection and has been a useful construct for experimental studies. Using historic data from 1,107 cattle, collected as part of a population based study of endemic FMD in 2000, we developed a mixed effects logistic regression model to predict the probability of recovering viable FMDV by probang and culture, conditional on the animal’s age and time since last reported outbreak. We constructed a second set of models to predict the probability of an animal being probang positive given its antibody response in three common non-structural protein (NSP) ELISAs and its age. We argue that, in natural ecological settings, the current definition of a ”carrier” fails to capture the dynamics of either persistence of the virus (as measured by recovery using probangs) or the uncertainty in transmission from such animals that the term implies. In these respects it is not particularly useful. We therefore propose the first predictive statistical models for identifying persistently infected cattle in an endemic setting that captures some of the dynamics of the probability of persistence. Furthermore, we provide a set of predictive tools to use alongside NSP ELISAs to help target persistently infected cattle

Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing

The cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21) is a cell-cycle checkpoint effector and inducer of senescence, regulated by p53. Yet, evidence suggests that p21 could also be oncogenic, through a mechanism that has so far remained obscure. We report that a subset of atypical cancerous cells strongly expressing p21 showed proliferation features. This occurred predominantly in p53-mutant human cancers, suggesting p53-independent upregulation of p21 selectively in more aggressive tumour cells. Multifaceted phenotypic and genomic analyses of p21-inducible, p53-null, cancerous and near-normal cellular models showed that after an initial senescence-like phase, a subpopulation of p21-expressing proliferating cells emerged, featuring increased genomic instability, aggressiveness and chemoresistance. Mechanistically, sustained p21 accumulation inhibited mainly the CRL4–CDT2 ubiquitin ligase, leading to deregulated origin licensing and replication stress. Collectively, our data reveal the tumour-promoting ability of p21 through deregulation of DNA replication licensing machinery—an unorthodox role to be considered in cancer treatment, since p21 responds to various stimuli including some chemotherapy drugs