Multilayer perceptron with local constraint as an emerging method in spatial data analysis

The use of Geographic Information Systems has revolutionalized the handling and the visualization of geo-referenced data and has underlined the critic role of spatial analysis. The usual tools for such a purpose are geostatistics which are widely used in Earth science. Geostatistics are based upon several hypothesis which are not always verified in practice. On the other hand, Artificial Neural Network (ANN) a priori can be used without special assumptions and are known to be flexible. This paper proposes to discuss the application of ANN in the case of the interpolation of a geo-referenced variable.

IQRray, a new method for Affymetrix microarray quality control, and the homologous organ conservation score, a new benchmark method for quality control metrics.

MOTIVATION: Microarray results accumulated in public repositories are widely reused in meta-analytical studies and secondary databases. The quality of the data obtained with this technology varies from experiment to experiment, and an efficient method for quality assessment is necessary to ensure their reliability. RESULTS: The lack of a good benchmark has hampered evaluation of existing methods for quality control. In this study, we propose a new independent quality metric that is based on evolutionary conservation of expression profiles. We show, using 11 large organ-specific datasets, that IQRray, a new quality metrics developed by us, exhibits the highest correlation with this reference metric, among 14 metrics tested. IQRray outperforms other methods in identification of poor quality arrays in datasets composed of arrays from many independent experiments. In contrast, the performance of methods designed for detecting outliers in a single experiment like Normalized Unscaled Standard Error and Relative Log Expression was low because of the inability of these methods to detect datasets containing only low-quality arrays and because the scores cannot be directly compared between experiments. AVAILABILITY AND IMPLEMENTATION: The R implementation of IQRray is available at: ftp://lausanne.isb-sib.ch/pub/databases/Bgee/general/IQRray.R. CONTACT: Marta.Rosikiewicz@unil.ch SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Multiplex ultra-performance liquid chromatography-tandem mass spectrometry method for simultaneous quantification in human plasma of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, anidulafungin, and caspofungin.

Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (<9.2%), and analytical recovery (80.1 to 107%). The method is sensitive (lower limits of azole quantification, 0.01 to 0.1 μg/ml; those of echinocandin quantification, 0.06 to 0.1 μg/ml), accurate (intra- and interassay biases of -9.9 to +5% and -4.0 to +8.8%, respectively), and precise (intra- and interassay coefficients of variation of 1.2 to 11.1% and 1.2 to 8.9%, respectively) over clinical concentration ranges (upper limits of quantification, 5 to 50 μg/ml). Thus, we developed a simple, rapid, and robust multiplex UPLC-MS/MS assay for simultaneous quantification of plasma concentrations of six antifungals and two metabolites. This offers, by optimized and cost-effective lab resource utilization, an efficient tool for daily routine TDM aimed at maximizing the real-time efficacy and safety of different recommended single-drug antifungal regimens and combination salvage therapies, as well as a tool for clinical research.

An optimized method for establishing high purity murine CD8+ T cell cultures.

Establishing CD8(+) T cell cultures has been empirical and the published methods have been largely individual laboratory based. In this study, we optimized culturing conditions and show that IL-2 concentration is the most critical factor for the success of establishing CD8(+) T cell cultures. High IL-2 concentration encouraged T cells to non-specifically proliferate, express a B cell marker, B220, and undergo apoptosis. These cells also lose typical irregular T cell morphology and are incapable of sustaining long-term cultures. Using tetramer and intracellular cytokine assessments, we further demonstrated that many antigen-specific T cells have been rendered nonfunctional when expanded under high IL-2 concentration. When IL-2 is used in the correct range, B220-mediated cell depletion greatly enhanced the success rate of such T cell cultures.

Glomus intraradices induces changes in root system architecture of rice independently of common symbiosis signaling

? Arbuscular mycorrhizal fungi colonize the roots of most monocotyledons and dicotyledons despite their different root architecture and cell patterning. Among the cereal hosts of arbuscular mycorrhizal fungi, Oryza sativa (rice) possesses a peculiar root system composed of three different types of roots: crown roots; large lateral roots; and fine lateral roots. Characteristic is the constitutive formation of aerenchyma in crown roots and large lateral roots and the absence of cortex from fine lateral roots. Here, we assessed the distribution of colonization by Glomus intraradices within this root system and determined its effect on root system architecture. ? Large lateral roots are preferentially colonized, and fine lateral roots are immune to arbuscular mycorrhizal colonization. Fungal preference for large lateral roots also occurred in sym mutants that block colonization of the root beyond rhizodermal penetration. ? Initiation of large lateral roots is significantly induced by G. intraradices colonization and does not require a functional common symbiosis signaling pathway from which some components are known to be needed for symbiosis-mediated lateral root induction in Medicago truncatula. ? Our results suggest variation of symbiotic properties among the different rice root-types and induction of the preferred tissue by arbuscular mycorrhizal fungi. Furthermore, signaling for arbuscular mycorrhizal-elicited alterations of the root system differs between rice and M. truncatula.

Oral insecticidal activity of root colonizing Pseudomonas fluorescens CHA0: a biocontrol agent with potential to control plant pests and diseases

The application of microbial biocontrol agents for the control of fungal plant diseases and plant insect pests is a promising approach in the development of environmentally benign pest management strategies. The ideal biocontrol organism would be a bacterium or a fungus with activity against both, insect pests and fungal pathogens. Here we demonstrate the oral insecticidal activity of the root colonizing Pseudomonas fluorescens CHA0, which is so far known for its capacity to efficiently suppress fungal plant pathogens. Feeding assays with CHA0-sprayed leaves showed that this strain displays oral insecticidal activity and is able to efficiently kill larvae of three important insect pests. We further show data indicating that the Fit insect toxin produced by CHA0 and also metabolites controlled by the global regulator GacA contribute to oral insect toxicity.

Colonoscopy is the preferred colorectal cancer screening method in a population-based program.

BACKGROUND AND STUDY AIMS: Various screening methods for colorectal cancer (CRC) are promoted by professional societies; however, few data are available about the factors that determine patient participation in screening, which is crucial to the success of population-based programs. This study aimed (i) to identify factors that determine acceptance of screening and preference of screening method, and (ii) to evaluate procedure success, detection of colorectal neoplasia, and patient satisfaction with screening colonoscopy. PATIENTS AND METHODS: Following a public awareness campaign, the population aged 50 - 80 years was offered CRC screening in the form of annual fecal occult blood tests, flexible sigmoidoscopy, a combination of both, or colonoscopy. RESULTS: 2731 asymptomatic persons (12.0 % of the target population) registered with and were eligible to take part in the screening program. Access to information and a positive attitude to screening were major determinants of participation. Colonoscopy was the method preferred by 74.8 % of participants. Advanced colorectal neoplasia was present in 8.5 %; its prevalence was higher in males and increased with age. Significant complications occurred in 0.5 % of those undergoing colonoscopy and were associated with polypectomy or sedation. Most patients were satisfied with colonoscopy and over 90 % would choose it again for CRC screening. CONCLUSIONS: In this population-based study, only a small proportion of the target population underwent CRC screening despite an extensive information campaign. Colonoscopy was the preferred method and was safe. The determinants of participation in screening and preference of screening method, together with the distribution of colorectal neoplasia in different demographic categories, provide a rationale for improving screening procedures.

Inter-informant agreement and prevalence estimates for substance use disorders: direct interview versus family history method.

OBJECTIVES: Family studies typically use multiple sources of information on each individual including direct interviews and family history information. The aims of the present study were to: (1) assess agreement for diagnoses of specific substance use disorders between direct interviews and the family history method; (2) compare prevalence estimates according to the two methods; (3) test strategies to approximate prevalence estimates according to family history reports to those based on direct interviews; (4) determine covariates of inter-informant agreement; and (5) identify covariates that affect the likelihood of reporting disorders by informants. METHODS: Analyses were based on family study data which included 1621 distinct informant (first-degree relatives and spouses) - index subject pairs. RESULTS: Our main findings were: (1) inter-informant agreement was fair to good for all substance disorders, except for alcohol abuse; (2) the family history method underestimated the prevalence of drug but not alcohol use disorders; (3) lowering diagnostic thresholds for drug disorders and combining multiple family histories increased the accuracy of prevalence estimates for these disorders according to the family history method; (4) female sex of index subjects was associated with higher agreement for nearly all disorders; and (5) informants who themselves had a history of the same substance use disorder were more likely to report this disorder in their relatives, which entails the risk of overestimation of the size of familial aggregation. CONCLUSION: Our findings have important implications for the best-estimate procedure applied in family studies.

Analysis of a finite volume element method for the Stokes problem

In this paper we propose a stabilized conforming finite volume element method for the Stokes equations. On stating the convergence of the method, optimal a priori error estimates in different norms are obtained by establishing the adequate connection between the finite volume and stabilized finite element formulations. A superconvergence result is also derived by using a postprocessing projection method. In particular, the stabilization of the continuous lowest equal order pair finite volume element discretization is achieved by enriching the velocity space with local functions that do not necessarily vanish on the element boundaries. Finally, some numerical experiments that confirm the predicted behavior of the method are provided.

Development of a method to investigate the hydrolysis of xenobiotic esters by a Mycobacterium smegmatis homogenate.

One of the main problems in combating tuberculosis is caused by a poor penetration of drugs into the mycobacterial cells. A prodrug approach via activation inside mycobacterial cells is a possible strategy to overcome this hurdle and achieve efficient drug uptake. Esters are attractive candidates for such a strategy and we and others communicated previously the activity of esters of weak organic acids against mycobacteria. However very little is known about ester hydrolysis by mycobacteria and no biological model is available to study the activation of prodrugs by these microorganisms. To begin filling this gap, we have embarked in a project to develop an in vitro method to study prodrug activation by mycobacteria using Mycobacterium smegmatis homogenates. Model ester substrates were ethyl nicotinate and ethyl benzoate whose hydrolysis was monitored and characterized kinetically. Our studies showed that in M. smegmatis most esterase activity is associated with the soluble fraction (cytosol) and is preserved by storage at 5°C or at room temperature for one hour, or by storage at -80°C up to one year. In the range of homogenate concentrations studied (5-80% in buffer), k(obs) varied linearly with homogenate concentration for both substrates. We also found that the homogenates showed Michaelis-Menten kinetics behavior with both prodrugs. Since ethyl benzoate is a good substrate for the mycobacterial esterases, this compound can be used to standardize the esterasic activity of homogenates, allowing results of incubations of prodrugs with homogenates from different batches to be readily compared.

Structural prediction of peptides bound to MHC class I.

An ab initio structure prediction approach adapted to the peptide-major histocompatibility complex (MHC) class I system is presented. Based on structure comparisons of a large set of peptide-MHC class I complexes, a molecular dynamics protocol is proposed using simulated annealing (SA) cycles to sample the conformational space of the peptide in its fixed MHC environment. A set of 14 peptide-human leukocyte antigen (HLA) A0201 and 27 peptide-non-HLA A0201 complexes for which X-ray structures are available is used to test the accuracy of the prediction method. For each complex, 1000 peptide conformers are obtained from the SA sampling. A graph theory clustering algorithm based on heavy atom root-mean-square deviation (RMSD) values is applied to the sampled conformers. The clusters are ranked using cluster size, mean effective or conformational free energies, with solvation free energies computed using Generalized Born MV 2 (GB-MV2) and Poisson-Boltzmann (PB) continuum models. The final conformation is chosen as the center of the best-ranked cluster. With conformational free energies, the overall prediction success is 83% using a 1.00 Angstroms crystal RMSD criterion for main-chain atoms, and 76% using a 1.50 Angstroms RMSD criterion for heavy atoms. The prediction success is even higher for the set of 14 peptide-HLA A0201 complexes: 100% of the peptides have main-chain RMSD values &lt; or =1.00 Angstroms and 93% of the peptides have heavy atom RMSD values &lt; or =1.50 Angstroms. This structure prediction method can be applied to complexes of natural or modified antigenic peptides in their MHC environment with the aim to perform rational structure-based optimizations of tumor vaccines.

Postmortem computed tomography angiography vs. conventional autopsy: advantages and inconveniences of each method.

PURPOSE: Postmortem computed tomography angiography (PMCTA) was introduced into forensic investigations a few years ago. It provides reliable images that can be consulted at any time. Conventional autopsy remains the reference standard for defining the cause of death, but provides only limited possibility of a second examination. This study compares these two procedures and discusses findings that can be detected exclusively using each method. MATERIALS AND METHODS: This retrospective study compared radiological reports from PMCTA to reports from conventional autopsy for 50 forensic autopsy cases. Reported findings from autopsy and PMCTA were extracted and compared to each other. PMCTA was performed using a modified heart-lung machine and the oily contrast agent Angiofil® (Fumedica AG, Muri, Switzerland). RESULTS: PMCTA and conventional autopsy would have drawn similar conclusions regarding causes of death. Nearly 60 % of all findings were visualized with both techniques. PMCTA demonstrates a higher sensitivity for identifying skeletal and vascular lesions. However, vascular occlusions due to postmortem blood clots could be falsely assumed to be vascular lesions. In contrast, conventional autopsy does not detect all bone fractures or the exact source of bleeding. Conventional autopsy provides important information about organ morphology and remains the only way to diagnose a vital vascular occlusion with certitude. CONCLUSION: Overall, PMCTA and conventional autopsy provide comparable findings. However, each technique presents advantages and disadvantages for detecting specific findings. To correctly interpret findings and clearly define the indications for PMCTA, these differences must be understood.