270 research outputs found

    Evaluation of machine-learning methods for ligand-based virtual screening

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    Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed

    A new, large-bodied omnivorous bat (Noctilionoidea: Mystacinidae) reveals lost morphological and ecological diversity since the Miocene in New Zealand

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    A new genus and species of fossil bat is described from New Zealand's only pre-Pleistocene Cenozoic terrestrial fauna, the early Miocene St Bathans Fauna of Central Otago, South Island. Bayesian total evidence phylogenetic analysis places this new Southern Hemisphere taxon among the burrowing bats (mystacinids) of New Zealand and Australia, although its lower dentition also resembles Africa's endemic sucker-footed bats (myzopodids). As the first new bat genus to be added to New Zealand's fauna in more than 150 years, it provides new insight into the original diversity of chiropterans in Australasia. It also underscores the significant decline in morphological diversity that has taken place in the highly distinctive, semi-terrestrial bat family Mystacinidae since the Miocene. This bat was relatively large, with an estimated body mass of ~40 g, and its dentition suggests it had an omnivorous diet. Its striking dental autapomorphies, including development of a large hypocone, signal a shift of diet compared with other mystacinids, and may provide evidence of an adaptive radiation in feeding strategy in this group of noctilionoid bats

    Penetration of Sodium Hypochlorite Modified with Surfactants into Root Canal Dentin

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    Abstract The aim of this study was to evaluate the effect of concentration, exposure time and temperature of sodium hypochlorite (NaOCl) added with surfactants on its penetration into dentinal tubules. Sixty-five extracted human permanent maxillary anterior teeth with single canals were prepared by ProTaper SX hand-operated instruments. The teeth were then sectioned perpendicular to the long axis. The crowns and apical thirds of all the teeth were removed. The remaining roots were processed into 4-mm-long blocks and stained overnight in crystal violet. One hundred and thirty stained blocks were further split into halves and treated by nine different types of NaOCl-based solutions. Three solutions were added with surfactants (Hypoclean, H6, Chlor-Xtra) and the others were regular hypochlorites at increasing concentrations (1%, 2%, 4%, 5.25%, <6%, 6% NaOCl) from different brands. The dentin blocks were exposed to the solutions for 2, 5, and 20 min at 20 °C, 37 °C and 45 °C, respectively. The depth of NaOCl penetration was determined by bleaching of the stain and measured by light microscopy at 20&#61472;&#61620; and 40&#61620;. Statistical comparisons were made by using a generalized linear model with Bonferroni's post-hoc correction. The shortest penetration (81±6.6 &#956;m) was obtained after incubation in 1% NaOCl for 2 min at 20 °C; the highest penetration (376.3±3.8 &#956;m) was obtained with Chlor-Xtra for 20 min at 45 °C. Varying NaOCl concentration produced a minimal effect while temperature and exposure time had a significant direct relationship with NaOCl penetration into dentinal tubules, especially those with lowered surface tension. The exposure time and temperature of sodium hypochlorite as well as the addition of surfactants may influence the penetration depth of irrigants into dentinal tubules

    A Computational Method for Prediction of Excretory Proteins and Application to Identification of Gastric Cancer Markers in Urine

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    A novel computational method for prediction of proteins excreted into urine is presented. The method is based on the identification of a list of distinguishing features between proteins found in the urine of healthy people and proteins deemed not to be urine excretory. These features are used to train a classifier to distinguish the two classes of proteins. When used in conjunction with information of which proteins are differentially expressed in diseased tissues of a specific type versus control tissues, this method can be used to predict potential urine markers for the disease. Here we report the detailed algorithm of this method and an application to identification of urine markers for gastric cancer. The performance of the trained classifier on 163 proteins was experimentally validated using antibody arrays, achieving >80% true positive rate. By applying the classifier on differentially expressed genes in gastric cancer vs normal gastric tissues, it was found that endothelial lipase (EL) was substantially suppressed in the urine samples of 21 gastric cancer patients versus 21 healthy individuals. Overall, we have demonstrated that our predictor for urine excretory proteins is highly effective and could potentially serve as a powerful tool in searches for disease biomarkers in urine in general

    Biological-effective versus conventional dose volume histograms correlated with late genitourinary and gastrointestinal toxicity after external beam radiotherapy for prostate cancer: a matched pair analysis

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    BACKGROUND: To determine whether the dose-volume histograms (DVH's) for the rectum and bladder constructed using biological-effective dose (BED-DVH's) better correlate with late gastrointestinal (GI) and genitourinary (GU) toxicity after treatment with external beam radiotherapy for prostate cancer than conventional DVH's (C-DVH's). METHODS: The charts of 190 patients treated with external beam radiotherapy with a minimum follow-up of 2 years were reviewed. Six patients (3.2%) were found to have RTOG grade 3 GI toxicity, and similarly 6 patients (3.2%) were found to have RTOG grade 3 GU toxicity. Average late C-DVH's and BED-DVH's of the bladder and rectum were computed for these patients as well as for matched-pair control patients. For each matched pair the following measures of normalized difference in the DVH's were computed: (a) δ(AUC )= (Area Under Curve [AUC] in grade 3 patient – AUC in grade 0 patient)/(AUC in grade 0 patient) and (b) δ(V60 )= (Percent volume receiving = 60 Gy [V60] in grade 3 patient – V60 in grade 0 patient)/(V60 in grade 0 patient). RESULTS: As expected, the grade 3 curve is to the right of and above the grade 0 curve for all four sets of average DVH's – suggesting that both the C-DVH and the BED-DVH can be used for predicting late toxicity. δ(AUC )was higher for the BED-DVH's than for the C-DVH's – 0.27 vs 0.23 (p = 0.036) for the rectum and 0.24 vs 0.20 (p = 0.065) for the bladder. δ(V60 )was also higher for the BED-DVH's than for the C-DVH's – 2.73 vs 1.49 for the rectum (p = 0.021) and 1.64 vs 0.71 (p = 0.021) for the bladder. CONCLUSIONS: When considering well-established dosimetric endpoints used in evaluating treatment plans, BED-DVH's for the rectum and bladder correlate better with late toxicity than C-DVH's and should be considered when attempting to minimize late GI and GU toxicity after external beam radiotherapy for prostate cancer

    Tegumentary leishmaniasis and coinfections other than HIV

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    <div><p>Background</p><p>Tegumentary leishmaniasis (TL) is a disease of skin and/or mucosal tissues caused by <i>Leishmania</i> parasites. TL patients may concurrently carry other pathogens, which may influence the clinical outcome of TL.</p><p>Methodology and principal findings</p><p>This review focuses on the frequency of TL coinfections in human populations, interactions between <i>Leishmania</i> and other pathogens in animal models and human subjects, and implications of TL coinfections for clinical practice. For the purpose of this review, TL is defined as all forms of cutaneous (localised, disseminated, or diffuse) and mucocutaneous leishmaniasis. Human immunodeficiency virus (HIV) coinfection, superinfection with skin bacteria, and skin manifestations of visceral leishmaniasis are not included. We searched MEDLINE and other databases and included 73 records: 21 experimental studies in animals and 52 studies about human subjects (mainly cross-sectional and case studies). Several reports describe the frequency of <i>Trypanosoma cruzi</i> coinfection in TL patients in Argentina (about 41%) and the frequency of helminthiasis in TL patients in Brazil (15% to 88%). Different hypotheses have been explored about mechanisms of interaction between different microorganisms, but no clear answers emerge. Such interactions may involve innate immunity coupled with regulatory networks that affect quality and quantity of acquired immune responses. Diagnostic problems may occur when concurrent infections cause similar lesions (e.g., TL and leprosy), when different pathogens are present in the same lesions (e.g., <i>Leishmania</i> and <i>Sporothrix schenckii</i>), or when similarities between phylogenetically close pathogens affect accuracy of diagnostic tests (e.g., serology for leishmaniasis and Chagas disease). Some coinfections (e.g., helminthiasis) appear to reduce the effectiveness of antileishmanial treatment, and drug combinations may cause cumulative adverse effects.</p><p>Conclusions and significance</p><p>In patients with TL, coinfection is frequent, it can lead to diagnostic errors and delays, and it can influence the effectiveness and safety of treatment. More research is needed to unravel how coinfections interfere with the pathogenesis of TL.</p></div
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