Incorporating significant amino acid pairs to identify O-linked glycosylation sites on transmembrane proteins and non-transmembrane proteins

<p>Abstract</p> <p>Background</p> <p>While occurring enzymatically in biological systems, O-linked glycosylation affects protein folding, localization and trafficking, protein solubility, antigenicity, biological activity, as well as cell-cell interactions on membrane proteins. Catalytic enzymes involve glycotransferases, sugar-transferring enzymes and glycosidases which trim specific monosaccharides from precursors to form intermediate structures. Due to the difficulty of experimental identification, several works have used computational methods to identify glycosylation sites.</p> <p>Results</p> <p>By investigating glycosylated sites that contain various motifs between Transmembrane (TM) and non-Transmembrane (non-TM) proteins, this work presents a novel method, GlycoRBF, that implements radial basis function (RBF) networks with significant amino acid pairs (SAAPs) for identifying O-linked glycosylated serine and threonine on TM proteins and non-TM proteins. Additionally, a membrane topology is considered for reducing the false positives on glycosylated TM proteins. Based on an evaluation using five-fold cross-validation, the consideration of a membrane topology can reduce 31.4% of the false positives when identifying O-linked glycosylation sites on TM proteins. Via an independent test, GlycoRBF outperforms previous O-linked glycosylation site prediction schemes.</p> <p>Conclusion</p> <p>A case study of Cyclic AMP-dependent transcription factor ATF-6 alpha was presented to demonstrate the effectiveness of GlycoRBF. Web-based GlycoRBF, which can be accessed at <url>http://GlycoRBF.bioinfo.tw</url>, can identify O-linked glycosylated serine and threonine effectively and efficiently. Moreover, the structural topology of Transmembrane (TM) proteins with glycosylation sites is provided to users. The stand-alone version of GlycoRBF is also available for high throughput data analysis.</p

Rapid Detection of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Based on Matrix-Assisted Laser Desorption Ionization Time-of-Flight: Using a Machine Learning Approach and Unbiased Validation

Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) is an emerging superbug with implicit drug resistance to vancomycin. Detecting hVISA can guide the correct administration of antibiotics. However, hVISA cannot be detected in most clinical microbiology laboratories because the required diagnostic tools are either expensive, time consuming, or labor intensive. By contrast, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) is a cost-effective and rapid tool that has potential for providing antibiotics resistance information. To analyze complex MALDI-TOF mass spectra, machine learning (ML) algorithms can be used to generate robust hVISA detection models. In this study, MALDI-TOF mass spectra were obtained from 35 hVISA/vancomycin-intermediate S. aureus (VISA) and 90 vancomycin-susceptible S. aureus isolates. The vancomycin susceptibility of the isolates was determined using an Etest and modified population analysis profile–area under the curve. ML algorithms, namely a decision tree, k-nearest neighbors, random forest, and a support vector machine (SVM), were trained and validated using nested cross-validation to provide unbiased validation results. The area under the curve of the models ranged from 0.67 to 0.79, and the SVM-derived model outperformed those of the other algorithms. The peaks at m/z 1132, 2895, 3176, and 6591 were noted as informative peaks for detecting hVISA/VISA. We demonstrated that hVISA/VISA could be detected by analyzing MALDI-TOF mass spectra using ML. Moreover, the results are particularly robust due to a strict validation method. The ML models in this study can provide rapid and accurate reports regarding hVISA/VISA and thus guide the correct administration of antibiotics in treatment of S. aureus infection

Comparison of three dimensional quasi-linear large swirl theory with measured outflow from a high-work compressor rotor

September 1975Includes bibliographical references (page 37)A three-dimensional perturbation theory for incompressible strongly swirling flow in an annulus is applied to predict the outflow from a high-work compressor rotor (1)(2). A comparison of the analytical result with the experimental result is presented. The theory treats inviscid, incompressible flow through a highly loaded blade row in a long annular duct with uniform inlet. Trailing vorticity is shed from each blade which is represented by a lifting line of bound vorticity. The flow field between successive sheets of vorticity is assumed to be irrotational. The theoretical results are compared to data obtained in the M.I.T. Blowdown Compressor Test Facility (3). The mean circulation distribution is estimated from the mean pitchwise Mach number obtained from the experiment. The agreement of the predicted mean axial and radial velocity with the experimental results represents one confirmation of the theory. The pitchwise-varying velocity are evaluated by the theory at an axial distance of .02 tip radius which corresponds to the probe position if the lifting line is placed slightly ahead, but almost along the trailing edge of the blade. The theory predicts well the pitchwise variation of the velocity due to the effect of shed vorticity which results from the spanwise variation of circulation. The effect is pronounced near the blade tips. Corrections of the theory due to compressibility are omitted here, but will be available shortly.Research supported by the Air Office of Scientific Research under Grant AFOSR-75-278

Ontology-based Fuzzy Markup Language Agent for Student and Robot Co-Learning

An intelligent robot agent based on domain ontology, machine learning mechanism, and Fuzzy Markup Language (FML) for students and robot co-learning is presented in this paper. The machine-human co-learning model is established to help various students learn the mathematical concepts based on their learning ability and performance. Meanwhile, the robot acts as a teacher's assistant to co-learn with children in the class. The FML-based knowledge base and rule base are embedded in the robot so that the teachers can get feedback from the robot on whether students make progress or not. Next, we inferred students' learning performance based on learning content's difficulty and students' ability, concentration level, as well as teamwork sprit in the class. Experimental results show that learning with the robot is helpful for disadvantaged and below-basic children. Moreover, the accuracy of the intelligent FML-based agent for student learning is increased after machine learning mechanism.Comment: This paper is submitted to IEEE WCCI 2018 Conference for revie

A framework of firms' business sustainability endeavours with internal and external stakeholders through time across oriental and occidental business contexts

Purpose The purpose of the paper is to test and compare a framework of firms' business sustainability endeavours with internal and external stakeholders in an oriental business context and to verify the validity and reliability of a stakeholder framework through time and across oriental and occidental business contexts. Design/methodology/approach Quantitative approach based on a questionnaire survey in corporate Taiwan with a response rate of 68.5%. Multivariate analysis is undertaken to uncover the measurement properties of a stakeholder framework. Findings A framework of firms' business sustainability endeavours with internal and external stakeholders appears valid and reliable through time and across occidental and oriental business contexts. Research limitations/implications This study verifies and fortifies a stakeholder framework through time and across business contexts consisting of five stakeholder groups: upstream, the focal firm, downstream, market and societal. Practical implications The framework of firms' business sustainability endeavours provides guidance to firms in their endeavours of business sustainability with internal and external stakeholders. Originality/value This study contributes to existing theory and previous studies by validating a stakeholder framework of business sustainability with internal and external stakeholders beyond occidental business context to be also valid and reliable in oriental ones

Early Detection of Tumor Response by FLT/MicroPET Imaging in a C26 Murine Colon Carcinoma Solid Tumor Animal Model

Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging demonstrated the change of glucose consumption of tumor cells, but problems with specificity and difficulties in early detection of tumor response to chemotherapy have led to the development of new PET tracers. Fluorine-18-fluorothymidine (18F-FLT) images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study, we evaluate the early response of colon carcinoma to the chemotherapeutic drug, lipo-Dox, in C26 murine colorectal carcinoma-bearing mice by 18F-FDG and 18F-FLT. The male BALB/c mice were bilaterally inoculated with 1 × 105 and 1 × 106 C26 tumor cells per flank. Mice were intravenously treated with 10 mg/kg lipo-Dox at day 8 after 18F-FDG and 18F-FLT imaging. The biodistribution of 18F-FDG and 18F-FLT were followed by the microPET imaging at day 9. For the quantitative measurement of microPET imaging at day 9, 18F-FLT was superior to 18F-FDG for early detection of tumor response to Lipo-DOX at various tumor sizes (P < 0.05). The data of biodistribution showed similar results with those from the quantification of SUV (standard uptake value) by microPET imaging. The study indicates that 18F-FLT/microPET is a useful imaging modality for early detection of chemotherapy in the colorectal mouse model

TBL dominant logic for sustainability in oriental businesses

Purpose This paper aims to examine the common denominators of measurement properties of a Triple Bottom Line (TBL) dominant logic for business sustainability through time and across business contexts. Design/methodology/approach The method was based on a quantitative approach and a questionnaire survey in corporate Taiwan with a response rate of 68.5%. Findings This article uncovers and fortifies common denominators through time between oriental and occidental business contexts. Practical implications The framework of TBL dominant logic for business sustainability establishes a toolbox for practitioners to examine economic, social and environmental elements as the marketing strategy in connection with business sustainability. Social implications This enables to validate the framework of TBL dominant logic for business sustainability in previous research. Multiple dimensions are validated through time and across business contexts. Originality/value This study contributes to existing theory and previous research by fortifying the framework of TBL-dominant logic for business sustainability. The twenty-dimensional framework demonstrates universal measurement properties through time and across oriental and occidental business contexts

Atypical Antipsychotic Drug Olanzapine Deregulates Hepatic Lipid Metabolism and Aortic Inflammation and Aggravates Atherosclerosis

Background/Aims: Olanzapine, an atypical antipsychotic drug, has therapeutic effects for schizophrenia. However, clinical reports indicate that patients taking atypical antipsychotic drugs are at high risk of metabolic syndrome with unclear mechanisms. We investigated the effect of olanzapine on atherosclerosis and the mechanisms in apolipoprotein E-null (apoE-/-) mice. Methods: ApoE-/- mice were used as in vivo models. Western blot analysis was used to evaluate protein expression. Conventional assay kits were applied to assess the levels of cholesterol, triglycerides, free cholesterol, cholesteryl ester, fatty acids, glycerol, and cytokines. Results: Daily treatment with olanzapine (3 mg/kg body weight) for four weeks increased mean arterial blood pressure and the whitening of brown adipose tissue in mice. In addition, olanzapine impaired aortic cholesterol homeostasis and exacerbated hyperlipidemia and aortic inflammation, which accelerated atherosclerosis in mice. Moreover, lipid accumulation in liver, particularly total cholesterol, free cholesterol, fatty acids, and glycerol, was increased with olanzapine treatment in apoE-/- mice by upregulating the expression of de novo lipid synthesis-related proteins and downregulating that of cholesterol clearance- or very low-density lipoprotein secretion-related proteins. Conclusion: Olanzapine may exacerbate atherosclerosis by deregulating hepatic lipid metabolism and worsening hyperlipidemia and aortic inflammation