New horizons in mouse immunoinformatics:reliable in silico prediction of mouse class I histocompatibility major complex peptide binding affinity

Quantitative structure–activity relationship (QSAR) analysis is a main cornerstone of modern informatic disciplines. Predictive computational models, based on QSAR technology, of peptide-major histocompatibility complex (MHC) binding affinity have now become a vital component of modern day computational immunovaccinology. Historically, such approaches have been built around semi-qualitative, classification methods, but these are now giving way to quantitative regression methods. The additive method, an established immunoinformatics technique for the quantitative prediction of peptide–protein affinity, was used here to identify the sequence dependence of peptide binding specificity for three mouse class I MHC alleles: H2–Db, H2–Kb and H2–Kk. As we show, in terms of reliability the resulting models represent a significant advance on existing methods. They can be used for the accurate prediction of T-cell epitopes and are freely available online (http://www.jenner.ac.uk/MHCPred).

Coupling in silico and in vitro analysis of peptide-MHC binding:a bioinformatic approach enabling prediction of superbinding peptides and anchorless epitopes

The ability to define and manipulate the interaction of peptides with MHC molecules has immense immunological utility, with applications in epitope identification, vaccine design, and immunomodulation. However, the methods currently available for prediction of peptide-MHC binding are far from ideal. We recently described the application of a bioinformatic prediction method based on quantitative structure-affinity relationship methods to peptide-MHC binding. In this study we demonstrate the predictivity and utility of this approach. We determined the binding affinities of a set of 90 nonamer peptides for the MHC class I allele HLA-A*0201 using an in-house, FACS-based, MHC stabilization assay, and from these data we derived an additive quantitative structure-affinity relationship model for peptide interaction with the HLA-A*0201 molecule. Using this model we then designed a series of high affinity HLA-A2-binding peptides. Experimental analysis revealed that all these peptides showed high binding affinities to the HLA-A*0201 molecule, significantly higher than the highest previously recorded. In addition, by the use of systematic substitution at principal anchor positions 2 and 9, we showed that high binding peptides are tolerant to a wide range of nonpreferred amino acids. Our results support a model in which the affinity of peptide binding to MHC is determined by the interactions of amino acids at multiple positions with the MHC molecule and may be enhanced by enthalpic cooperativity between these component interactions.

G-protein-coupled receptor solubilization and purification for biophysical analysis and functional studies, in the total absence of detergent

G-protein coupled receptors (GPCRs) constitute the largest class of membrane proteins and are a major drug target. A serious obstacle to studying GPCR structure/function characteristics is the requirement to extract the receptors from their native environment in the plasma membrane, coupled with the inherent instability of GPCRs in the detergents required for their solubilization. In the present study, we report the first solubilization and purification of a functional GPCR [human adenosine A2A receptor (A2AR)], in the total absence of detergent at any stage, by exploiting spontaneous encapsulation by styrene maleic acid (SMA) co-polymer direct from the membrane into a nanoscale SMA lipid particle (SMALP). Furthermore, the A2AR-SMALP, generated from yeast (Pichia pastoris) or mammalian cells, exhibited increased thermostability (∼5°C) compared with detergent [DDM (n-dodecyl-β-D-maltopyranoside)]-solubilized A2AR controls. The A2AR-SMALP was also stable when stored for prolonged periods at 4°C and was resistant to multiple freeze-thaw cycles, in marked contrast with the detergent-solubilized receptor. These properties establish the potential for using GPCR-SMALP in receptor-based drug discovery assays. Moreover, in contrast with nanodiscs stabilized by scaffold proteins, the non-proteinaceous nature of the SMA polymer allowed unobscured biophysical characterization of the embedded receptor. Consequently, CD spectroscopy was used to relate changes in secondary structure to loss of ligand binding ([³H]ZM241385) capability. SMALP-solubilization of GPCRs, retaining the annular lipid environment, will enable a wide range of therapeutic targets to be prepared in native-like state to aid drug discovery and understanding of GPCR molecular mechanisms.

A Sensitive Metric of Class Cohesion

Metrics estimate the quality of different aspects of software. In particular, cohesion indicates how well the parts of a system hold together. A metric to evaluate class cohesion is important in object-oriented programming because it gives an indication of a good design of classes. There are several proposals of metrics for class cohesion but they have several problems (for instance, low discrimination). In this paper, a new metric to evaluate class cohesion is proposed, called SCOM, which has several relevant features. It has an intuitive and analytical formulation, what is necessary to apply it to large-size software systems. It is normalized to produce values in the range [0..1], thus yielding meaningful values. It is also more sensitive than those previously reported in the literature. The attributes and methods used to evaluate SCOM are unambiguously stated. SCOM has an analytical threshold, which is a very useful but rare feature in software metrics. We assess the metric with several sample cases, showing that it gives more sensitive values than other well know cohesion metrics.

Computer-aided System of Semantic Text Analysis of a Technical Specification

The given work is devoted to development of the computer-aided system of semantic text analysis of a technical specification. The purpose of this work is to increase efficiency of software engineering based on automation of semantic text analysis of a technical specification. In work it is offered and investigated the model of the analysis of the text of the technical project is submitted, the attribute grammar of a technical specification, intended for formalization of limited Russian is constructed with the purpose of analysis of offers of text of a technical specification, style features of the technical project as class of documents are considered, recommendations on preparation of text of a technical specification for the automated processing are formulated. The computer-aided system of semantic text analysis of a technical specification is considered. This system consists of the following subsystems: preliminary text processing, the syntactic and semantic analysis and construction of software models, storage of documents and interface.

Using the e-Class Open Platform for e-Learning Support at the TEI of Larissa, Greece

In the current paper we firstly give a short introduction on e-learning platforms and review the case of the e-class open e-learning platform being used by the Greek tertiary education sector. Our analysis includes strategic selection issues and outcomes in general and operational and adoption issues in the case of the Technological Educational Institute (TEI) of Larissa, Greece. The methodology is being based on qualitative analysis of interviews with key actors using the platform, and statistical analysis of quantitative data related to adoption and usage in the relevant populations. The author has been a key actor in all stages and describes his insights as an early adopter, diffuser and innovative user. We try to explain the issues under consideration using existing past research outcomes and we also arrive to some conclusions and points for further research.

Computer Support of Semantic Text Analysis of a Technical Specification on Designing Software

The given work is devoted to development of the computer-aided system of semantic text analysis of a technical specification. The purpose of this work is to increase efficiency of software engineering based on automation of semantic text analysis of a technical specification. In work it is offered and investigated a technique of the text analysis of a technical specification is submitted, the expanded fuzzy attribute grammar of a technical specification, intended for formalization of limited Russian language is constructed with the purpose of analysis of offers of text of a technical specification, style features of the technical specification as class of documents are considered, recommendations on preparation of text of a technical specification for the automated processing are formulated. The computer-aided system of semantic text analysis of a technical specification is considered. This system consist of the following subsystems: preliminary text processing, the syntactic and semantic analysis and construction of software models, storage of documents and interface.

On Two Saigo’s Fractional Integral Operators in the Class of Univalent Functions

2000 Mathematics Subject Classification: Primary 26A33, 30C45; Secondary 33A35

Applications of the Owa-Srivastava Operator to the Class of K-Uniformly Convex Functions

2000 Mathematics Subject Classification: Primary 30C45, 26A33; Secondary 33C15

On a Class of Fractional Type Integral Equations in Variable Exponent Spaces

2000 Mathematics Subject Classification: 45A05, 45B05, 45E05,45P05, 46E30

Some Notes about a Class of Univalent Functions with Negative Coefficients

MSC 2010: 30C45, 30C50

Note on Radius Problems for Certain Class of Analytic Functions

MSC 2010: 30C45

A fuzzy expected value approach under generalized data envelopment analysis

Fuzzy data envelopment analysis (DEA) models emerge as another class of DEA models to account for imprecise inputs and outputs for decision making units (DMUs). Although several approaches for solving fuzzy DEA models have been developed, there are some drawbacks, ranging from the inability to provide satisfactory discrimination power to simplistic numerical examples that handles only triangular fuzzy numbers or symmetrical fuzzy numbers. To address these drawbacks, this paper proposes using the concept of expected value in generalized DEA (GDEA) model. This allows the unification of three models - fuzzy expected CCR, fuzzy expected BCC, and fuzzy expected FDH models - and the ability of these models to handle both symmetrical and asymmetrical fuzzy numbers. We also explored the role of fuzzy GDEA model as a ranking method and compared it to existing super-efficiency evaluation models. Our proposed model is always feasible, while infeasibility problems remain in certain cases under existing super-efficiency models. In order to illustrate the performance of the proposed method, it is first tested using two established numerical examples and compared with the results obtained from alternative methods. A third example on energy dependency among 23 European Union (EU) member countries is further used to validate and describe the efficacy of our approach under asymmetric fuzzy numbers.

On a Class of Elliptic Equations for the N-Laplacian in R^n with One-Sided Exponential Growth

2000 Mathematics Subject Classification: 35J40, 49J52, 49J40, 46E30

Regularity analysis of nocturnal oximetry recordings to assist in the diagnosis of sleep apnoea syndrome

The relationship between sleep apnoea–hypopnoea syndrome (SAHS) severity and the regularity of nocturnal oxygen saturation (SaO2) recordings was analysed. Three different methods were proposed to quantify regularity: approximate entropy (AEn), sample entropy (SEn) and kernel entropy (KEn). A total of 240 subjects suspected of suffering from SAHS took part in the study. They were randomly divided into a training set (96 subjects) and a test set (144 subjects) for the adjustment and assessment of the proposed methods, respectively. According to the measurements provided by AEn, SEn and KEn, higher irregularity of oximetry signals is associated with SAHS-positive patients. Receiver operating characteristic (ROC) and Pearson correlation analyses showed that KEn was the most reliable predictor of SAHS. It provided an area under the ROC curve of 0.91 in two-class classification of subjects as SAHS-negative or SAHS-positive. Moreover, KEn measurements from oximetry data exhibited a linear dependence on the apnoea–hypopnoea index, as shown by a correlation coefficient of 0.87. Therefore, these measurements could be used for the development of simplified diagnostic techniques in order to reduce the demand for polysomnographies. Furthermore, KEn represents a convincing alternative to AEn and SEn for the diagnostic analysis of noisy biomedical signals.