Comparison of bottom-up protein identification methods

With the rapid development of proteomics, a number of different methods appeared for the basic task of protein identification. We made a simple comparison between a common liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflow using an ion trap mass spectrometer and a combined LC-MS and LC-MS/MS method using Fourier transform ion cyclotron resonance (FTICR) mass spectrometry and accurate peptide masses. To compare the two methods for protein identification, we grew and extracted proteins from E. coli using established protocols. Cystines were reduced and alkylated, and proteins digested by trypsin. The resulting peptide mixtures were separated by reversed-phase liquid chromatography using a 4 h gradient from 0 to 50% acetonitrile over a C18 reversed-phase column. The LC separation was coupled on-line to either a Bruker Esquire HCT ion trap or a Bruker 7 tesla APEX-Qe Qh-FTICR hybrid mass spectrometer. Data-dependent Qh-FTICR-MS/MS spectra were acquired using the quadrupole mass filter and collisionally induced dissociation into the external hexapole trap. Proteins were in both schemes identified by Mascot MS/MS ion searches and the peptides identified from these proteins in the FTICR MS/MS data were used for automatic internal calibration of the FTICR-MS data, together with ambient polydimethylcyclosiloxane ions.

Application of a hybrid tracking algorithm to motion analysis

An algorithm for tracking multiple feature positions in a dynamic image sequence is presented. This is achieved using a combination of two trajectory-based methods, with the resulting hybrid algorithm exhibiting the advantages of both. An optimizing exchange algorithm is described which enables short feature paths to be tracked without prior knowledge of the motion being studied. The resulting partial trajectories are then used to initialize a fast predictor algorithm which is capable of rapidly tracking multiple feature paths. As this predictor algorithm becomes tuned to the feature positions being tracked, it is shown how the location of occluded or poorly detected features can be predicted. The results of applying this tracking algorithm to data obtained from real-world scenes are then presented.

Molecular modelling studies of binding of DACD derivatives into G-Quadruplex DNA: comparison of force field and quantum polarized ligand docking methods

The DNA G-qadruplexes are one of the targets being actively explored for anti-cancer therapy by inhibiting them through small molecules. This computational study was conducted to predict the binding strengths and orientations of a set of novel dimethyl-amino-ethyl-acridine (DACA) analogues that are designed and synthesized in our laboratory, but did not diffract in Synchrotron light.Thecrystal structure of DNA G-Quadruplex(TGGGGT)4(PDB: 1O0K) was used as target for their binding properties in our studies.We used both the force field (FF) and QM/MM derived atomic charge schemes simultaneously for comparing the predictions of drug binding modes and their energetics. This study evaluates the comparative performance of fixed point charge based Glide XP docking and the quantum polarized ligand docking schemes. These results will provide insights on the effects of including or ignoring the drug-receptor interfacial polarization events in molecular docking simulations, which in turn, will aid the rational selection of computational methods at different levels of theory in future drug design programs. Plenty of molecular modelling tools and methods currently exist for modelling drug-receptor or protein-protein, or DNA-protein interactionssat different levels of complexities.Yet, the capasity of such tools to describevarious physico-chemical propertiesmore accuratelyis the next step ahead in currentresearch.Especially, the usage of most accurate methods in quantum mechanics(QM) is severely restricted by theirtedious nature. Though the usage of massively parallel super computing environments resulted in a tremendous improvement in molecular mechanics (MM) calculations like molecular dynamics,they are still capable of dealing with only a couple of tens to hundreds of atoms for QM methods. One such efficient strategy that utilizes thepowers of both MM and QM are the QM/MM hybrid methods. Lately, attempts have been directed towards the goal of deploying several different QM methods for betterment of force field based simulations, but with practical restrictions in place. One of such methods utilizes the inclusion of charge polarization events at the drug-receptor interface, that is not explicitly present in the MM FF.

Iterative Methods for Equality-Constrained Least Squares Problems

We consider the linear equality-constrained least squares problem (LSE) of minimizing ${\|c - Gx\|}_2 $, subject to the constraint $Ex = p$. A preconditioned conjugate gradient method is applied to the Kuhn–Tucker equations associated with the LSE problem. We show that our method is well suited for structural optimization problems in reliability analysis and optimal design. Numerical tests are performed on an Alliant FX/8 multiprocessor and a Cray-X-MP using some practical structural analysis data.

Numerical-asymptotic boundary integral methods in high-frequency acoustic scattering

In this article we describe recent progress on the design, analysis and implementation of hybrid numerical-asymptotic boundary integral methods for boundary value problems for the Helmholtz equation that model time harmonic acoustic wave scattering in domains exterior to impenetrable obstacles. These hybrid methods combine conventional piecewise polynomial approximations with high-frequency asymptotics to build basis functions suitable for representing the oscillatory solutions. They have the potential to solve scattering problems accurately in a computation time that is (almost) independent of frequency and this has been realized for many model problems. The design and analysis of this class of methods requires new results on the analysis and numerical analysis of highly oscillatory boundary integral operators and on the high-frequency asymptotics of scattering problems. The implementation requires the development of appropriate quadrature rules for highly oscillatory integrals. This article contains a historical account of the development of this currently very active field, a detailed account of recent progress and, in addition, a number of original research results on the design, analysis and implementation of these methods.

J-measure based hybrid pruning for complexity reduction in classification rules

Prism is a modular classification rule generation method based on the ‘separate and conquer’ approach that is alternative to the rule induction approach using decision trees also known as ‘divide and conquer’. Prism often achieves a similar level of classification accuracy compared with decision trees, but tends to produce a more compact noise tolerant set of classification rules. As with other classification rule generation methods, a principle problem arising with Prism is that of overfitting due to over-specialised rules. In addition, over-specialised rules increase the associated computational complexity. These problems can be solved by pruning methods. For the Prism method, two pruning algorithms have been introduced recently for reducing overfitting of classification rules - J-pruning and Jmax-pruning. Both algorithms are based on the J-measure, an information theoretic means for quantifying the theoretical information content of a rule. Jmax-pruning attempts to exploit the J-measure to its full potential because J-pruning does not actually achieve this and may even lead to underfitting. A series of experiments have proved that Jmax-pruning may outperform J-pruning in reducing overfitting. However, Jmax-pruning is computationally relatively expensive and may also lead to underfitting. This paper reviews the Prism method and the two existing pruning algorithms above. It also proposes a novel pruning algorithm called Jmid-pruning. The latter is based on the J-measure and it reduces overfitting to a similar level as the other two algorithms but is better in avoiding underfitting and unnecessary computational effort. The authors conduct an experimental study on the performance of the Jmid-pruning algorithm in terms of classification accuracy and computational efficiency. The algorithm is also evaluated comparatively with the J-pruning and Jmax-pruning algorithms.

Acoustic scattering : high frequency boundary element methods and unified transform methods

We describe some recent advances in the numerical solution of acoustic scattering problems. A major focus of the paper is the efficient solution of high frequency scattering problems via hybrid numerical-asymptotic boundary element methods. We also make connections to the unified transform method due to A. S. Fokas and co-authors, analysing particular instances of this method, proposed by J. A. De-Santo and co-authors, for problems of acoustic scattering by diffraction gratings.

A new hybrid BCI paradigm based on P300 and SSVEP

Background: P300 and steady-state visual evoked potential(SSVEP) approaches have been widely used for brain–computer interface (BCI) systems. However, neither of these approaches can work for all subjects. Some groups have reported that a hybrid BCI that combines two or more approaches might provide BCI functionality to more users. Hybrid P300/SSVEP BCIs have only recently been developed and validated, and very few avenues to improve performance have been explored. New method: The present study compares an established hybrid P300/SSVEP BCIs paradigm to a new paradigm in which shape changing, instead of color changing, is adopted for P300 evocation to decrease the degradation on SSVEP strength. Result: The result shows that the new hybrid paradigm presented in this paper yields much better performance than the normal hybrid paradigm. Comparison with existing method: A performance increase of nearly 20% in SSVEP classification is achieved using the new hybrid paradigm in comparison with the normal hybrid paradigm.Allthe paradigms except the normal hybrid paradigm used in this paper obtain 100% accuracy in P300 classification. Conclusions: The new hybrid P300/SSVEP BCIs paradigm in which shape changing, instead of color changing, could obtain as high classification accuracy of SSVEP as the traditional SSVEP paradigm and could obtain as high classification accuracy of P300 as the traditional P300 paradigm. P300 did not interfere with the SSVEP response using the new hybrid paradigm presented in this paper, which was superior to the normal hybrid P300/SSVEP paradigm.

Methods to assess the effectiveness of naturally ventilated classrooms in Gauteng, South Africa

There is a tendency to reduce ventilation rates and natural or hybrid ventilation systems to ensure the conservation of energy in school buildings. However, high indoor pollutant concentration, due to natural or hybrid ventilation systems may have a significant adverse impact on the health and academic performance of pupils and students. Reviewed evidence shows that this can be detrimental to health and wellbeing in schools because of the learner density within a small area, eventually indicating that CO2 concentrations can rise to very high levels (about 4000 ppm) in classrooms during occupancy periods. In South Africa’s naturally ventilated classrooms, it is not clear whether the environmental conditions are conducive for learning. In addition, natural ventilation will be minimized given the fact that in cold, wet or windy weather, doors and windows will commonly remain closed. Evidence from literature based studies indicates that the significance of ventilation techniques is not understood satisfactorily and additional information concerning naturally ventilated schools has to be provided for better design and policy formulation. To develop a thorough understanding of the environments in classrooms, many other parameters have to be considered as well, such as outdoor air quality, CO2 concentrations, temperature and relative humidity and safety issues that may be important drawbacks for naturally ventilated schools. The aim of this paper is to develop a conceptual understanding of methods that can be implemented to assess the effectiveness of naturally ventilated classrooms in Gauteng, South Africa. A theoretical concept with an embedded practical methodology have been proposed for the research programme to investigate the relationship between ventilation rates and learning in schools in Gauteng , a province in South Africa. It is important that existing and future school buildings must include adequate outdoor ventilation, control of moisture, and avoidance of indoor exposures to microbiologic and chemical substances considered likely to have adverse effects in South Africa. Adequate ventilation in classrooms is necessary to reduce and/or eradicate the transmission of indoor pollutants.

Conditioning of the weak-constraint variational data assimilation problem for numerical weather prediction

4-Dimensional Variational Data Assimilation (4DVAR) assimilates observations through the minimisation of a least-squares objective function, which is constrained by the model flow. We refer to 4DVAR as strong-constraint 4DVAR (sc4DVAR) in this thesis as it assumes the model is perfect. Relaxing this assumption gives rise to weak-constraint 4DVAR (wc4DVAR), leading to a different minimisation problem with more degrees of freedom. We consider two wc4DVAR formulations in this thesis, the model error formulation and state estimation formulation. The 4DVAR objective function is traditionally solved using gradient-based iterative methods. The principle method used in Numerical Weather Prediction today is the Gauss-Newton approach. This method introduces a linearised `inner-loop' objective function, which upon convergence, updates the solution of the non-linear `outer-loop' objective function. This requires many evaluations of the objective function and its gradient, which emphasises the importance of the Hessian. The eigenvalues and eigenvectors of the Hessian provide insight into the degree of convexity of the objective function, while also indicating the difficulty one may encounter while iterative solving 4DVAR. The condition number of the Hessian is an appropriate measure for the sensitivity of the problem to input data. The condition number can also indicate the rate of convergence and solution accuracy of the minimisation algorithm. This thesis investigates the sensitivity of the solution process minimising both wc4DVAR objective functions to the internal assimilation parameters composing the problem. We gain insight into these sensitivities by bounding the condition number of the Hessians of both objective functions. We also precondition the model error objective function and show improved convergence. We show that both formulations' sensitivities are related to error variance balance, assimilation window length and correlation length-scales using the bounds. We further demonstrate this through numerical experiments on the condition number and data assimilation experiments using linear and non-linear chaotic toy models.

Data Assimilation and Inverse Methods in Terms of a Probabilistic Formulation

The weak-constraint inverse for nonlinear dynamical models is discussed and derived in terms of a probabilistic formulation. The well-known result that for Gaussian error statistics the minimum of the weak-constraint inverse is equal to the maximum-likelihood estimate is rederived. Then several methods based on ensemble statistics that can be used to find the smoother (as opposed to the filter) solution are introduced and compared to traditional methods. A strong point of the new methods is that they avoid the integration of adjoint equations, which is a complex task for real oceanographic or atmospheric applications. they also avoid iterative searches in a Hilbert space, and error estimates can be obtained without much additional computational effort. the feasibility of the new methods is illustrated in a two-layer quasigeostrophic model.

A hybrid approach to learn with imbalanced classes using evolutionary algorithms

There is an increasing interest in the application of Evolutionary Algorithms (EAs) to induce classification rules. This hybrid approach can benefit areas where classical methods for rule induction have not been very successful. One example is the induction of classification rules in imbalanced domains. Imbalanced data occur when one or more classes heavily outnumber other classes. Frequently, classical machine learning (ML) classifiers are not able to learn in the presence of imbalanced data sets, inducing classification models that always predict the most numerous classes. In this work, we propose a novel hybrid approach to deal with this problem. We create several balanced data sets with all minority class cases and a random sample of majority class cases. These balanced data sets are fed to classical ML systems that produce rule sets. The rule sets are combined creating a pool of rules and an EA is used to build a classifier from this pool of rules. This hybrid approach has some advantages over undersampling, since it reduces the amount of discarded information, and some advantages over oversampling, since it avoids overfitting. The proposed approach was experimentally analysed and the experimental results show an improvement in the classification performance measured as the area under the receiver operating characteristics (ROC) curve.

Second-order negative-curvature methods for box-constrained and general constrained optimization

A Nonlinear Programming algorithm that converges to second-order stationary points is introduced in this paper. The main tool is a second-order negative-curvature method for box-constrained minimization of a certain class of functions that do not possess continuous second derivatives. This method is used to define an Augmented Lagrangian algorithm of PHR (Powell-Hestenes-Rockafellar) type. Convergence proofs under weak constraint qualifications are given. Numerical examples showing that the new method converges to second-order stationary points in situations in which first-order methods fail are exhibited.

A Robust, Fully Adaptive Hybrid Level-Set/Front-Tracking Method for Two-Phase Flows with an Accurate Surface Tension Computation

We present a variable time step, fully adaptive in space, hybrid method for the accurate simulation of incompressible two-phase flows in the presence of surface tension in two dimensions. The method is based on the hybrid level set/front-tracking approach proposed in [H. D. Ceniceros and A. M. Roma, J. Comput. Phys., 205, 391400, 2005]. Geometric, interfacial quantities are computed from front-tracking via the immersed-boundary setting while the signed distance (level set) function, which is evaluated fast and to machine precision, is used as a fluid indicator. The surface tension force is obtained by employing the mixed Eulerian/Lagrangian representation introduced in [S. Shin, S. I. Abdel-Khalik, V. Daru and D. Juric, J. Comput. Phys., 203, 493-516, 2005] whose success for greatly reducing parasitic currents has been demonstrated. The use of our accurate fluid indicator together with effective Lagrangian marker control enhance this parasitic current reduction by several orders of magnitude. To resolve accurately and efficiently sharp gradients and salient flow features we employ dynamic, adaptive mesh refinements. This spatial adaption is used in concert with a dynamic control of the distribution of the Lagrangian nodes along the fluid interface and a variable time step, linearly implicit time integration scheme. We present numerical examples designed to test the capabilities and performance of the proposed approach as well as three applications: the long-time evolution of a fluid interface undergoing Rayleigh-Taylor instability, an example of bubble ascending dynamics, and a drop impacting on a free interface whose dynamics we compare with both existing numerical and experimental data.