AlignHUSH: Alignment of HMMs using structure and hydrophobicity information

Background: Sensitive remote homology detection and accurate alignments especially in the midnight zone of sequence similarity are needed for better function annotation and structural modeling of proteins. An algorithm, AlignHUSH for HMM-HMM alignment has been developed which is capable of recognizing distantly related domain families The method uses structural information, in the form of predicted secondary structure probabilities, and hydrophobicity of amino acids to align HMMs of two sets of aligned sequences. The effect of using adjoining column(s) information has also been investigated and is found to increase the sensitivity of HMM-HMM alignments and remote homology detection. Results: We have assessed the performance of AlignHUSH using known evolutionary relationships available in SCOP. AlignHUSH performs better than the best HMM-HMM alignment methods and is observed to be even more sensitive at higher error rates. Accuracy of the alignments obtained using AlignHUSH has been assessed using the structure-based alignments available in BaliBASE. The alignment length and the alignment quality are found to be appropriate for homology modeling and function annotation. The alignment accuracy is found to be comparable to existing methods for profile-profile alignments. Conclusions: A new method to align HMMs has been developed and is shown to have better sensitivity at error rates of 10% and above when compared to other available programs. The proposed method could effectively aid obtaining clues to functions of proteins of yet unknown function. A web-server incorporating the AlignHUSH method is available at http://crick.mbu.iisc.ernet.in/similar to alignhush/

Progressive structure-based alignment of homologous proteins: Adopting sequence comparison strategies

Comparison of multiple protein structures has a broad range of applications in the analysis of protein structure, function and evolution. Multiple structure alignment tools (MSTAs) are necessary to obtain a simultaneous comparison of a family of related folds. In this study, we have developed a method for multiple structure comparison largely based on sequence alignment techniques. A widely used Structural Alphabet named Protein Blocks (PBs) was used to transform the information on 3D protein backbone conformation as a ID sequence string. A progressive alignment strategy similar to CLUSTALW was adopted for multiple PB sequence alignment (mulPBA). Highly similar stretches identified by the pairwise alignments are given higher weights during the alignment. The residue equivalences from PB based alignments are used to obtain a three dimensional fit of the structures followed by an iterative refinement of the structural superposition. Systematic comparisons using benchmark datasets of MSTAs underlines that the alignment quality is better than MULTIPROT, MUSTANG and the alignments in HOMSTRAD, in more than 85% of the cases. Comparison with other rigid-body and flexible MSTAs also indicate that mulPBA alignments are superior to most of the rigid-body MSTAs and highly comparable to the flexible alignment methods. (C) 2012 Elsevier Masson SAS. All rights reserved.

The relationship between classification of multi-domain proteins using an alignment-free approach and their functions: a case study with immunoglobulins

Establishing functional relationships between multi-domain protein sequences is a non-trivial task. Traditionally, delineating functional assignment and relationships of proteins requires domain assignments as a prerequisite. This process is sensitive to alignment quality and domain definitions. In multi-domain proteins due to multiple reasons, the quality of alignments is poor. We report the correspondence between the classification of proteins represented as full-length gene products and their functions. Our approach differs fundamentally from traditional methods in not performing the classification at the level of domains. Our method is based on an alignment free local matching scores (LMS) computation at the amino-acid sequence level followed by hierarchical clustering. As there are no gold standards for full-length protein sequence classification, we resorted to Gene Ontology and domain-architecture based similarity measures to assess our classification. The final clusters obtained using LMS show high functional and domain architectural similarities. Comparison of the current method with alignment based approaches at both domain and full-length protein showed superiority of the LMS scores. Using this method we have recreated objective relationships among different protein kinase sub-families and also classified immunoglobulin containing proteins where sub-family definitions do not exist currently. This method can be applied to any set of protein sequences and hence will be instrumental in analysis of large numbers of full-length protein sequences.

CLAP: A web-server for automatic classification of proteins with special reference to multi-domain proteins

Background: The function of a protein can be deciphered with higher accuracy from its structure than from its amino acid sequence. Due to the huge gap in the available protein sequence and structural space, tools that can generate functionally homogeneous clusters using only the sequence information, hold great importance. For this, traditional alignment-based tools work well in most cases and clustering is performed on the basis of sequence similarity. But, in the case of multi-domain proteins, the alignment quality might be poor due to varied lengths of the proteins, domain shuffling or circular permutations. Multi-domain proteins are ubiquitous in nature, hence alignment-free tools, which overcome the shortcomings of alignment-based protein comparison methods, are required. Further, existing tools classify proteins using only domain-level information and hence miss out on the information encoded in the tethered regions or accessory domains. Our method, on the other hand, takes into account the full-length sequence of a protein, consolidating the complete sequence information to understand a given protein better. Results: Our web-server, CLAP (Classification of Proteins), is one such alignment-free software for automatic classification of protein sequences. It utilizes a pattern-matching algorithm that assigns local matching scores (LMS) to residues that are a part of the matched patterns between two sequences being compared. CLAP works on full-length sequences and does not require prior domain definitions. Pilot studies undertaken previously on protein kinases and immunoglobulins have shown that CLAP yields clusters, which have high functional and domain architectural similarity. Moreover, parsing at a statistically determined cut-off resulted in clusters that corroborated with the sub-family level classification of that particular domain family. Conclusions: CLAP is a useful protein-clustering tool, independent of domain assignment, domain order, sequence length and domain diversity. Our method can be used for any set of protein sequences, yielding functionally relevant clusters with high domain architectural homogeneity. The CLAP web server is freely available for academic use at http://nslab.mbu.iisc.ernet.in/clap/.

Ferroelectric liquid crystal mixture integrated into optical waveguides

We report an on-chip integrated ferroelectric liquid crystal (FLC) waveguide structure suitable for telecommunication applications. Single gaps with different widths of 5, 10, and 20 μ m inside individual silica waveguides were filled with an FLC mixture. The waveguide devices operate as a binary switch or an attenuator in a temperature range from 30 °C to 60 °C. The FLC mixture exhibited a good alignment quality in these gaps without alignment layers. A good extinction ratio of up to 33.9 dB and a low insertion loss of <4.3 dB at λ = 1550 nm were observed. Switching times of <100 μs were obtained for the low electric fields applied in this experiment. © 2012 IEEE.

Alignement de phrases parallèles dans des corpus bruités

La traduction statistique requiert des corpus parallèles en grande quantité. L’obtention de tels corpus passe par l’alignement automatique au niveau des phrases. L’alignement des corpus parallèles a reçu beaucoup d’attention dans les années quatre vingt et cette étape est considérée comme résolue par la communauté. Nous montrons dans notre mémoire que ce n’est pas le cas et proposons un nouvel aligneur que nous comparons à des algorithmes à l’état de l’art. Notre aligneur est simple, rapide et permet d’aligner une très grande quantité de données. Il produit des résultats souvent meilleurs que ceux produits par les aligneurs les plus élaborés. Nous analysons la robustesse de notre aligneur en fonction du genre des textes à aligner et du bruit qu’ils contiennent. Pour cela, nos expériences se décomposent en deux grandes parties. Dans la première partie, nous travaillons sur le corpus BAF où nous mesurons la qualité d’alignement produit en fonction du bruit qui atteint les 60%. Dans la deuxième partie, nous travaillons sur le corpus EuroParl où nous revisitons la procédure d’alignement avec laquelle le corpus Europarl a été préparé et montrons que de meilleures performances au niveau des systèmes de traduction statistique peuvent être obtenues en utilisant notre aligneur.

Improvements in the score matrix calculation method using parallel score estimating algorithm

The increasing amount of sequences stored in genomic databases has become unfeasible to the sequential analysis. Then, the parallel computing brought its power to the Bioinformatics through parallel algorithms to align and analyze the sequences, providing improvements mainly in the running time of these algorithms. In many situations, the parallel strategy contributes to reducing the computational complexity of the big problems. This work shows some results obtained by an implementation of a parallel score estimating technique for the score matrix calculation stage, which is the first stage of a progressive multiple sequence alignment. The performance and quality of the parallel score estimating are compared with the results of a dynamic programming approach also implemented in parallel. This comparison shows a significant reduction of running time. Moreover, the quality of the final alignment, using the new strategy, is analyzed and compared with the quality of the approach with dynamic programming.

Registration-by-regression of coronary CTA and X-ray angiography

We evaluate the integration of 3D preoperative computed tomography angiography of the coronary arteries with intraoperative 2D X-ray angiographies by a recently proposed novel registration-by-regression method. The method relates image features of 2D projection images to the transformation parameters of the 3D image. We compared different sets of features and studied the influence of preprocessing the training set. For the registration evaluation, a gold standard was developed from eight X-ray angiography sequences from six different patients. The alignment quality was measured using the 3D mean target registration error (mTRE). The registration-by-regression method achieved moderate accuracy (median mTRE of 15 mm) on real images. It does therefore not provide yet a complete solution to the 3D–2D registration problem but it could be used as an initialisation method to eliminate the need for manual initialisation.

HIGH VOLTAGE ELECTROPHORETIC DEPOSITION FOR ELECTROCHEMICAL ENERGY STORAGE AND OTHER APPLICATIONS

High voltage electrophoretic deposition (HVEPD) has been developed as a novel technique to obtain vertically aligned forests of one-dimensional nanomaterials for efficient energy storage. The ability to control and manipulate nanomaterials is critical for their effective usage in a variety of applications. Oriented structures of one-dimensional nanomaterials provide a unique opportunity to take full advantage of their excellent mechanical and electrochemical properties. However, it is still a significant challenge to obtain such oriented structures with great process flexibility, ease of processing under mild conditions and the capability to scale up, especially in context of efficient device fabrication and system packaging. This work presents HVEPD as a simple, versatile and generic technique to obtain vertically aligned forests of different one-dimensional nanomaterials on flexible, transparent and scalable substrates. Improvements on material chemistry and reduction of contact resistance have enabled the fabrication of high power supercapacitor electrodes using the HVEPD method. The investigations have also paved the way for further enhancements of performance by employing hybrid material systems and AC/DC pulsed deposition. Multi-walled carbon nanotubes (MWCNTs) were used as the starting material to demonstrate the HVEPD technique. A comprehensive study of the key parameters was conducted to better understand the working mechanism of the HVEPD process. It has been confirmed that HVEPD was enabled by three key factors: high deposition voltage for alignment, low dispersion concentration to avoid aggregation and simultaneous formation of holding layer by electrodeposition for reinforcement of nanoforests. A set of suitable parameters were found to obtain vertically aligned forests of MWCNTs. Compared with their randomly oriented counterparts, the aligned MWCNT forests showed better electrochemical performance, lower electrical resistance and a capability to achieve superhydrophpbicity, indicating their potential in a broad range of applications. The versatile and generic nature of the HVEPD process has been demonstrated by achieving deposition on flexible and transparent substrates, as well as aligned forests of manganese dioxide (MnO2) nanorods. A continuous roll-printing HVEPD approach was then developed to obtain aligned MWCNT forest with low contact resistance on large, flexible substrates. Such large-scale electrodes showed no deterioration in electrochemical performance and paved the way for practical device fabrication. The effect of a holding layer on the contact resistance between aligned MWCNT forests and the substrate was studied to improve electrochemical performance of such electrodes. It was found that a suitable precursor salt like nickel chloride could be used to achieve a conductive holding layer which helped to significantly reduce the contact resistance. This in turn enhanced the electrochemical performance of the electrodes. High-power scalable redox capacitors were then prepared using HVEPD. Very high power/energy densities and excellent cyclability have been achieved by synergistically combining hydrothermally synthesized, highly crystalline α-MnO2 nanorods, vertically aligned forests and reduced contact resistance. To further improve the performance, hybrid electrodes have been prepared in the form of vertically aligned forest of MWCNTs with branches of α-MnO2 nanorods on them. Large- scale electrodes with such hybrid structures were manufactured using continuous HVEPD and characterized, showing further improved power and energy densities. The alignment quality and density of MWCNT forests were also improved by using an AC/DC pulsed deposition technique. In this case, AC voltage was first used to align the MWCNTs, followed by immediate DC voltage to deposit the aligned MWCNTs along with the conductive holding layer. Decoupling of alignment from deposition was proven to result in better alignment quality and higher electrochemical performance.

Towards a Contingency Theory perspective of Quality Management in Enabling Strategic Alignment

The aim of this paper is to explore the role of Quality Management (QM) theory and practice using a contingency theory perspective. The study is grounded in the role of QM in improving strategic alignment within Small and Medium Sized Enterprises (SMEs) using Contingency Theory rather than adopting best practice approaches. An inductive theory building research methodology was used involving multiple case analyses of five SMEs, involving repeat interviews (n=45), focus groups (n=5) and document analysis. From the findings, it was found that Contingency Variables (strategy, culture, lifecycle and customer focus) and their respective typologies were found to interact with QM practices in helping to shape strategic alignment between the SMEs and their environments. This shaping process based on contingency approaches occurred in a manner unique to each SME and their respective environments rather than in an overarching best practice manner.

The necessary alignment between technology innovation effectiveness and operational effectiveness

Organisations are increasingly investing in complex technological innovations such as enterprise information systems with the aim of improving the operations of the business, and in this way gaining competitive advantage. However, the implementation of technological innovations tends to have an excessive focus on either technology innovation effectiveness (also known as system effectiveness), or the resulting operational effectiveness; focusing on either one of them is detrimental to the long-term enterprise benefits through failure to achieve the real value of technological innovations. The lack of research on the dimensions and performance objectives that organisations must be focusing on is the main reason for this misalignment. This research uses a combination of qualitative and quantitative, three-stage methodological approach. Initial findings suggest that factors such as quality of information from technology innovation effectiveness, and quality and speed from operational effectiveness are important and significantly well correlated factors that promote the alignment between technology innovation effectiveness and operational effectiveness.

Formative and summative assessment and the notion of constructive alignment

This paper discusses the different perceptions of first year accounting students about their tutorial activities and their engagements in assessment. As the literature suggests, unless participation in learning activities forms part of graded assessment, it is often difficult to engage students in these activities. Using an action research model, this paper reports the study of first year accounting students' responses to action-oriented learning tasks in tutorials. The paper focuses on the importance of aligning curriculum objectives, learning and teaching activities and assessment, i.e. the notion of constructive alignment. However, as the research findings indicate, without support at institutional level, applying constructive alignment to facilitate quality student learning outcomes is a difficult task. Thus, the impacts of policy constraints on curriculum issues are also discussed, focusing on the limitations faced by tutors and their lack of involvement in curriculum development.

A Systems-level approach to building sustainable assessment cultures : moderation, quality task design and dependability of judgement

This paper considers the conditions that are necessary at system and local levels for teacher assessment to be valid, reliable and rigorous. With sustainable assessment cultures as a goal, the paper examines how education systems can support local level efforts for quality learning and dependable teacher assessment. This is achieved through discussion of relevant research and consideration of a case study involving an evaluation of a cross-sectoral approach to promoting confidence in school-based assessment in Queensland, Australia. Building on the reported case study, essential characteristics for developing sustainable assessment cultures are presented, including: leadership in learning; alignment of curriculum, pedagogy and assessment; the design of quality assessment tasks and accompanying standards, and evidence-based judgement and moderation. Taken together, these elements constitute a new framework for building assessment capabilities and promoting quality assurance.