Abstract

Computed tomographic (CT) images are widely used in the diagnosis of stroke. In this paper, we present an automated method to detect and classify an abnormality into acute infarct, chronic infarct and hemorrhage at the slice level of non-contrast CT images. The proposed method consists of three main steps: image enhancement, detection of mid-line symmetry and classification of abnormal slices. A windowing operation is performed on the intensity distribution to enhance the region of interest. Domain knowledge about the anatomical structure of the skull and the brain is used to detect abnormalities in a rotation- and translation-invariant manner. A two-level classification scheme is used to detect abnormalities using features derived in the intensity and the wavelet domain. The proposed method has been evaluated on a dataset of 15 patients (347 image slices). The method gives 90% accuracy and 100% recall in detecting abnormality at patient level; and achieves an average precision of 91% and recall of 90% at the slice level.

Abstract

There is a need to create quality open source educational resources to address the needs of Indian schools. In this paper,we describe a virtual physics lab which we built based on open source components. This is basically an authoring tool that lets user create their own experiments. We first discuss for the need for virtual labs. We then present the architecture of our tool and the technical challenges we faced in creating it. We also present the feedback we received from school students on this tool.

Abstract

Registration is a primary step in tracking pathological changes in medical images. Point-based registration requires a set of distinct, identifiable and comparable landmark points to be extracted from images. In this work, we illustrate a method for obtaining landmarks based on changes in a topographic descriptor of a retinal image. Building on the curvature primal sketch introduced by Asada and Brady1 for describing interest points on planar curves, we extend the notion to grayscale images. We view an image as a topographic surface and propose to identify interest points on the surface using the surface curvature as a descriptor. This is illustrated by modeling retinal vessels as trenches and identifying landmarks as points where the trench behaviour changes, such as it splits or bends sharply. Based on this model, we present a method which uses the surface curvature to characterise landmark points on retinal vessels as points of high dispersion in the curvature orientation histogram computed around the points. This approach yields junction/crossover points of retinal vessels and provides a means to derive additional information about the type of junction. A scheme is developed for using such information and determining the correspondence between sets of landmarks from two images related by a rigid transformation. In this paper we present the details of the proposed approach and results of testing on images from public domain datasets. Results include comparison of landmark detection with two other methods, and results of correspondence derivation. Results show the approach to be successful and fast.

Abstract

We propose a method for synthetic zooming of tomographic images by applying super resolution technique on reconstructed data via a union of rotated lattices (URL). The proposed method consists of two steps: (i) sinogram data is filtered and back projected on to two lattices, which are rotated versions of each other and (ii) the samples from the two lattices are interpolated to generate the upsampled image. Square and hexagonal lattices have been investigated for URL. Results of subjective and objective evaluations of the proposed method on analytic phantoms are presented and compared with direct upsampling of data reconstructed on a single square lattice and upsampled image generated by union of low resolution shifted images (USL). The proposed method shows qualitative and quantitative improvement over direct up sampling but when compared with USL, generated up sampled images are of comparable quality.

Abstract

In this paper, a novel and effective method for impulse noise removal in corrupted color images is discussed. The new method consists of two phases. The first phase is a noise detection phase where a modified Hopfield neural network is used to detect impulse noise pixels. The second is a noise filtering phase where the disadvantage of taking Vector Median in a single color space is addressed and a new algorithm based on performing Vector Median first in RGB space and then in HSI space is presented. The results of simulations performed on a set of standard test images on a wide range of noise corruption show that the proposed method is capable of detecting all the impulse noise pixels with almost zero false positive rates and removes noise while retaining finer image details. It outperforms the standard procedures and is yet simple and suitable for real time applications.

Abstract

Protonated base pairs constitute an important class of RNA base pairing systems, several of which nucleate higher order structures and participate in tertiary interactions joining distant regions in RNA structures. These base pairs are involved in the formation of functionally important regions of RNA such as ribozyme cleavage sites, protein recognition sites, and rRNA motifs. Our earlier report [1] on Hartree Fock level quantum chemical studies on the geometries and interaction energies of a few protonated base pairs, in crystal contexts and gas phase optimized geometries, shows that these base pairs have high interaction energies and display stable geometries. Here we report results of higher level ab initio studies on an extended set of protonated base pairs. The structures of 18 systems, with one of the bases being protonated, were optimized at B3LYP/cc-pVTZ level and their interaction energies were calculated at MP2/aug-cc-pVDZ level. To mimic the solvent effect COSMO calculations have also been carried out on some the systems. The interaction patterns of protonated base pairs are highly diverse, with gas-phase optimized interaction energies in the range from -24 to -49 kcal/mol. The interaction energy values, for all base pairs studied, were found to be dominated by the HF term. This suggests that, in contrast with observations on nonprotonated base pairs, interaction energies of protonated base pairs have higher electrostatic contribution with noticeably reduced electron correlation component. As is also indicated by Mulliken population analysis, Morokuma decomposition analysis of interaction energies shows charge transfer as one of the dominant components in these base pair systems.

Abstract

Riboswitches are ligand dependent cis-acting regulatory elements found in diverse species, in some of their mRNA transcripts in the 5’-untranslated regions (UTRs). They are composed of two distinct, yet mutually interacting, domains: a ‘ligand-binding’ or aptamer domain and an expression platform involved in gene regulation. Conformational changes due to ligand binding affect the folding patterns in the expression platform, enabling riboswitches to exercise a variety of ligand dependent controls on downstream gene expressions. Purine riboswitches have been most widely investigated computationally as well as experimentally, for their remarkable ligand (adenine/guanine) specificity and variation in functional mechanism, despite their small size and their sequence similarities. Though the crystal structures of the ligand bound CLOSED states of the aptamer domains of two of the adenine and guanine riboswitches are known, the characterization of the ligand-free OPEN state is limited primarily to results derived from chemical probing, NMR, fluorescence, single labeled FRET and single molecule force spectroscopy experiments. Consequently, a complete molecular level understanding of mechanism of ligand binding, ligand discrimination and switching is still limited. We have addressed this issue for the aptamer domain of the add A-riboswitch by carrying out ab initio quantum chemical studies on the geometries and interaction energies of ligand-bound binding pocket1 and by studying explicit-solvent molecular dynamics simulations of the adenine riboswitch structure (1Y26), both in the adenine-bound (CLOSED) state and in the adenine-free (OPEN) state.2 Dynamic cross correlation (DCC), root mean square fluctuation (RMSF) and backbone torsion angle analyses of the two trajectories and analysis of the average OPEN and CLOSED state structures reveal, alternative hydrogen bonding schemes involving bases that are not directly involved in ligand binding, but, which constitute the lining of the binding pocket and possibly participate in the communication with the expression platform. Our model provides molecular level explanations for existing experimental data, including thermodynamic and kinetic data, related to the ligand binding and switching process.

Abstract

Riboswitches are ligand dependent regulatory elements, found in mRNA transcripts, which are composed of two distinct, yet mutually interacting domains: a ‘ligand-binding’ or aptamer domain and an expression platform involved in gene regulation. Conformational changes due to ligand binding, controls downstream gene expressions. Purine riboswitches have been widely investigated for their remarkable ligand specificity and variation in functional mechanism, despite their sequence similarities. Yet, a complete molecular level understanding of the mechanism of ligand binding, ligand discrimination and switching is still limited because the characterization of the ligand-free OPEN state is limited primarily to results derived from chemical probing, NMR, fluorescence, single labeled FRET and single molecule force spectroscopy experiments. We have carried out ab initio quantum chemical studies on the binding pocket1 and studied explicit-solvent molecular dynamics simulations of the aptamer domain of the adenine riboswitch both in the adenine-bound (CLOSED) and the adenine-free (OPEN) state.2 Dynamic cross correlation, root mean square fluctuation and backbone torsion angle analyses of the trajectories and analysis of the average OPEN and CLOSED state structures, reveal alternative hydrogen bonding schemes leading to the switch and provides molecular level explanations for existing experimental data related to the ligand binding and switching process

Abstract

Unlike regular double stranded DNAs, which are stabilized through the formation of canonical Watson Crick base pairs, 3D structures of self-folded single stranded RNA molecules utilize a variety of noncanonical base pairs in order to attain their stable native geometry. Understanding the protein-like complex functionality of RNA molecules, at the molecular level, requires detailed studies on the geometries, interaction energies and stabilities of these base pairs in their respective structural and functional context of occurrence. Rapid growth in the number of solved RNA structures, and the availability of algorithms for automated detection and geometric classification of base pairs, have provided us with a challenging opening for quantum chemical inputs in the exciting area of RNA structural biology.[1-8] Here we specifically discuss noncanonical base pairs belonging to the Cis Hoogsteen-sugar edge (H:S) family, also known as the platform family, which play important structural role in folded RNA molecules.[1] We present results of detailed theoretical investigations of these base pairs, which involve sugar-base hydrogen bonding through 2-OH group of ribose. The studied structures were relaxed at the B3LYP/6-31G(d,p) level, and interaction energies were derived at the RIMP2/aug-cc-pVDZ level of theory. The geometries for each of the studied base pairs were characterized in terms of number and nature of H-bonds, RMSD values observed on optimization, base pair geometrical parameters and sugar pucker analysis. The rich variety of hydrogen bonding pattern, involving the flexible sugar edge, appears to hold the key to several features of structural motifs, such as planarity and propensity to participate in triplets, observed in this family of base pairs. Our studies explore these aspects by integrating database analysis, and detailed base pairing geometry analysis at the atomistic level, with ab-initio computation of interaction energies. In addition, alternative classification of base pairs and triplets, which provides insights into intrinsic properties of these base pairs and their possible structural and functional roles, will be discussed.

Abstract

Noncanonical base pairs are of key significance for the complex protein-like functionality of RNA molecules. Availability of a large number of solved crystal structures of functional RNA molecules, such as tRNAs, rRNAs and a variety of ribozymes and riboswitches, and that of an efficient scheme for geometric classification of base pairs, have vastly facilitated quantum chemical investigations in the exciting area of RNA structural biology. Here we report results of our combined quantum chemical and database analysis study on base pairs belonging to two of the twelve geometric families: the cis and trans H:H base pairs. We identify three previously unreported base pair combinations, two from cis H:H, and one from trans H:H family. We also sort out the relative order of strengths of interbase interaction, and correlate it with the observed occurrence frequencies of these base pairs. We find that some base pairs which are nonplanar in their isolated minimum energy geometries attain planarity and stability on triplet formation. The strongest and also the most frequently occurring among these, the A:A H:H trans base pair, occurs at many distinctly conserved positions in known rRNA and tRNA structures. Our quantum chemical studies reveal that though this base pair is intrinsically nonplanar, it has the tendency to attain stable planar geometry in RNA crystal structures through participation in higher order tertiary interactions including additional base-phosphate interactions. The tendency to form such additional interactions correlates well with their high occurrence frequency and is suggestive of their significant role in the context of RNA folding.