Molecular Design of Synthetic Benzimidazoles for the Switchover of the Duplex to G-quadruplex DNA Recognition

Benzimidazole derivatives are well known for their antibacterial, antiviral, anticonvulsant, antihistaminic, anthelmintic and antidepressant activities. Benzimidazole's unique base-selective DNA recognition property has been studied widely. However, most of the early benzimidazole systems have been targeted towards the binding of duplex DNA. Here we have shown the evolution and progress of the design and synthesis of new benzimidazole systems towards selective recognition of the double-stranded DNA first. Then in order to achieve selective recognition of the G-quadruplex DNA and utilize their potential as future anti-cancer drug candidates, we have demonstrated their selective cytotoxicity towards the cancer cells and potent telomerase inhibition ability.

Differential cellular recognition pattern to M. tuberculosis targets defined by IFN-gamma and IL-17 production in blood from TB plus patients from Honduras as compared to health care workers: TB and immune responses in patients from Honduras

Background: A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates. Methods: Recombinant proteins (n = 8) and peptide pools (n = 14) from M. tuberculosis (M.tb) targets were used to compare cellular immune responses defined by IFN-gamma and IL-17 production using a Whole Blood Assay (WBA) in a cohort of 148 individuals, i.e. patients with TB + (n = 38), TB- individuals with other pulmonary diseases (n = 81) and individuals exposed to TB without evidence of clinical TB (health care workers, n = 29). Results: M.tb antigens Rv2958c (glycosyltransferase), Rv2962c (mycolyltransferase), Rv1886c (Ag85B), Rv3804c (Ag85A), and the PPE family member Rv3347c were frequently recognized, defined by IFN-gamma production, in blood from healthy individuals exposed to M.tb (health care workers). A different recognition pattern was found for IL-17 production in blood from M.tb exposed individuals responding to TB10.4 (Rv0288), Ag85B (Rv1886c) and the PPE family members Rv0978c and Rv1917c. Conclusions: The pattern of immune target recognition is different in regard to IFN-gamma and IL-17 production to defined molecular M.tb targets in PBMCs from individuals frequently exposed to M.tb. The data represent the first mapping of cellular immune responses against M.tb targets in TB patients from Honduras.

Power-law transformation for enhanced recognition of born-digital word images

In this paper, we discuss the issues related to word recognition in born-digital word images. We introduce a novel method of power-law transformation on the word image for binarization. We show the improvement in image binarization and the consequent increase in the recognition performance of OCR engine on the word image. The optimal value of gamma for a word image is automatically chosen by our algorithm with fixed stroke width threshold. We have exhaustively experimented our algorithm by varying the gamma and stroke width threshold value. By varying the gamma value, we found that our algorithm performed better than the results reported in the literature. On the ICDAR Robust Reading Systems Challenge-1: Word Recognition Task on born digital dataset, as compared to the recognition rate of 61.5% achieved by TH-OCR after suitable pre-processing by Yang et. al. and 63.4% by ABBYY Fine Reader (used as baseline by the competition organizers without any preprocessing), we achieved 82.9% using Omnipage OCR applied on the images after being processed by our algorithm.

Recognition of Kannada characters extracted from scene images

In this paper, we describe a method for feature extraction and classification of characters manually isolated from scene or natural images. Characters in a scene image may be affected by low resolution, uneven illumination or occlusion. We propose a novel method to perform binarization on gray scale images by minimizing energy functional. Discrete Cosine Transform and Angular Radial Transform are used to extract the features from characters after normalization for scale and translation. We have evaluated our method on the complete test set of Chars74k dataset for English and Kannada scripts consisting of handwritten and synthesized characters, as well as characters extracted from camera captured images. We utilize only synthesized and handwritten characters from this dataset as training set. Nearest neighbor classification is used in our experiments.

Language models for online handwritten Tamil word recognition

N-gram language models and lexicon-based word-recognition are popular methods in the literature to improve recognition accuracies of online and offline handwritten data. However, there are very few works that deal with application of these techniques on online Tamil handwritten data. In this paper, we explore methods of developing symbol-level language models and a lexicon from a large Tamil text corpus and their application to improving symbol and word recognition accuracies. On a test database of around 2000 words, we find that bigram language models improve symbol (3%) and word recognition (8%) accuracies and while lexicon methods offer much greater improvements (30%) in terms of word recognition, there is a large dependency on choosing the right lexicon. For comparison to lexicon and language model based methods, we have also explored re-evaluation techniques which involve the use of expert classifiers to improve symbol and word recognition accuracies.

Benchmarking recognition results on camera captured word image data sets

We have benchmarked the maximum obtainable recognition accuracy on five publicly available standard word image data sets using semi-automated segmentation and a commercial OCR. These images have been cropped from camera captured scene images, born digital images (BDI) and street view images. Using the Matlab based tool developed by us, we have annotated at the pixel level more than 3600 word images from the five data sets. The word images binarized by the tool, as well as by our own midline analysis and propagation of segmentation (MAPS) algorithm are recognized using the trial version of Nuance Omnipage OCR and these two results are compared with the best reported in the literature. The benchmark word recognition rates obtained on ICDAR 2003, Sign evaluation, Street view, Born-digital and ICDAR 2011 data sets are 83.9%, 89.3%, 79.6%, 88.5% and 86.7%, respectively. The results obtained from MAPS binarized word images without the use of any lexicon are 64.5% and 71.7% for ICDAR 2003 and 2011 respectively, and these values are higher than the best reported values in the literature of 61.1% and 41.2%, respectively. MAPS results of 82.8% for BDI 2011 dataset matches the performance of the state of the art method based on power law transform.

A cyclic peptide mimic of an RNA recognition motif of human La protein is a potent inhibitor of hepatitis C virus

Due to limited available therapeutic options, developing new lead compounds against hepatitis C virus is an urgent need. Human La protein stimulates hepatitis C virus translation through interaction with the hepatitis C viral RNA. A cyclic peptide mimicking the beta-turn of the human La protein that interacts with the viral RNA was synthesized. It inhibits hepatitis C viral RNA translation significantly better than the corresponding linear peptide at longer post-treatment times. The cyclic peptide also inhibited replication as measured by replicon RNA levels using real time RT-PCR. The cyclic peptide emerges as a promising lead compound against hepatitis C.

Subject independent human action recognition using spatio-depth information and meta-cognitive RBF network

In this paper, we present a machine learning approach for subject independent human action recognition using depth camera, emphasizing the importance of depth in recognition of actions. The proposed approach uses the flow information of all 3 dimensions to classify an action. In our approach, we have obtained the 2-D optical flow and used it along with the depth image to obtain the depth flow (Z motion vectors). The obtained flow captures the dynamics of the actions in space time. Feature vectors are obtained by averaging the 3-D motion over a grid laid over the silhouette in a hierarchical fashion. These hierarchical fine to coarse windows capture the motion dynamics of the object at various scales. The extracted features are used to train a Meta-cognitive Radial Basis Function Network (McRBFN) that uses a Projection Based Learning (PBL) algorithm, referred to as PBL-McRBFN, henceforth. PBL-McRBFN begins with zero hidden neurons and builds the network based on the best human learning strategy, namely, self-regulated learning in a meta-cognitive environment. When a sample is used for learning, PBLMcRBFN uses the sample overlapping conditions, and a projection based learning algorithm to estimate the parameters of the network. The performance of PBL-McRBFN is compared to that of a Support Vector Machine (SVM) and Extreme Learning Machine (ELM) classifiers with representation of every person and action in the training and testing datasets. Performance study shows that PBL-McRBFN outperforms these classifiers in recognizing actions in 3-D. Further, a subject-independent study is conducted by leave-one-subject-out strategy and its generalization performance is tested. It is observed from the subject-independent study that McRBFN is capable of generalizing actions accurately. The performance of the proposed approach is benchmarked with Video Analytics Lab (VAL) dataset and Berkeley Multimodal Human Action Database (MHAD). (C) 2013 Elsevier Ltd. All rights reserved.

NESP: Nonlinear enhancement and selection of plane for optimal segmentation and recognition of scene word images

In this paper, we report a breakthrough result on the difficult task of segmentation and recognition of coloured text from the word image dataset of ICDAR robust reading competition challenge 2: reading text in scene images. We split the word image into individual colour, gray and lightness planes and enhance the contrast of each of these planes independently by a power-law transform. The discrimination factor of each plane is computed as the maximum between-class variance used in Otsu thresholding. The plane that has maximum discrimination factor is selected for segmentation. The trial version of Omnipage OCR is then used on the binarized words for recognition. Our recognition results on ICDAR 2011 and ICDAR 2003 word datasets are compared with those reported in the literature. As baseline, the images binarized by simple global and local thresholding techniques were also recognized. The word recognition rate obtained by our non-linear enhancement and selection of plance method is 72.8% and 66.2% for ICDAR 2011 and 2003 word datasets, respectively. We have created ground-truth for each image at the pixel level to benchmark these datasets using a toolkit developed by us. The recognition rate of benchmarked images is 86.7% and 83.9% for ICDAR 2011 and 2003 datasets, respectively.

STUDENT'S-t MIXTURE MODEL BASED MULTI-INSTRUMENT RECOGNITION IN POLYPHONIC MUSIC

We address the problem of multi-instrument recognition in polyphonic music signals. Individual instruments are modeled within a stochastic framework using Student's-t Mixture Models (tMMs). We impose a mixture of these instrument models on the polyphonic signal model. No a priori knowledge is assumed about the number of instruments in the polyphony. The mixture weights are estimated in a latent variable framework from the polyphonic data using an Expectation Maximization (EM) algorithm, derived for the proposed approach. The weights are shown to indicate instrument activity. The output of the algorithm is an Instrument Activity Graph (IAG), using which, it is possible to find out the instruments that are active at a given time. An average F-ratio of 0 : 7 5 is obtained for polyphonies containing 2-5 instruments, on a experimental test set of 8 instruments: clarinet, flute, guitar, harp, mandolin, piano, trombone and violin.

Common recognition principles across diverse sequence and structural families of sialic acid binding proteins

Sialic acids form a large family of 9-carbon monosaccharides and are integral components of glycoconjugates. They are known to bind to a wide range of receptors belonging to diverse sequence families and fold classes and are key mediators in a plethora of cellular processes. Thus, it is of great interest to understand the features that give rise to such a recognition capability. Structural analyses using a non-redundant data set of known sialic acid binding proteins was carried out, which included exhaustive binding site comparisons and site alignments using in-house algorithms, followed by clustering and tree computation, which has led to derivation of sialic acid recognition principles. Although the proteins in the data set belong to several sequence and structure families, their binding sites could be grouped into only six types. Structural comparison of the binding sites indicates that all sites contain one or more different combinations of key structural features over a common scaffold. The six binding site types thus serve as structural motifs for recognizing sialic acid. Scanning the motifs against a non-redundant set of binding sites from PDB indicated the motifs to be specific for sialic acid recognition. Knowledge of determinants obtained from this study will be useful for detecting function in unknown proteins. As an example analysis, a genome-wide scan for the motifs in structures of Mycobacterium tuberculosis proteome identified 17 hits that contain combinations of the features, suggesting a possible function of sialic acid binding by these proteins.

Triarylborane-Appended New Triad and Tetrad: Chromogenic and Fluorogenic Anion Recognition

Facile synthesis of triad 3 and tetrad 4 incorporating -B(Mes)(2) (Mes = mesityl (2,4,6-trimethylphenyl)), boron dipyrromethene (BODIPY), and triphenylamine is reported. Introduction of two dissimilar acceptors (triarylborane and BODIPY) on a single donor resulted in two distinct intramolecular charge transfer processes (amine-to-borane and amine-to-BODIPY). The absorption and emission properties of the new triad and tetrad are highly dependent on individual building units. The nature of electronic communication among the individual fluorophore units has been comprehensively investigated and compared with building units. Compounds 3 and 4 showed chromogenic and fluorogenic responses for small anions such as fluoride and cyanide.

Dual Binding Site Assisted Chromogenic and Fluorogenic Recognition and Discrimination of Fluoride and Cyanide by a Peripherally Borylated Metalloporphyrin: Overcoming Anion Interference in Organoboron Based Sensors

Peripherally triarylborane decorated porphyrin (2) and its Zn(II) complex (3) have been synthesized. Compound 3 contains of two different Lewis acidic binding sites (Zn(II) and boron center). Unlike all previously known triarylborane based sensors, the optical responses of 3 toward fluoride and cyanide are distinctively different, thus enabling the discrimination of these two interfering anions. Metalloporphyrin 3 shows a multiple channel fluorogenic response toward fluoride and cyanide and also a selective visual colorimetric response toward cyanide. By comparison with model systems and from detailed photophysical studies on 2 and 3, we conclude that the preferential binding of fluoride occurs at the peripheral borane moieties resulting in the cessation of the EET (electronic energy transfer) process from borane to porphyrin core and with negligible negetive cooperative effects. On the other hand, cyanide binding occurs at the Zn(II) core leading to drastic changes in its absorption behavior which can be followed by the naked eye. Such changes are not observed when the boryl substituent is absent (e.g., Zn-TPP and TPP). Compounds 2 and 3 were also found to be capable of extracting fluoride from aqueous medium.

Conserved water-mediated recognition and dynamics of NAD(+) (carboxamide group) to hIMPDH enzyme: water mimic approach toward the design of isoform-selective inhibitor

Inosine monophosphate dehydrogenase (IMPDH) enzyme involves in GMP biosynthesis pathway. Type I hIMPDH is expressed at lower levels in all cells, whereas type II is especially observed in acute myelogenous leukemia, chronic myelogenous leukemia cancer cells, and 10 ns simulation of the IMP-NAD(+) complex structures (PDB ID. 1B3O and 1JCN) have revealed the presence of a few conserved hydrophilic centers near carboxamide group of NAD(+). Three conserved water molecules (W1, W, and W1 `) in di-nucleotide binding pocket of enzyme have played a significant role in the recognition of carboxamide group (of NAD(+)) to D274 and H93 residues. Based on H-bonding interaction of conserved hydrophilic (water molecular) centers within IMP-NAD(+)-enzyme complexes and their recognition to NAD(+), some covalent modification at carboxamide group of di-nucleotide (NAD(+)) has been made by substituting the -CONH(2)group by -CONHNH2 (carboxyl hydrazide group) using water mimic inhibitor design protocol. The modeled structure of modified ligand may, though, be useful for the development of antileukemic agent or it could be act as better inhibitor for hIMPDH-II.

Gammatone Wavelet Cepstral Coefficients for Robust Speech Recognition

We develop noise robust features using Gammatone wavelets derived from the popular Gammatone functions. These wavelets incorporate the characteristics of human peripheral auditory systems, in particular the spatially-varying frequency response of the basilar membrane. We refer to the new features as Gammatone Wavelet Cepstral Coefficients (GWCC). The procedure involved in extracting GWCC from a speech signal is similar to that of the conventional Mel-Frequency Cepstral Coefficients (MFCC) technique, with the difference being in the type of filterbank used. We replace the conventional mel filterbank in MFCC with a Gammatone wavelet filterbank, which we construct using Gammatone wavelets. We also explore the effect of Gammatone filterbank based features (Gammatone Cepstral Coefficients (GCC)) for robust speech recognition. On AURORA 2 database, a comparison of GWCCs and GCCs with MFCCs shows that Gammatone based features yield a better recognition performance at low SNRs.