This paper presents an algorithm to find out the path of an object which is moving in different frames. These objects are coming from different background. To detect a moving object from different frames correlation is useful but... more
This paper presents an algorithm to find out the path of an object which is moving in different frames. These objects are coming from different background. To detect a moving object from different frames correlation is useful but correlation process consumes huge time. So to reduce searching time here selective correlation is used. The proposed algorithm can significantly speed up
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This article traces the history of the fine art of decorative binding in India, Egypt, Central Asia and Europe where it was mostly prevalent during ancient and medieval times and the cross cultural influences. Early modern era too had... more
This article traces the history of the fine art of decorative binding in India, Egypt, Central Asia and Europe where it was mostly prevalent during ancient and medieval times and the cross cultural influences. Early modern era too had beautiful work on binding covers. Some works have even been called ‘treasure bindings’ made for important people in high social positions. The book bindings are still available across libraries, museums and private collections. Great care was taken to make the binding of a revered text strong and look appealing. The ancient and medieval times craftsmen used various methods and materials like wood, leather to make the bindings and used ivory, metal and pigments for embellishment. The article briefly describes the technique of book binding and showcases some specimens of fine book covers from across the world.
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Although two growth factor receptors, EGFR and HER2, are amongst the best targets for cancer treatment, no agents targeting HER3, their kinase-defective family member, have so far been approved. Because emergence of resistance of lung... more
Although two growth factor receptors, EGFR and HER2, are amongst the best targets for cancer treatment, no agents targeting HER3, their kinase-defective family member, have so far been approved. Because emergence of resistance of lung tumors to EGFR kinase inhibitors (EGFRi) associates with compensatory up-regulation of HER3 and several secreted forms, we anticipated that blocking HER3 would prevent resistance. As demonstrated herein, a neutralizing anti-HER3 antibody we generated can clear HER3 from the cell surface, as well as reduce HER3 cleavage by ADAM10, a surface metalloproteinase. When combined with a kinase inhibitor and an anti-EGFR antibody, the antibody completely blocked patient-derived xenograft models that acquired resistance to EGFRi. We found that the underlying mechanism involves posttranslational downregulation of HER3, suppression of MET and AXL upregulation, as well as concomitant inhibition of AKT signaling and upregulation of BIM, which mediates apoptosis. Thu...
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Every two years groups worldwide participate in the Critical Assessment of Protein Structure Prediction (CASP) experiment to blindly test the strengths and weaknesses of their computational methods. CASP has significantly advanced the... more
Every two years groups worldwide participate in the Critical Assessment of Protein Structure Prediction (CASP) experiment to blindly test the strengths and weaknesses of their computational methods. CASP has significantly advanced the field but many hurdles still remain, which may require new ideas and collaborations. In 2012 a web-based effort called WeFold, was initiated to promote collaboration within the CASP community and attract researchers from other fields to contribute new ideas to CASP. Members of the WeFold coopetition (cooperation and competition) participated in CASP as individual teams, but also shared components of their methods to create hybrid pipelines and actively contributed to this effort. We assert that the scale and diversity of integrative prediction pipelines could not have been achieved by any individual lab or even by any collaboration among a few partners. The models contributed by the participating groups and generated by the pipelines are publicly avail...
Redundancy has been referred to as a state of no longer being needed or useful. Microbiologists often theorize that the only case of true redundancy in a haploid organism would be a recent gene duplication event, prior to divergence... more
Redundancy has been referred to as a state of no longer being needed or useful. Microbiologists often theorize that the only case of true redundancy in a haploid organism would be a recent gene duplication event, prior to divergence through selective pressure. However, a growing number of examples exist where an organism encodes two genes that appear to perform the same function. For example, many pathogens translocate multiple effector proteins into hosts. While disruption of individual effector genes does not result in a discernable phenotype, deleting genes in combination impairs pathogenesis: this has been described as redundancy. In many cases, this apparent redundancy could be due to limitations of laboratory models of pathogenesis that do not fully recapitulate the disease process. Alternatively, it is possible that the selective advantage achieved by this perceived redundancy is too subtle to be measured in the laboratory. Moreover, there are numerous possibilities for diffe...
The Food and Drug Administration approved niraparib, a poly ADP ribose polymerase (PARP) inhibitor, on March 27, 2017, for maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer... more
The Food and Drug Administration approved niraparib, a poly ADP ribose polymerase (PARP) inhibitor, on March 27, 2017, for maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response to platinum-based chemotherapy. Approval was based on data from the NOVA trial comparing niraparib with placebo in two independent cohorts, based on germline BRCA mutation status (gBRCAm vs. non-gBRCAm). Progression-free survival (PFS) in each cohort was the primary endpoint. In the gBRCAm cohort, estimated median PFS on niraparib was 21 months vs. 5.5 months on placebo (HR 0.26; 95% CI: 0.17, 0.41; p-value <0.0001). In the non-gBRCAm cohort, estimated median PFS for niraparib and placebo was 9.3 months and 3.9 months, respectively (HR 0.45; 95% CI: 0.34, 0.61; p<0.0001). Common adverse reactions (>20% and higher incidence in niraparib arm) with niraparib include thrombocytopenia, anemia, neutropenia, nausea, constipation...
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Downregulation of microRNA-31 has been linked with enhanced stress resistance, while its overexpression leads to cell death. In this study, we found mediatory role of microRNA-31 in γ-radiation-induced apoptosis in a model insect cell... more
Downregulation of microRNA-31 has been linked with enhanced stress resistance, while its overexpression leads to cell death. In this study, we found mediatory role of microRNA-31 in γ-radiation-induced apoptosis in a model insect cell line Sf9 carrying well-conserved apoptotic machinery. Mature microRNA-31 is perfectly conserved amongst insects; hence we used biotinylated probes designed from Bombyx mori sequence for its successful detection in Sf9 cells. Target identification using Bombyx mori 3'UTRs predicted miR-31's potential role in Lepidopteran apoptosis, which prompted us to investigate alterations in its expression during radiation-induced cell death. We found significant overexpression of Sf-miR-31 following lethal dose (1,000Gy-3,000Gy) irradiation. Its mediatory role was finally confirmed as antisense-microRNA-31 could successfully inhibit radiation-induced cytochrome-c release, caspase-3 activation and apoptosis. While Bax/Bcl-2 expression remained unchanged, let...
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Pedilanthus tithymaloides (PT), a widely used ethnomedicinal plant, has been employed to treat a number of skin conditions. To extend its utility and to fully exploit its medicinal potential, we have evaluated the in vitro antiviral... more
Pedilanthus tithymaloides (PT), a widely used ethnomedicinal plant, has been employed to treat a number of skin conditions. To extend its utility and to fully exploit its medicinal potential, we have evaluated the in vitro antiviral activity of a methanolic extract of PT leaves and its isolated compounds against Herpes Simplex Virus type 2 (HSV-2). Bioactivity-guided studies revealed that the extract and one of its constituents, luteolin, had potent antiviral activity against wild-type and clinical isolates of HSV-2 (EC50 48.5-52.6 and 22.4-27.5 μg/ml, respectively), with nearly complete inhibition at 86.5-101.8 and 40.2-49.6 μg/ml, respectively. The inhibitory effect was significant (p<0.001) when the drug was added 2 h prior to infection, and was effective up to 4 h post-infection. As viral replication requires NF-κB activation, we examined whether the observed extract-induced inhibition of HSV-2 was related to NF-κB inhibition. Interestingly, we observed that treatment of HSV-...
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Faithful transmission of genetic information through generations ensures genomic stability and integrity. However, genetic alterations occur every now and then during the course of genome duplication. In order to repair these genetic... more
Faithful transmission of genetic information through generations ensures genomic stability and integrity. However, genetic alterations occur every now and then during the course of genome duplication. In order to repair these genetic defects and lesions, nature has devised several repair pathways which function promptly to prevent the cell from accumulating permanent mutations. These repair mechanisms seem to be significantly impacted by posttranslational modifications of proteins like phosphorylation and ubiquitination. Protein ubiquitination is emerging as a critical regulatory mechanism of DNA damage response. Non-proteolytic, proteasome-independent functions of ubiquitin involving monoubiquitination and polyubiquitination of DNA repair proteins contribute significantly to the signaling of DNA repair pathways. In this paper, we will particularly highlight the work on ubiquitin-mediated signaling in the repair processes involving the Fanconi anemia pathway, translesional synthesis...
The greatest interpretive challenge of modern medicine may be to functionally annotate the vast variation of human genomes. Demonstrating a proposed approach, we created a library of BRCA2 exon 27 shotgun-mutant plasmids including... more
The greatest interpretive challenge of modern medicine may be to functionally annotate the vast variation of human genomes. Demonstrating a proposed approach, we created a library of BRCA2 exon 27 shotgun-mutant plasmids including solitary and multiplex mutations to generate human knockin clones using homologous recombination. This 55-mutation, 13-clone syngeneic variance library (SyVaL) comprised severely affected clones having early-stop nonsense mutations, functionally hypomorphic clones having multiple missense mutations emphasizing the potential to identify and assess hypomorphic mutations in novel proteomic and epidemiologic studies, and neutral clones having multiple missense mutations. Efficient coverage of nonessential amino acids was provided by mutation multiplexing. Severe mutations were distinguished from hypomorphic or neutral changes by chemosensitivity assays (hypersensitivity to mitomycin C and acetaldehyde), by analysis of RAD51 focus formation, and by mitotic multipolarity. A multiplex unbiased approach of generating all-human SyVaLs in medically important genes, with random mutations in native genes, would provide databases of variants that could be functionally annotated without concerns arising from exogenous cDNA constructs or interspecies interactions, as a basis for subsequent proteomic domain mapping or clinical calibration if desired. Such gene-irrelevant approaches could be scaled up for multiple genes of clinical interest, providing distributable cellular libraries linked to public-shared functional databases.
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Determining the correct structure of a protein given its sequence still remains an arduous task with many researchers working towards this goal. Most structure prediction methodologies result in the generation of a large number of... more
Determining the correct structure of a protein given its sequence still remains an arduous task with many researchers working towards this goal. Most structure prediction methodologies result in the generation of a large number of probable candidates with the final challenge being to select the best amongst these. In this work, we have used Protein Structure Networks of native and modeled proteins in combination with Support Vector Machines to estimate the quality of a protein structure model and finally to provide ranks for these models. Model ranking is performed using regression analysis and helps in model selection from a group of many similar and good quality structures. Our results show that structures with a rank greater than 16 exhibit native protein-like properties while those below 10 are non-native like. The tool is also made available as a web-server(http://vishgraph.mbu.iisc.ernet.in/GraProStr/native_non_native_ranking.html), where, 5 modelled structures can be evaluate...
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To establish itself within the host system, Mycobacterium tuberculosis (Mtb) has formulated various means of attacking the host system. One such crucial strategy is the exploitation of the iron resources of the host system. Obtaining and... more
To establish itself within the host system, Mycobacterium tuberculosis (Mtb) has formulated various means of attacking the host system. One such crucial strategy is the exploitation of the iron resources of the host system. Obtaining and maintaining the required concentration of iron becomes a matter of contest between the host and the pathogen, both trying to achieve this through complex molecular networks. The extent of complexity makes it important to obtain a systems perspective of the interplay between the host and the pathogen with respect to iron homeostasis. We have reconstructed a systems model comprising 92 components and 85 protein-protein or protein-metabolite interactions, which have been captured as a set of 194 rules. Apart from the interactions, these rules also account for protein synthesis and decay, RBC circulation and bacterial production and death rates. We have used a rule-based modelling approach, Kappa, to simulate the system separately under infection and non-infection conditions. Various perturbations including knock-outs and dual perturbation were also carried out to monitor the behavioral change of important proteins and metabolites. From this, key components as well as the required controlling factors in the model that are critical for maintaining iron homeostasis were identified. The model is able to re-establish the importance of iron-dependent regulator (ideR) in Mtb and transferrin (Tf) in the host. Perturbations, where iron storage is increased, appear to enhance nutritional immunity and the analysis indicates how they can be harmful for the host. Instead, decreasing the rate of iron uptake by Tf may prove to be helpful. Simulation and perturbation studies help in identifying Tf as a possible drug target. Regulating the mycobactin (myB) concentration was also identified as a possible strategy to control bacterial growth. The simulations thus provide significant insight into iron homeostasis and also for identifying possible drug targets for tuberculosis.
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Protein structure space is believed to consist of a finite set of discrete folds, unlike the protein sequence space which is astronomically large, indicating that proteins from the available sequence space are likely to adopt one of the... more
Protein structure space is believed to consist of a finite set of discrete folds, unlike the protein sequence space which is astronomically large, indicating that proteins from the available sequence space are likely to adopt one of the many folds already observed. In spite of extensive sequence-structure correlation data, protein structure prediction still remains an open question with researchers having tried different approaches (experimental as well as computational). One of the challenges of protein structure prediction is to identify the native protein structures from a milieu of decoys/models. In this work, a rigorous investigation of Protein Structure Networks (PSNs) has been performed to detect native structures from decoys/models. Ninety four parameters obtained from network studies have been optimally combined with Support Vector Machines (SVM) to derive a general metric to distinguish decoys/models from the native protein structures with an accuracy of 94.11%. Recently, for the first time in the literature we had shown that PSN has the capability to distinguish native proteins from decoys. A major difference between the present work and the previous study is to explore the transition profiles at different strengths of non-covalent interactions and SVM has indeed identified this as an important parameter. Additionally, the SVM trained algorithm is also applied to the recent CASP10 predicted models. The novelty of the network approach is that it is based on general network properties of native protein structures and that a given model can be assessed independent of any reference structure. Thus, the approach presented in this paper can be valuable in validating the predicted structures. A web-server has been developed for this purpose and is freely available at .
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Research Interests: Complementary and Alternative Medicine, Plant Biology, Ethnopharmacology, Phytotherapy, Animals, and 15 moreCandida, Male, Methanol, Bacteria, Plant extracts, Rats, Topical Drug Administration, Microbial Sensitivity Tests, Cryptococcus, Euphorbia, Solvents, Ointments, Plant Leaves, Povidone Iodine, and Pharmacology and pharmaceutical sciences
Different parts of Indian ethnomedicinal plant Shorea robusta is traditionally used for several ailments including wounds and burn by different tribal groups, since ages. Here we have validated, for the first time, the effectiveness and... more
Different parts of Indian ethnomedicinal plant Shorea robusta is traditionally used for several ailments including wounds and burn by different tribal groups, since ages. Here we have validated, for the first time, the effectiveness and the possible mechanism of action of young leaf extracts of Shorea robusta, used by two distinct tribes of India, and its isolated compounds as a topical formulation in three wound models in rats. Bioactivity-guided study of the active extract resulted in the isolation of two known compounds. The prepared ointment containing extracts (2.5 and 5%, w/w), fractions (5% w/w) and isolated compounds (0.25% w/w) were evaluated on excision, incision and dead space wound models in rats by the rate of wound closure, period of epithelialisation, tensile strength, granulation tissue weight, hydroxyproline content and histopathology. The animals treated with the extracts and fractions (5%) showed significant reduction in wound area 96.55 and 96.41% with faster epithelialisation (17.50 and 17.86), while the isolated compounds bergenin and ursolic acid heal the wound faster, but complete epithelialisation with 100% wound contraction was evident with 5% povidone-iodine group on 18th post-wounding day. Moreover, the tensile strength of incision wound, granuloma tissue weight, and hydroxyproline content was significantly increased in both the extract and compound(s) treated animals. Furthermore, the tissue histology of animals treated with the isolated compound(s) showed complete epithelialisation with increased collagenation, similar to povidone-iodine group. Thus, our results validated the traditional use of Shorea robusta young leaves in wound management.
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ABSTRACT
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... Kausik K. Nanda,la Sasankasekhar Mohanta,la Soma Ghosh,lb Monika Mukherjee,lb Madeleine Helliwell,lc and Kamalaksha Nag*Ja ... (14) (a) Neves, A.; Ceccatto, A. S.; Erasmus-Buhr, C.; Gehring, S.; Hasse, W.; Paulus, H.; Nascimento, 0.... more
... Kausik K. Nanda,la Sasankasekhar Mohanta,la Soma Ghosh,lb Monika Mukherjee,lb Madeleine Helliwell,lc and Kamalaksha Nag*Ja ... (14) (a) Neves, A.; Ceccatto, A. S.; Erasmus-Buhr, C.; Gehring, S.; Hasse, W.; Paulus, H.; Nascimento, 0. R.; Batista, AA J . Chem. Soc., Chem. ...
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The origin of diastereoselectivity in the addition of alkyl lithium to chiral Schiff bases has been investigated experimentally and theoretically and the formation of the major diastereomer can be explained from the energy minimized... more
The origin of diastereoselectivity in the addition of alkyl lithium to chiral Schiff bases has been investigated experimentally and theoretically and the formation of the major diastereomer can be explained from the energy minimized structure of the Schiff base in which the phenyl group has been found to orient in such a manner that it posed lesser steric hindrance to the incoming nucleophile as compared to the alkyl group.
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A new model to explain the diastereoselectivity observed in the alkyl lithium addition to Schiff bases bearing an N-stereogenic center is proposed. In addition, it is shown that Schiff bases (V) show superior C=N π facial selectivity... more
A new model to explain the diastereoselectivity observed in the alkyl lithium addition to Schiff bases bearing an N-stereogenic center is proposed. In addition, it is shown that Schiff bases (V) show superior C=N π facial selectivity compared to those derived from 1-...
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Page 1. Cyclodextrins are chemically and physically stable molecules formed by the enzy-matic modification of starch (1). They are cyclomalto oligosaccharides composed of six, seven or eight α-D-glucopyranose units (α-, β-, g-CD,... more
Page 1. Cyclodextrins are chemically and physically stable molecules formed by the enzy-matic modification of starch (1). They are cyclomalto oligosaccharides composed of six, seven or eight α-D-glucopyranose units (α-, β-, g-CD, respectively). ...