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In Silico Structural Homology Modelling and Docking for Assessment of Pandemic Potential of a Novel H7N9 Influenza Virus and Its Ability to Be Neutralized by Existing Anti-Hemagglutinin Antibodies
Harinda Rajapaksha, Nikolai Petrovsky
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0102618
Abstract: The unpredictable nature of pandemic influenza and difficulties in early prediction of pandemic potential of new isolates present a major challenge for health planners. Vaccine manufacturers, in particular, are reluctant to commit resources to development of a new vaccine until after a pandemic is declared. We hypothesized that a structural bioinformatics approach utilising homology-based molecular modelling and docking approaches would assist prediction of pandemic potential of new influenza strains alongside more traditional laboratory and sequence-based methods. The newly emerged Chinese A/Hangzhou/1/2013 (H7N9) influenza virus provided a real-life opportunity to test this hypothesis. We used sequence data and a homology-based approach to construct a 3D-structural model of H7-Hangzhou hemagglutinin (HA) protein. This model was then used to perform docking to human and avian sialic acid receptors to assess respective binding affinities. The model was also used to perform docking simulations with known neutralizing antibodies to assess their ability to neutralize the newly emerged virus. The model predicted H7N9 could bind to human sialic acid receptors thereby indicating pandemic potential. The model also confirmed that existing antibodies against the HA head region are unable to neutralise H7N9 whereas antibodies, e.g. Cr9114, targeting the HA stalk region should bind with high affinity to H7N9. This indicates that existing stalk antibodies initially raised against H5N1 or other influenza A viruses could be therapeutically beneficial in prevention and/or treatment of H7N9 infections. The subsequent publication of the H7N9 HA crystal structure confirmed the accuracy of our in-silico structural model. Antibody docking studies performed using the H7N9 HA crystal structure supported the model's prediction that existing stalk antibodies could cross-neutralise the H7N9 virus. This study demonstrates the value of using in-silico structural modelling approaches to complement physical studies in characterization of new influenza viruses.
Asynchronous Realization of Algebraic Integer-Based 2D DCT Using Achronix Speedster SPD60 FPGA
Nilanka Rajapaksha,Amila Edirisuriya,Arjuna Madanayake,Renato J. Cintra
Journal of Electrical and Computer Engineering , 2013, DOI: 10.1155/2013/834793
Abstract:
The Alzheimer's β-secretase enzyme BACE1 is required for accurate axon guidance of olfactory sensory neurons and normal glomerulus formation in the olfactory bulb
Tharinda W Rajapaksha, William A Eimer, Thomas C Bozza, Robert Vassar
Molecular Neurodegeneration , 2011, DOI: 10.1186/1750-1326-6-88
Abstract: We bred BACE1-/- mice with gene-targeted mice in which GFP is expressed from the loci of two odorant-receptors (ORs), MOR23 and M72, and olfactory marker protein (OMP) to produce offspring that were heterozygous for MOR23-GFP, M72-GFP, or OMP-GFP and were either BACE1+/+ or BACE1-/-. BACE1-/- mice had olfactory bulbs (OBs) that were smaller and weighed less than OBs of BACE1+/+ mice. In wild-type mice, BACE1 was present in OSN axon terminals in OB glomeruli. In whole-mount preparations and tissue sections, many OB glomeruli from OMP-GFP; BACE1-/- mice were malformed compared to wild-type glomeruli. MOR23-GFP; BACE1-/- mice had an irregular MOR23 glomerulus that was innervated by randomly oriented, poorly fasciculated OSN axons compared to BACE1+/+ mice. Most importantly, M72-GFP; BACE1-/- mice exhibited M72 OSN axons that were mis-targeted to ectopic glomeruli, indicating impaired axon guidance in BACE1-/- mice.Our results demonstrate that BACE1 is required for the accurate targeting of OSN axons and the proper formation of glomeruli in the OB, suggesting a role for BACE1 in axon guidance. OSNs continually undergo regeneration and hence require ongoing axon guidance. Neurogenesis and the regeneration of neurons and axons occur in other adult populations of peripheral and central neurons that also require axon guidance throughout life. Therefore, BACE1 inhibitors under development for the treatment of AD may potentially cause axon targeting defects in these neuronal populations as well.Proteolytic processing of the amyloid precursor protein (APP) by the β- and γ-secretases produces the Aβ peptide that forms amyloid plaques and plays a central role in AD pathogenesis. The β-secretase has been identified as the transmembrane aspartic protease BACE1 [1-5]. BACE1 cuts APP to produce a membrane-bound C-terminal fragment C99 that is further processed by γ-secretase to generate Aβ. BACE1 gene deletion in mice abrogates Aβ generation. Thus, BACE1 is considered a prime therap
Asynchronous Realization of Algebraic Integer-Based 2D DCT Using Achronix Speedster SPD60 FPGA
Nilanka Rajapaksha,Amila Edirisuriya,Arjuna Madanayake,Renato J. Cintra,Dennis Onen,Ihab Amer,Vassil S. Dimitrov
Journal of Electrical and Computer Engineering , 2013, DOI: 10.1155/2013/834793
Abstract: Transformation and quantization play a critical role in video codecs. Recently proposed algebraic-integer-(AI-) based discrete cosine transform (DCT) algorithms are analyzed in the presence of quantization, using the High Efficiency Video Coding (HEVC) standard. AI DCT is implemented and tested on asynchronous quasi delay-insensitive logic, using Achronix SPD60 field programmable gate array (FPGA), which leads to lower complexity, higher speed of operation, and insensitivity to process-voltage-temperature variations. Performance of AI DCT with HEVC is measured in terms of the accuracy of the transform coefficients and the overall rate-distortion (R-D) characteristics, using HM 7.1 reference software. Results indicate a 31% improvement over the integer DCT in the number of transform coefficients having error within 1%. The performance of the 65?nm asynchronous hardware in terms of speed of operation is investigated and compared with the 65?nm synchronous Xilinx FPGA. Considering word lengths of 5 and 6 bits, a speed increase of 230% and 199% is observed, respectively. These results indicate that AI DCT can be potentially utilized in HEVC for applications demanding high accuracy as well as high throughput. However, novel quantization schemes are required to allow the accuracy improvements obtained. 1. Introduction High dynamic range (HDR) video and image transmission over digital communication channels is undergoing exponential growth [1]. With the increasing demand for high-definition programming, there exists a strong need for efficient digital video coding (DVC) that provides high data compression ratios which in turn leads to better utilization of network resources [2]. The H.264/AVC standard [3] does not provide the required compression ratios for emerging capture and display technologies such as ultra high definition (UHD) [4], multiview [5], and autostereoscopy [6]. To address such emerging needs, the Joint Collaborative Team on Video Coding (JCT-VC) has developed the successor for H.264/AVC, called High Efficiency Video Coding (HEVC) [4]. The HEVC standard aims at achieving a 50% reduction in data rate compared with its predecessors while maintaining low complexity computation. Video compression systems operating at high frequencies and resolutions require hardware capable of significant throughput with tolerable area and power requirements. Real-time video compression circuits having high numerical accuracy are needed for next-generation video [1], coding systems [2, 3, 7], and retina displays [8]. The two-dimensional (2D) 8 8 discrete cosine
A survey of odonate assemblages associated with selected wetland localities in southern Sri Lanka
Chandana, E.P.S.,Rajapaksha, A.C.D.,Samarasekara, W.G.K.H.
Asian Journal of Conservation Biology , 2012,
Abstract: The dragonflies and damselflies are a major insect group (Class Insecta; Order Odonata) associated with water courses. Odonate assemblages with reference to their habitat characters have not been widely studied in Sri Lanka. We have investigated odonate assemblages for a period of three months in selected localities in southern Sri Lanka with reference to the habitat characters. Bundala and Embillakala lagoons in Bundala National Park (A Ramsar wetland in Sri Lanka), “Kirala Kele” Eco-tourism Zone-Matara, Bandaththara marshland system-Matara, “Kirala Kele” Biological Garden-Ambalanthota and Kosgahadola stream which belongs to Mulatiyana Rain forest reserve were selected as study sites since these sites are important in conservation of biodiversity. A total of 28 species were identified during the study period. Our data reveals odonate assemblages specific to the studied habitats such as bushlands, marshlands, lagoons, flowing water bodies, stagnant water bodies and vegetation type (wet zone and dry zone). These data will be useful in future studies and conservation of biodiversity in the studied habitats.
PIPER BETLE LINN: AS A REMEDY FOR DIABETES MELLITUS
Horadugoda Gamage Sujatha Pushpakanthi Hewageegana,Liyanage Dona Ashanthi Menuka Arawwawala,Lakshmi Sriyani Rajapaksha Arambewela,Hettiarachchige Sami Ariyawansa
International Journal of Research in Ayurveda and Pharmacy , 2011,
Abstract: Present study was carried out to evaluate the possibility of Piper betle Linn. (F: Piperaceae) to be used as a neutraceutical for Diabetes Mellitus. Newly diagnosed, Type 2 diabetes patients from either sex were selected (n=50/group) after measuring fasting blood glucose levels. Either P. betle or triphala (a known antidiabetic herbal drug) were given to patients for 30 consecutive days. Treated subjects were checked for fasting blood glucose levels and serum creatinine, urea, aspartate transaminase (AST), alanine transaminase (ALT) levels and selected hematological parameters. According to the results blood glucose levels of P. betle treated patients were significantly reduced by 22% and 25% at the end of 2nd and 4th week of the treatment while the blood glucose levels of triphala treated patients were significantly reduced by 14% and 24% at the end of 2nd and 4th week of the treatment compared to their respective pre-treatments. There were no toxic effects as judged by hepatotoxicity, renotoxicity and hematological parameters in both groups. In conclusion, P. betle can be used as a potential pharmaceutical for Type 2 diabetic patients. KEY WORDS: Present study was carried out to evaluate the possibility of Piper betle Linn. (F: Piperaceae) to be used as a neutraceutical for Diabetes Mellitus. Newly diagnosed, Type 2 diabetes patients from either sex were selected (n=50/group) after measuring fasting blood glucose levels. Either P. betle or triphala (a known antidiabetic herbal drug) were given to patients for 30 consecutive days. Treated subjects were checked for fasting blood glucose levels and serum creatinine, urea, aspartate transaminase (AST), alanine transaminase (ALT) levels and selected hematological parameters. According to the results blood glucose levels of P. betle treated patients were significantly reduced by 22% and 25% at the end of 2nd and 4th week of the treatment while the blood glucose levels of triphala treated patients were significantly reduced by 14% and 24% at the end of 2nd and 4th week of the treatment compared to their respective pre-treatments. There were no toxic effects as judged by hepatotoxicity, renotoxicity and hematological parameters in both groups. In conclusion, P. betle can be used as a potential pharmaceutical for Type 2 diabetic patients.
A Row-parallel 8$\times$8 2-D DCT Architecture Using Algebraic Integer Based Exact Computation
A. Madanayake,R. J. Cintra,D. Onen,V. S. Dimitrov,N. T. Rajapaksha,L. T. Bruton,A. Edirisuriya
Computer Science , 2015, DOI: 10.1109/TCSVT.2011.2181232
Abstract: An algebraic integer (AI) based time-multiplexed row-parallel architecture and two final-reconstruction step (FRS) algorithms are proposed for the implementation of bivariate AI-encoded 2-D discrete cosine transform (DCT). The architecture directly realizes an error-free 2-D DCT without using FRSs between row-column transforms, leading to an 8$\times$8 2-D DCT which is entirely free of quantization errors in AI basis. As a result, the user-selectable accuracy for each of the coefficients in the FRS facilitates each of the 64 coefficients to have its precision set independently of others, avoiding the leakage of quantization noise between channels as is the case for published DCT designs. The proposed FRS uses two approaches based on (i) optimized Dempster-Macleod multipliers and (ii) expansion factor scaling. This architecture enables low-noise high-dynamic range applications in digital video processing that requires full control of the finite-precision computation of the 2-D DCT. The proposed architectures and FRS techniques are experimentally verified and validated using hardware implementations that are physically realized and verified on FPGA chip. Six designs, for 4- and 8-bit input word sizes, using the two proposed FRS schemes, have been designed, simulated, physically implemented and measured. The maximum clock rate and block-rate achieved among 8-bit input designs are 307.787 MHz and 38.47 MHz, respectively, implying a pixel rate of 8$\times$307.787$\approx$2.462 GHz if eventually embedded in a real-time video-processing system. The equivalent frame rate is about 1187.35 Hz for the image size of 1920$\times$1080. All implementations are functional on a Xilinx Virtex-6 XC6VLX240T FPGA device.
Molecular Detection and Partial Characterization of Tomato Yellow Leaf Curl Virus in Sri Lanka
S.A.M.C. Samarakoon,A. Balasuriya,R.G.A.S. Rajapaksha,W.A.R.T. Wickramarachchi
Pakistan Journal of Biological Sciences , 2012,
Abstract: Tomato Yellow Leaf Curl Virus (TYLCV) is an important plant virus on one of the economically most important vegetable crops; tomato (Lycopersicon esculentum Mill.). This had not been molecularly detected before, in Sri Lanka. TYLCV-GN-SL was isolated from apparently infected tomato plants using modified Cetyltrimethyl Ammonium Bromide (CTAB) method in Gannoruwa. Associated Begomoviruses were detected using Deng 541/Deng 540 and AV 494/AC 1048 primer pairs. TYLCV was detected for the first time in tomato in Sri Lanka using P1V/P4C, TYLCV specific primer pair. Nucleotide sequence of coat protein of isolated TYLCV-GN-SL proved that the Indian strain of ToLC virus was closely related to Tomato Leaf Curl Sri Lanka Virus (TLCV-SL: 97%) and Tomato leaf curl Geminivirus (TLCGV: 93%) through direct sequencing data. TLCV-SL was confirmed as TYLCV isolate. TYLCV was molecularly detected from major tomato growing districts like Badulla, Nuwara-Eliya, Kandy and Matale in Sri Lanka.
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