High Performance Computing Techniques to Better Understand Protein Conformational Space

This thesis presents an amalgamation of high performance computing techniques to get better insight into protein molecular dynamics. Key aspects of protein function and dynamics can be learned from their conformational space. Datasets that represent the complex nuances of a protein molecule are high dimensional. Efficient dimensionality reduction becomes indispensable for the analysis of such exorbitant datasets. Dimensionality reduction forms a formidable portion of this work and its application has been explored for other datasets as well. It begins with the parallelization of a known non-liner feature reduction algorithm called Isomap. The code for the algorithm was re-written in C with portions of it parallelized using OpenMP. Next, a novel data instance reduction method was devised which evaluates the information content offered by each data point, which ultimately helps in truncation of the dataset with much fewer data points to evaluate. Once a framework has been established to reduce the number of variables representing a dataset, the work is extended to explore algebraic topology techniques to extract meaningful information from these datasets. This step is the one that helps in sampling the conformations of interest of a protein molecule. The method employs the notion of hierarchical clustering to identify classes within a molecule, thereafter, algebraic topology is used to analyze these classes. Finally, the work is concluded by presenting an approach to solve the open problem of protein folding. A Monte-Carlo based tree search algorithm is put forth to simulate the pathway that a certain protein conformation undertakes to reach another conformation. The dissertation, in its entirety, offers solutions to a few problems that hinder the progress of solution for the vast problem of understanding protein dynamics. The motion of a protein molecule is guided by changes in its energy profile. In this course the molecule gradually slips from one energy class to another. Structurally, this switch is transient spanning over milliseconds or less and hence is difficult to be captured solely by the work in wet laboratories

COMPARISON OF LIPID PROFILE BETWEEN MIDDLE AGED YOGA PRACTITIONERS AND NON PRACTITIONERS

The purpose of the study was to compare the “Lipid Profile between Middle Aged Yoga Practitioners and Non-practitioners. Method: The study was conducted on 60 (N=60) middle aged male people from the Rishikesh, Uttarakhand India, age ranging from 40 to 45 years. Out of 60, the 30 subjects were practicing different types of Yogic exercises like Asana and Shatkarmas and remaining 30 subjects were not practicing any types of yogic exercises. The necessary data on lipid profile (Total blood Cholesterol, Triglycerides, High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL)) were collected by administration of laboratory tests. The tests were administered after giving them instruction and taking consent from the subjects. Lipid profile test were taken place after 8 to 10 hours of fasting. It was hypothesized that there would be significant difference of lipid profile between Middle Aged Yoga Practitioners and Non-practitioners. The data collected on each lipid profile parameters (Total blood Cholesterol, Triglycerides, High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL)) was analyzed by independent “t” test. The level of significance for testing the hypothesis was set at 0.05. P < 0.05. Findings: The mean values and standard deviation of total blood Cholesterol of Yoga Practitioners and Non-practitioners were 181.43±13.91 mg/dl and 271.06±18.56 mg/dl respectively. The analysis of the data shows significant difference of total blood Cholesterol between Yoga Practitioners and Non-practitioners (tcal=21.15>ttab=2.009). In case of Triglycerides, the mean and standard deviation of Triglycerides level of Yoga Practitioners and Non-practitioners were 141.30±5.72 mg/dl and 299.63±14.48 mg/dl respectively. The analysis of the data showed significant difference of Triglycerides level between Yoga Practitioners and Non-practitioners (tcal=10.90>ttab=2.009). The mean and standard deviation of High Density Lipoprotein (HDL) level of Yoga Practitioners and Non-practitioners were 61.47±2.29 mg/dl and 34.97±2.91 mg/dl respectively. The analysis of the data showed significant difference of High Density Lipoprotein level between Yoga Practitioners and Non-practitioners (tcal=39.25>ttab=2.009). The mean and standard deviation of Low Density Lipoprotein (LDL) level of Yoga Practitioners and Non-practitioners were 116.20±12.57 mg/dl and 161.23±7.28 mg/dl respectively. The analysis of the data showed significant difference of Low Density Lipoprotein (LDL) between Yoga Practitioners and Non-practitioners (tcal=16.98>ttab=2.009). The result showed that yoga Practitioners have better lipid profile as compare to non- Practitioners. Regular yoga practices decrease the risk of coronary heart diseases.  Article visualizations

Modification of Hilbert's Space-Filling Curve to Avoid Obstacles: A Robotic Path-Planning Strategy

This paper addresses the problem of exploring a region using the Hilbert's space-filling curve in the presence of obstacles. No prior knowledge of the region being explored is assumed. An online algorithm is proposed which can implement evasive strategies to avoid obstacles comprising a single or two blocked unit squares placed side by side and successfully explore the entire region. The strategies are specified by the change in the waypoint array which robot going to follow. The fractal nature of the Hilbert's space-filling curve has been exploited in proving the validity of the solution

Consistency and Variation in Kernel Neural Ranking Model

This paper studies the consistency of the kernel-based neural ranking model K-NRM, a recent state-of-the-art neural IR model, which is important for reproducible research and deployment in the industry. We find that K-NRM has low variance on relevance-based metrics across experimental trials. In spite of this low variance in overall performance, different trials produce different document rankings for individual queries. The main source of variance in our experiments was found to be different latent matching patterns captured by K-NRM. In the IR-customized word embeddings learned by K-NRM, the query-document word pairs follow two different matching patterns that are equally effective, but align word pairs differently in the embedding space. The different latent matching patterns enable a simple yet effective approach to construct ensemble rankers, which improve K-NRM's effectiveness and generalization abilities.Comment: 4 pages, 4 figures, 2 table

Extraintestinal Infections Caused by Non-toxigenic Vibrio cholerae non-O1/non-O139

Vibrio cholerae is an aerobic, sucrose fermentative Gram-negative bacterium that generally prevails in the environment. Pathogenic V. cholerae is well-known as causative agent of acute diarrhea. Apart from enteric infections, V. cholerae may also cause other diseases. However, their role in causing extraintestinal infections is not fully known as it needs proper identification and evaluation. Four cases of extraintestinal infections due to V. cholerae non-O1/non-O139 have been investigated. The isolates were screened for phenotypic and genetic characteristics with reference to their major virulence genes. Serologically distinct isolates harbored rtx, msh, and hly but lacked enteric toxin encoding genes that are generally present in toxigenic V. cholerae. Timely detection of this organism can prevent fatalities in hospital settings. The underlying virulence potential of V. cholerae needs appropriate testing and intervention

High Precision Measurements of Interstellar Dispersion Measure with the upgraded GMRT

Pulsar radio emission undergoes dispersion due to the presence of free electrons in the interstellar medium (ISM). The dispersive delay in the arrival time of pulsar signal changes over time due to the varying ISM electron column density along the line of sight. Correcting for this delay accurately is crucial for the detection of nanohertz gravitational waves using Pulsar Timing Arrays. In this work, we present in-band and inter-band DM estimates of four pulsars observed with uGMRT over the timescale of a year using two different template alignment methods. The DMs obtained using both these methods show only subtle differences for PSR 1713+0747 and J1909$-$3744. A considerable offset is seen in the DM of PSR J1939+2134 and J2145$-$0750 between the two methods. This could be due to the presence of scattering in the former and profile evolution in the latter. We find that both methods are useful but could have a systematic offset between the DMs obtained. Irrespective of the template alignment methods followed, the precision on the DMs obtained is about $10^{-3}$ pc cm$^{-3}$ using only BAND3 and $10^{-4}$ pc cm$^{-3}$ after combining data from BAND3 and BAND5 of the uGMRT. In a particular result, we have detected a DM excess of about $5\times10^{-3}$ pc cm$^{-3}$ on 24 February 2019 for PSR J2145$-$0750. This excess appears to be due to the interaction region created by fast solar wind from a coronal hole and a coronal mass ejection (CME) observed from the Sun on that epoch. A detailed analysis of this interesting event is presented.Comment: 11 pages, 6 figures, 2 tables. Accepted by A&

Drug Susceptibility in Leishmania Isolates Following Miltefosine Treatment in Cases of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis

Resistance to antimonials has emerged as a major hurdle to the treatment and control of VL and led to the introduction of Miltefosine as first line treatment in the Indian subcontinent. MIL is an oral drug with a long half-life, and it is feared that resistance may emerge rapidly, threatening control efforts under the VL elimination program. There is an urgent need for monitoring treatment efficacy and emergence of drug resistance in the field. In a set of VL/PKDL cases recruited for MIL treatment, we observed comparable drug susceptibility in pre- and post-treatment isolates from cured VL patients while MIL susceptibility was significantly reduced in isolates from VL relapse and PKDL cases. The PKDL isolates showed higher tolerance to MIL as compared to VL isolates. Both VL and PKDL isolates were uniformly susceptible to PMM. MIL transporter genes LdMT/LdRos3 were previously reported as potential resistance markers in strains in which MIL resistance was experimentally induced. The point mutations and the down-regulated expression of these transporters observed in vitro could, however, not be verified in natural populations of parasites. LdMT/LdRos3 genes therefore, do not appear to be suitable markers so far for monitoring drug susceptibility in clinical leishmanial isolates

Mono-, di- and tri- substituted S-triazine as anti cancer agents: A comparative molecular docking study

816-822In this paper, a series of 1,3,5-triazine derivatives with mono-, di-, tri- substitutions at 2,4,6 positions of S-triazine have been designed. The molecular docking studies have been carried out against cancer therapeutic target protein (Heat Shock Protein 90, HSP90). The most active structure has been predicted based on the binding energy and mode of interactions of compounds with the help of molecular modeling software AUTODOCK Vina. Of all the substitutions (mono-, di- and tri-) of 1,3,5-triazine derivatives, trisubstituted triazine i.e. tri-4 shows better activity than mono- and di- substitutions having binding affinity −12.1 kcal/mol. This is due to the presence of strong π-π interactions of hydrophobic substituted part of 1,3,5-triazine with phenylalanine 138 (PHE138) present in the hydrophobic region of HSP90