Solving an MRI spin relaxometry problem using Parallel Java

Magnetic resonance imaging (MRI) is an imaging technique used primarily in the medical profession to produce high quality images of the inside of the human body, without using x-rays. The process of obtaining the spin density spectrum from the time samples of the spin signal for each pixel of a magnetic resonance image is known as MRI spin relaxometry. The spin density spectrum is obtained by performing linear regularization on samples of magnetic resonance images obtained at different times. The spin density spectrum obtained from the body is used by radiologists to diagnose disease in its early stage. However, the computation involved is substantial, and processing the pixels of the images in parallel reduces the time it takes to obtain the spin density spectrum. Parallel computing is suitable for the computations because the value of each pixel is independently calculated. This project involved developing a parallel algorithm implementation using the Parallel Java Library (developed by Prof. Alan Kaminsky) and an MPI implementation in C. The algorithm implementation was done using both linear regularization and the non-linear least squares approach along with proper load balancing. Also, a performance comparison was done between both the implementations for C as well as Java. Appropriate user interfaces were also developed for both the implementations

FRAND Licensing and Standards-Essential Patents: Concocting for Impending Technologies

Engineering of innumerable advancement in telecommunications placed India at a plinth of one of the largest telecommunication markets. In essence, most of these ingenuities pivot around a strong information, communication technology (“ITC”) platform; therefore, at the juncture of business and innovation Intellectual Property Rights (“IPR”) has a perilous role to play. Specifically, the success of India’s national development aspirations will depend on a court system and the competition Commission of India (“CCI”) to set enforcement standards and guidelines across the Intellectual Property Rights (“IPR”) regime associated with those initiatives. In this section we review decisions by Indian courts to explore emergence of any trends or standards of review.  Specifically, this paper explores how Indian courts have approached the Fair Reasonable and Non-Discriminatory (“FRAND”) terms to adjudicate disputes arising from standard-essential patents (“SEPs”). Further, the paper compares and contrasts court decisions on disputes arising from SEP licensing under FRAND terms across various international jurisdictions to set a benchmark for considerations by Indian legal experts. The work outlines the multidimensional nature of IPR in relation to licensing SEPs which presents not only legal issues but also business, technology and associated government policy issues

Understanding Molecular Interactions: Application of HINT-based Tools in the Structural Modeling of Novel Anticancer and Antiviral Targets, and in Protein-Protein Docking

Computationally driven drug design/discovery efforts generally rely on accurate assessment of the forces that guide the molecular recognition process. HINT (Hydropathic INTeraction) is a natural force field, derived from experimentally determined partition coefficients that quantifies all non-bonded interactions in the biological environment, including hydrogen bonding, electrostatic and hydrophobic interactions, and the energy of desolvation. The overall goal of this work is to apply the HINT-based atomic level description of molecular systems to biologically important proteins, to better understand their biochemistry – a key step in exploiting them for therapeutic purposes. This dissertation discusses the results of three diverse projects: i) structural modeling of human sphingosine kinase 2 (SphK2, a novel anticancer target) and binding mode determination of an isoform selective thiazolidine-2,4-dione (TZD) analog; ii) structural modeling of human cytomegalorvirus (HCMV) alkaline nuclease (AN) UL98 (a novel antiviral target) and subsequent virtual screening of its active site; and iii) explicit treatment of interfacial waters during protein-protein docking process using HINT-based computational tools. SphK2 is a key regulator of the sphingosine-rheostat, and its upregulation /overexpression has been associated with cancer development. We report structural modeling studies of a novel TZD-analog that selectively inhibits SphK2, in a HINT analysis that identifies the key structural features of ligand and protein binding site responsible for isoform selectivity. The second aim was to build a three-dimensional structure of a novel HCMV target – AN UL98, to identify its catalytically important residues. HINT analysis of the interaction of 5’ DNA end at its active site is reported. A parallel aim to perform in silico screening with a site-based pharmacophore model, identified several novel hits with potentially desirable chemical features for interaction with UL98 AN. The majority of current protein-protein docking algorithms fail to account for water molecules involved in bridging interactions between partners, mediating and stabilizing their association. HINT is capable of reproducing the physical and chemical properties of such waters, while accounting for their energetic stabilizing contributions. We have designed a solvated protein-protein docking protocol that explicitly models the Relevant bridging waters, and demonstrate that more accurate results are obtained when water is not ignored

Identification of Small-Molecule Inhibitors against Meso-2, 6-Diaminopimelate Dehydrogenase from Porphyromonas gingivalis

Species-specific antimicrobial therapy has the potential to combat the increasing threat of antibiotic resistance and alteration of the human microbiome. We therefore set out to demonstrate the beginning of a pathogen-selective drug discovery method using the periodontal pathogen Porphyromonas gingivalis as a model. Through our knowledge of metabolic networks and essential genes we identified a “druggable” essential target, meso-diaminopimelate dehydrogenase, which is found in a limited number of species. We adopted a high-throughput virtual screen method on the ZINC chemical library to select a group of potential small-molecule inhibitors. Meso-diaminopimelate dehydrogenase from P. gingivaliswas first expressed and purified in Escherichia coli then characterized for enzymatic inhibitor screening studies. Several inhibitors with similar structural scaffolds containing a sulfonamide core and aromatic substituents showed dose-dependent inhibition. These compounds were further assayed showing reasonable whole-cell activity and the inhibition mechanism was determined. We conclude that the establishment of this target and screening strategy provides a model for the future development of new antimicrobials

Isolation and Characterization of Bacterial Endophytes from Lycopersicon esculentum Plant and their Plant Growth Promoting Characteristics

The study was designed to isolate and characterize bacterial endophytes from root and stem of Lycopersicon esculentum plant which was collected form different region of Gujarat. Total 18 isolates of endophytic bacteria were selected in which, all the endophytic bacteria produced one or the other different characteristics involved in plant growth promotion. They either produced phytohormones like indole acetic acid, siderophore, protease, pectinase, organic acid showed antifungal activity, chromium tolerance and solubilized phosphate. Four of the strains among the 18 showed maximum positive results of plant growth promoting regulators (PGPR) test and among them best probable isolate was selected and thus its 16SrDNA was amplified and sequenced. Only HR7 endophyte of tomato turned out to be Pseudomonas aeruginosa. It’s a gram negative coccobacili, sporeforming motile bacilli and show maximum PGPR activity. The results of our present studies indicated that above strains might be endophytic and therefore, were associated with the plant growth. Keywords: Lycopersicon esculentum; endophytic bacteria; PGPR; IAA; 16SrDNA DOI: http://dx.doi.org/10.3126/njb.v2i1.5679   Nepal Journal of Biotechnology Jan.2012, Vol.2(1): 37-5

Rare mutations and potentially damaging missense variants in genes encoding fibrillar collagens and proteins involved in their production are candidates for risk for preterm premature rupture of membranes

Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm birth with ~ 40% of preterm births being associated with PPROM and occurs in 1% - 2% of all pregnancies. We hypothesized that multiple rare variants in fetal genes involved in extracellular matrix synthesis would associate with PPROM, based on the assumption that impaired elaboration of matrix proteins would reduce fetal membrane tensile strength, predisposing to unscheduled rupture. We performed whole exome sequencing (WES) on neonatal DNA derived from pregnancies complicated by PPROM (49 cases) and healthy term deliveries (20 controls) to identify candidate mutations/variants. Genotyping for selected variants from the WES study was carried out on an additional 188 PPROM cases and 175 controls. All mothers were self-reported African Americans, and a panel of ancestry informative markers was used to control for genetic ancestry in all genetic association tests. In support of the primary hypothesis, a statistically significant genetic burden (all samples combined, SKAT-O p-value = 0.0225) of damaging/potentially damaging rare variants was identified in the genes of interest—fibrillar collagen genes, which contribute to fetal membrane strength and integrity. These findings suggest that the fetal contribution to PPROM is polygenic, and driven by an increased burden of rare variants that may also contribute to the disparities in rates of preterm birth among African Americans

Stratification of phaco-trabectome surgery results using a glaucoma severity index

The outcomes of phacoemulsification combined with trabectome surgery was analyzed using a glaucoma severity index based on preoperative intraocular pressure (IOP), number of preoperative medications, and visual field damage. Despite a less absolute indication to lower IOP, a substantial pressure reduction was seen in patients with more advanced glaucoma

Matched comparison of phaco-trabectome to trabectome in phakic patients

Coarsened Exact Matching allowed for a balanced comparison between phakic patients who received ab interno trabeculectomy and trabectome with same session phacoemulsification. Phacoemulsification was not found to be a statistically significant contributor to IOP reduction when combined with this microincisional glaucoma surgery