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author:("mazumdar, A.")
Ancient Science of Life  2002;21(3):191-197.
The mycotoxin Citrinin was obtained from the fungus Penicillium citrinum. It was tested for it's Minimum Inhibitory Concentration (MIC) against some gram positive strains viz. Staphylococcus aureus, Bacillus pumilus, Bacillus subtillis, Bacillus cereus, Klebsiella pneumoniae, Streptococcus pneumoniae, Lactobacillus arabinosus and gram negative strains E.Coli, Shigella dysenteriae, shigella sonnei, shigella boydii, Salmonella typhimurium, Proteus mirabilis and Vibrio cholerae. Further the zones of inhibition produced by the fungal extract against the bacterial strains were assayed and compared with those produced by the standard antibiotic ciprofloxacin.
PMCID: PMC3331043  PMID: 22557053
2.  Pharmacognostical and Phytochemical Evaluation of the leaves of Bauhinia purpurea Linn. 
Ancient Science of Life  2010;30(2):28-32.
Various pharmacognostic parameters including macroscopy, microscopy, chemomicroscopy and behaviour of powdered drug on treatment with different chemical reagents were studied on the leaves of Bauhinia purpurea Linn. (Family Caesalpinaceae). Phytochemical screening of the plant part with various solvents revealed the presence of phenolic compounds, tannins, flavonoids, phytosterols, saponins and glycosides in it.
PMCID: PMC3336273  PMID: 22557422
3.  Arsenic Contamination of Ground Water and its Health Impact on Population of District of Nadia, West Bengal, India 
The global health impact and disease burden due to chronic arsenic toxicity has not been well studied in West Bengal.
To ascertain these, a scientific epidemiological study was carried out in a district of the state.
Materials and Methods:
Epidemiological study was carried out by house-to-house survey of arsenic affected villages in the district of Nadia. A stratified multi-stage design has been adopted for this survey for the selection of the participants. A total number of 2297 households of 37 arsenic affected villages in all the 17 blocks were surveyed in the district.
Out of 10469 participants examined, prevalence rate of arsenicosis was found to be 15.43%. Out of 0.84 million people suspected to be exposed to arsenic, 0.14 million people are estimated to be suffering from arsenicosis in the district. Highest level of arsenic in drinking water sources was found to be 1362 μg/l, and in 23% cases it was above 100 μg/l. Majority of the population living in the arsenic affected villages were of low socio-economic condition, inadequate education and were farmers or doing physical labour. Chronic lung disease was found in 207 (12.81%) subjects among cases and 69 (0.78%) in controls. Peripheral neuropathy was found in 257 (15.9%) cases and 136 (1.5%) controls.
Large number of people in the district of Nadia are showing arsenical skin lesion. However, insufficient education, poverty, lack of awareness and ineffective health care support are major factors causing immense plight to severely arsenic affected people.
PMCID: PMC2940197  PMID: 20922118
Arsenic; toxicants; arsenic and systemic manifestations; arsenic and socio-economic issues; disease burden; skin manifestations
4.  Anthelmintic activity of root bark of Carissa carandas 
Ancient Science of Life  2007;27(1):11-13.
The anthelmintic activity of the Imethanolic extract of the root bark of Carissa carandas was evaluated on adult Indian earthworm (Pheretima posthuma) using albendazole as a reference standard. The extract caused paralysis followed by the death of worm at the tested dose level. The extract at the highest tested concentration has anthelmintic activity comparable with that of standard drug albendazole.
PMCID: PMC3330840  PMID: 22557253
5.  Studies on Pharmacognostical features of Curcuma domestica Val. 
Ancient Science of Life  2007;26(4):37-41.
The microscopic and macroscopic characters of the rhizome of Curcuma domestica Val. were studied. The behavior of the powdered drug in the presence of various chemicals was also studied. Preliminary phytochemical screening on the various extracts of the rhizome was done in order to ascertain the various chemical constituents present. These studies were carried out to identify this plant for future research work.
PMCID: PMC3330885  PMID: 22557249
Ancient Science of Life  2005;25(2):74-78.
The leaves and seeds of Cassia tora (Family Caesalpinaceae) are used in the treatment of leprosy, ring worm, flatulence, colic, dyspepsia, constipation, cough, bronchitis and cardiac disorders in the Ayurvedic systems of medicine. The present study deals with the study of macroscopic characters of the leaves, ash values, extractive values, behavior on treatment with different chemical reagents and fluorescence characters under ultraviolet light. Preliminary phytochemical studies on different extractives of the leaves were also performed. These studies will help in the identification of the plant for further research.
PMCID: PMC3330902  PMID: 22557196
Ancient Science of Life  2003;22(4):160-165.
The methanolic extract of leaves of Mesua ferrea Linn. were tested for its antibacterial potentiality against 103 various strains of bacteria including Staphylococcus aureus, Bacillus spps. Klebsiella spps., Streptococus pneumoniae, Sarcina lutea, Lactobacilus arabinosus, Escherichia coli, shigellae, salmonellae, Proteus spps., Pseudomonas spps. and the vibrios. Significant antibacterial effects were produced by the extract against Staphylococcus aureus, Bacillus sppa., lactobacilli, Escherichia coli, shigellae and salmonellae and the results were compared with standard antibiotic ciprofloxacin. Further the extract was proved to be bacterial in its action.
PMCID: PMC3331016  PMID: 22557104
8.  ANTIMICROBIAL ACTION OF THE LEAF EXTRACT OF Lagerstroemia parviflora Roxb 
Ancient Science of Life  2002;21(3):198-201.
The benzene extract of the leaves of Lagerstroemia paviflora Roxb was tested for its Minimum Inhibitory Concentration (MIC) against Gram Positive Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Klebsiella pneumoniae, Streptococcus pneumoniae, Lactobacillus arabinosus and gram negative strains E.Coli, Shigella dysenteriae, shigella sonnei, shigella boydii, Salmonella typhimurium, Proteus mirabilis and Vibrio cholerae. Further the zones of inhibition Produced by the crude extract against four selected bacterial strains were measured and compared with those produced by the standard antibiotic Ciprofloxacin against the same bacterial strains.
PMCID: PMC3331035  PMID: 22557054
9.  Antimicrobial Potency of the Leaf – Stalk Extract of Curcuma longa (LINN) 
Ancient Science of Life  2000;20(1-2):92-96.
The methanolic extract of the leaf-stalk of curcuma longa LINN, was tested for its minimum Inhibitor concentration (MIC) against Gram positive-staphylococcus aureus, Bacillus pumilus, Bacillus subtilis, klebsiella pnemoniae, bacillus cereus, streptococcus pneumoniae, Lactobacillus arabinosus and gram negative E.coli, shigella dysenteriae, shigella sonnei, shigella boydii, salmonella typhimurium, proteus mirabilis, and Vibrio cholerae strains, further, the ones of inhibition produced by the crude extract against four selected bacterial strains were measured and compared with those produced by the standard antibiotic ciprofloxacin against the same bacterial strains.
PMCID: PMC3336426  PMID: 22557005
11.  Association of Heme Oxygenase 1 with the Restoration of Liver Function after Damage in Murine Malaria by Plasmodium yoelii 
Infection and Immunity  2014;82(8):3113-3126.
The liver efficiently restores function after damage induced during malarial infection once the parasites are cleared from the blood. However, the molecular events leading to the restoration of liver function after malaria are still obscure. To study this, we developed a suitable model wherein mice infected with Plasmodium yoelii (45% parasitemia) were treated with the antimalarial α/β-arteether to clear parasites from the blood and, subsequently, restoration of liver function was monitored. Liver function tests clearly indicated that complete recovery of liver function occurred after 25 days of parasite clearance. Analyses of proinflammatory gene expression and neutrophil infiltration further indicated that hepatic inflammation, which was induced immediately after parasite clearance from the blood, was gradually reduced. Moreover, the inflammation in the liver after parasite clearance was found to be correlated positively with oxidative stress and hepatocyte apoptosis. We investigated the role of heme oxygenase 1 (HO-1) in the restoration of liver function after malaria because HO-1 normally renders protection against inflammation, oxidative stress, and apoptosis under various pathological conditions. The expression and activity of HO-1 were found to be increased significantly after parasite clearance. We even found that chemical silencing of HO-1 by use of zinc protoporphyrin enhanced inflammation, oxidative stress, hepatocyte apoptosis, and liver injury. In contrast, stimulation of HO-1 by cobalt protoporphyrin alleviated liver inflammation and reduced oxidative stress, hepatocyte apoptosis, and associated tissue injury. Therefore, we propose that selective induction of HO-1 in the liver would be beneficial for the restoration of liver function after parasite clearance.
PMCID: PMC4136231  PMID: 24818663
12.  Extraribosomal L13a Is a Specific Innate Immune Factor for Antiviral Defense 
Journal of Virology  2014;88(16):9100-9110.
We report a novel extraribosomal innate immune function of mammalian ribosomal protein L13a, whereby it acts as an antiviral agent. We found that L13a is released from the 60S ribosomal subunit in response to infection by respiratory syncytial virus (RSV), an RNA virus of the Pneumovirus genus and a serious lung pathogen. Unexpectedly, the growth of RSV was highly enhanced in L13a-knocked-down cells of various lineages as well as in L13a knockout macrophages from mice. In all L13a-deficient cells tested, translation of RSV matrix (M) protein was specifically stimulated, as judged by a greater abundance of M protein and greater association of the M mRNA with polyribosomes, while general translation was unaffected. In silico RNA folding analysis and translational reporter assays revealed a putative hairpin in the 3′untranslated region (UTR) of M mRNA with significant structural similarity to the cellular GAIT (gamma-activated inhibitor of translation) RNA hairpin, previously shown to be responsible for assembling a large, L13a-containing ribonucleoprotein complex that promoted translational silencing in gamma interferon (IFN-γ)-activated myeloid cells. However, RNA-protein interaction studies revealed that this complex, which we named VAIT (respiratory syncytial virus-activated inhibitor of translation) is functionally different from the GAIT complex. VAIT is the first report of an extraribosomal L13a-mediated, IFN-γ-independent innate antiviral complex triggered in response to virus infection. We provide a model in which the VAIT complex strongly hinders RSV replication by inhibiting the translation of the rate-limiting viral M protein, which is a new paradigm in antiviral defense.
IMPORTANCE The innate immune mechanisms of host cells are diverse in nature and act as a broad-spectrum cellular defense against viruses. Here, we report a novel innate immune mechanism functioning against respiratory syncytial virus (RSV), in which the cellular ribosomal protein L13a is released from the large ribosomal subunit soon after infection and inhibits the translation of a specific viral mRNA, namely, that of the matrix protein M. Regarding its mechanism, we show that the recognition of a specific secondary structure in the 3′ untranslated region of the M mRNA leads to translational arrest of the mRNA. We also show that the level of M protein in the infected cell is rate limiting for viral morphogenesis, providing a rationale for L13a to target the M mRNA for suppression of RSV growth. Translational silencing of a viral mRNA by a deployed ribosomal protein is a new paradigm in innate immunity.
PMCID: PMC4136244  PMID: 24899178
13.  Personalization of cancer treatment using predictive simulation 
The personalization of cancer treatments implies the reconsideration of a one-size-fits-all paradigm. This move has spawned increased use of next generation sequencing to understand mutations and copy number aberrations in cancer cells. Initial personalization successes have been primarily driven by drugs targeting one patient-specific oncogene (e.g., Gleevec, Xalkori, Herceptin). Unfortunately, most cancers include a multitude of aberrations, and the overall impact on cancer signaling and metabolic networks cannot be easily nullified by a single drug.
We used a novel predictive simulation approach to create an avatar of patient cancer cells using point mutations and copy number aberration data. Simulation avatars of myeloma patients were functionally screened using various molecularly targeted drugs both individually and in combination to identify drugs that are efficacious and synergistic. Repurposing of drugs that are FDA-approved or under clinical study with validated clinical safety and pharmacokinetic data can provide a rapid translational path to the clinic. High-risk multiple myeloma patients were modeled, and the simulation predictions were assessed ex vivo using patient cells.
Here, we present an approach to address the key challenge of interpreting patient profiling genomic signatures into actionable clinical insights to make the personalization of cancer therapy a practical reality. Through the rational design of personalized treatments, our approach also targets multiple patient-relevant pathways to address the emergence of single therapy resistance. Our predictive platform identified drug regimens for four high-risk multiple myeloma patients. The predicted regimes were found to be effective in ex vivo analyses using patient cells.
These multiple validations confirm this approach and methodology for the use of big data to create personalized therapeutics using predictive simulation approaches.
Electronic supplementary material
The online version of this article (doi:10.1186/s12967-015-0399-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4320499  PMID: 25638213
Multiple myeloma; Rational drug design; Personalized therapy
14.  Impact on inequities in health indicators: Effect of implementing the integrated management of neonatal and childhood illness programme in Haryana, India 
Journal of Global Health  null;5(1):010401.
A trial to evaluate the Integrated Management of Neonatal and Childhood Illness (IMNCI) strategy showed that the intervention resulted in lower infant mortality and improved infant care practices. In this paper, we present the results of a secondary analysis to examine the effect of the IMNCI strategy on inequities in health indicators.
The trial was a cluster–randomized controlled trial in 18 primary health centre areas. For this analysis, the population was divided into subgroups by wealth status (using Principal Component Analysis), religion and caste, education of mother and sex of the infant. Multiple linear regression analysis was used to examine inequity gradients in neonatal and post–neonatal mortality, care practices and care seeking, and the differences in these gradients between intervention and control clusters.
Inequity in post–neonatal infant mortality by wealth status was lower in the intervention as compared to control clusters (adjusted difference in gradients 2.2 per 1000, 95% confidence interval (CI) 0 to 4.4 per 1000, P = 0.053). The intervention had no effect on inequities in neonatal mortality. The intervention resulted in a larger effect on breastfeeding within one hour of birth in poorer families (difference in inequity gradients 3.0%, CI 1.5 to 4.5, P < 0.001), in lower caste and minorities families, and in infants of mothers with fewer years of schooling. The intervention also reduced gender inequity in care seeking for severe neonatal illness from an appropriate provider (difference in inequity gradients 9.3%, CI 0.4 to 18.2, P = 0.042).
Implementation of IMNCI reduced inequities in post–neonatal mortality, and newborn care practices (particularly starting breastfeeding within an hour of birth) and health care–seeking for severe illness. In spite of the intervention substantial inequities remained in the intervention group and therefore further efforts to ensure that health programs reach the vulnerable population subgroups are required.
Trial Registration NCT00474981; ICMR Clinical Trial Registry CTRI/2009/091/000715
PMCID: PMC4306296
15.  SparseNet: Coordinate Descent With Nonconvex Penalties 
We address the problem of sparse selection in linear models. A number of nonconvex penalties have been proposed in the literature for this purpose, along with a variety of convex-relaxation algorithms for finding good solutions. In this article we pursue a coordinate-descent approach for optimization, and study its convergence properties. We characterize the properties of penalties suitable for this approach, study their corresponding threshold functions, and describe a df-standardizing reparametrization that assists our pathwise algorithm. The MC+ penalty is ideally suited to this task, and we use it to demonstrate the performance of our algorithm. Certain technical derivations and experiments related to this article are included in the Supplementary Materials section.
PMCID: PMC4286300  PMID: 25580042
Degrees of freedom; LASSO; Nonconvex optimization; Regularization surface; Sparse regression; Variable selection
16.  The graphical lasso: New insights and alternatives 
The graphical lasso [5] is an algorithm for learning the structure in an undirected Gaussian graphical model, using ℓ1 regularization to control the number of zeros in the precision matrix Θ = Σ−1 [2, 11]. The R package GLASSO [5] is popular, fast, and allows one to efficiently build a path of models for different values of the tuning parameter. Convergence of GLASSO can be tricky; the converged precision matrix might not be the inverse of the estimated covariance, and occasionally it fails to converge with warm starts. In this paper we explain this behavior, and propose new algorithms that appear to outperform GLASSO.
By studying the “normal equations” we see that, GLASSO is solving the dual of the graphical lasso penalized likelihood, by block coordinate ascent; a result which can also be found in [2]. In this dual, the target of estimation is Σ, the covariance matrix, rather than the precision matrix Θ. We propose similar primal algorithms P-GLASSO and DP-GLASSO, that also operate by block-coordinate descent, where Θ is the optimization target. We study all of these algorithms, and in particular different approaches to solving their coordinate sub-problems. We conclude that DP-GLASSO is superior from several points of view.
PMCID: PMC4281944  PMID: 25558297
Graphical lasso; sparse inverse covariance selection; precision matrix; convex analysis/optimization; positive definite matrices; sparsity; semidefinite programming
17.  Assessment of Insulin Resistance and Metabolic Syndrome in Drug Naive Patients of Bipolar Disorder 
The levels of fasting glucose, fasting insulin, insulin resistance (IR) and the prevalence of metabolic syndrome (MS) in a sample population of bipolar disorder (BPD) patients who were newly diagnosed and psychotropically naïve were assessed and compared with an age, sex and racially matched control population. 55 BPD-I patients (15–65 years) who were non-diabetic, nonpregnant, and drug naïve for a period of at least 6 months were included in the study. Diagnosis was made using the structured clinical interview for DSM-IV axis I disorders (SCID IV). IR was assessed using homeostasis model of insulin resistance (HOMA-IR); MS was defined according to National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Data were compared with 25 healthy controls. BPD patients had significantly higher mean levels of fasting plasma insulin (13.2 ± 9.2 vs. 4.68 ± 3.1 μIU/ml, p < 0.05), postprandial plasma insulin (27.2 ± 14.5 vs. 18.1 ± 9.3 μIU/ml, p < 0.05) and a higher value of HOMA-IR (3.16 ± 2.2 vs. 1.19 ± 0.8, p < 0.05) when compared to the controls. A significantly higher proportion of patients of BPD compared to controls were manifesting levels of fasting plasma glucose, serum triglyceride and blood pressure higher than the cut off while waist circumference and serum HDL cholesterol failed to show any significant difference in the proportion. There was a significantly higher proportion of prevalence of IR between BPD cases and controls (26/55 vs. 2/25, z value 9.97, p < 0.05) while there was no significant difference in proportion of prevalence of MS between these two groups. Within BPD patients, logistic regression analysis showed that age, sex or current mood status (depressed/manic) were not significantly predictive of presence or absence of MS or increased IR.
PMCID: PMC3903932  PMID: 24478549
Bipolar disorder; Metabolic syndrome; Insulin resistance; HOMA-IR
18.  Massive ossifying pleomorphic adenoma of the maxillary antrum: A rare presentation 
Contemporary Clinical Dentistry  2015;6(1):139-141.
Pleomorphic adenoma is the most common benign neoplasm of salivary gland origin involving both major and minor glands. Though parotid is the most common site of origin, it has been reported to arise from various unusual locations. Incidence of its origin in the respiratory tract is extremely rare, and the occurrence is even lower in the maxillary sinus. We report a case of a huge antral pleomorphic adenoma in a 33-year-old male patient presented as a swelling in the maxilla which was mistaken of odontogenic origin. Histological findings showed extensive ossification and hyalinization of the stroma as a striking feature. The patient has undergone hemimaxillectomy and is in 8 months follow-up without any sign and symptom of recurrence.
PMCID: PMC4319336
Maxillary antrum; ossification; pleomorphic adenoma
19.  Crystal Structure of Calcium Binding Protein-5 from Entamoeba histolytica and Its Involvement in Initiation of Phagocytosis of Human Erythrocytes 
PLoS Pathogens  2014;10(12):e1004532.
Entamoeba histolytica is the etiological agent of human amoebic colitis and liver abscess, and causes a high level of morbidity and mortality worldwide, particularly in developing countries. There are a number of studies that have shown a crucial role for Ca2+ and its binding protein in amoebic biology. EhCaBP5 is one of the EF hand calcium-binding proteins of E. histolytica. We have determined the crystal structure of EhCaBP5 at 1.9 Å resolution in the Ca2+-bound state, which shows an unconventional mode of Ca2+ binding involving coordination to a closed yet canonical EF-hand motif. Structurally, EhCaBP5 is more similar to the essential light chain of myosin than to Calmodulin despite its somewhat greater sequence identity with Calmodulin. This structure-based analysis suggests that EhCaBP5 could be a light chain of myosin. Surface plasmon resonance studies confirmed this hypothesis, and in particular showed that EhCaBP5 interacts with the IQ motif of myosin 1B in calcium independent manner. It also appears from modelling of the EhCaBP5-IQ motif complex that EhCaBP5 undergoes a structural change in order to bind the IQ motif of myosin. This specific interaction was further confirmed by the observation that EhCaBP5 and myosin 1B are colocalized in E. histolytica during phagocytic cup formation. Immunoprecipitation of EhCaBP5 from total E. histolytica cellular extract also pulls out myosin 1B and this interaction was confirmed to be Ca2+ independent. Confocal imaging of E. histolytica showed that EhCaBP5 and myosin 1B are part of phagosomes. Overexpression of EhCaBP5 increases slight rate (∼20%) of phagosome formation, while suppression reduces the rate drastically (∼55%). Taken together, these experiments indicate that EhCaBP5 is likely to be the light chain of myosin 1B. Interestingly, EhCaBP5 is not present in the phagosome after its formation suggesting EhCaBP5 may be playing a regulatory role.
Author Summary
Entamoeba histolytica is the etiologic agent of amoebiasis, a major cause of morbidity and mortality in developing countries. The genome of this organism encodes 27 EF-hand containing calcium binding proteins suggesting an intricate Ca2+ signalling system that plays crucial role in phagocytosis and pathogenesis. Calcium binding protein-5 (EhCaBP5) is one of these CaBPs that displays sequence similarity with Calmodulin (CaM) but has only two possible calcium binding EF-hand loops in two separate domains. Interestingly crystal structure of EhCaPB5 showed more structural similarity with essential light chain (ELC) of myosin than that of CaM. The binding studies of EhCaBP5 with IQ motif peptides of myosins, showed that it interacts with IQ motif of unconventional Myosin IB. A number of experiments were carried out to show that EhCaBP5 indeed binds myosin IB and that this binding is Ca2+ independent. We also show here that EhCaBP5 participates in erythrophagocytosis and that its role in phagocytosis is different from that of EhCaBP3, another myosin 1B interacting calcium binding protein of E. histolytica. Our results presented here and in a number of other reports point towards a unique phagocytic pathway involving a number of calcium binding proteins in E. histolytica.
PMCID: PMC4263763  PMID: 25502654
20.  Paediatric cerebrovascular CT angiography—towards better image quality 
Paediatric cerebrovascular CT angiography (CTA) can be challenging to perform due to variable cardiovascular physiology between different age groups and the risk of movement artefact. This analysis aimed to determine what proportion of CTA at our institution was of diagnostic quality and identify technical factors which could be improved.
Materials and methods
a retrospective analysis of 20 cases was performed at a national paediatric neurovascular centre assessing image quality with a subjective scoring system and Hounsfield Unit (HU) measurements. Demographic data, contrast dose, flow rate and triggering times were recorded for each patient.
Using a qualitative scoring system, 75% of studies were found to be of diagnostic quality (n=9 ‘good’, n=6 ‘satisfactory’) and 25% (n=5) were ‘poor’. Those judged subjectively to be poor had arterial contrast density measured at less than 250 HU. Increased arterial opacification was achieved for cases performed with an increased flow rate (2.5-4 mL/s) and higher intravenous contrast dose (2 mL/kg). Triggering was found to be well timed in nine cases, early in four cases and late in seven cases. Of the scans triggered early, 75% were poor. Of the scans triggered late, less (29%) were poor.
High flow rates (>2.5 mL/s) were a key factor for achieving high quality paediatric cerebrovascular CTA imaging. However, appropriate triggering by starting the scan immediately on contrast opacification of the monitoring vessel plays an important role and could maintain image quality when flow rates were lower. Early triggering appeared more detrimental than late.
PMCID: PMC4256249  PMID: 25525579
CT angiography (CTA); neurosurgery; paediatric angiography; paediatric neuroradiology
21.  High-Performance Integrated Virtual Environment (HIVE) Tools and Applications for Big Data Analysis 
Genes  2014;5(4):957-981.
The High-performance Integrated Virtual Environment (HIVE) is a high-throughput cloud-based infrastructure developed for the storage and analysis of genomic and associated biological data. HIVE consists of a web-accessible interface for authorized users to deposit, retrieve, share, annotate, compute and visualize Next-generation Sequencing (NGS) data in a scalable and highly efficient fashion. The platform contains a distributed storage library and a distributed computational powerhouse linked seamlessly. Resources available through the interface include algorithms, tools and applications developed exclusively for the HIVE platform, as well as commonly used external tools adapted to operate within the parallel architecture of the system. HIVE is composed of a flexible infrastructure, which allows for simple implementation of new algorithms and tools. Currently, available HIVE tools include sequence alignment and nucleotide variation profiling tools, metagenomic analyzers, phylogenetic tree-building tools using NGS data, clone discovery algorithms, and recombination analysis algorithms. In addition to tools, HIVE also provides knowledgebases that can be used in conjunction with the tools for NGS sequence and metadata analysis.
PMCID: PMC4276921  PMID: 25271953
big data; bioinformatics; high-performance cloud computing; high-throughput sequencing; next-generation sequencing; genomics
22.  Molecular Characterization of Legionellosis Drug Target Candidate Enzyme Phosphoglucosamine Mutase from Legionella pneumophila (strain Paris): An In Silico Approach 
Genomics & Informatics  2014;12(4):268-275.
The harshness of legionellosis differs from mild Pontiac fever to potentially fatal Legionnaire's disease. The increasing development of drug resistance against legionellosis has led to explore new novel drug targets. It has been found that phosphoglucosamine mutase, phosphomannomutase, and phosphoglyceromutase enzymes can be used as the most probable therapeutic drug targets through extensive data mining. Phosphoglucosamine mutase is involved in amino sugar and nucleotide sugar metabolism. The purpose of this study was to predict the potential target of that specific drug. For this, the 3D structure of phosphoglucosamine mutase of Legionella pneumophila (strain Paris) was determined by means of homology modeling through Phyre2 and refined by ModRefiner. Then, the designed model was evaluated with a structure validation program, for instance, PROCHECK, ERRAT, Verify3D, and QMEAN, for further structural analysis. Secondary structural features were determined through self-optimized prediction method with alignment (SOPMA) and interacting networks by STRING. Consequently, we performed molecular docking studies. The analytical result of PROCHECK showed that 95.0% of the residues are in the most favored region, 4.50% are in the additional allowed region and 0.50% are in the generously allowed region of the Ramachandran plot. Verify3D graph value indicates a score of 0.71 and 89.791, 1.11 for ERRAT and QMEAN respectively. Arg419, Thr414, Ser412, and Thr9 were found to dock the substrate for the most favorable binding of S-mercaptocysteine. However, these findings from this current study will pave the way for further extensive investigation of this enzyme in wet lab experiments and in that way assist drug design against legionellosis.
PMCID: PMC4330265
docking analysis; drug delivery systems; homology modeling; Legionella pneumophila; legionellosis
23.  Protocol for the economic evaluation of the diarrhea alleviation through zinc and oral rehydration salt therapy at scale through private and public providers in rural Gujarat and Uttar Pradesh, India 
Child diarrhea persists as a leading public health problem in India despite evidence supporting zinc and low osmolarity oral rehydration salts as effective treatments. Across 2 years in 2010–2013, the Diarrhea Alleviation using Zinc and Oral Rehydration Salts Therapy (DAZT) program was implemented to operationalize delivery of these interventions at scale through private and public sector providers in rural Gujarat and Uttar Pradesh, India.
This study evaluates the cost-effectiveness of DAZT program activities relative to status quo conditions existing before the study, comparing a Monte Carlo simulation method with net-benefit regression, discussing the strengths and weaknesses of each approach. A control group was not included in the ‘before and after’ study design as zinc has proven effectiveness for diarrhea treatment. Costs will be calculated using a societal perspective including program implementation and household out-of-pocket payments for care seeking, as well as estimates of wages lost. Outcomes will be measured in terms of episodes averted in net-benefit regression and in terms of the years of life lost component of disability-adjusted life years in the method based on Monte Carlo simulation. The Lives Saved Tool will be used to model anticipated changes in mortality over time and deaths averted based on incremental changes in coverage of oral rehydration salts and zinc. Data will derive from cross-sectional surveys at the start, midpoint, and endpoint of the program. In addition, Lives Saved Tool (LiST) projections will be used to define the reference case value for the ceiling ratio in terms of natural units.
This study will be useful both in its application to an economic evaluation of a public health program in its implementation phase but also in its comparison of two methodological approaches to cost-effectiveness analysis. Both policy recommendations and methodological lessons learned will be discussed, recognizing the limitations in drawing strong policy conclusions due to the uncontrolled study design. It is expected that this protocol will be useful to researchers planning what method to use for the evaluation of similar before and after studies.
PMCID: PMC4335371  PMID: 25407053
Diarrhea; Zinc; Cost-effectiveness; Implementation science; India; Private sector; Community health
24.  Exact Covariance Thresholding into Connected Components for Large-Scale Graphical Lasso 
We consider the sparse inverse covariance regularization problem or graphical lasso with regularization parameter λ. Suppose the sample covariance graph formed by thresholding the entries of the sample covariance matrix at λ is decomposed into connected components. We show that the vertex-partition induced by the connected components of the thresholded sample covariance graph (at λ) is exactly equal to that induced by the connected components of the estimated concentration graph, obtained by solving the graphical lasso problem for the same λ. This characterizes a very interesting property of a path of graphical lasso solutions. Furthermore, this simple rule, when used as a wrapper around existing algorithms for the graphical lasso, leads to enormous performance gains. For a range of values of λ, our proposal splits a large graphical lasso problem into smaller tractable problems, making it possible to solve an otherwise infeasible large-scale problem. We illustrate the graceful scalability of our proposal via synthetic and real-life microarray examples.
PMCID: PMC4225650  PMID: 25392704
sparse inverse covariance selection; sparsity; graphical lasso; Gaussian graphical models; graph connected components; concentration graph; large scale covariance estimation
25.  Census-based rapid and accurate metagenome taxonomic profiling 
BMC Genomics  2014;15(1):918.
Understanding the taxonomic composition of a sample, whether from patient, food or environment, is important to several types of studies including pathogen diagnostics, epidemiological studies, biodiversity analysis and food quality regulation. With the decreasing costs of sequencing, metagenomic data is quickly becoming the preferred typed of data for such analysis.
Rapidly defining the taxonomic composition (both taxonomic profile and relative frequency) in a metagenomic sequence dataset is challenging because the task of mapping millions of sequence reads from a metagenomic study to a non-redundant nucleotide database such as the NCBI non-redundant nucleotide database (nt) is a computationally intensive task. We have developed a robust subsampling-based algorithm implemented in a tool called CensuScope meant to take a ‘sneak peak’ into the population distribution and estimate taxonomic composition as if a census was taken of the metagenomic landscape. CensuScope is a rapid and accurate metagenome taxonomic profiling tool that randomly extracts a small number of reads (based on user input) and maps them to NCBI’s nt database. This process is repeated multiple times to ascertain the taxonomic composition that is found in majority of the iterations, thereby providing a robust estimate of the population and measures of the accuracy for the results.
CensuScope can be run on a laptop or on a high-performance computer. Based on our analysis we are able to provide some recommendations in terms of the number of sequence reads to analyze and the number of iterations to use. For example, to quantify taxonomic groups present in the sample at a level of 1% or higher a subsampling size of 250 random reads with 50 iterations yields a statistical power of >99%. Windows and UNIX versions of CensuScope are available for download at CensuScope is also available through the High-performance Integrated Virtual Environment (HIVE) and can be used in conjunction with other HIVE analysis and visualization tools.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-918) contains supplementary material, which is available to authorized users.
PMCID: PMC4218995  PMID: 25336203
Metagenome; Census-based; Next-gen sequence analysis; Taxonomic profiling; Diagnostics

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