Search results for: Santosh Prajapati

Authors: Yau-Luen Ng, Nathan Banka, Santosh Devasia

Abstract:

In this paper, a method based on soft artificial cilia is introduced to separate particles based on size and mass. In nature, cilia are used for fluid propulsion in the mammalian circulatory system, as well as for swimming and size-selective particle entrainment for feeding in microorganisms. Inspired by biological cilia, an array of artificial cilia was fabricated using Polydimethylsiloxane (PDMS) to simulate the actual motion. A row of four individually-controlled magnetic artificial cilia in a semi-circular channel are actuated by the magnetic fields from four permanent magnets. Each cilium is a slender rectangular cantilever approximately 13mm long made from a composite of PDMS and carbonyl iron particles. A time-varying magnetic force is achieved by periodically varying the out-of-plane distance from the permanent magnets to the cilia, resulting in large-amplitude deflections of the cilia that can be used to drive fluid motion. Previous results have shown that this system of individually-controlled magnetic cilia can generate effective mixing flows; the purpose of the present work is to apply the individual cilia control to a particle separation task. Based on the observed beating patterns of cilia arrays in nature, the experimental beating patterns were selected as a metachronal wave, in which a fixed phase lead or lag is imposed between adjacent cilia. Additionally, the beating frequency was varied. For each set of experimental parameters, the channel was filled with water and polyethylene microspheres introduced at the center of the cilia array. Two types of particles were used: large red microspheres with density 0.9971 g/cm³ and 850-1000 μm avg. diameter, and small blue microspheres with density 1.06 g/cm³ and diameter 30 μm. At low beating frequencies, all particles were propelled in the mean flow direction. However, the large particles were observed to reverse directions above about 4.8 Hz, whereas reversal of the small particle transport direction did not occur until 6 Hz. Between these two transition frequencies, the large and small particles can be separated as they move in opposite directions. The experimental results show that selecting an appropriate cilia beating pattern can lead to selective transport of neutrally-buoyant particles based on their size. Importantly, the separation threshold can be chosen dynamically by adjusting the actuation frequency. However, further study is required to determine the range of particle sizes that can be effectively separated for a given system geometry.

Keywords: magnetic cilia, particle separation, tunable separation, soft actutors

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Authors: Bhupendra G. Prajapati, Alpesh R. Patel

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The aim of this research work is to develop sustained release multi-particulates dosage form of Dexketoprofen trometamol, which is the pharmacologically active isomer of ketoprofen. The objective is to utilization of active enantiomer with minimal dose and administration frequency, extended release multi-particulates dosage form development for better patience compliance was explored. Drug loaded and sustained release coated pellets were prepared by fluidized bed coating principle by wurster coater. Microcrystalline cellulose as core pellets, povidone as binder and talc as anti-tacking agents were selected during drug loading while Kollicoat SR 30D as sustained release polymer, triethyl citrate as plasticizer and micronized talc as an anti-adherent were used in sustained release coating. Binder optimization trial in drug loading showed that there was increase in process efficiency with increase in the binder concentration. 5 and 7.5%w/w concentration of Povidone K30 with respect to drug amount gave more than 90% process efficiency while higher amount of rejects (agglomerates) were observed for drug layering trial batch taken with 7.5% binder. So for drug loading, optimum Povidone concentration was selected as 5% of drug substance quantity since this trial had good process feasibility and good adhesion of the drug onto the MCC pellets. 2% w/w concentration of talc with respect to total drug layering solid mass shows better anti-tacking property to remove unnecessary static charge as well as agglomeration generation during spraying process. Optimized drug loaded pellets were coated for sustained release coating from 16 to 28% w/w coating to get desired drug release profile and results suggested that 22% w/w coating weight gain is necessary to get the required drug release profile. Three critical process parameters of Wurster coating for sustained release were further statistically optimized for desired quality target product profile attributes like agglomerates formation, process efficiency, and drug release profile using central composite design (CCD) by Minitab software. Results show that derived design space consisting 1.0 to 1.2 bar atomization air pressure, 7.8 to 10.0 gm/min spray rate and 29-34°C product bed temperature gave pre-defined drug product quality attributes. Scanning Image microscopy study results were also dictate that optimized batch pellets had very narrow particle size distribution and smooth surface which were ideal properties for reproducible drug release profile. The study also focused on optimized dexketoprofen trometamol pellets formulation retain its quality attributes while administering with common vehicle, a liquid (water) or semisolid food (apple sauce). Conclusion: Sustained release multi-particulates were successfully developed for dexketoprofen trometamol which may be useful to improve acceptability and palatability of a dosage form for better patient compliance.

Keywords: dexketoprofen trometamol, pellets, fluid bed technology, central composite design

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Authors: Priyanka Mondal, Santosh K. Sarkar

Abstract:

The present study investigated the spatiotemporal distribution and ecological risk assessment of trace elements of surface sediments (top 0 - 5 cm; grain size ≤ 0.63 µm) in relevance to sediment quality characteristics along the Ganges River Estuary, India. Sediment samples were collected during ebb tide from intertidal regions covering seven sampling sites of diverse environmental stresses. The elements were analyzed with the help of ICPAES. This positive, mixohaline, macro-tidal estuary has global significance contributing ecological and economic services. Presence of fine-clayey particle (47.03%) enhances the adsorption as well as transportation of trace elements. There is a remarkable inter-metallic variation (mg kg-1 dry weight) in the distribution pattern in the following manner: Al (31801± 15943) > Fe (23337± 7584) > Mn (461±147) > S(381±235) > Zn(54 ±18) > V(43 ±14) > Cr(39 ±15) > As (34±15) > Cu(27 ±11) > Ni (24 ±9) > Se (17 ±8) > Co(11 ±3) > Mo(10 ± 2) > Hg(0.02 ±0.01). An overall trend of enrichment of majority of trace elements was very much pronounced at the site Lot 8, ~ 35km upstream of the estuarine mouth. In contrast, the minimum concentration was recorded at site Gangasagar, mouth of the estuary, with high energy profile. The prevalent variations in trace element distribution are being liable for a set of cumulative factors such as hydrodynamic conditions, sediment dispersion pattern and textural variations as well as non-homogenous input of contaminants from point and non-point sources. In order to gain insight into the trace elements distribution, accumulation, and their pollution status, geoaccumulation index (Igeo) and enrichment factor (EF) were used. The Igeo indicated that surface sediments were moderately polluted with As (0.60) and Mo (1.30) and strongly contaminated with Se (4.0). The EF indicated severe pollution of Se (53.82) and significant pollution of As (4.05) and Mo (6.0) and indicated the influx of As, Mo and Se in sediments from anthropogenic sources (such as industrial and municipal sewage, atmospheric deposition, agricultural run-off, etc.). The significant role of the megacity Calcutta in relevance to the untreated sewage discharge, atmospheric inputs and other anthropogenic activities is worthwhile to mention. The ecological risk for different trace elements was evaluated using sediment quality guidelines, effects range low (ERL), and effect range median (ERM). The concentration of As, Cu and Ni at 100%, 43% and 86% of the sampling sites has exceeded the ERL value while none of the element concentration exceeded ERM. The potential ecological risk index values revealed that As at 14.3% of the sampling sites would pose relatively moderate risk to benthic organisms. The effective role of finer clay particles for trace element distribution was revealed by multivariate analysis. The authors strongly recommend regular monitoring emphasizing on accurate appraisal of the potential risk of trace elements for effective and sustainable management of this estuarine environment.

Keywords: pollution assessment, sediment contamination, sediment quality, trace elements

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Authors: Nirmal Sugathan, Santosh Maruthy

Abstract:

Background: A considerable number of studies have evidenced that phonological encoding (PE) and working memory (WM) skills operate differently in adults who stutter (AWS). In order to tap these skills, several paradigms have been employed such as phonological priming, phoneme monitoring, and nonword repetition tasks. This study, however, utilizes a word jumble paradigm to assess both PE and WM using different modalities and this may give a better understanding of phonological processing deficits in AWS. Aim: The present study investigated PE and WM abilities in conjunction with lexical access in AWS using jumbled words. The study also aimed at investigating the effect of increase in cognitive load on phonological processing in AWS by comparing the speech reaction time (SRT) and accuracy scores across various syllable lengths. Method: Participants were 11 AWS (Age range=19-26) and 11 adults who do not stutter (AWNS) (Age range=19-26) matched for age, gender and handedness. Stimuli: Ninety 3-, 4-, and 5-syllable jumbled words (JWs) (n=30 per syllable length category) constructed from Kannada words served as stimuli for jumbled word paradigm. In order to generate jumbled words (JWs), the syllables in the real words were randomly transpositioned. Procedures: To assess PE, the JWs were presently visually using DMDX software and for WM task, JWs were presented through auditory mode through headphones. The participants were asked to silently manipulate the jumbled words to form a Kannada real word and verbally respond once. The responses for both tasks were audio recorded using record function in DMDX software and the recorded responses were analyzed using PRAAT software to calculate the SRT. Results: SRT: Mann-Whitney test results demonstrated that AWS performed significantly slower on both tasks (p < 0.001) as indicated by increased SRT. Also, AWS presented with increased SRT on both the tasks in all syllable length conditions (p < 0.001). Effect of syllable length: Wilcoxon signed rank test was carried out revealed that, on task assessing PE, the SRT of 4syllable JWs were significantly higher in both AWS (Z= -2.93, p=.003) and AWNS (Z= -2.41, p=.003) when compared to 3-syllable words. However, the findings for 4- and 5-syllable words were not significant. Task Accuracy: The accuracy scores were calculated for three syllable length conditions for both PE and PM tasks and were compared across the groups using Mann-Whitney test. The results indicated that the accuracy scores of AWS were significantly below that of AWNS in all the three syllable conditions for both the tasks (p < 0.001). Conclusion: The above findings suggest that PE and WM skills are compromised in AWS as indicated by increased SRT. Also, AWS were progressively less accurate in descrambling JWs of increasing syllable length and this may be interpreted as, rather than existing as a uniform deficiency, PE and WM deficits emerge when the cognitive load is increased. AWNS exhibited increased SRT and increased accuracy for JWs of longer syllable length whereas AWS was not benefited from increasing the reaction time, thus AWS had to compromise for both SRT and accuracy while solving JWs of longer syllable length.

Keywords: adults who stutter, phonological ability, working memory, encoding, jumbled words

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Authors: Dibyendu Rakshit, Santosh K. Sarkar

Abstract:

The study illustrates a comprehensive account of large-scale changes plankton community structure in relevance to water quality characteristics due to anthropogenic stresses, mainly concerned for Annual Gangasagar Festival (AGF) at the southern tip of Sagar Island of Indian Sundarban wetland for 3-year duration (2012-2014; n=36). This prograding, vulnerable and tide-dominated megadelta has been formed in the estuarine phase of the Hooghly Estuary infested by largest continuous tract of luxurious mangrove forest, enriched with high native flora and fauna. The sampling strategy was designed to characterize the changes in plankton community and water quality considering three diverse phases, namely during festival period (January) and its pre - (December) as well as post (February) events. Surface water samples were collected for estimation of different environmental variables as well as for phytoplankton and microzooplankton biodiversity measurement. The preservation and identification techniques of both biotic and abiotic parameters were carried out by standard chemical and biological methods. The intensive human activities lead to sharp ecological changes in the context of poor water quality index (WQI) due to high turbidity (14.02±2.34 NTU) coupled with low chlorophyll a (1.02±0.21 mg m-3) and dissolved oxygen (3.94±1.1 mg l-1), comparing to pre- and post-festival periods. Sharp reduction in abundance (4140 to 2997 cells l-1) and diversity (H′=2.72 to 1.33) of phytoplankton and microzooplankton tintinnids (450 to 328 ind l-1; H′=4.31 to 2.21) was very much pronounced. The small size tintinnid (average lorica length=29.4 µm; average LOD=10.5 µm) composed of Tintinnopsis minuta, T. lobiancoi, T. nucula, T. gracilis are predominant and reached some of the greatest abundances during the festival period. Results of ANOVA revealed a significant variation in different festival periods with phytoplankton (F= 1.77; p=0.006) and tintinnid abundance (F= 2.41; P=0.022). RELATE analyses revealed a significant correlation between the variations of planktonic communities with the environmental data (R= 0.107; p= 0.005). Three distinct groups were delineated from principal component analysis, in which a set of hydrological parameters acted as the causative factor(s) for maintaining diversity and distribution of the planktonic organisms. The pronounced adverse impact of anthropogenic stresses on plankton community could lead to environmental deterioration, disrupting the productivity of benthic and pelagic ecosystems as well as fishery potentialities which directly related to livelihood services. The festival can be considered as multiple drivers of changes in relevance to beach erosion, shoreline changes, pollution from discarded plastic and electronic wastes and destruction of natural habitats resulting loss of biodiversity. In addition, deterioration in water quality was also evident from immersion of idols, causing detrimental effects on aquatic biota. The authors strongly recommend for adopting integrated scientific and administrative strategies for resilience, sustainability and conservation of this megadelta.

Keywords: Gangasagar festival, phytoplankton, Sundarban megadelta, tintinnid

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Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

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A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

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