Search results for: Santosh Thapa
Commenced in January 2007
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Edition: International
Paper Count: 71

Search results for: Santosh Thapa

11 Metaphysics of the Unified Field of the Universe

Authors: Santosh Kaware, Dnyandeo Patil, Moninder Modgil, Hemant Bhoir, Debendra Behera

Abstract:

The Unified Field Theory has been an area of intensive research since many decades. This paper focuses on philosophy and metaphysics of unified field theory at Planck scale - and its relationship with super string theory and Quantum Vacuum Dynamic Physics. We examined the epistemology of questions such as - (1) what is the Unified Field of universe? (2) can it actually - (a) permeate the complete universe - or (b) be localized in bound regions of the universe - or, (c) extend into the extra dimensions? - -or (d) live only in extra dimensions? (3) What should be the emergent ontological properties of Unified field? (4) How the universe is manifesting through its Quantum Vacuum energies? (5) How is the space time metric coupled to the Unified field? We present a number of ansatz - which we outline below. It is proposed that the unified field possesses consciousness as well as a memory - a recording of past history - analogous to ‘Consistent Histories’ interpretation of quantum mechanics. We proposed Planck scale geometry of Unified Field with circle like topology and having 32 energy points on its periphery which are the connected to each other by 10 dimensional meta-strings which are sources for manifestation of different fundamentals forces and particles of universe through its Quantum Vacuum energies. It is also proposed that the sub energy levels of ‘Conscious Unified Field’ are used for the process of creation, preservation and rejuvenation of the universe over a period of time by means of negentropy. These epochs can be for the complete universe, or for localized regions such as galaxies or cluster of galaxies. It is proposed that Unified field operates through geometric patterns of its Quantum Vacuum energies - manifesting as various elementary particles by giving spins to zero point energy elements. Epistemological relationship between unified field theory and super-string theories is examined. Properties of ‘consciousness’ and 'memory' cascades from universe, into macroscopic objects - and further onto the elementary particles - via a fractal pattern. Other properties of fundamental particles - such as mass, charge, spin, iso-spin also spill out of such a cascade. The manifestations of the unified field can reach into the parallel universes or the ‘multi-verse’ and essentially have an existence independent of the space-time. It is proposed that mass, length, time scales of the unified theory are less than even the Planck scale - and can be called at a level which we call that of 'Super Quantum Gravity (SQG)'.

Keywords: super string theory, Planck scale geometry, negentropy, super quantum gravity

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10 Smart Irrigation Systems and Website: Based Platform for Farmer Welfare

Authors: Anusha Jain, Santosh Vishwanathan, Praveen K. Gupta, Shwetha S., Kavitha S. N.

Abstract:

Agriculture has a major impact on the Indian economy, with the highest employment ratio than any sector of the country. Currently, most of the traditional agricultural practices and farming methods are manual, which results in farmers not realizing their maximum productivity often due to increasing in labour cost, inefficient use of water sources leading to wastage of water, inadequate soil moisture content, subsequently leading to food insecurity of the country. This research paper aims to solve this problem by developing a full-fledged web application-based platform that has the capacity to associate itself with a Microcontroller-based Automated Irrigation System which schedules the irrigation of crops based on real-time soil moisture content employing soil moisture sensors centric to the crop’s requirements using WSN (Wireless Sensor Networks) and M2M (Machine To Machine Communication) concepts, thus optimizing the use of the available limited water resource, thereby maximizing the crop yield. This robust automated irrigation system provides end-to-end automation of Irrigation of crops at any circumstances such as droughts, irregular rainfall patterns, extreme weather conditions, etc. This platform will also be capable of achieving a nationwide united farming community and ensuring the welfare of farmers. This platform is designed to equip farmers with prerequisite knowledge on tech and the latest farming practices in general. In order to achieve this, the MailChimp mailing service is used through which interested farmers/individuals' email id will be recorded and curated articles on innovations in the world of agriculture will be provided to the farmers via e-mail. In this proposed system, service is enabled on the platform where nearby crop vendors will be able to enter their pickup locations, accepted prices and other relevant information. This will enable farmers to choose their vendors wisely. Along with this, we have created a blogging service that will enable farmers and agricultural enthusiasts to share experiences, helpful knowledge, hardships, etc., with the entire farming community. These are some of the many features that the platform has to offer.

Keywords: WSN (wireless sensor networks), M2M (M/C to M/C communication), automation, irrigation system, sustainability, SAAS (software as a service), soil moisture sensor

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9 Characterisation of Meteorological Drought at Sub-Catchment Scale in Afghanistan Using Time-Series Climate Data

Authors: Yun Chen, David Penton, Fazlul Karim, Santosh Aryal, Shahriar Wahid, Peter Taylor, Susan M. Cuddy

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Droughts have severely affected Afghanistan over the last four decades, leading to critical food shortages where two-thirds of the country’s population are in a food crisis. Long years of conflict have lowered the country’s ability to deal with hazards such as drought, which can rapidly escalate into disasters. Understanding the spatial and temporal distribution of droughts is needed to be able to respond effectively to disasters and plan for future occurrences. This study used Standardized Precipitation Evapotranspiration Index (SPEI) at monthly, seasonal, and annual temporal scales to map the spatiotemporal change dynamics of drought characteristics (distribution, frequency, duration, and severity) in Afghanistan. SPEI indices were mapped for river basins, disaggregated into 189 sub-catchments, using monthly precipitation and potential evapotranspiration derived from temperature station observations from 1980 to 2017. The results show these multi-dimensional drought characteristics vary along different years, change among sub-catchments, and differ across temporal scales. During the 38 years, the driest decade and period are the 2000s and 1999–2022, respectively. The 2000–01 water year is the driest, with the whole country experiencing ‘severe’ to ‘extreme’ drought, more than 53% (87 sub-catchments) suffering the worst drought in history, and about 58% (94 sub-catchments) having ‘very frequent’ drought (7 to 8 months) or ‘extremely frequent’ drought (9 to 10 months). The estimated seasonal duration and severity present significant variations across the study area and throughout the study period. The nation also suffered from recurring droughts with varying length and intensity in 2004, 2006, 2008, and, most recently, 2011. There is a trend towards increasing drought with longer duration and higher severity extending all over sub-catchments from southeast to north and central regions. These datasets and maps help to fill the knowledge gap on detailed sub-catchment scale meteorological drought characteristics in Afghanistan. The study findings improve our understanding of the influences of climate change on drought dynamics and can guide catchment planning for reliable adaptation to and mitigation against future droughts.

Keywords: SPEI, precipitation, evapotranspiration, climate extremes

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8 Adjustment with Changed Lifestyle at Old Age Homes: A Perspective of Elderly in India

Authors: Priyanka V. Janbandhu, Santosh B. Phad, Dhananjay W. Bansod

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The current changing scenario of the family is a compelling aged group not only to be alone in a nuclear family but also to join the old age institutions. The consequences of it are feeling of neglected or left alone by the children, adding a touch of helpless in the absence of lack of expected care and support. The accretion of all these feelings and unpleasant events ignite a question in their mind that – who is there for me? The efforts have taken to highlight the issues of the elderly after joining the old age home and their perception about the current life as an institutional inmate. This attempt to cover up the condition, adjustment, changed lifestyle and perspective in the association with several issues of the elderly, which have an essential effect on their well-being. The present research piece has collected the information about institutionalized elderly with the help of a semi-structured questionnaire. This study interviewed 500 respondents from 22 old age homes of Pune city of Maharashtra State, India. This data collection methodology consists of Multi-stage random sampling. In which the stratified random sampling adopted for the selection of old age homes and sample size determination, sample selection probability proportional to the size and simple random sampling techniques implemented. The study provides that around five percent of the elderly shifted to old age home along with their spouse, whereas ten percent of the elderly are staying away from their spouse. More than 71 percent of the elderly have children, and they are an involuntary inmate of the old age institution, even less than one-third of the elderly consulted to the institution before the joining it. More than sixty percent of the elderly have children, but they joined institution due to the unpleasant response of their children only. Around half of the elderly responded that there are issues while adjusting to this environment, many of them are still persistent. At least one elderly out of ten is there who is suffering from the feeling of loneliness and left out by children and other family members. In contrast, around 97 percent of the elderly are very happy or satisfied with the institutional facilities. It illustrates that the issues are associated with their children and other family members, even though they left their home before a year or more. When enquired about this loneliness feeling few of them are suffering from it before leaving their homes, it was due to lack of interaction with children, as they are too busy to have time for the aged parents. Additionally, the conflicts or fights within the family due to the presence of old persons in the family contributed to establishing another feeling of insignificance among the elderly parents. According to these elderly, have more than 70 percent of the share, the children are ready to spend money indirectly for us through these institutions, but not prepared to provide some time and very few amounts of all this expenditure directly for us.

Keywords: elderly, old age homes, life style changes and adjustment, India

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7 Development of a Bioprocess Technology for the Production of Vibrio midae, a Probiotic for Use in Abalone Aquaculture

Authors: Ghaneshree Moonsamy, Nodumo N. Zulu, Rajesh Lalloo, Suren Singh, Santosh O. Ramchuran

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The abalone industry of South Africa is under severe pressure due to illegal harvesting and poaching of this seafood delicacy. These abalones are harvested excessively; as a result, these animals do not have a chance to replace themselves in their habitats, ensuing in a drastic decrease in natural stocks of abalone. Abalone has an extremely slow growth rate and takes approximately four years to reach a size that is market acceptable; therefore, it was imperative to investigate methods to boost the overall growth rate and immunity of the animal. The University of Cape Town (UCT) began to research, which resulted in the isolation of two microorganisms, a yeast isolate Debaryomyces hansenii and a bacterial isolate Vibrio midae, from the gut of the abalone and characterised them for their probiotic abilities. This work resulted in an internationally competitive concept technology that was patented. The next stage of research was to develop a suitable bioprocess to enable commercial production. Numerous steps were taken to develop an efficient production process for V. midae, one of the isolates found by UCT. The initial stages of research involved the development of a stable and robust inoculum and the optimization of physiological growth parameters such as temperature and pH. A range of temperature and pH conditions were evaluated, and data obtained revealed an optimum growth temperature of 30ᵒC and a pH of 6.5. Once these critical growth parameters were established further media optimization studies were performed. Corn steep liquor (CSL) and high test molasses (HTM) were selected as suitable alternatives to more expensive, conventionally used growth medium additives. The optimization of CSL (6.4 g.l⁻¹) and HTM (24 g.l⁻¹) concentrations in the growth medium resulted in a 180% increase in cell concentration, a 5716-fold increase in cell productivity and a 97.2% decrease in the material cost of production in comparison to conventional growth conditions and parameters used at the onset of the study. In addition, a stable market-ready liquid probiotic product, encompassing the viable but not culturable (VBNC) state of Vibrio midae cells, was developed during the downstream processing aspect of the study. The demonstration of this technology at a full manufacturing scale has further enhanced the attractiveness and commercial feasibility of this production process.

Keywords: probiotics, abalone aquaculture, bioprocess technology, manufacturing scale technology development

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6 Particle Separation Using Individually-Controlled Magnetic Soft Artificial Cilia

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

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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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5 Lessons Learned from Implementation of Remote Pregnant and Newborn Care Service for Vulnerable Women and Children During COVID-19 and Political Crisis in Myanmar

Authors: Wint Wint Thu, Htet Ko Ko Win, Myat Mon San, Zaw Lin Tun, Nandar Than Aye, Khin Nyein Myat, Hayman Nyo Oo, Nay Aung Lin, Kusum Thapa, Kyaw Htet Aung

Abstract:

Background: In Myanmar, the intense political instability happened to start in Feb-2021, while the COVID-19 pandemic waves are also threatening the public health system, which subsequently led to severe health sector crisis, including difficulties in accessing maternal and newborn health care for vulnerable women and children. The Remote Pregnant and Newborn Care (RPNC) uses a telehealth approach United States Agency for International Development (USAID)-funded Essential Health Project. Implementation: The Remote Pregnant and Newborn Care (RPNC) service has adapted to the MNCH needs of vulnerable pregnant women and was implemented to mitigate the risk of limited access to essential quality MNH care in Yangon, Myanmar, under women, and the project trained 13 service providers on a telehealth care package for pregnancy and newborn developed Jhpiego to ensure understanding of evidence-based MNCH care practices. The phone numbers of the pregnant women were gathered through the preexisting and functioning community volunteers, who reach the most vulnerable pregnant women in the project's targeted area. A total of 212 pregnant women have been reached by service providers for RPNC during the implementation period. The trained service providers offer quality antenatal and postnatal care, including newborn care, via telephone calls. It includes 24/7 incoming calls and time-allotted outgoing calls to the pregnant women during antenatal and postnatal periods, including the newborn care. The required data were collected daily in time with the calls, and the quality of the medical services is made assured with the track of the calls, ensuring data privacy and patient confidentiality. Lessons learned: The key lessons are 1) cost-effectiveness: RPNC service could reduce out of pocket expenditure of pregnant women as it only costs 1.6 United States dollars (USD) per one telehealth call while it costs 8 to 10 USD per one time in-person care service at private service providers, including transportation cost, 2) network of care: telehealth call could not replace the in-person antenatal and postnatal care services, and integration of telehealth calls with in-person care by local healthcare providers with the support of the community is crucial for accessibility to essential MNH services by poor and vulnerable women, and 3) sharing information on health access points: most of the women seem to have financial barriers in accessing private health facilities while public health system collapse and telehealthcare could provide information on low-cost facilities and connect women to relevant health facilities. These key lessons are important for future efforts regarding the implementation of remote pregnancy and newborn care in Myanmar, especially during the political crisis and COVID-19 pandemic situation.

Keywords: telehealth, accessibility, maternal care, newborn care

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4 Distribution and Ecological Risk Assessment of Trace Elements in Sediments along the Ganges River Estuary, India

Authors: Priyanka Mondal, Santosh K. Sarkar

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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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3 Phonological Encoding and Working Memory in Kannada Speaking Adults Who Stutter

Authors: Nirmal Sugathan, Santosh Maruthy

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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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2 Impact of Anthropogenic Stresses on Plankton Biodiversity in Indian Sundarban Megadelta: An Approach towards Ecosystem Conservation and Sustainability

Authors: Dibyendu Rakshit, Santosh K. Sarkar

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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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1 Leveraging the HDAC Inhibitory Pharmacophore to Construct Deoxyvasicinone Based Tractable Anti-Lung Cancer Agent and pH-Responsive Nanocarrier

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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