Search results for: Parimal Karmakar
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 19

Search results for: Parimal Karmakar

19 Targeted Delivery of Novel Copper-Based Nanoparticles for Advance Cancer Therapeutics

Authors: Arindam Pramanik, Parimal Karmakar

Abstract:

We have explored the synergistic anti-cancer activity of copper ion and acetylacetone complex containing 1,3 diketone group (like curcumin) in metallorganic compound “Copper acetylacetonate” (CuAA). The cytotoxicity mechanism of CuAA complex was evaluated on various cancer cell lines in vitro. Among these, reactive oxygen species (ROS), glutathione level (GSH) in the cell was found to increase. Further mitochondrial membrane damage was observed. The fate of cell death was found to be induced by apoptosis. For application purpose, we have developed a novel biodegradable, non-toxic polymer-based nanoparticle which has hydrophobically modified core for loading of the CuAA. Folic acid is conjugated on the surface of the polymer (chitosan) nanoparticle for targeting to cancer cells for minimizing toxicity to normal cells in-vivo. Thus, this novel drug CuAA has an efficient anticancer activity which has been targeted specifically to cancer cells through polymer nanoparticle.

Keywords: anticancer, apoptosis, copper nanoparticle, targeted drug delivery

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18 Therapeutical Role of Copper Oxide Nanoparticles (CuO NPs) for Breast Cancer Therapy

Authors: Dipranjan Laha, Parimal Karmakar

Abstract:

Metal oxide nanoparticles are well known to generate oxidative stress and deregulate normal cellular activities. Among these, transition metals copper oxide nanoparticles (CuO NPs) are more compelling than others and able to modulate different cellular responses. In this work, we have synthesized and characterized CuO NPs by various biophysical methods. These CuO NPs (~30 nm) induce autophagy in human breast cancer cell line, MCF7 in a time and dose-dependent manner. Cellular autophagy was tested by MDC staining, induction of green fluorescent protein light chain 3 (GFP-LC3B) foci by confocal microscopy, transfection of pBABE-puro mCherry-EGFP-LC3B plasmid and western blotting of autophagy marker proteins LC3B, beclin1, and ATG5. Further, inhibition of autophagy by 3-Methyladenine (3-MA) decreased LD50 doses of CuO NPs. Such cell death was associated with the induction of apoptosis as revealed by FACS analysis, cleavage of PARP, dephosphorylation of Bad and increased cleavage product of caspase3. siRNA-mediated inhibition of autophagy-related gene beclin1 also demonstrated similar results. Finally, induction of apoptosis by 3-MA in CuO NPs treated cells were observed by TEM. This study indicates that CuO NPs are a potent inducer of autophagy which may be a cellular defense against the CuO NPs mediated toxicity and inhibition of autophagy switches the cellular response into apoptosis. A combination of CuO NPs with the autophagy inhibitor is essential to induce apoptosis in breast cancer cells. Acknowledgments: The authors would like to acknowledge for financial support for this research work to the Department of Biotechnology (No. BT/PR14661/NNT/28/494/2010), Government of India.

Keywords: nanoparticle, autophagy, apoptosis, siRNA-mediated inhibition

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17 Effect of Coal Fly Ash on Morphological and Biochemical Characteristics of Helianthus Annuus L. Sunflower

Authors: Patel P. Kailash, Patel M. Parimal

Abstract:

An investigation was conducted to study the different concentration of coal fly ash solution on morphological and biochemical parameters of Helianthus annuus L. The seeds of Helianthus annuus L. were placed in petri dishes in three replicates and allowed to grow for 16 days in different concentration of coal fly ash solution. Shoot length, root length and fresh weight, dry weight declined with increasing concentration of fly ash. Semidiluted and concentrated fly ash solution exhibited significant reduction in chlorophyll, protein,sugar and ascorbic acid. Concentration dependent changes were observed in most of parameters. Diluted solution of fly ash revealed the maximum increase morphological and biochemical changes of seedlings.

Keywords: Helianthus annuus L., protein, sugar, chlorophyll, coal fly ash

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16 Method Comprising One to One Web Based Real Time Communications

Authors: Lata Kiran Dey, Rajendra Kumar, Biren Karmakar

Abstract:

Web Real Time Communications is a collection of standards, protocols, which provides real-time communications capabilities between web browsers and devices. This paper outlines the design and further implementation of web real-time communications on secure web applications having audio and video call capabilities. This proposed application may put up a system that will be able to work over both desktops as well as the mobile browser. Though, WebRTC also gives a set of JavaScript standard RTC APIs, which primarily works over the real-time communication framework. This helps to build a suitable communication application, which enables the audio, video, and message transfer in between the today’s modern browsers having WebRTC support.

Keywords: WebRTC, SIP, RTC, JavaScript, SRTP, secure web sockets, browser

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15 Vibration of Nonhomogeneous Timoshenko Nanobeam Resting on Winkler-Pasternak Foundation

Authors: Somnath Karmakar, S. Chakraverty

Abstract:

This work investigates the vibration of nonhomogeneous Timoshenko nanobeam resting on the Winkler-Pasternak foundation. Eringen’s nonlocal theory has been used to investigate small-scale effects. The Differential Quadrature method is used to obtain the frequency parameters with various classical boundary conditions. The nonhomogeneous beam model has been considered, where Young’s modulus and density of the beam material vary linearly and quadratically. Convergence of frequency parameters is also discussed. The influence of mechanical properties and scaling parameters on vibration frequencies are investigated for different boundary conditions.

Keywords: Timoshenko beam, Eringen's nonlocal theory, differential quadrature method, nonhomogeneous nanobeam

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14 Identification and Characterization of 18S rRNA Gene of Demodex Canis From the Dog Population of Mizoram, India

Authors: Moneesh Thakur, Hridayesh Prasad, Nikitasha Bora, Parimal Roy Choudhary, A. K. Samanta, Sanjeev Kumar

Abstract:

Canine demodicosis is a common parasitic condition which involves dog skin. Demodicosis in dogs is due the prominent growth of Demodex. Out of various canine Demodex spp., Demodex canis is the most often involved species. Canine demodicosis can occur as either a localized or generalized form of demodicosis severely affect the dogs and in non-treated dogs may cause death. This study was planned with the aim to screen and characterize the 18S rRNA gene of isolated Demodex canis. A total of 1200 dogs were screened during this study period. The skin scrapings of all the suspected dogs were examined under a microscope at 100X magnification for the presence of Demodex canis. The skin scrapings positive for Demodex canis were examined using PCR for confirmation. A total of 35 dogs were confirmed a positive result for D. canis based on 18S rRNA gene amplification by PCR. Further, the 18S rRNA gene of isolated Demodex canis was cloned and sequenced for genome analysis. On the sequence analysis, it was found that isolated sequence (GenBank Accession No. MK177513) had close similarity (99.7%) to that of D. canis genotype of China (Accession No. MG372254).

Keywords: PCR, phylogenetic analysis, cloning and sequening, Demodex canis

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13 Modelling of Silicon Solar Cell with Anti-reflecting Coating

Authors: Ankita Gaur, Mouli Karmakar, Shyam

Abstract:

In this study, a silicon solar cell has been modeled and analyzed to enhance its electrical performance by improving the optical properties using an antireflecting coating (ARC). The dynamic optical reflectance, transmittance along with the net transmissivity absorptivity product of each layer are assessed as per the diurnal variation of the angle of incidence using MATLAB 2019. The model is tested with various Anti-Reflective coatings and the performance has also been compared with uncoated cells. ARC improves the optical transmittance of the photon. Higher transmittance of ⁓96.57% with lowest reflectance of ⁓ 1.74% at 12.00 hours was obtained with MgF₂ coated silicon cells. The electrical efficiency of the configured solar cell was evaluated for a composite climate of New Delhi, India, for all weather conditions. The annual electricity generation for Anti-reflective coated and uncoated crystalline silicon PV Module was observed to be 103.14 KWh and 99.51 KWh, respectively.

Keywords: antireflecting coating, electrical efficiency, reflectance, solar cell, transmittance

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12 Ag (I) Catalyzed Domino Carbonyl and Alkyne Activation: A Smooth Entry to 2, 2′-Di-Substituted 3, 3′-Bisindolylarylmethanes

Authors: Swastik Karmakar, Prasanta Das, Shital K. Chattopadhyay

Abstract:

An efficient synthesis of symmetrical 2, 2′-Di-substituted 3, 3′-bisindolylarylmethanes (BIAMs) having different aryl and hetero-aryl moieties has been developed by Ag(I)-catalyzed indolyzation and a sequential deoxygenative addition involving o-alkynylanilines and aryl/hetero-aryl aldehydes as substrates. Alkyne and carbonyl units could be activated by Ag (I) simultaneously which results in a domino 5-endo-dig indole annulation, addition of C3 of this indole nucleus to the carbonyl carbon in addition to second indole annulation, and its dehydroxylative addition to the same carbonyl carbon to furnish BIAMs in excellent yield. As 3, 3′-bisindolylmethanes (BIMs) are biologically significant scaffolds, this moiety with further substitutions at the indole core could find some important use in medicinal chemistry. The methodology developed is atom-economic and involves more accessible silver salts, which could be useful for large-scale synthesis.

Keywords: alkyne, 3, 3′-Bisindolylarylmethanes, carbonyl, domino, 5-endo-dig indole annulation, silver catalyst

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11 The Genotoxic Effect of Coal Fly Ash of Thermal Power Plant on Raphanus sativus L. (Radish)

Authors: Patel Kailash P, Patel Parimal M

Abstract:

The effect of coal fly ash treatment on the chromosomes of Raphanus sativus L. was investigated. The seeds of Raphanus sativusL. were placed in petri dishes in three replicates and allowed to germinate for five days in different concentration of coal fly ash solution. The root was treated with the diluted, semidiluted, and concentrated solution of fly ash while the control group had distilled water.The total aberration were examined. The mitotic index was calculated and the results were statically evaluated by the analysis of variance 5% significant level. The mitotic index decreased as the concentration increased. The highest mitotic index value was diluted fly ash solution while the least was concentrated fly ash treatment. The results show the most frequent chromosomal abnormalities observed included: chromatid bridge, c-mitosis, and stickiness. Concentrated fly ash solution is much more genotoxic than semidiluted fly ash solution, as it induced more aberrations having percentage abnormalities for the highest concentration tested. Increased fly ash pollution can lead to some irreversible cytogenetic effect in plants. The study is an attempt to corroborate the toxic effect of coal fly ash of thermal power plant on the chromosome of plants. These results will be useful in environmental monitoring of the cytotoxicity of coal fly ash.

Keywords: coal fly-ash, genotoxic, cytogenetic, mitotic index, Raphanus sativus L.

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10 Assessment of Social Vulnerability of Urban Population to Floods – a Case Study of Mumbai

Authors: Sherly M. A., Varsha Vijaykumar, Subhankar Karmakar, Terence Chan, Christian Rau

Abstract:

This study aims at proposing an indicator-based framework for assessing social vulnerability of any coastal megacity to floods. The final set of indicators of social vulnerability are chosen from a set of feasible and available indicators which are prepared using a Geographic Information System (GIS) framework on a smaller scale considering 1-km grid cell to provide an insight into the spatial variability of vulnerability. The optimal weight for each individual indicator is assigned using data envelopment analysis (DEA) as it avoids subjective weights and improves the confidence on the results obtained. In order to de-correlate and reduce the dimension of multivariate data, principal component analysis (PCA) has been applied. The proposed methodology is demonstrated on twenty four wards of Mumbai under the jurisdiction of Municipal Corporation of Greater Mumbai (MCGM). This framework of vulnerability assessment is not limited to the present study area, and may be applied to other urban damage centers.

Keywords: urban floods, vulnerability, data envelopment analysis, principal component analysis

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9 Not so Street Theatre: Politics in Theatre of Roots

Authors: Dani Karmakar

Abstract:

In India, the journey of street theatre was started with Indian peoples Theatre Association (IPTA) as a tool for anti-establishment that was categorized as by the people and for the people. It has expressed common people’s feelings, problems, day to day life. It has brought a social change that is downtrodden. By its nature, it is based on communist ideology. Street theatre is a theatre of protest. In India, many folk theatres translate directly ‘Street Theatre’, those are Veedhi Natakam in Andhra Pradesh and Therukoothu in Tamil Nadu. But they do not covey to common definition of street theatre. There are different folk theatres of different regions in India. All folk theatres have individual characteristic, criteria, taste and flavor that can render distinctive each others. In festivals or special occasions, whole communities come together to enjoy collectively and express their feelings. The Veedhi Natakam means 'street theatre'. Theru koothu is a traditional street theatre in the northern districts of Tamilnadu. Folk theatre has potential to deliver strong messages. It has a socially significant role. At Veedhi Natakam, Vidhushaka takes part for social criticism. Gambhira is also a socio-political folk drama presentation in West Bengal.

Keywords: folk theatre, Gambhira, politics, street theatre

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8 Groundwater Level Prediction Using hybrid Particle Swarm Optimization-Long-Short Term Memory Model and Performance Evaluation

Authors: Sneha Thakur, Sanjeev Karmakar

Abstract:

This paper proposed hybrid Particle Swarm Optimization (PSO) – Long-Short Term Memory (LSTM) model for groundwater level prediction. The evaluation of the performance is realized using the parameters: root mean square error (RMSE) and mean absolute error (MAE). Ground water level forecasting will be very effective for planning water harvesting. Proper calculation of water level forecasting can overcome the problem of drought and flood to some extent. The objective of this work is to develop a ground water level forecasting model using deep learning technique integrated with optimization technique PSO by applying 29 years data of Chhattisgarh state, In-dia. It is important to find the precise forecasting in case of ground water level so that various water resource planning and water harvesting can be managed effectively.

Keywords: long short-term memory, particle swarm optimization, prediction, deep learning, groundwater level

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7 Determination of Safe Ore Extraction Methodology beneath Permanent Extraction in a Lead Zinc Mine with the Help of FLAC3D Numerical Model

Authors: Ayan Giri, Lukaranjan Phukan, Shantanu Karmakar

Abstract:

Structure and tectonics play a vital role in ore genesis and deposition. The existence of a swelling structure below the current level of a mine leads to the discovery of ores below some permeant developments of the mine. The discovery and the extraction of the ore body are very critical to sustain the business requirement of the mine. The challenge was to extract the ore without hampering the global stability of the mine. In order to do so, different mining options were considered and analysed by numerical modelling in FLAC3d software. The constitutive model prepared for this simulation is the improved unified constitutive model, which can better and more accurately predict the stress-strain relationships in a continuum model. The IUCM employs the Hoek-Brown criterion to determine the instantaneous Mohr-Coulomb parameters cohesion (c) and friction (ɸ) at each level of confining stress. The extra swelled part can be dimensioned as north-south strike width 50m, east-west strike width 50m. On the north side, already a stope (P1) is excavated of the dimension of 25m NS width. The different options considered were (a) Open stoping of extraction of southern part (P0) of 50m to the full extent, (b) Extraction of the southern part of 25m, then filling of both the primaries and extraction of secondary (S0) 25m in between. (c) Extraction of the southern part (P0) completely, preceded by backfill and modify the design of the secondary (S0) for the overall stability of the permanent excavation above the stoping.

Keywords: extraction, IUCM, FLAC 3D, stoping, tectonics

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6 A Study on the Different Components of a Typical Back-Scattered Chipless RFID Tag Reflection

Authors: Fatemeh Babaeian, Nemai Chandra Karmakar

Abstract:

Chipless RFID system is a wireless system for tracking and identification which use passive tags for encoding data. The advantage of using chipless RFID tag is having a planar tag which is printable on different low-cost materials like paper and plastic. The printed tag can be attached to different items in the labelling level. Since the price of chipless RFID tag can be as low as a fraction of a cent, this technology has the potential to compete with the conventional optical barcode labels. However, due to the passive structure of the tag, data processing of the reflection signal is a crucial challenge. The captured reflected signal from a tag attached to an item consists of different components which are the reflection from the reader antenna, the reflection from the item, the tag structural mode RCS component and the antenna mode RCS of the tag. All these components are summed up in both time and frequency domains. The effect of reflection from the item and the structural mode RCS component can distort/saturate the frequency domain signal and cause difficulties in extracting the desired component which is the antenna mode RCS. Therefore, it is required to study the reflection of the tag in both time and frequency domains to have a better understanding of the nature of the captured chipless RFID signal. The other benefits of this study can be to find an optimised encoding technique in tag design level and to find the best processing algorithm the chipless RFID signal in decoding level. In this paper, the reflection from a typical backscattered chipless RFID tag with six resonances is analysed, and different components of the signal are separated in both time and frequency domains. Moreover, the time domain signal corresponding to each resonator of the tag is studied. The data for this processing was captured from simulation in CST Microwave Studio 2017. The outcome of this study is understanding different components of a measured signal in a chipless RFID system and a discovering a research gap which is a need to find an optimum detection algorithm for tag ID extraction.

Keywords: antenna mode RCS, chipless RFID tag, resonance, structural mode RCS

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5 Mapping the Quotidian Life of Practitioners of Various Religious Sects in Late Medieval Bengal: Portrayals on the Front Façades of the Baranagar Temple Cluster

Authors: I. Gupta, B. Karmakar

Abstract:

Bengal has a long history (8th century A.D. onwards) of decorating the wall of brick-built temples with curved terracotta plaques on a diverse range of subjects. These could be considered as one of the most significant visual archives to understand the various facets of the then contemporary societies. The temples under focus include Char-bangla temple complex (circa 1755 A.D.), Bhavanishvara temple (circa 1755 A.D.) and the Gangeshvara Shiva Jor-bangla temple (circa 1753 A.D.), located within a part of the river Bhagirathi basin in Baranagar, Murshidabad, West Bengal, India. Though, a diverse range of subjects have been intricately carved mainly on the front façades of the Baranagar temple cluster, the study specifically concentrates on depictions related to religious and non-religious acts performed by practitioners of various religious sects of late medieval Bengal with the intention to acquire knowledge about the various facets of their life. Apart from this, the paper also mapped the spatial location of these religious performers on the temples’ façades to examine if any systematic plan or arrangement had been employed for connoting a particular idea. Further, an attempt is made to provide a commentary on the attire worn by followers of various religious sects of late medieval Bengal. The primary materials for the study comprise the depictions which denote religious activities carved on the terracotta plaques. The secondary material has been collected from published and unpublished theses, journals and books. These data have been further supplemented with photographic documentation, some useful line-drawings and descriptions in table format to get a clear understanding of the concerned issues.

Keywords: attire, scheme of allocation, terracotta temple, various religious sect

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4 Urban Flood Risk Mapping–a Review

Authors: Sherly M. A., Subhankar Karmakar, Terence Chan, Christian Rau

Abstract:

Floods are one of the most frequent natural disasters, causing widespread devastation, economic damage and threat to human lives. Hydrologic impacts of climate change and intensification of urbanization are two root causes of increased flood occurrences, and recent research trends are oriented towards understanding these aspects. Due to rapid urbanization, population of cities across the world has increased exponentially leading to improperly planned developments. Climate change due to natural and anthropogenic activities on our environment has resulted in spatiotemporal changes in rainfall patterns. The combined effect of both aggravates the vulnerability of urban populations to floods. In this context, an efficient and effective flood risk management with its core component as flood risk mapping is essential in prevention and mitigation of flood disasters. Urban flood risk mapping involves zoning of an urban region based on its flood risk, which depicts the spatiotemporal pattern of frequency and severity of hazards, exposure to hazards, and degree of vulnerability of the population in terms of socio-economic, environmental and infrastructural aspects. Although vulnerability is a key component of risk, its assessment and mapping is often less advanced than hazard mapping and quantification. A synergic effort from technical experts and social scientists is vital for the effectiveness of flood risk management programs. Despite an increasing volume of quality research conducted on urban flood risk, a comprehensive multidisciplinary approach towards flood risk mapping still remains neglected due to which many of the input parameters and definitions of flood risk concepts are imprecise. Thus, the objectives of this review are to introduce and precisely define the relevant input parameters, concepts and terms in urban flood risk mapping, along with its methodology, current status and limitations. The review also aims at providing thought-provoking insights to potential future researchers and flood management professionals.

Keywords: flood risk, flood hazard, flood vulnerability, flood modeling, urban flooding, urban flood risk mapping

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3 Synthesis of Methanol through Photocatalytic Conversion of CO₂: A Green Chemistry Approach

Authors: Sankha Chakrabortty, Biswajit Ruj, Parimal Pal

Abstract:

Methanol is one of the most important chemical products and intermediates. It can be used as a solvent, intermediate or raw material for a number of higher valued products, fuels or additives. From the last one decay, the total global demand of methanol has increased drastically which forces the scientists to produce a large amount of methanol from a renewable source to meet the global demand with a sustainable way. Different types of non-renewable based raw materials have been used for the synthesis of methanol on a large scale which makes the process unsustainable. In this circumstances, photocatalytic conversion of CO₂ into methanol under solar/UV excitation becomes a viable approach to give a sustainable production approach which not only meets the environmental crisis by recycling CO₂ to fuels but also reduces CO₂ amount from the atmosphere. Development of such sustainable production approach for CO₂ conversion into methanol still remains a major challenge in the current research comparing with conventional energy expensive processes. In this backdrop, the development of environmentally friendly materials, like photocatalyst has taken a great perspective for methanol synthesis. Scientists in this field are always concerned about finding an improved photocatalyst to enhance the photocatalytic performance. Graphene-based hybrid and composite materials with improved properties could be a better nanomaterial for the selective conversion of CO₂ to methanol under visible light (solar energy) or UV light. The present invention relates to synthesis an improved heterogeneous graphene-based photocatalyst with improved catalytic activity and surface area. Graphene with enhanced surface area is used as coupled material of copper-loaded titanium oxide to improve the electron capture and transport properties which substantially increase the photoinduced charge transfer and extend the lifetime of photogenerated charge carriers. A fast reduction method through H₂ purging has been adopted to synthesis improved graphene whereas ultrasonication based sol-gel method has been applied for the preparation of graphene coupled copper loaded titanium oxide with some enhanced properties. Prepared photocatalysts were exhaustively characterized using different characterization techniques. Effects of catalyst dose, CO₂ flow rate, reaction temperature and stirring time on the efficacy of the system in terms of methanol yield and productivity have been studied in the present study. The study shown that the newly synthesized photocatalyst with an enhanced surface resulting in a sustained productivity and yield of methanol 0.14 g/Lh, and 0.04 g/gcat respectively, after 3 h of illumination under UV (250W) at an optimum catalyst dosage of 10 g/L having 1:2:3 (Graphene: TiO₂: Cu) weight ratio.

Keywords: renewable energy, CO₂ capture, photocatalytic conversion, methanol

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2 A Computational Model of the Thermal Grill Illusion: Simulating the Perceived Pain Using Neuronal Activity in Pain-Sensitive Nerve Fibers

Authors: Subhankar Karmakar, Madhan Kumar Vasudevan, Manivannan Muniyandi

Abstract:

Thermal Grill Illusion (TGI) elicits a strong and often painful sensation of burn when interlacing warm and cold stimuli that are individually non-painful, excites thermoreceptors beneath the skin. Among several theories of TGI, the “disinhibition” theory is the most widely accepted in the literature. According to this theory, TGI is the result of the disinhibition or unmasking of the pain-sensitive HPC (Heat-Pinch-Cold) nerve fibers due to the inhibition of cold-sensitive nerve fibers that are responsible for masking HPC nerve fibers. Although researchers focused on understanding TGI throughexperiments and models, none of them investigated the prediction of TGI pain intensity through a computational model. Furthermore, the comparison of psychophysically perceived TGI intensity with neurophysiological models has not yet been studied. The prediction of pain intensity through a computational model of TGI can help inoptimizing thermal displays and understanding pathological conditions related to temperature perception. The current studyfocuses on developing a computational model to predict the intensity of TGI pain and experimentally observe the perceived TGI pain. The computational model is developed based on the disinhibition theory and by utilizing the existing popular models of warm and cold receptors in the skin. The model aims to predict the neuronal activity of the HPC nerve fibers. With a temperature-controlled thermal grill setup, fifteen participants (ten males and five females) were presented with five temperature differences between warm and cold grills (each repeated three times). All the participants rated the perceived TGI pain sensation on a scale of one to ten. For the range of temperature differences, the experimentally observed perceived intensity of TGI is compared with the neuronal activity of pain-sensitive HPC nerve fibers. The simulation results show a monotonically increasing relationship between the temperature differences and the neuronal activity of the HPC nerve fibers. Moreover, a similar monotonically increasing relationship is experimentally observed between temperature differences and the perceived TGI intensity. This shows the potential comparison of TGI pain intensity observed through the experimental study with the neuronal activity predicted through the model. The proposed model intends to bridge the theoretical understanding of the TGI and the experimental results obtained through psychophysics. Further studies in pain perception are needed to develop a more accurate version of the current model.

Keywords: thermal grill Illusion, computational modelling, simulation, psychophysics, haptics

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1 Resveratrol Ameliorates Benzo(a)Pyrene Induced Testicular Dysfunction and Apoptosis: Involvement of p38 MAPK/ATF2/iNOS Signaling

Authors: Kuladip Jana, Bhaswati Banerjee, Parimal C. Sen

Abstract:

Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems along with carcinogenesis in skin, prostate, ovary, lung and mammary glands. Our study was focused on elucidating the molecular mechanism of B(a)P induced male reproductive toxicity and its prevention with phytochemical like resveratrol. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of Wistar rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased Reactive Oxygen Species (ROS), altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38 mitogen activated protein kinase (p38MAPK), cytosolic translocation of cytochrome-c, upregulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of poly ADP ribose polymerase (PARP) and down regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like steroidogenic acute regulatory protein (StAR), cytochrome P450 IIA1 (CYPIIA1), 3β hydroxy steroid dehydrogenase (3β HSD), 17β hydroxy steroid dehydrogenase (17β HSD) showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis. Next we investigated the role of resveratrol on B(a)P induced male reproductive toxicity. Our study highlighted that resveratrol co-treatment with B(a)P maintained testicular redox potential, increased serum testosterone level and prevented steroidogenic dysfunction with enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3β HSD,17β HSD) relative to treatment with B(a)P only. Resveratrol suppressed B(a)P-induced testicular activation of p38 MAPK, ATF2, iNOS and ROS production; cytosolic translocation of Cytochome c and Caspase 3 activation thereby prevented oxidative stress of testis and inhibited apoptosis. Resveratrol co-treatment also decreased B(a)P-induced AhR protein level, its nuclear translocation and subsequent CYP1A1 promoter activation, thereby decreased protein and mRNA levels of testicular cytochrome P4501A1 (CYP1A1) and prevented BPDE-DNA adduct formation. Our findings cumulatively suggest that resveratrol prevents activation of B(a)P by modulating the transcriptional regulation of CYP1A1 and acting as an antioxidant thus prevents B(a)P-induced oxidative stress and testicular apoptosis.

Keywords: benzo(a)pyrene, resveratrol, testis, apoptosis, cytochrome P450 1A1 (CYP1A1), aryl hydrocarbon receptor (AhR), p38 MAPK/ATF2/iNOS

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