Search results for: Shweta Hoyani

Authors: Devender Sharma, Shweta Goyal

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Sustainable development is a key to protect the environment for a secure future. Accelerated carbonation curing is a comparatively new technique for curing of concrete which involves sequestration of carbon dioxide gas into the precast concrete, resulting in improvement of the properties of concrete. This paper presents the results of a study to evaluate the effect of carbonation curing on cement mortars incorporating cement kiln dust (CKD) as partial replacement of cement. The mortar specimens were prepared by replacing cement with CKD in varying percentages of 0-50% by the weight of cement. The specimens were subjected to 12 hour carbonation curing, followed by sealed packing till testing age. The results were compared with the normal curing procedure, in which the specimens were water cured till the testing age. Compressive strength and microstructure of the mix were studied. It was noted that on increasing the percentage of CKD up to 10% by the weight of the cement, no considerable change was observed in the compressive strength. But as the percentage of CKD was further increased, there was a decrease in compressive strength, with strength decreasing up to 40% when 50% of the cement was replaced with CKD. The decrease in strength is due to the lesser lime content in CKD as compared to cement. High ettringite formation was observed in mixes with high percentages of CKD, thus indicating a decrease in the compressive strength. With carbonation curing, an early age strength gain was observed in mortars, even with higher percentages of CKD. The early strength of the carbonation cured mixes was found to be greater than water cured mixes irrespective of the percentage of CKD. 7 days and 28 days compressive strength of the mix was comparable for both the carbonation cured and water cured specimen. The increase in compressive strength can be attributed to the conversion of unstable Ca(OH)2 into stable CaCO3, which causes densification of the mix. CaCO3 precipitation and greater CSH gel formation was clearly observed in the SEM images of carbonation cured specimen, indicating higher compressive strength. Thus, carbonation curing can be used as an efficient method to enhance the properties of concrete.

Keywords: carbonation, cement kiln dust, compressive strength, microstructure

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Authors: Sonal Gupta, Rakhi Bansal, Javed Ali, Reema Gabrani, Shweta Dang

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Nanoemulsions (NEs) and microemulsions (MEs) have been an attractive tool for encapsulation of both hydrophilic and lipophillic actives. Both these systems are composed of oil phase, surfactant, co-surfactant and aqueous phase. Depending upon the application and intended use, both oil-in-water and water-in-oil emulsions can be designed. NEs are fabricated using high energy methods employing less percentage of surfactant as compared to MEs which are self assembled drug delivery systems. Owing to the nanometric size of the droplets these systems have been widely used to enhance solubility and bioavailability of natural as well as synthetic molecules. The aim of the present study is to assess the effect of % age of surfactants on cell viability of Vero cells (African Green Monkeys’ Kidney epithelial cells) via MTT assay. Green tea catechin (Polyphenon 60) loaded ME employing low energy vortexing and NE employing high energy ultrasonication were prepared using same excipients (labrasol as oil, cremophor EL as surfactant and glycerol as co-surfactant) however, the % age of oil and surfactant needed to prepare the ME was higher as compared to NE. These formulations along with their excipients (oilME=13.3%, SmixME=26.67%; oilNE=10%, SmixNE=13.52%) were added to Vero cells for 24 hrs. The tetrazolium dye, 3-(4,5-dimethylthia/ol-2-yl)-2,5-diphi-iiyltclrazolium bromide (MTT), is reduced by live cells and this reaction is used as the end point to evaluate the cytoxicity level of a test formulation. Results of MTT assay indicated that oil at different percentages exhibited almost equal cell viability (oilME ≅ oilNE) while surfactant mixture had a significant difference in the cell viability values (SmixME < SmixNE). Polyphenon 60 loaded ME and its PlaceboME showed higher toxicity as compared to Polyphenon 60 loaded NE and its PlaceboNE that can be attributed to the higher concentration of surfactants present in MEs. Another probable reason for high % cell viability of Polyphenon 60 loaded NE might be due to the effective release of Polyphenon 60 from NE formulation that helps in the sustenance of Vero cells.

Keywords: cell viability, microemulsion, MTT, nanoemulsion, surfactants, ultrasonication

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Authors: Rashima Mahajan, Dipali Bansal, Shweta Singh

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Real time non-invasive Brain Computer Interfaces have a significant progressive role in restoring or maintaining a quality life for medically challenged people. This manuscript provides a comprehensive review of emerging research in the field of cognitive/affective computing in context of human neural responses. The perspectives of different emotion assessment modalities like face expressions, speech, text, gestures, and human physiological responses have also been discussed. Focus has been paid to explore the ability of EEG (Electroencephalogram) signals to portray thoughts, feelings, and unspoken words. An automated workflow-based protocol to design an EEG-based real time Brain Computer Interface system for analysis and classification of human emotions elicited by external audio/visual stimuli has been proposed. The front end hardware includes a cost effective and portable Emotive EEG Neuroheadset unit, a personal computer and a set of external stimulators. Primary signal analysis and processing of real time acquired EEG shall be performed using MATLAB based advanced brain mapping toolbox EEGLab/BCILab. This shall be followed by the development of MATLAB based self-defined algorithm to capture and characterize temporal and spectral variations in EEG under emotional stimulations. The extracted hybrid feature set shall be used to classify emotional states using artificial intelligence tools like Artificial Neural Network. The final system would result in an inexpensive, portable and more intuitive Brain Computer Interface in real time scenario to control prosthetic devices by translating different brain states into operative control signals.

Keywords: brain computer interface, electroencephalogram, EEGLab, BCILab, emotive, emotions, interval features, spectral features, artificial neural network, control applications

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Authors: Abhaydeep Pandey, Shweta Shukla, Saptamita Goswami, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Sudhanshu Vrati, Arup Banerjee

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Dengue virus infection is now considered as one of the most important mosquito-borne infection in human. The virus is known to promote vascular permeability, cerebral edema leading to Dengue hemorrhagic fever (DHF) or Dengue shock syndrome (DSS). Dengue infection has known to be endemic in India for over two centuries as a benign and self-limited disease. In the last couple of years, the disease symptoms have changed, manifesting severe secondary complication. So far, Delhi has experienced 12 outbreaks of dengue virus infection since 1997 with the last reported in 2014-15. Without specific antivirals, the case management of high-risk dengue patients entirely relies on supportive care, involving constant monitoring and timely fluid support to prevent hypovolemic shock. Nonetheless, the diverse clinical spectrum of dengue disease, as well as its initial similarity to other viral febrile illnesses, presents a challenge in the early identification of this high-risk group. WHO recommends the use of warning signs to identify high-risk patients, but warning signs generally appear during, or just one day before the development of severe illness, thus, providing only a narrow window for clinical intervention. The ability to predict which patient may develop DHF and DSS may improve the triage and treatment. With the recent discovery of high throughput RNA sequencing allows us to understand the disease progression at the genomic level. Here, we will collate the results of RNA-Sequencing data obtained recently from PBMC of different categories of dengue patients from India and will discuss the possible role of deregulated genes and long non-coding RNAs NEAT1 for development of disease progression.

Keywords: long non-coding RNA (lncRNA), dengue, peripheral blood mononuclear cell (PBMC), nuclear enriched abundant transcript 1 (NEAT1), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS)

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Authors: Vaibhav Baliyan, Shweta Mehrotra, S. S. Parihar

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The agricultural productivity is challenged by climate change and depletion in natural resources, including water and land, which significantly affects the crop yield. Wheat is a thermo-sensitive crop and is prone to heat stress. High temperature decreases crop duration, yield attributes, and, subsequently, grain yield and biomass production. Terminal heat stress affects grain filling duration, grain yield, and yield attributes, thus causing a reduction in wheat yield. A field experiment was conducted at Indian Agricultural Research Institute, New Delhi, for two consecutive rabi seasons (2017-18 and 2018-19) on six varieties of wheat (early sown - HD 2967, HD 3086, HD 2894 and late sown - WR 544, HD 3059, HD 3117 ) with three moisture regimes (100%, 80%, and 60% ETc, and no irrigation) and six sowing dates in three replications to investigate the effect of different moisture regimes and sowing dates on growth, yield and water use efficiency of wheat for development of best management practices for mitigation of terminal heat stress. HD3086 and HD3059 gave higher grain yield than others under early sown and late sown conditions, respectively. Maximum soil moisture extraction was recorded from 0-30 cm soil depth across the sowing dates, irrigation regimes, and varieties. Delayed sowing resulted in reducing crop growth period and forced maturity, in turn, led to significant deterioration in all the yield attributing characters and, there by, reduction in yield, suggesting that terminal heat stress had greater impact on yield. Early sowing and irrigation at 80% ETc resulted in improved growth and yield attributes and water use efficiency in both the seasons and helped to some extent in reducing the risk of terminal heat stress of wheat grown on sandy loam soils of semi-arid regions of India.

Keywords: sowing, irrigation, yield, heat stress

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Authors: Isabel Lopez-Oliva, Akshay Paropkari, Shweta Saraswat, Stefan Serban, Paola de Pablo, Karim Raza, Andrew Filer, Iain Chapple, Thomas Dietrich, Melissa Grant, Purnima Kumar

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Objective: We aimed to explicate the role of the subgingival microbiome in the causal link between rheumatoid arthritis (RA) and periodontitis (PD). Methods: Subjects with/without RA and with/without PD were randomized for treatment with scaling and root planing (SRP) or oral hygiene instructions. Subgingival biofilm, gingival crevicular fluid, and serum were collected at baseline and at 3- and 6-months post-operatively. Correlations were generated between 72 million 16S rDNA sequences, immuno-inflammatory mediators, circulating antibodies to oral microbial antigens, serum inflammatory molecules, and clinical metrics of RA. The dynamics of inter-microbial and host-microbial interactions were modeled using differential network analysis. Results: RA superseded periodontitis as a determinant of microbial composition, and DAS28 score superseded the severity of periodontitis as a driver of microbial assemblages (p=0.001, ANOSIM). RA subjects evidenced higher serum anti-PPAD (p=0.0013), anti-Pg-enolase (p=0.0031), anti-RPP3, anti- Pg-OMP and anti- Pi-OMP (p=0.001) antibodies than non-RA controls (with and without periodontitis). Following SRP, bacterial networks anchored by IL-1b, IL-4, IL-6, IL-10, IL-13, MIP-1b, and PDGF-b underwent ≥5-fold higher rewiring; and serum antibodies to microbial antigens decreased significantly. Conclusions: Our data suggest a circular relationship between RA and PD, beginning with an RA-influenced dysbiosis within the healthy subgingival microbiome that leads to exaggerated local inflammation in periodontitis and circulating antibodies to periodontal pathogens and positive correlation between severity of periodontitis and RA activity. Periodontal therapy restores host-microbial homeostasis, reduces local inflammation, and decreases circulating microbial antigens. Our data highlights the importance of integrating periodontal care into the management of RA patients.

Keywords: rheumatoid arthritis, periodontal, subgingival, DNA sequence analysis, oral microbiome

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Authors: Shilpa Sharma, Lakshmi Ganesh, Mantra Gurumurthy, Shweta Sharma

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Board games provide affordances of 21st-century skills like collaboration, critical thinking, and strategy. Board games such as chess, Catan, Battleship, Scrabble, and Taboo can enhance learning in these areas. While board games are popular in informal child settings, their use in formal K-12 education is limited. To encourage teachers to incorporate board games, it's essential to grasp their perceptions and tailor professional development programs accordingly. This paper aims to explore teacher attitudes toward board games and propose interventions to motivate teachers to integrate and create board games in the classroom. A user study was conceived, designed, and administered with teachers (n=38) to understand their experience in playing board games and using board games in the classroom. Purposive sampling was employed as the questionnaire was floated to teacher groups that the authors were aware of. The teachers taught in K-12 affordable private schools. The majority of them had experience ranging from 2-5 years. The questionnaire consisted of questions on teacher perceptions and beliefs of board game usage in the classroom. From the responses, it was observed that ~90% of teachers, though they had experience of playing board games, rarely did it translate to using board games in the classroom. Additionally, it was observed that translating learning objectives to board game objectives is the key factor that teachers consider while using board games in the classroom. Based on the results from the questionnaire, a professional development workshop was co-designed with the objective of motivating teachers to design, create and use board games in the classroom. The workshop is based on the principles of gamification. This is to ensure that the teachers experience a board game in a learning context. Additionally, the workshop is based on the principles of andragogy, such as agency, pertinence, and relevance. The workshop will begin by modifying and reusing known board games in the learning context so that the teachers do not find it difficult and daunting. The intention is to verify the face validity and content validity of the workshop design, orchestration and content with experienced teacher development professionals and education researchers. The results from this study will be published in the full paper.

Keywords: board games, professional development, teacher motivation, teacher perception

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Authors: Bharti Jain, Rajeev Jain, Abuzar Kabir, Torki Zughaibi, Shweta Sharma

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Drug-facilitated crimes (DFCs) entail the use of a single drug or a mixture of drugs to render a victim unable. Traditionally, biological samples have been gathered from victims and conducted analysis to establish evidence of drug administration. Nevertheless, the rapid metabolism of various drugs and delays in analysis can impede the identification of such substances. For this, the present article describes a rapid, sustainable, highly efficient and miniaturized protocol for the identification and quantification of three sedative-hypnotic drugs, namely diazepam, chlordiazepoxide and ketamine in alcoholic beverages and complex food samples (cream of biscuit, flavored milk, juice, cake, tea, sweets and chocolate). The methodology involves utilizing fabric phase sorptive extraction (FPSE) to extract diazepam (DZ), chlordiazepoxide (CDP), and ketamine (KET). Subsequently, the extracted samples are subjected to analysis using gas chromatography-mass spectrometry (GC-MS). Several parameters, including the type of membrane, pH, agitation time and speed, ionic strength, sample volume, elution volume and time, and type of elution solvent, were screened and thoroughly optimized. Sol-gel Carbowax 20M (CW-20M) has demonstrated the most effective extraction efficiency for the target analytes among all evaluated membranes. Under optimal conditions, the method displayed linearity within the range of 0.3–10 µg mL–¹ (or µg g–¹), exhibiting a coefficient of determination (R2) ranging from 0.996–0.999. The limits of detection (LODs) and limits of quantification (LOQs) for liquid samples range between 0.020-0.069 µg mL-¹ and 0.066-0.22 µg mL-¹, respectively. Correspondingly, the LODs for solid samples ranged from 0.056-0.090 µg g-¹, while the LOQs ranged from 0.18-0.29 µg g-¹. Notably, the method showcased better precision, with repeatability and reproducibility both below 5% and 10%, respectively. Furthermore, the FPSE-GC-MS method proved effective in determining diazepam (DZ) in forensic food samples connected to drug-facilitated crimes (DFCs). Additionally, the proposed method underwent evaluation for its whiteness using the RGB12 algorithm.

Keywords: drug facilitated crime, fabric phase sorptive extraction, food forensics, white analytical chemistry

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Authors: Pedro Augusto Da Silva E Souza Miranda, Niloofar Jalali, Shweta Mistry

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BACKGROUND: Software developers utilize automated solutions to scrape users’ reviews to extract meaningful knowledge to identify problems (e.g., bugs, compatibility issues) and possible enhancements (e.g., users’ requests) to their solutions. However, most of these solutions do not consider the health risk aspects to users. Recent works have shed light on the importance of including health risk considerations in the development cycle of mHealth apps to prevent harm to its users. PROBLEM: The COVID-19 Pandemic in Canada (and World) is currently forcing physical distancing upon the general population. This new lifestyle made the usage of mHealth applications more essential than ever, with a projected market forecast of 332 billion dollars by 2025. However, this new insurgency in mHealth usage comes with possible risks to users’ health due to mHealth apps problems (e.g., wrong insulin dosage indication due to a UI error). OBJECTIVE: These works aim to raise awareness amongst mHealth developers of the importance of considering risks to users’ health within their development lifecycle. Moreover, this work also aims to help mHealth developers with a Proof-of-Concept (POC) solution to understand, process, and identify possible health risks to users of mHealth apps based on users’ reviews. METHODS: We conducted a mixed-method study design. We developed a crawler to mine the negative reviews from two samples of mHealth apps (my fitness, medisafe) from the Google Play store users. For each mHealth app, we performed the following steps: • The reviews are divided into two groups, before starting the COVID-19 (reviews’ submission date before 15 Feb 2019) and during the COVID-19 (reviews’ submission date starts from 16 Feb 2019 till Dec 2020). For each period, the Latent Dirichlet Allocation (LDA) topic model was used to identify the different clusters of reviews based on similar topics of review The topics before and during COVID-19 are compared, and the significant difference in frequency and severity of similar topics are identified. RESULTS: We successfully scraped, filtered, processed, and identified health-related topics in both qualitative and quantitative approaches. The results demonstrated the similarity between topics before and during the COVID-19.

Keywords: natural language processing (NLP), topic modeling, mHealth, COVID-19, software engineering, telemedicine, health risks

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Authors: Divya Kanchibhotla, Shashank Kulkarni, Shweta Singh

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Chronic stress and sleep quality reduces mental health and increases the risk of developing depression and anxiety as well. There is increasing evidence for the utility of meditation as an adjunct clinical intervention for conditions like depression and anxiety. The present study is an attempt to explore the impact of Sahaj Samadhi Meditation (SSM), a category of Automatic Self Transcending Meditation (ASTM), on perceived stress and sleep quality in adults. The study design was a single group pre-post assessment. Perceived Stress Scale (PSS) and the Pittsburgh Sleep Quality Index (PSQI) were used in this study. Fifty-two participants filled PSS, and 60 participants filled PSQI at the beginning of the program (day 0), after two weeks (day 16) and at two months (day 60). Significant pre-post differences for the perceived stress level on Day 0 - Day 16 (p < 0.01; Cohen's d = 0.46) and Day 0 - Day 60 (p < 0.01; Cohen's d = 0.76) clearly demonstrated that by practicing SSM, participants experienced reduction in the perceived stress. The effect size of the intervention observed on the 16th day of assessment was small to medium, but on the 60th day, a medium to large effect size of the intervention was observed. In addition to this, significant pre-post differences for the sleep quality on Day 0 - Day 16 and Day 0 - Day 60 (p < 0.05) clearly demonstrated that by practicing SSM, participants experienced improvement in the sleep quality. Compared with Day 0 assessment, participants demonstrated significant improvement in the quality of sleep on Day 16 and Day 60. The effect size of the intervention observed on the 16th day of assessment was small, but on the 60th day, a small to medium effect size of the intervention was observed. In the current study we found out that after practicing SSM for two months, participants reported a reduction in the perceived stress, they felt that they are more confident about their ability to handle personal problems, were able to cope with all the things that they had to do, felt that they were on top of the things, and felt less angered. Participants also reported that their overall sleep quality improved; they took less time to fall asleep; they had less disturbances in sleep and less daytime dysfunction due to sleep deprivation. The present study provides clear evidence of the efficacy and safety of non-pharmacological interventions such as SSM in reducing stress and improving sleep quality. Thus, ASTM may be considered a useful intervention to reduce psychological distress in healthy, non-clinical populations, and it can be an alternative remedy for treating poor sleep among individuals and decreasing the use of harmful sedatives.

Keywords: automatic self transcending meditation, Sahaj Samadhi meditation, sleep, stress

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Authors: Salima Bijapuri, Shweta Bhatbolan, Sejalben Patel

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Ergonomics concerns the fitting of the environment and the equipment to the worker. Ergonomic principles can be employed in different dimensions of the industrial sector. Participation of all the stakeholders is the key to the formulation of a multifaceted and comprehensive approach to lessen the burden of occupational hazards. Taking responsibility for one’s own work activities by acquiring sufficient knowledge and potential to influence the practices and outcomes is the basis of participatory ergonomics and even hastens the process to identify workplace hazards. The study was aimed to check how participatory ergonomics can be effective in the management of work-related musculoskeletal disorders. Method: A mega kitchen was identified in a twin city of Karnataka, India. Consent was taken, and the screening of workers was done using observation methods. Kitchen work was structured to include different tasks, which included preparation, cooking, distributing, and serving food, packing food to be delivered to schools, dishwashing, cleaning and maintenance of kitchen and equipment, and receiving and storing raw material. Total 100 workers attended the education session on participatory ergonomics and its role in implementing the correct ergonomic practices, thus preventing WRMSDs. Demographic details and baseline data on related musculoskeletal pain and discomfort were collected using the Nordic pain questionnaire and VAS score pre- and post-study. Monthly visits were made, and the education sessions were reiterated on each visit, thus reminding, correcting, and problem-solving of each worker. After 9 months with a total of 4 such education session, the post education data was collected. The software SPSS 20 was used to analyse the collected data. Results: The majority of them (78%), depending on the availability and feasibility, participated in the intervention workshops were arranged four times. The average age of the participants was 39 years. The percentage of female participants was 79.49%, and 20.51% of participants comprised of males. The Nordic Musculoskeletal Questionnaire (NMQ) showed that knee pain was the most commonly reported complaint (62%) from the last 12 months with a mean VAS of 6.27, followed by low back pain. Post intervention, the mean VAS Score was reduced significantly to 2.38. The comparison of pre-post scores was made using Wilcoxon matched pairs test. Upon enquiring, it was found that, the participants learned the importance of applying ergonomics at their workplace which inturn was beneficial for them to handle any problems arising at their workplace on their own with self confidence. Conclusion: The participatory ergonomics proved effective with workers of mega kitchen, and it is a feasible and practical approach. The advantage of the given study area was that it had a sophisticated and ergonomically designed workstation; thus it was the lack of education and practical knowledge to use these stations was of utmost need. There was a significant reduction in VAS scores with the implementation of changes in the working style, and the knowledge of ergonomics helped to decrease physical load and improve musculoskeletal health.

Keywords: ergonomic awareness session, mega kitchen, participatory ergonomics, work related musculoskeletal disorders

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Authors: Shweta Pinjarkar, Shrutika Yawale, Mayuri Patil, Reshma Adagale

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Face recognition is the technique which can be applied to the wide variety of problems like image and film processing, human computer interaction, criminal identification etc. This has motivated researchers to develop computational models to identify the faces, which are easy and simple to implement. In this, demonstrates the face recognition system in android device using eigenface. The system can be used as the base for the development of the recognition of human identity. Test images and training images are taken directly with the camera in android device.The test results showed that the system produces high accuracy. The goal is to implement model for particular face and distinguish it with large number of stored faces. face recognition system detects the faces in picture taken by web camera or digital camera and these images then checked with training images dataset based on descriptive features. Further this algorithm can be extended to recognize the facial expressions of a person.recognition could be carried out under widely varying conditions like frontal view,scaled frontal view subjects with spectacles. The algorithm models the real time varying lightning conditions. The implemented system is able to perform real-time face detection, face recognition and can give feedback giving a window with the subject's info from database and sending an e-mail notification to interested institutions using android application. Face recognition is the technique which can be applied to the wide variety of problems like image and film processing, human computer interaction, criminal identification etc. This has motivated researchers to develop computational models to identify the faces, which are easy and simple to implement. In this , demonstrates the face recognition system in android device using eigenface. The system can be used as the base for the development of the recognition of human identity. Test images and training images are taken directly with the camera in android device.The test results showed that the system produces high accuracy. The goal is to implement model for particular face and distinguish it with large number of stored faces. face recognition system detects the faces in picture taken by web camera or digital camera and these images then checked with training images dataset based on descriptive features. Further this algorithm can be extended to recognize the facial expressions of a person.recognition could be carried out under widely varying conditions like frontal view,scaled frontal view subjects with spectacles. The algorithm models the real time varying lightning conditions. The implemented system is able to perform real-time face detection, face recognition and can give feedback giving a window with the subject's info from database and sending an e-mail notification to interested institutions using android application.

Keywords: face detection, face recognition, eigen faces, algorithm

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Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

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Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

Procedia PDF Downloads 481