Search results for: visual inspection with acetic acid
343 Non-Melanoma Skin Cancer of Cephalic Extremity – Clinical and Histological Aspects
Authors: Razvan Mercut, Mihaela Ionescu, Vlad Parvanescu, Razvan Ghita, Tudor-Gabriel Caragea, Cristina Simionescu, Marius-Eugen Ciurea
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Introduction: Over the past years, the incidence of non-melanoma skin cancer (NMSC) has continuously increased, being one of the most commonly diagnosed carcinomasofthe cephalic extremity. NMSC regroups basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Merkel cell carcinoma, cutaneous lymphoma, and sarcoma. The most common forms are BCC and SCC, both still implying a significant level of morbidity due to local invasion (especially BCC), even if the overall death rates are declining. The objective of our study was the evaluation of clinical and histological aspects of NMSC for a group of patients with BCC and SCC, from Craiova, a south-western major city in Romania. Materialand method: Our study lot comprised 65 patients, with an almost equal distribution of sexes, and ages between 23-91 years old (mean value±standard deviation62.61±16.67), all treated within the Clinic of Plastic Surgery and Reconstructive Microsurgery, Clinical Emergency County Hospital Craiova, Romania, between 2019-2020. In order to determine the main morphological characteristics of both studied cancers, we used paraffin embedding techniques, with various staining methods:hematoxylin-eosin, Masson's trichrome stain with aniline blue, and Periodic acid-schiffAlcian Blue. The statistical study was completed using Microsoft Excel (Microsoft Corp., Redmond, WA, USA), with XLSTAT (Addinsoft SARL, Paris, France). Results: The overall results of our study indicate that BCC accounts for 67.69% of all NMSC forms; SCC covers 27.69%, while 4.62% are representedby other forms. The most frequent site is the nose for BCC (27.69%, 18 patients), being followed by preauricular regions, forehead, and periorbital areas. For patients with SCC, tumors were mainly located at lips level (66.67%, 12 patients). The analysis of NMSC histological forms indicated that nodular BCC is predominant (45.45%, 20 patients), as well as ulcero-vegetant SCC (38.89%, 7 patients). We have not identified any topographic characteristics or NMSC forms significantly related to age or sex. Conclusions: The most frequent NMSC form identified for our study lot was BCC. The preferred location was the nose for BCC. For SCC, the oral cavity is the most frequent anatomical site, especially the lips level. Nodular BCC and ulcero-vegetant SCC were the most commonly identified histological types. Our findings emphasize the need for periodic screening, in order to improve prevention and early treatment for these malignancies.Keywords: non-melanoma skin cancer, basal cell carcinoma, squamous cell carcinoma, histological
Procedia PDF Downloads 182342 The Diagnostic Utility and Sensitivity of the Xpert® MTB/RIF Assay in Diagnosing Mycobacterium tuberculosis in Bone Marrow Aspirate Specimens
Authors: Nadhiya N. Subramony, Jenifer Vaughan, Lesley E. Scott
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In South Africa, the World Health Organisation estimated 454000 new cases of Mycobacterium tuberculosis (M.tb) infection (MTB) in 2015. Disseminated tuberculosis arises from the haematogenous spread and seeding of the bacilli in extrapulmonary sites. The gold standard for the detection of MTB in bone marrow is TB culture which has an average turnaround time of 6 weeks. Histological examinations of trephine biopsies to diagnose MTB also have a time delay owing mainly to the 5-7 day processing period prior to microscopic examination. Adding to the diagnostic delay is the non-specific nature of granulomatous inflammation which is the hallmark of MTB involvement of the bone marrow. A Ziehl-Neelson stain (which highlights acid-fast bacilli) is therefore mandatory to confirm the diagnosis but can take up to 3 days for processing and evaluation. Owing to this delay in diagnosis, many patients are lost to follow up or remain untreated whilst results are awaited, thus encouraging the spread of undiagnosed TB. The Xpert® MTB/RIF (Cepheid, Sunnyvale, CA) is the molecular test used in the South African national TB program as the initial diagnostic test for pulmonary TB. This study investigates the optimisation and performance of the Xpert® MTB/RIF on bone marrow aspirate specimens (BMA), a first since the introduction of the assay in the diagnosis of extrapulmonary TB. BMA received for immunophenotypic analysis as part of the investigation into disseminated MTB or in the evaluation of cytopenias in immunocompromised patients were used. Processing BMA on the Xpert® MTB/RIF was optimised to ensure bone marrow in EDTA and heparin did not inhibit the PCR reaction. Inactivated M.tb was spiked into the clinical bone marrow specimen and distilled water (as a control). A volume of 500mcl and an incubation time of 15 minutes with sample reagent were investigated as the processing protocol. A total of 135 BMA specimens had sufficient residual volume for Xpert® MTB/RIF testing however 22 specimens (16.3%) were not included in the final statistical analysis as an adequate trephine biopsy and/or TB culture was not available. Xpert® MTB/RIF testing was not affected by BMA material in the presence of heparin or EDTA, but the overall detection of MTB in BMA was low compared to histology and culture. Sensitivity of the Xpert® MTB/RIF compared to both histology and culture was 8.7% (95% confidence interval (CI): 1.07-28.04%) and sensitivity compared to histology only was 11.1% (95% CI: 1.38-34.7%). Specificity of the Xpert® MTB/RIF was 98.9% (95% CI: 93.9-99.7%). Although the Xpert® MTB/RIF generates a faster result than histology and TB culture and is less expensive than culture and drug susceptibility testing, the low sensitivity of the Xpert® MTB/RIF precludes its use for the diagnosis of MTB in bone marrow aspirate specimens and warrants alternative/additional testing to optimise the assay.Keywords: bone marrow aspirate , extrapulmonary TB, low sensitivity, Xpert® MTB/RIF
Procedia PDF Downloads 164341 Ensuring Safety in Fire Evacuation by Facilitating Way-Finding in Complex Buildings
Authors: Atefeh Omidkhah, Mohammadreza Bemanian
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The issue of way-finding earmarks a wide range of literature in architecture and despite the 50 year background of way-finding studies, it still lacks a comprehensive theory for indoor settings. Way-finding has a notable role in emergency evacuation as well. People in the panic situation of a fire emergency need to find the safe egress route correctly and in as minimum time as possible. In this regard the parameters of an appropriate way-finding are mentioned in the evacuation related researches albeit scattered. This study reviews the fire safety related literature to extract a way-finding related framework for architectural purposes of the design of a safe evacuation route. In this regard a research trend review in addition with applied methodological approaches review is conducted. Then by analyzing eight original researches related to way-finding parameters in fire evacuation, main parameters that affect way-finding in emergency situation of a fire incident are extracted and a framework was developed based on them. Results show that the issues related to exit route and emergency evacuation can be chased in task oriented studies of way-finding. This research trend aims to access a high-level framework and in the best condition a theory that has an explanatory capability to define differences in way-finding in indoor/outdoor settings, complex/simple buildings and different building types or transitional spaces. The methodological advances demonstrate the evacuation way-finding researches in line with three approaches that the latter one is the most up-to-date and precise method to research this subject: real actors and hypothetical stimuli as in evacuation experiments, hypothetical actors and stimuli as in agent-based simulations and real actors and semi-real stimuli as in virtual reality environment by adding multi-sensory simulation. Findings on data-mining of 8 sample of original researches in way-finding in evacuation indicate that emergency way-finding design of a building should consider two level of space cognition problems in the time of emergency and performance consequences of them in the built environment. So four major classes of problems in way-finding which are visual information deficiency, confusing layout configuration, improper navigating signage and demographic issues had been defined and discussed as the main parameters that should be provided with solutions in design and interior of a building. In the design phase of complex buildings, which face more reported problem in way-finding, it is important to consider the interior components regarding to the building type of occupancy and behavior of its occupants and determine components that tend to become landmarks and set the architectural features of egress route in line with the directions that they navigate people. Research on topological cognition of environmental and its effect on way-finding task in emergency evacuation is proposed for future.Keywords: architectural design, egress route, way-finding, fire safety, evacuation
Procedia PDF Downloads 168340 Biofiltration Odour Removal at Wastewater Treatment Plant Using Natural Materials: Pilot Scale Studies
Authors: D. Lopes, I. I. R. Baptista, R. F. Vieira, J. Vaz, H. Varela, O. M. Freitas, V. F. Domingues, R. Jorge, C. Delerue-Matos, S. A. Figueiredo
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Deodorization is nowadays a need in wastewater treatment plants. Nitrogen and sulphur compounds, volatile fatty acids, aldehydes and ketones are responsible for the unpleasant odours, being ammonia, hydrogen sulphide and mercaptans the most common pollutants. Although chemical treatments of the air extracted are efficient, these are more expensive than biological treatments, namely due the use of chemical reagents (commonly sulphuric acid, sodium hypochlorite and sodium hydroxide). Biofiltration offers the advantage of avoiding the use of reagents (only in some cases, nutrients are added in order to increase the treatment efficiency) and can be considered a sustainable process when the packing medium used is of natural origin. In this work the application of some natural materials locally available was studied both at laboratory and pilot scale, in a real wastewater treatment plant. The materials selected for this study were indigenous Portuguese forest materials derived from eucalyptus and pinewood, such as woodchips and bark, and coconut fiber was also used for comparison purposes. Their physico-chemical characterization was performed: density, moisture, pH, buffer and water retention capacity. Laboratory studies involved batch adsorption studies for ammonia and hydrogen sulphide removal and evaluation of microbiological activity. Four pilot-scale biofilters (1 cubic meter volume) were installed at a local wastewater treatment plant treating odours from the effluent receiving chamber. Each biofilter contained a different packing material consisting of mixtures of eucalyptus bark, pine woodchips and coconut fiber, with added buffering agents and nutrients. The odour treatment efficiency was monitored over time, as well as other operating parameters. The operation at pilot scale suggested that between the processes involved in biofiltration - adsorption, absorption and biodegradation - the first dominates at the beginning, while the biofilm is developing. When the biofilm is completely established, and the adsorption capacity of the material is reached, biodegradation becomes the most relevant odour removal mechanism. High odour and hydrogen sulphide removal efficiencies were achieved throughout the testing period (over 6 months), confirming the suitability of the materials selected, and mixtures thereof prepared, for biofiltration applications.Keywords: ammonia hydrogen sulphide and removal, biofiltration, natural materials, odour control in wastewater treatment plants
Procedia PDF Downloads 298339 Spatial Design Transformation of Mount Merapi's Dwellings Using Diachronic Approach
Authors: Catharina Dwi Astuti Depari, Gregorius Agung Setyonugroho
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In concern for human safety, living in disaster-prone areas is twofold: it is profoundly cataclysmic yet perceptibly contributive. This paradox could be identified in Kalitengah Lor Sub-village community who inhabit Mount Merapi’s most hazardous area, putting them to the highest exposure to eruptions’ cataclysmic impacts. After the devastating incident in 2010, through the Action Plan for Rehabilitation and Reconstruction, the National Government with immediate aid from humanitarian agencies initiated a relocation program by establishing nearly 2,613 temporary shelters throughout the mountain’s region. The problem arose as some of the most affected communities including those in Kalitengah Lor Sub-village, persistently refused to relocate. The obnoxious experience of those living in temporary shelters resulted from the program’s failure to support a long-term living was assumed to instigate the rejection. From the psychological standpoint, this phenomenon reflects the emotional bond between the affected communities with their former dwellings. Regarding this, the paper aims to reveal the factors influencing the emotional attachment of Kalitengah Lor community to their former dwellings including the dwellings’ spatial design transformation prior and post the eruption in 2010. The research adopted Likert five scale-questionnaire comprising a wide range of responses from strongly agree to strongly disagree. The responses were then statistically measured, leading to consensus that provides bases for further interpretations toward the local’s characteristics. Using purposive unit sampling technique, 50 respondents from 217 local households were randomly selected. Questions in the questionnaire were developed with concerns on the aspects of place attachment concept: affection, cognitive, behavior, and perception. Combined with quantitative method, the research adopted diachronic method which was aimed to analyze the spatial design transformation of each dwelling in relation to the inhabitant’s daily activities and personal preferences. The research found that access to natural resources like sand mining, agricultural farms and wood forests, social relationship and physical proximity from house to personal asset like cattle shed, are the dominant factors encouraging the locals to emotionally attached to their former dwellings. Consequently, each dwelling’s spatial design is suffered from changes in which the current house is typically larger in dimension and the bathroom is replaced by public toilet located outside the house’s backyard. Relatively unchanged, the cattle shed is still located in front of the house, the continuous visual relationship, particularly between the living and family room, is maintained, as well as the main orientation of the house towards the local street.Keywords: diachronic method, former dwellings, local’s characteristics, place attachment, spatial design transformation
Procedia PDF Downloads 159338 Folding of β-Structures via the Polarized Structure-Specific Backbone Charge (PSBC) Model
Authors: Yew Mun Yip, Dawei Zhang
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Proteins are the biological machinery that executes specific vital functions in every cell of the human body by folding into their 3D structures. When a protein misfolds from its native structure, the machinery will malfunction and lead to misfolding diseases. Although in vitro experiments are able to conclude that the mutations of the amino acid sequence lead to incorrectly folded protein structures, these experiments are unable to decipher the folding process. Therefore, molecular dynamic (MD) simulations are employed to simulate the folding process so that our improved understanding of the folding process will enable us to contemplate better treatments for misfolding diseases. MD simulations make use of force fields to simulate the folding process of peptides. Secondary structures are formed via the hydrogen bonds formed between the backbone atoms (C, O, N, H). It is important that the hydrogen bond energy computed during the MD simulation is accurate in order to direct the folding process to the native structure. Since the atoms involved in a hydrogen bond possess very dissimilar electronegativities, the more electronegative atom will attract greater electron density from the less electronegative atom towards itself. This is known as the polarization effect. Since the polarization effect changes the electron density of the two atoms in close proximity, the atomic charges of the two atoms should also vary based on the strength of the polarization effect. However, the fixed atomic charge scheme in force fields does not account for the polarization effect. In this study, we introduce the polarized structure-specific backbone charge (PSBC) model. The PSBC model accounts for the polarization effect in MD simulation by updating the atomic charges of the backbone hydrogen bond atoms according to equations derived between the amount of charge transferred to the atom and the length of the hydrogen bond, which are calculated from quantum-mechanical calculations. Compared to other polarizable models, the PSBC model does not require quantum-mechanical calculations of the peptide simulated at every time-step of the simulation and maintains the dynamic update of atomic charges, thereby reducing the computational cost and time while accounting for the polarization effect dynamically at the same time. The PSBC model is applied to two different β-peptides, namely the Beta3s/GS peptide, a de novo designed three-stranded β-sheet whose structure is folded in vitro and studied by NMR, and the trpzip peptides, a double-stranded β-sheet where a correlation is found between the type of amino acids that constitute the β-turn and the β-propensity.Keywords: hydrogen bond, polarization effect, protein folding, PSBC
Procedia PDF Downloads 261337 Electromagnetic-Mechanical Stimulation on PC12 for Enhancement of Nerve Axonal Extension
Authors: E. Nakamachi, K. Matsumoto, K. Yamamoto, Y. Morita, H. Sakamoto
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In recently, electromagnetic and mechanical stimulations have been recognized as the effective extracellular environment stimulation technique to enhance the defected peripheral nerve tissue regeneration. In this study, we developed a new hybrid bioreactor by adopting 50 Hz uniform alternative current (AC) magnetic stimulation and 4% strain mechanical stimulation. The guide tube for nerve regeneration is mesh structured tube made of biodegradable polymer, such as polylatic acid (PLA). However, when neural damage is large, there is a possibility that peripheral nerve undergoes necrosis. So it is quite important to accelerate the nerve tissue regeneration by achieving enhancement of nerve axonal extension rate. Therefore, we try to design and fabricate the system that can simultaneously load the uniform AC magnetic field stimulation and the stretch stimulation to cells for enhancement of nerve axonal extension. Next, we evaluated systems performance and the effectiveness of each stimulation for rat adrenal pheochromocytoma cells (PC12). First, we designed and fabricated the uniform AC magnetic field system and the stretch stimulation system. For the AC magnetic stimulation system, we focused on the use of pole piece structure to carry out in-situ microscopic observation. We designed an optimum pole piece structure using the magnetic field finite element analyses and the response surface methodology. We fabricated the uniform AC magnetic field stimulation system as a bio-reactor by adopting analytically determined design specifications. We measured magnetic flux density that is generated by the uniform AC magnetic field stimulation system. We confirmed that measurement values show good agreement with analytical results, where the uniform magnetic field was observed. Second, we fabricated the cyclic stretch stimulation device under the conditions of particular strains, where the chamber was made of polyoxymethylene (POM). We measured strains in the PC12 cell culture region to confirm the uniform strain. We found slightly different values from the target strain. Finally, we concluded that these differences were allowable in this mechanical stimulation system. We evaluated the effectiveness of each stimulation to enhance the nerve axonal extension using PC12. We confirmed that the average axonal extension length of PC12 under the uniform AC magnetic stimulation was increased by 16 % at 96 h in our bio-reactor. We could not confirm that the axonal extension enhancement under the stretch stimulation condition, where we found the exfoliating of cells. Further, the hybrid stimulation enhanced the axonal extension. Because the magnetic stimulation inhibits the exfoliating of cells. Finally, we concluded that the enhancement of PC12 axonal extension is due to the magnetic stimulation rather than the mechanical stimulation. Finally, we confirmed that the effectiveness of the uniform AC magnetic field stimulation for the nerve axonal extension using PC12 cells.Keywords: nerve cell PC12, axonal extension, nerve regeneration, electromagnetic-mechanical stimulation, bioreactor
Procedia PDF Downloads 262336 Real-Time Neuroimaging for Rehabilitation of Stroke Patients
Authors: Gerhard Gritsch, Ana Skupch, Manfred Hartmann, Wolfgang Frühwirt, Hannes Perko, Dieter Grossegger, Tilmann Kluge
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Rehabilitation of stroke patients is dominated by classical physiotherapy. Nowadays, a field of research is the application of neurofeedback techniques in order to help stroke patients to get rid of their motor impairments. Especially, if a certain limb is completely paralyzed, neurofeedback is often the last option to cure the patient. Certain exercises, like the imagination of the impaired motor function, have to be performed to stimulate the neuroplasticity of the brain, such that in the neighboring parts of the injured cortex the corresponding activity takes place. During the exercises, it is very important to keep the motivation of the patient at a high level. For this reason, the missing natural feedback due to a movement of the effected limb may be replaced by a synthetic feedback based on the motor-related brain function. To generate such a synthetic feedback a system is needed which measures, detects, localizes and visualizes the motor related µ-rhythm. Fast therapeutic success can only be achieved if the feedback features high specificity, comes in real-time and without large delay. We describe such an approach that offers a 3D visualization of µ-rhythms in real time with a delay of 500ms. This is accomplished by combining smart EEG preprocessing in the frequency domain with source localization techniques. The algorithm first selects the EEG channel featuring the most prominent rhythm in the alpha frequency band from a so-called motor channel set (C4, CZ, C3; CP6, CP4, CP2, CP1, CP3, CP5). If the amplitude in the alpha frequency band of this certain electrode exceeds a threshold, a µ-rhythm is detected. To prevent detection of a mixture of posterior alpha activity and µ-activity, the amplitudes in the alpha band outside the motor channel set are not allowed to be in the same range as the main channel. The EEG signal of the main channel is used as template for calculating the spatial distribution of the µ - rhythm over all electrodes. This spatial distribution is the input for a inverse method which provides the 3D distribution of the µ - activity within the brain which is visualized in 3D as color coded activity map. This approach mitigates the influence of lid artifacts on the localization performance. The first results of several healthy subjects show that the system is capable of detecting and localizing the rarely appearing µ-rhythm. In most cases the results match with findings from visual EEG analysis. Frequent eye-lid artifacts have no influence on the system performance. Furthermore, the system will be able to run in real-time. Due to the design of the frequency transformation the processing delay is 500ms. First results are promising and we plan to extend the test data set to further evaluate the performance of the system. The relevance of the system with respect to the therapy of stroke patients has to be shown in studies with real patients after CE certification of the system. This work was performed within the project ‘LiveSolo’ funded by the Austrian Research Promotion Agency (FFG) (project number: 853263).Keywords: real-time EEG neuroimaging, neurofeedback, stroke, EEG–signal processing, rehabilitation
Procedia PDF Downloads 379335 Malaysian ESL Writing Process: A Comparison with England’s
Authors: Henry Nicholas Lee, George Thomas, Juliana Johari, Carmilla Freddie, Caroline Val Madin
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Research in comparative and international education often provides value-laden views of an education system within and in between other countries. These views are frequently used by policy makers or educators to explore similarities and differences for, among others, benchmarking purposes. In this study, a comparison is made between Malaysia and England, focusing on the process of writing children went through to create a text, using a multimodal theoretical framework to analyse this comparison. The main purpose is political in nature as it served as an answer to Malaysia’s call for benchmarking of best practices for language learning. Furthermore, the focus on writing in this study adds into more empirical findings about early writers’ writing development and writing improvement, especially for children at the ages of 5-9. In research, comparative studies in English as a Second Language (ESL) writing pedagogy – particularly in Malaysia since the introduction of the Standard- based English Language Curriculum (KSSR) in 2011 as a draft and its full implementation in 2017; reviewed 2018 KSSR-CEFR aligned – has not been done comparatively. In theory, a multimodal theoretical framework somehow allows a logical comparison between first language and ESL which would provide useful insights to illuminate the writing process between Malaysia and England. The comparisons are not representative because of the different school systems in both countries. So far, the literature informs us that the curriculum for language learning is very much emphasised on children’s linguistic abilities, which include their proficiency and mastery of the language, its conventions, and technicalities. However, recent empirical findings suggested that literacy in its concepts and characters need change. In view of this suggestion, the comparison will look at how the process of writing is implemented through the five modes of communication: linguistic, visual, aural, spatial, and gestural. This project draws on data from Malaysia and England, involving 10 teachers, 26 classroom observations, 20 lesson plans, 20 interviews, and 20 brief conversations with teachers. The research focused upon 20 primary children of different genders aged 5-9, and in addition to primary data descriptions, 40 children’s works, 40 brief classroom conversations, 30 classroom photographs, and 30 school compound photographs were undertaken to investigate teachers and children’s use of modes and semiotic resources to design a text. The data were analysed by means of within-case analysis, cross-case analysis, and constant comparative analysis, with an initial stage of data categorisation, followed by general and specific coding, which clustered the data into thematic groups. The study highlights the importance of teachers’ and children’s engagement and interaction with various modes of communication, an adaptation from the English approaches to teaching writing within the KSSR framework and providing ‘voice’ to ESL writers to ensure that both have access to the knowledge and skills required to make decisions in developing multimodal texts and artefacts.Keywords: comparative education, early writers, KSSR, multimodal theoretical framework, writing development
Procedia PDF Downloads 62334 Effect of Packaging Material and Water-Based Solutions on Performance of Radio Frequency Identification for Food Packaging Applications
Authors: Amelia Frickey, Timothy (TJ) Sheridan, Angelica Rossi, Bahar Aliakbarian
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The growth of large food supply chains demanded improved end-to-end traceability of food products, which has led to companies being increasingly interested in using smart technologies such as Radio Frequency Identification (RFID)-enabled packaging to track items. As technology is being widely used, there are several technological or economic issues that should be overcome to facilitate the adoption of this track-and-trace technology. One of the technological challenges of RFID technology is its sensitivity to different environmental form factors, including packaging materials and the content of the packaging. Although researchers have assessed the performance loss due to the proximity of water and aqueous solutions, there is still the need to further investigate the impacts of food products on the reading range of RFID tags. However, to the best of our knowledge, there are not enough studies to determine the correlation between RFID tag performance and food beverages properties. The goal of this project was to investigate the effect of the solution properties (pH and conductivity) and different packaging materials filled with food-like water-based solutions on the performance of an RFID tag. Three commercially available ultra high-frequency RFID tags were placed on three different bottles and filled with different concentrations of water-based solutions, including sodium chloride, citric acid, sucrose, and ethanol. Transparent glass, Polyethylneterephtalate (PET), and Tetrapak® were used as the packaging materials commonly used in the beverage industries. Tag readability (Theoretical Read Range, TRR) and sensitivity (Power on Tag Forward, PoF) were determined using an anechoic chamber. First, the best place to attach the tag for each packaging material was investigated using empty and water-filled bottles. Then, the bottles were filled with the food-like solutions and tested with the three different tags and the PoF and TRR at the fixed frequency of 915MHz. In parallel, the pH and conductivity of solutions were measured. The best-performing tag was then selected to test the bottles filled with wine, orange, and apple juice. Despite various solutions altering the performance of each tag, the change in tag performance had no correlation with the pH or conductivity of the solution. Additionally, packaging material played a significant role in tag performance. Each tag tested performed optimally under different conditions. This study is the first part of comprehensive research to determine the regression model for the prediction of tag performance behavior based on the packaging material and the content. More investigations, including more tags and food products, are needed to be able to develop a robust regression model. The results of this study can be used by RFID tag manufacturers to design suitable tags for specific products with similar properties.Keywords: smart food packaging, supply chain management, food waste, radio frequency identification
Procedia PDF Downloads 108333 Controlling the Release of Cyt C and L- Dopa from pNIPAM-AAc Nanogel Based Systems
Authors: Sulalit Bandyopadhyay, Muhammad Awais Ashfaq Alvi, Anuvansh Sharma, Wilhelm R. Glomm
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Release of drugs from nanogels and nanogel-based systems can occur under the influence of external stimuli like temperature, pH, magnetic fields and so on. pNIPAm-AAc nanogels respond to the combined action of both temperature and pH, the former being mostly determined by hydrophilic-to-hydrophobic transitions above the volume phase transition temperature (VPTT), while the latter is controlled by the degree of protonation of the carboxylic acid groups. These nanogels based systems are promising candidates in the field of drug delivery. Combining nanogels with magneto-plasmonic nanoparticles (NPs) introduce imaging and targeting modalities along with stimuli-response in one hybrid system, thereby incorporating multifunctionality. Fe@Au core-shell NPs possess optical signature in the visible spectrum owing to localized surface plasmon resonance (LSPR) of the Au shell, and superparamagnetic properties stemming from the Fe core. Although there exist several synthesis methods to control the size and physico-chemical properties of pNIPAm-AAc nanogels, yet, there is no comprehensive study that highlights the dependence of incorporation of one or more layers of NPs to these nanogels. In addition, effective determination of volume phase transition temperature (VPTT) of the nanogels is a challenge which complicates their uses in biological applications. Here, we have modified the swelling-collapse properties of pNIPAm-AAc nanogels, by combining with Fe@Au NPs using different solution based methods. The hydrophilic-hydrophobic transition of the nanogels above the VPTT has been confirmed to be reversible. Further, an analytical method has been developed to deduce the average VPTT which is found to be 37.3°C for the nanogels and 39.3°C for nanogel coated Fe@Au NPs. An opposite swelling –collapse behaviour is observed for the latter where the Fe@Au NPs act as bridge molecules pulling together the gelling units. Thereafter, Cyt C, a model protein drug and L-Dopa, a drug used in the clinical treatment of Parkinson’s disease were loaded separately into the nanogels and nanogel coated Fe@Au NPs, using a modified breathing-in mechanism. This gave high loading and encapsulation efficiencies (L Dopa: ~9% and 70µg/mg of nanogels, Cyt C: ~30% and 10µg/mg of nanogels respectively for both the drugs. The release kinetics of L-Dopa, monitored using UV-vis spectrophotometry was observed to be rather slow (over several hours) with highest release happening under a combination of high temperature (above VPTT) and acidic conditions. However, the release of L-Dopa from nanogel coated Fe@Au NPs was the fastest, accounting for release of almost 87% of the initially loaded drug in ~30 hours. The chemical structure of the drug, drug incorporation method, location of the drug and presence of Fe@Au NPs largely alter the drug release mechanism and the kinetics of these nanogels and Fe@Au NPs coated with nanogels.Keywords: controlled release, nanogels, volume phase transition temperature, l-dopa
Procedia PDF Downloads 323332 Molecular Characterization of Arginine Sensing Response in Unravelling Host-Pathogen Interactions in Leishmania
Authors: Evanka Madan, Madhu Puri, Dan Zilberstein, Rohini Muthuswami, Rentala Madhubala
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The extensive interaction between the host and pathogen metabolic networks decidedly shapes the outcome of infection. Utilization of arginine by the host and pathogen is critical for determining the outcome of pathogenic infection. Infections with L. donovani, an intracellular parasite, will lead to an extensive competition of arginine between the host and the parasite donovani infection. One of the major amino acid (AA) sensing signaling pathways in mammalian cells are the mammalian target of rapamycin complex I (mTORC1) pathway. mTORC1, as a sensor of nutrient, controls numerous metabolic pathways. Arginine is critical for mTORC1 activation. SLC38A9 is the arginine sensor for the mTORC1, being activated during arginine sufficiency. L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by arginine deficiency response (ADR) in intracellular amastigotes. This study, to author’s best knowledge, investigates the interaction between two arginine sensing systems that act in the same compartment, the lysosome. One is important for macrophage defense, and the other is essential for pathogen virulence. We hypothesize that the latter modulates lysosome arginine to prevent host defense response. The work presented here identifies an upstream regulatory role of LdAAP3 in regulating the expression of SLC38A9-mTORC1 pathway, and consequently, their function in L. donovani infected THP-1 cells cultured in 0.1 mM and 1.5 mM arginine. It was found that in physiological levels of arginine (0.1 mM), infecting THP-1 with Leishmania leads to increased levels of SLC38A9 and mTORC1 via an increase in the expression of RagA. However, the reversal was observed with LdAAP3 mutants, reflecting the positive regulatory role of LdAAP3 on the host SLC38A9. At the molecular level, upon infection, mTORC1 and RagA were found to be activated at the surface of phagolysosomes which was found to form a complex with phagolysosomal localized SLC38A9. To reveal the relevance of SLC38A9 under physiological levels of arginine, endogenous SLC38A9 was depleted and a substantial reduction in the expression of host mTORC1, its downstream active substrate, p-P70S6K1 and parasite LdAAP3, was observed, thereby showing that silencing SLC38A9 suppresses ADR. In brief, to author’s best knowledge, these results reveal an upstream regulatory role of LdAAP3 in manipulating SLC38A9 arginine sensing in host macrophages. Our study indicates that intra-macrophage survival of L. donovani depends on the availability and transport of extracellular arginine. An understanding of the sensing pathway of both parasite and host will open a new perspective on the molecular mechanism of host-parasite interaction and consequently, as a treatment for Leishmaniasis.Keywords: arginine sensing, LdAAP3, L. donovani, mTORC1, SLC38A9, THP-1
Procedia PDF Downloads 114331 Investigation of the Carbon Dots Optical Properties Using Laser Scanning Confocal Microscopy and TimE-resolved Fluorescence Microscopy
Authors: M. S. Stepanova, V. V. Zakharov, P. D. Khavlyuk, I. D. Skurlov, A. Y. Dubovik, A. L. Rogach
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Carbon dots are small carbon-based spherical nanoparticles, which are typically less than 10 nm in size that can be modified with surface passivation and heteroatoms doping. The light-absorbing ability of carbon dots has attracted a significant amount of attention in photoluminescence for bioimaging and fluorescence sensing applications owing to their advantages, such as tunable fluorescence emission, photo- and thermostability and low toxicity. In this study, carbon dots were synthesized by the solvothermal method from citric acid and ethylenediamine dissolved in water. The solution was heated for 5 hours at 200°C and then cooled down to room temperature. The carbon dots films were obtained by evaporation from a high-concentration aqueous solution. The increase of both luminescence intensity and light transmission was obtained as a result of a 405 nm laser exposure to a part of the carbon dots film, which was detected using a confocal laser scanning microscope (LSM 710, Zeiss). Blueshift up to 35 nm of the luminescence spectrum is observed as luminescence intensity, which is increased more than twofold. The exact value of the shift depends on the time of the laser exposure. This shift can be caused by the modification of surface groups at the carbon dots, which are responsible for long-wavelength luminescence. In addition, a shift of the absorption peak by 10 nm and a decrease in the optical density at the wavelength of 350 nm is detected, which is responsible for the absorption of surface groups. The obtained sample was also studied with time-resolved confocal fluorescence microscope (MicroTime 100, PicoQuant), which made it possible to receive a time-resolved photoluminescence image and construct emission decays of the laser-exposed and non-exposed areas. 5 MHz pulse rate impulse laser has been used as a photoluminescence excitation source. Photoluminescence decay was approximated by two exhibitors. The laser-exposed area has the amplitude of the first-lifetime component (A1) twice as much as before, with increasing τ1. At the same time, the second-lifetime component (A2) decreases. These changes evidence a modification of the surface groups of carbon dots. The detected effect can be used to create thermostable fluorescent marks, the physical size of which is bounded by the diffraction limit of the optics (~ 200-300 nm) used for exposure and to improve the optical properties of carbon dots or in the field of optical encryption. Acknowledgements: This work was supported by the Ministry of Science and Higher Education of Russian Federation, goszadanie no. 2019-1080 and financially supported by Government of Russian Federation, Grant 08-08.Keywords: carbon dots, photoactivation, optical properties, photoluminescence and absorption spectra
Procedia PDF Downloads 159330 Enhancement to Green Building Rating Systems for Industrial Facilities by Including the Assessment of Impact on the Landscape
Authors: Lia Marchi, Ernesto Antonini
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The impact of industrial sites on people’s living environment both involves detrimental effects on the ecosystem and perceptual-aesthetic interferences with the scenery. These, in turn, affect the economic and social value of the landscape, as well as the wellbeing of workers and local communities. Given the diffusion of the phenomenon and the relevance of its effects, it emerges the need for a joint approach to assess and thus mitigate the impact of factories on the landscape –being this latest assumed as the result of the action and interaction of natural and human factors. However, the impact assessment tools suitable for the purpose are quite heterogeneous and mostly monodisciplinary. On the one hand, green building rating systems (GBRSs) are increasingly used to evaluate the performance of manufacturing sites, mainly by quantitative indicators focused on environmental issues. On the other hand, methods to detect the visual and social impact of factories on the landscape are gradually emerging in the literature, but they generally adopt only qualitative gauges. The research addresses the integration of the environmental impact assessment and the perceptual-aesthetic interferences of factories on the landscape. The GBRSs model is assumed as a reference since it is adequate to simultaneously investigate different topics which affect sustainability, returning a global score. A critical analysis of GBRSs relevant to industrial facilities has led to select the U.S. GBC LEED protocol as the most suitable to the scope. A revision of LEED v4 Building Design+Construction has then been provided by including specific indicators to measure the interferences of manufacturing sites with the perceptual-aesthetic and social aspects of the territory. To this end, a new impact category was defined, namely ‘PA - Perceptual-aesthetic aspects’, comprising eight new credits which are specifically designed to assess how much the buildings are in harmony with their surroundings: these investigate, for example the morphological and chromatic harmonization of the facility with the scenery or the site receptiveness and attractiveness. The credits weighting table was consequently revised, according to the LEED points allocation system. As all LEED credits, each new PA credit is thoroughly described in a sheet setting its aim, requirements, and the available options to gauge the interference and get a score. Lastly, each credit is related to mitigation tactics, which are drawn from a catalogue of exemplary case studies, it also developed by the research. The result is a modified LEED scheme which includes compatibility with the landscape within the sustainability assessment of the industrial sites. The whole system consists of 10 evaluation categories, which contain in total 62 credits. Lastly, a test of the tool on an Italian factory was performed, allowing the comparison of three mitigation scenarios with increasing compatibility level. The study proposes a holistic and viable approach to the environmental impact assessment of factories by a tool which integrates the multiple involved aspects within a worldwide recognized rating protocol.Keywords: environmental impact, GBRS, landscape, LEED, sustainable factory
Procedia PDF Downloads 108329 Reading Comprehension in Profound Deaf Readers
Authors: S. Raghibdoust, E. Kamari
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Research show that reduced functional hearing has a detrimental influence on the ability of an individual to establish proper phonological representations of words, since the phonological representations are claimed to mediate the conceptual processing of written words. Word processing efficiency is expected to decrease with a decrease in functional hearing. In other words, it is predicted that hearing individuals would be more capable of word processing than individuals with hearing loss, as their functional hearing works normally. Studies also demonstrate that the quality of the functional hearing affects reading comprehension via its effect on their word processing skills. In other words, better hearing facilitates the development of phonological knowledge, and can promote enhanced strategies for the recognition of written words, which in turn positively affect higher-order processes underlying reading comprehension. The aims of this study were to investigate and compare the effect of deafness on the participants’ abilities to process written words at the lexical and sentence levels through using two online and one offline reading comprehension tests. The performance of a group of 8 deaf male students (ages 8-12) was compared with that of a control group of normal hearing male students. All the participants had normal IQ and visual status, and came from an average socioeconomic background. None were diagnosed with a particular learning or motor disability. The language spoken in the homes of all participants was Persian. Two tests of word processing were developed and presented to the participants using OpenSesame software, in order to measure the speed and accuracy of their performance at the two perceptual and conceptual levels. In the third offline test of reading comprehension which comprised of semantically plausible and semantically implausible subject relative clauses, the participants had to select the correct answer out of two choices. The data derived from the statistical analysis using SPSS software indicated that hearing and deaf participants had a similar word processing performance both in terms of speed and accuracy of their responses. The results also showed that there was no significant difference between the performance of the deaf and hearing participants in comprehending semantically plausible sentences (p > 0/05). However, a significant difference between the performances of the two groups was observed with respect to their comprehension of semantically implausible sentences (p < 0/05). In sum, the findings revealed that the seriously impoverished sentence reading ability characterizing the profound deaf subjects of the present research, exhibited their reliance on reading strategies that are based on insufficient or deviant structural knowledge, in particular in processing semantically implausible sentences, rather than a failure to efficiently process written words at the lexical level. This conclusion, of course, does not mean to say that deaf individuals may never experience deficits at the word processing level, deficits that impede their understanding of written texts. However, as stated in previous researches, it sounds reasonable to assume that the more deaf individuals get familiar with written words, the better they can recognize them, despite having a profound phonological weakness.Keywords: deafness, reading comprehension, reading strategy, word processing, subject and object relative sentences
Procedia PDF Downloads 332328 Effects of the Natural Compound on SARS-CoV-2 Spike Protein-Mediated Metabolic Alteration in THP-1 Cells Explored by the ¹H-NMR-Based Metabolomics Approach
Authors: Gyaltsen Dakpa, K. J. Senthil Kumar, Nai-Wen Tsao, Sheng-Yang Wang
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Context: Coronavirus disease 2019 (COVID-19) is a severe respiratory illness caused by the SARS-CoV-2 virus. One of the hallmarks of COVID-19 is a change in metabolism, which can lead to increased severity and mortality. The mechanism of SARS-CoV-2-mediated perturbations of metabolic pathways has yet to be fully understood. Research Aim: This study aimed to investigate the metabolic alteration caused by SARS-CoV-2 spike protein in Phorbol 12-myristate 13-acetate (PMA)-induced human monocytes (THP-1) and to examine the regulatory effect of natural compounds like Antcins A on SARS-CoV-2 spike protein-induced metabolic alteration. Methodology: The study used a combination of proton nuclear magnetic resonance (1H-NMR) and MetaboAnalyst 5.0 software. THP-1 cells were treated with SARS-CoV-2 spike protein or control, and the metabolomic profiles of the cells were compared. Antcin A was also added to the cells to assess its regulatory effect on SARS-CoV-2 spike protein-induced metabolic alteration. Findings: The study results showed that treatment with SARS-CoV-2 spike protein significantly altered the metabolomic profiles of THP-1 cells. Eight metabolites, including glycerol-phosphocholine, glycine, canadine, sarcosine, phosphoenolpyruvic acid, glutamine, glutamate, and N, N-dimethylglycine, were significantly different between control and spike-protein treatment groups. Antcin A significantly reversed the changes in these metabolites. In addition, treatment with antacid A significantly inhibited SARS-CoV-2 spike protein-mediated up-regulation of TLR-4 and ACE2 receptors. Theoretical Importance The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19. Data Collection: The data for this study was collected from THP-1 cells that were treated with SARS-CoV-2 spike protein or a control. The metabolomic profiles of the cells were then compared using 1H-NMR and MetaboAnalyst 5.0 software. Analysis Procedures: The metabolomic profiles of the THP-1 cells were analyzed using 1H-NMR and MetaboAnalyst 5.0 software. The software was used to identify and quantify the cells' metabolites and compare the control and spike-protein treatment groups. Questions Addressed: The question addressed by this study was whether SARS-CoV-2 spike protein could cause metabolic alterations in THP-1 cells and whether Antcin A can reverse these alterations. Conclusion: The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19.Keywords: SARS-CoV-2-spike, ¹H-NMR, metabolomics, antcin-A, taiwanofungus camphoratus
Procedia PDF Downloads 65327 Approach to Honey Volatiles' Profiling by Gas Chromatography and Mass Spectrometry
Authors: Igor Jerkovic
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Biodiversity of flora provides many different nectar sources for the bees. Unifloral honeys possess distinctive flavours, mainly derived from their nectar sources (characteristic volatile organic components (VOCs)). Specific or nonspecific VOCs (chemical markers) could be used for unifloral honey characterisation as addition to the melissopalynologycal analysis. The main honey volatiles belong, in general, to three principal categories: terpenes, norisoprenoids, and benzene derivatives. Some of these substances have been described as characteristics of the floral source, and other compounds, like several alcohols, branched aldehydes, and furan derivatives, may be related to the microbial purity of honey processing and storage conditions. Selection of the extraction method for the honey volatiles profiling should consider that heating of the honey produce different artefacts and therefore conventional methods of VOCs isolation (such as hydrodistillation) cannot be applied for the honey. Two-way approach for the isolation of the honey VOCs was applied using headspace solid-phase microextraction (HS-SPME) and ultrasonic solvent extraction (USE). The extracts were analysed by gas chromatography and mass spectrometry (GC-MS). HS-SPME (with the fibers of different polarity such as polydimethylsiloxane/ divinylbenzene (PDMS/DVB) or divinylbenzene/carboxene/ polydimethylsiloxane (DVB/CAR/PDMS)) enabled isolation of high volatile headspace VOCs of the honey samples. Among them, some characteristic or specific compounds can be found such as 3,4-dihydro-3-oxoedulan (in Centaurea cyanus L. honey) or 1H-indole, methyl anthranilate, and cis-jasmone (in Citrus unshiu Marc. honey). USE with different solvents (mainly dichloromethane or the mixture pentane : diethyl ether 1 : 2 v/v) enabled isolation of less volatile and semi-volatile VOCs of the honey samples. Characteristic compounds from C. unshiu honey extracts were caffeine, 1H-indole, 1,3-dihydro-2H-indol-2-one, methyl anthranilate, and phenylacetonitrile. Sometimes, the selection of solvent sequence was useful for more complete profiling such as sequence I: pentane → diethyl ether or sequence II: pentane → pentane/diethyl ether (1:2, v/v) → dichloromethane). The extracts with diethyl ether contained hydroquinone and 4-hydroxybenzoic acid as the major compounds, while (E)-4-(r-1’,t-2’,c-4’-trihydroxy-2’,6’,6’-trimethylcyclo-hexyl)but-3-en-2-one predominated in dichloromethane extracts of Allium ursinum L. honey. With this two-way approach, it was possible to obtain a more detailed insight into the honey volatile and semi-volatile compounds and to minimize the risks of compound discrimination due to their partial extraction that is of significant importance for the complete honey profiling and identification of the chemical biomarkers that can complement the pollen analysis.Keywords: honey chemical biomarkers, honey volatile compounds profiling, headspace solid-phase microextraction (HS-SPME), ultrasonic solvent extraction (USE)
Procedia PDF Downloads 195326 Communicating Safety: A Digital Ethnography Investigating Social Media Use for Workplace Safety
Authors: Kelly Jaunzems
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Social media is a powerful instrument of communication, enabling the presentation of information in multiple forms and modes, amplifying the interactions between people, organisations, and stakeholders, and increasing the range of communication channels available. Younger generations are highly engaged with social media and more likely to use this channel than any other to seek information. Given this, it may appear extraordinary that occupational safety and health professionals have yet to seriously engage with social media for communicating safety messages to younger audiences who, in many industries, might be statistically more likely to encounter more workplace harm or injury. Millennials, defined as those born between 1981-2000, have distinctive characteristics that also impact their interaction patterns rendering many traditional occupational safety and health communication channels sub-optimal or near obsolete. Used to immediate responses, 280-character communication, shares, likes, and visual imagery, millennials struggle to take seriously the low-tech, top-down communication channels such as safety noticeboards, toolbox meetings, and passive tick-box online inductions favoured by traditional OSH professionals. This paper draws upon well-established communication findings, which argue that it is important to know a target audience and reach them using their preferred communication pathways, particularly if the aim is to impact attitudes and behaviours. Health practitioners have adopted social media as a communication channel with great success, yet safety practitioners have failed to follow this lead. Using a digital ethnography approach, this paper examines seven organisations’ Facebook posts from two one-month periods one year apart, one in 2018 and one in 2019. Each of the years informs organisation-based case studies. Comparing, contrasting, and drawing upon these case studies, the paper discusses and evaluates the (non) use of social media communication of safety information in terms of user engagement, shareability, and overall appeal. The success of health practitioners’ use of social media provides a compelling template for the implementation of social media into organisations’ safety communication strategies. Highly visible content such as that found on social media allows an organization to become more responsive and engage in two-way conversations with their audience, creating more engaged and participatory conversations around safety. Further, using social media to address younger audiences with a range of tonal qualities (for example, the use of humour) can achieve cut through in a way that grim statistics fail to do. On the basis of 18 months of interviews, filed work, and data analysis, the paper concludes with recommendations for communicating safety information via social media. It proposes exploration of the social media communication formula that, when utilised by safety practitioners, may create an effective social media presence. It is anticipated that such social media use will increase engagement, expand the number of followers and reduce the likelihood and severity of safety-related incidents. The tools offered may provide a path for safety practitioners to reach a disengaged generation of workers to build a cohesive and inclusive conversation around ways to keep people safe at work.Keywords: social media, workplace safety, communication strategies, young workers
Procedia PDF Downloads 107325 Role of Platelet Volume Indices in Diabetes Related Vascular Angiopathies
Authors: Mitakshara Sharma, S. K. Nema, Sanjeev Narang
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Diabetes mellitus (DM) is a group of metabolic disorders characterized by metabolic abnormalities, chronic hyperglycaemia and long term macrovascular & microvascular complications. Vascular complications are due to platelet hyperactivity and dysfunction, increased inflammation, altered coagulation and endothelial dysfunction. Large proportion of patients with Type II DM suffers from preventable vascular angiopathies, and there is need to develop risk factor modifications and interventions to reduce impact of complications. These complications are attributed to platelet activation, recognised by increase in Platelet Volume Indices (PVI) including Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW). The current study is prospective analytical study conducted over 2 years. Out of 1100 individuals, 930 individuals fulfilled inclusion criteria and were segregated into three groups on basis of glycosylated haemoglobin (HbA1C): - (a) Diabetic, (b) Non-Diabetic and (c) Subjects with Impaired fasting glucose (IFG) with 300 individuals in IFG and non-diabetic groups & 330 individuals in diabetic group. Further, diabetic group was divided into two groups on the basis of presence or absence of known diabetes related vascular complications. Samples for HbA1c and PVI were collected using Ethylene diamine tetraacetic acid (EDTA) as anticoagulant and processed on SYSMEX-X-800i autoanalyser. The study revealed gradual increase in PVI from non-diabetics to IFG to diabetics. PVI were markedly increased in diabetic patients. MPV and PDW of diabetics, IFG and non diabetics were (17.60 ± 2.04)fl, (11.76 ± 0.73)fl, (9.93 ± 0.64)fl and (19.17 ± 1.48)fl, (15.49 ± 0.67)fl, (10.59 ± 0.67)fl respectively with a significant p value 0.00 and a significant positive correlation (MPV-HbA1c r = 0.951; PDW-HbA1c r = 0.875). MPV & PDW of subjects with diabetes related complications were higher as compared to those without them and were (17.51±0.39)fl & (15.14 ± 1.04)fl and (20.09 ± 0.98) fl & (18.96 ± 0.83)fl respectively with a significant p value 0.00. There was a significant positive correlation between PVI and duration of diabetes across the groups (MPV-HbA1c r = 0.951; PDW-HbA1c r = 0.875). However, a significant negative correlation was found between glycaemic levels and total platelet count (PC- HbA1c r =-0.164). This is multi-parameter and comprehensive study with an adequately powered study design. It can be concluded from our study that PVI are extremely useful and important indicators of impending vascular complications in all patients with deranged glycaemic control. Introduction of automated cell counters has facilitated the availability of PVI as routine parameters. PVI is a useful means for identifying larger & active platelets which play important role in development of micro and macro angiopathic complications of diabetes leading to mortality and morbidity. PVI can be used as cost effective markers to predict and prevent impending vascular events in patients with Diabetes mellitus especially in developing countries like India. PVI, if incorporated into protocols for management of diabetes, could revolutionize care and curtail the ever increasing cost of patient management.Keywords: diabetes, IFG, HbA1C, MPV, PDW, PVI
Procedia PDF Downloads 254324 Impact of Alkaline Activator Composition and Precursor Types on Properties and Durability of Alkali-Activated Cements Mortars
Authors: Sebastiano Candamano, Antonio Iorfida, Patrizia Frontera, Anastasia Macario, Fortunato Crea
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Alkali-activated materials are promising binders obtained by an alkaline attack on fly-ashes, metakaolin, blast slag among others. In order to guarantee the highest ecological and cost efficiency, a proper selection of precursors and alkaline activators has to be carried out. These choices deeply affect the microstructure, chemistry and performances of this class of materials. Even if, in the last years, several researches have been focused on mix designs and curing conditions, the lack of exhaustive activation models, standardized mix design and curing conditions and an insufficient investigation on shrinkage behavior, efflorescence, additives and durability prevent them from being perceived as an effective and reliable alternative to Portland. The aim of this study is to develop alkali-activated cements mortars containing high amounts of industrial by-products and waste, such as ground granulated blast furnace slag (GGBFS) and ashes obtained from the combustion process of forest biomass in thermal power plants. In particular, the experimental campaign was performed in two steps. In the first step, research was focused on elucidating how the workability, mechanical properties and shrinkage behavior of produced mortars are affected by the type and fraction of each precursor as well as by the composition of the activator solutions. In order to investigate the microstructures and reaction products, SEM and diffractometric analyses have been carried out. In the second step, their durability in harsh environments has been evaluated. Mortars obtained using only GGBFS as binder showed mechanical properties development and shrinkage behavior strictly dependent on SiO2/Na2O molar ratio of the activator solutions. Compressive strengths were in the range of 40-60 MPa after 28 days of curing at ambient temperature. Mortars obtained by partial replacement of GGBFS with metakaolin and forest biomass ash showed lower compressive strengths (≈35 MPa) and shrinkage values when higher amount of ashes were used. By varying the activator solutions and binder composition, compressive strength up to 70 MPa associated with shrinkage values of about 4200 microstrains were measured. Durability tests were conducted to assess the acid and thermal resistance of the different mortars. They all showed good resistance in a solution of 5%wt of H2SO4 also after 60 days of immersion, while they showed a decrease of mechanical properties in the range of 60-90% when exposed to thermal cycles up to 700°C.Keywords: alkali activated cement, biomass ash, durability, shrinkage, slag
Procedia PDF Downloads 322323 Development of a Miniature Laboratory Lactic Goat Cheese Model to Study the Expression of Spoilage by Pseudomonas Spp. In Cheeses
Authors: Abirami Baleswaran, Christel Couderc, Loubnah Belahcen, Jean Dayde, Hélène Tormo, Gwénaëlle Jard
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Cheeses are often reported to be spoiled by Pseudomonas spp., responsible for defects in appearance, texture, taste, and smell, leading to their non-marketing and even their destruction. Despite preventive actions, problems linked to Pseudomonas spp. are difficult to control by the lack of knowledge and control of these contaminants during the cheese manufacturing. Lactic goat cheese producers are not spared by this problem and are looking for solutions to decrease the number of spoiled cheeses. To explore different hypotheses, experiments are needed. However, cheese-making experiments at the pilot scale are expensive and time consuming. Thus, there is a real need to develop a miniature cheeses model system under controlled conditions. In a previous study, several miniature cheese models corresponding to different type of commercial cheeses have been developed for different purposes. The models were, for example, used to study the influence of milk, starters cultures, pathogen inhibiting additives, enzymatic reactions, microflora, freezing process on cheese. Nevertheless, no miniature model was described on the lactic goat cheese. The aim of this work was to develop a miniature cheese model system under controlled laboratory conditions which resembles commercial lactic goat cheese to study Pseudomonas spp. spoilage during the manufacturing and ripening process. First, a protocol for the preparation of miniature cheeses (3.5 times smaller than a commercial one) was designed based on the cheese factorymanufacturing process. The process was adapted from “Rocamadour” technology and involves maturation of pasteurized milk, coagulation, removal of whey by centrifugation, moulding, and ripening in a little scale cellar. Microbiological (total bacterial count, yeast, molds) and physicochemical (pH, saltinmoisture, moisture in fat-free)analyses were performed on four key stages of the process (before salting, after salting, 1st day of ripening, and end of ripening). Factory and miniature cheeses volatilomewere also obtained after full scan Sift-MS cheese analysis. Then, Pseudomonas spp. strains isolated from contaminated cheeses were selected on their origin, their ability to produce pigments, and their enzymatic activities (proteolytic, lecithinasic, and lipolytic). Factory and miniature curds were inoculated by spotting selected strains on the cheese surface. The expression of cheese spoilage was evaluated by counting the level of Pseudomonas spp. during the ripening and by visual observation and under UVlamp. The physicochemical and microbiological compositions of miniature cheeses permitted to assess that miniature process resembles factory process. As expected, differences involatilomes were observed, probably due to the fact that miniature cheeses are made usingpasteurized milk to better control the microbiological conditions and also because the little format of cheese induced probably a difference during the ripening even if the humidity and temperature in the cellar were quite similar. The spoilage expression of Pseudomonas spp. was observed in miniature and factory cheeses. It confirms that the proposed model is suitable for the preparation of miniature cheese specimens in the spoilage study of Pseudomonas spp. in lactic cheeses. This kind of model could be deployed for other applications and other type of cheese.Keywords: cheese, miniature, model, pseudomonas spp, spoilage
Procedia PDF Downloads 130322 Golden Dawn's Rhetoric on Social Networks: Populism, Xenophobia and Antisemitism
Authors: Georgios Samaras
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New media such as Facebook, YouTube and Twitter introduced the world to a new era of instant communication. An era where online interactions could replace a lot of offline actions. Technology can create a mediated environment in which participants can communicate (one-to-one, one-to-many, and many-to-many) both synchronously and asynchronously and participate in reciprocal message exchanges. Currently, social networks are attracting similar academic attention to that of the internet after its mainstream implementation into public life. Websites and platforms are seen as the forefront of a new political change. There is a significant backdrop of previous methodologies employed to research the effects of social networks. New approaches are being developed to be able to adapt to the growth of social networks and the invention of new platforms. Golden Dawn was the first openly neo-Nazi party post World War II to win seats in the parliament of a European country. Its racist rhetoric and violent tactics on social networks were rewarded by their supporters, who in the face of Golden Dawn’s leaders saw a ‘new dawn’ in Greek politics. Mainstream media banned its leaders and members of the party indefinitely after Ilias Kasidiaris attacked Liana Kanelli, a member of the Greek Communist Party, on live television. This media ban was seen as a treasonous move by a significant percentage of voters, who believed that the system was desperately trying to censor Golden Dawn to favor mainstream parties. The shocking attack on live television received international coverage and while European countries were condemning this newly emerged neo-Nazi rhetoric, almost 7 percent of the Greek population rewarded Golden Dawn with 18 seats in the Greek parliament. Many seem to think that Golden Dawn mobilised its voters online and this approach played a significant role in spreading their message and appealing to wider audiences. No strict online censorship existed back in 2012 and although Golden Dawn was openly used neo-Nazi symbolism, it was allowed to use social networks without serious restrictions until 2017. This paper used qualitative methods to investigate Golden Dawn’s rise in social networks from 2012 to 2019. The focus of the content analysis was set on three social networking platforms: Facebook, Twitter and YouTube, while the existence of Golden Dawn’s website, which was used as a news sharing hub, was also taken into account. The content analysis included text and visual analyses that sampled content from their social networking pages to translate their political messaging through an ideological lens focused on extreme-right populism. The absence of hate speech regulations on social network platforms in 2012 allowed the free expression of those heavily ultranationalist and populist views, as they were employed by Golden Dawn in the Greek political scene. On YouTube, Facebook and Twitter, the influence of their rhetoric was particularly strong. Official channels and MPs profiles were investigated to explore the messaging in-depth and understand its ideological elements.Keywords: populism, far-right, social media, Greece, golden dawn
Procedia PDF Downloads 140321 A Case Report on Cognitive-Communication Intervention in Traumatic Brain Injury
Authors: Nikitha Francis, Anjana Hoode, Vinitha George, Jayashree S. Bhat
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The interaction between cognition and language, referred as cognitive-communication, is very intricate, involving several mental processes such as perception, memory, attention, lexical retrieval, decision making, motor planning, self-monitoring and knowledge. Cognitive-communication disorders are difficulties in communicative competencies that result from underlying cognitive impairments of attention, memory, organization, information processing, problem solving, and executive functions. Traumatic brain injury (TBI) is an acquired, non - progressive condition, resulting in distinct deficits of cognitive communication abilities such as naming, word-finding, self-monitoring, auditory recognition, attention, perception and memory. Cognitive-communication intervention in TBI is individualized, in order to enhance the person’s ability to process and interpret information for better functioning in their family and community life. The present case report illustrates the cognitive-communicative behaviors and the intervention outcomes of an adult with TBI, who was brought to the Department of Audiology and Speech Language Pathology, with cognitive and communicative disturbances, consequent to road traffic accident. On a detailed assessment, she showed naming deficits along with perseverations and had severe difficulty in recalling the details of the accident, her house address, places she had visited earlier, names of people known to her, as well as the activities she did each day, leading to severe breakdowns in her communicative abilities. She had difficulty in initiating, maintaining and following a conversation. She also lacked orientation to time and place. On administration of the Manipal Manual of Cognitive Linguistic Abilities (MMCLA), she exhibited poor performance on tasks related to visual and auditory perception, short term memory, working memory and executive functions. She attended 20 sessions of cognitive-communication intervention which followed a domain-general, adaptive training paradigm, with tasks relevant to everyday cognitive-communication skills. Compensatory strategies such as maintaining a dairy with reminders of her daily routine, names of people, date, time and place was also recommended. MMCLA was re-administered and her performance in the tasks showed significant improvements. Occurrence of perseverations and word retrieval difficulties reduced. She developed interests to initiate her day-to-day activities at home independently, as well as involve herself in conversations with her family members. Though she lacked awareness about her deficits, she actively involved herself in all the therapy activities. Rehabilitation of moderate to severe head injury patients can be done effectively through a holistic cognitive retraining with a focus on different cognitive-linguistic domains. Selection of goals and activities should have relevance to the functional needs of each individual with TBI, as highlighted in the present case report.Keywords: cognitive-communication, executive functions, memory, traumatic brain injury
Procedia PDF Downloads 343320 Role of Artificial Intelligence in Nano Proteomics
Authors: Mehrnaz Mostafavi
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Recent advances in single-molecule protein identification (ID) and quantification techniques are poised to revolutionize proteomics, enabling researchers to delve into single-cell proteomics and identify low-abundance proteins crucial for biomedical and clinical research. This paper introduces a different approach to single-molecule protein ID and quantification using tri-color amino acid tags and a plasmonic nanopore device. A comprehensive simulator incorporating various physical phenomena was designed to predict and model the device's behavior under diverse experimental conditions, providing insights into its feasibility and limitations. The study employs a whole-proteome single-molecule identification algorithm based on convolutional neural networks, achieving high accuracies (>90%), particularly in challenging conditions (95–97%). To address potential challenges in clinical samples, where post-translational modifications affecting labeling efficiency, the paper evaluates protein identification accuracy under partial labeling conditions. Solid-state nanopores, capable of processing tens of individual proteins per second, are explored as a platform for this method. Unlike techniques relying solely on ion-current measurements, this approach enables parallel readout using high-density nanopore arrays and multi-pixel single-photon sensors. Convolutional neural networks contribute to the method's versatility and robustness, simplifying calibration procedures and potentially allowing protein ID based on partial reads. The study also discusses the efficacy of the approach in real experimental conditions, resolving functionally similar proteins. The theoretical analysis, protein labeler program, finite difference time domain calculation of plasmonic fields, and simulation of nanopore-based optical sensing are detailed in the methods section. The study anticipates further exploration of temporal distributions of protein translocation dwell-times and the impact on convolutional neural network identification accuracy. Overall, the research presents a promising avenue for advancing single-molecule protein identification and quantification with broad applications in proteomics research. The contributions made in methodology, accuracy, robustness, and technological exploration collectively position this work at the forefront of transformative developments in the field.Keywords: nano proteomics, nanopore-based optical sensing, deep learning, artificial intelligence
Procedia PDF Downloads 76319 Navigating Complex Communication Dynamics in Qualitative Research
Authors: Kimberly M. Cacciato, Steven J. Singer, Allison R. Shapiro, Julianna F. Kamenakis
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This study examines the dynamics of communication among researchers and participants who have various levels of hearing, use multiple languages, have various disabilities, and who come from different social strata. This qualitative methodological study focuses on the strategies employed in an ethnographic research study examining the communication choices of six sets of parents who have Deaf-Disabled children. The participating families varied in their communication strategies and preferences including the use of American Sign Language (ASL), visual-gestural communication, multiple spoken languages, and pidgin forms of each of these. The research team consisted of two undergraduate students proficient in ASL and a Deaf principal investigator (PI) who uses ASL and speech as his main modes of communication. A third Hard-of-Hearing undergraduate student fluent in ASL served as an objective facilitator of the data analysis. The team created reflexive journals by audio recording, free writing, and responding to team-generated prompts. They discussed interactions between the members of the research team, their evolving relationships, and various social and linguistic power differentials. The researchers reflected on communication during data collection, their experiences with one another, and their experiences with the participating families. Reflexive journals totaled over 150 pages. The outside research assistant reviewed the journals and developed follow up open-ended questions and prods to further enrich the data. The PI and outside research assistant used NVivo qualitative research software to conduct open inductive coding of the data. They chunked the data individually into broad categories through multiple readings and recognized recurring concepts. They compared their categories, discussed them, and decided which they would develop. The researchers continued to read, reduce, and define the categories until they were able to develop themes from the data. The research team found that the various communication backgrounds and skills present greatly influenced the dynamics between the members of the research team and with the participants of the study. Specifically, the following themes emerged: (1) students as communication facilitators and interpreters as barriers to natural interaction, (2) varied language use simultaneously complicated and enriched data collection, and (3) ASL proficiency and professional position resulted in a social hierarchy among researchers and participants. In the discussion, the researchers reflected on their backgrounds and internal biases of analyzing the data found and how social norms or expectations affected the perceptions of the researchers in writing their journals. Through this study, the research team found that communication and language skills require significant consideration when working with multiple and complex communication modes. The researchers had to continually assess and adjust their data collection methods to meet the communication needs of the team members and participants. In doing so, the researchers aimed to create an accessible research setting that yielded rich data but learned that this often required compromises from one or more of the research constituents.Keywords: American Sign Language, complex communication, deaf-disabled, methodology
Procedia PDF Downloads 111318 Seismic Perimeter Surveillance System (Virtual Fence) for Threat Detection and Characterization Using Multiple ML Based Trained Models in Weighted Ensemble Voting
Authors: Vivek Mahadev, Manoj Kumar, Neelu Mathur, Brahm Dutt Pandey
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Perimeter guarding and protection of critical installations require prompt intrusion detection and assessment to take effective countermeasures. Currently, visual and electronic surveillance are the primary methods used for perimeter guarding. These methods can be costly and complicated, requiring careful planning according to the location and terrain. Moreover, these methods often struggle to detect stealthy and camouflaged insurgents. The object of the present work is to devise a surveillance technique using seismic sensors that overcomes the limitations of existing systems. The aim is to improve intrusion detection, assessment, and characterization by utilizing seismic sensors. Most of the similar systems have only two types of intrusion detection capability viz., human or vehicle. In our work we could even categorize further to identify types of intrusion activity such as walking, running, group walking, fence jumping, tunnel digging and vehicular movements. A virtual fence of 60 meters at GCNEP, Bahadurgarh, Haryana, India, was created by installing four underground geophones at a distance of 15 meters each. The signals received from these geophones are then processed to find unique seismic signatures called features. Various feature optimization and selection methodologies, such as LightGBM, Boruta, Random Forest, Logistics, Recursive Feature Elimination, Chi-2 and Pearson Ratio were used to identify the best features for training the machine learning models. The trained models were developed using algorithms such as supervised support vector machine (SVM) classifier, kNN, Decision Tree, Logistic Regression, Naïve Bayes, and Artificial Neural Networks. These models were then used to predict the category of events, employing weighted ensemble voting to analyze and combine their results. The models were trained with 1940 training events and results were evaluated with 831 test events. It was observed that using the weighted ensemble voting increased the efficiency of predictions. In this study we successfully developed and deployed the virtual fence using geophones. Since these sensors are passive, do not radiate any energy and are installed underground, it is impossible for intruders to locate and nullify them. Their flexibility, quick and easy installation, low costs, hidden deployment and unattended surveillance make such systems especially suitable for critical installations and remote facilities with difficult terrain. This work demonstrates the potential of utilizing seismic sensors for creating better perimeter guarding and protection systems using multiple machine learning models in weighted ensemble voting. In this study the virtual fence achieved an intruder detection efficiency of over 97%.Keywords: geophone, seismic perimeter surveillance, machine learning, weighted ensemble method
Procedia PDF Downloads 74317 Change of Substrate in Solid State Fermentation Can Produce Proteases and Phytases with Extremely Distinct Biochemical Characteristics and Promising Applications for Animal Nutrition
Authors: Paula K. Novelli, Margarida M. Barros, Luciana F. Flueri
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Utilization of agricultural by-products, wheat ban and soybean bran, as substrate for solid state fermentation (SSF) was studied, aiming the achievement of different enzymes from Aspergillus sp. with distinct biological characteristics and its application and improvement on animal nutrition. Aspergillus niger and Aspergillus oryzea were studied as they showed very high yield of phytase and protease production, respectively. Phytase activity was measure using p-nitrophenilphosphate as substrate and a standard curve of p-nitrophenol, as the enzymatic activity unit was the quantity of enzyme necessary to release one μmol of p-nitrophenol. Protease activity was measure using azocasein as substrate. Activity for phytase and protease substantially increased when the different biochemical characteristics were considered in the study. Optimum pH and stability of the phytase produced by A. niger with wheat bran as substrate was between 4.0 - 5.0 and optimum temperature of activity was 37oC. Phytase fermented in soybean bran showed constant values at all pHs studied, for optimal and stability, but low production. Phytase with both substrates showed stable activity for temperatures higher than 80oC. Protease from A. niger showed very distinct behavior of optimum pH, acid for wheat bran and basic for soybean bran, respectively and optimal values of temperature and stability at 50oC. Phytase produced by A. oryzae in wheat bran had optimum pH and temperature of 9 and 37oC, respectively, but it was very unstable. On the other hand, proteases were stable at high temperatures, all pH’s studied and showed very high yield when fermented in wheat bran, however when it was fermented in soybean bran the production was very low. Subsequently the upscale production of phytase from A. niger and proteases from A. oryzae were applied as an enzyme additive in fish fed for digestibility studies. Phytases and proteases were produced with stable enzyme activity of 7,000 U.g-1 and 2,500 U.g-1, respectively. When those enzymes were applied in a plant protein based fish diet for digestibility studies, they increased protein, mineral, energy and lipids availability, showing that these new enzymes can improve animal production and performance. In conclusion, the substrate, as well as, the microorganism species can affect the biochemical character of the enzyme produced. Moreover, the production of these enzymes by SSF can be up to 90% cheaper than commercial ones produced with the same fungi species but submerged fermentation. Add to that these cheap enzymes can be easily applied as animal diet additives to improve production and performance.Keywords: agricultural by-products, animal nutrition, enzymes production, solid state fermentation
Procedia PDF Downloads 321316 Sequential and Combinatorial Pre-Treatment Strategy of Lignocellulose for the Enhanced Enzymatic Hydrolysis of Spent Coffee Waste
Authors: Rajeev Ravindran, Amit K. Jaiswal
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Waste from the food-processing industry is produced in large amount and contains high levels of lignocellulose. Due to continuous accumulation throughout the year in large quantities, it creates a major environmental problem worldwide. The chemical composition of these wastes (up to 75% of its composition is contributed by polysaccharide) makes it inexpensive raw material for the production of value-added products such as biofuel, bio-solvents, nanocrystalline cellulose and enzymes. In order to use lignocellulose as the raw material for the microbial fermentation, the substrate is subjected to enzymatic treatment, which leads to the release of reducing sugars such as glucose and xylose. However, the inherent properties of lignocellulose such as presence of lignin, pectin, acetyl groups and the presence of crystalline cellulose contribute to recalcitrance. This leads to poor sugar yields upon enzymatic hydrolysis of lignocellulose. A pre-treatment method is generally applied before enzymatic treatment of lignocellulose that essentially removes recalcitrant components in biomass through structural breakdown. Present study is carried out to find out the best pre-treatment method for the maximum liberation of reducing sugars from spent coffee waste (SPW). SPW was subjected to a range of physical, chemical and physico-chemical pre-treatment followed by a sequential, combinatorial pre-treatment strategy is also applied on to attain maximum sugar yield by combining two or more pre-treatments. All the pre-treated samples were analysed for total reducing sugar followed by identification and quantification of individual sugar by HPLC coupled with RI detector. Besides, generation of any inhibitory compounds such furfural, hydroxymethyl furfural (HMF) which can hinder microbial growth and enzyme activity is also monitored. Results showed that ultrasound treatment (31.06 mg/L) proved to be the best pre-treatment method based on total reducing content followed by dilute acid hydrolysis (10.03 mg/L) while galactose was found to be the major monosaccharide present in the pre-treated SPW. Finally, the results obtained from the study were used to design a sequential lignocellulose pre-treatment protocol to decrease the formation of enzyme inhibitors and increase sugar yield on enzymatic hydrolysis by employing cellulase-hemicellulase consortium. Sequential, combinatorial treatment was found better in terms of total reducing yield and low content of the inhibitory compounds formation, which could be due to the fact that this mode of pre-treatment combines several mild treatment methods rather than formulating a single one. It eliminates the need for a detoxification step and potential application in the valorisation of lignocellulosic food waste.Keywords: lignocellulose, enzymatic hydrolysis, pre-treatment, ultrasound
Procedia PDF Downloads 360315 Evolutionary Analysis of Influenza A (H1N1) Pdm 09 in Post Pandemic Period in Pakistan
Authors: Nazish Badar
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In early 2009, Pandemic type A (H1N1) Influenza virus emerged globally. Since then, it has continued circulation causing considerable morbidity and mortality. The purpose of this study was to evaluate the evolutionary changes in Influenza A (H1N1) pdm09 viruses from 2009-15 and their relevance with the current vaccine viruses. Methods: Respiratory specimens were collected with influenza-like illness and Severe Acute Respiratory Illness. Samples were processed according to CDC protocol. Sequencing and phylogenetic analysis of Haemagglutinin (HA) and neuraminidase (NA) genes was carried out comparing representative isolates from Pakistan viruses. Results: Between Jan2009 - Feb 2016, 1870 (13.2%) samples were positive for influenza A out of 14086. During the pandemic period (2009–10), Influenza A/ H1N1pdm 09 was the dominant strain with 366 (45%) of total influenza positives. In the post-pandemic period (2011–2016), a total of 1066 (59.6%) cases were positive Influenza A/ H1N1pdm 09 with co-circulation of different Influenza A subtypes. Overall, the Pakistan A(H1N1) pdm09 viruses grouped in two genetic clades. Influenza A(H1N1)pdm09 viruses only ascribed to Clade 7 during the pandemic period whereas viruses belong to clade 7 (2011) and clade 6B (2015) during the post-pandemic years. Amino acid analysis of the HA gene revealed mutations at positions S220T, I338V and P100S specially associated with outbreaks in all the analyzed strains. Sequence analyses of post-pandemic A(H1N1)pdm09 viruses showed additional substitutions at antigenic sites; S179N,K180Q (SA), D185N, D239G (CA), S202A (SB) and at receptor binding sites; A13T, S200P when compared with pandemic period. Substitution at Genetic markers; A273T (69%), S200P/T (15%) and D239G (7.6%) associated with severity and E391K (69%) associated with virulence was identified in viruses isolated during 2015. Analysis of NA gene revealed outbreak markers; V106I (23%) among pandemic and N248D (100%) during post-pandemic Pakistan viruses. Additional N-Glycosylation site; HA S179N (23%), NA I23T(7.6%) and N44S (77%) in place of N386K(77%) were only found in post-pandemic viruses. All isolates showed histidine (H) at position 275 in NA indicating sensitivity to neuraminidase inhibitors. Conclusion: This study shows that the Influenza A(H1N1)pdm09 viruses from Pakistan clustered into two genetic clades, with co-circulation of some variants. Certain key substitutions in the receptor binding site and few changes indicative of virulence were also detected in post-pandemic strains. Therefore, it is imperative to continue monitoring of the viruses for early identification of potential variants of high virulence or emergence of drug-resistant variants.Keywords: Influenza A (H1N1) pdm09, evolutionary analysis, post pandemic period, Pakistan
Procedia PDF Downloads 202314 The Beneficial Effects of Inhibition of Hepatic Adaptor Protein Phosphotyrosine Interacting with PH Domain and Leucine Zipper 2 on Glucose and Cholesterol Homeostasis
Authors: Xi Chen, King-Yip Cheng
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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes
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