Search results for: takeover targets
309 Identification of Blood Biomarkers Unveiling Early Alzheimer's Disease Diagnosis Through Single-Cell RNA Sequencing Data and Autoencoders
Authors: Hediyeh Talebi, Shokoofeh Ghiam, Changiz Eslahchi
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Traditionally, Alzheimer’s disease research has focused on genes with significant fold changes, potentially neglecting subtle but biologically important alterations. Our study introduces an integrative approach that highlights genes crucial to underlying biological processes, regardless of their fold change magnitude. Alzheimer's Single-cell RNA-seq data related to the peripheral blood mononuclear cells (PBMC) was extracted from the Gene Expression Omnibus (GEO). After quality control, normalization, scaling, batch effect correction, and clustering, differentially expressed genes (DEGs) were identified with adjusted p-values less than 0.05. These DEGs were categorized based on cell-type, resulting in four datasets, each corresponding to a distinct cell type. To distinguish between cells from healthy individuals and those with Alzheimer's, an adversarial autoencoder with a classifier was employed. This allowed for the separation of healthy and diseased samples. To identify the most influential genes in this classification, the weight matrices in the network, which includes the encoder and classifier components, were multiplied, and focused on the top 20 genes. The analysis revealed that while some of these genes exhibit a high fold change, others do not. These genes, which may be overlooked by previous methods due to their low fold change, were shown to be significant in our study. The findings highlight the critical role of genes with subtle alterations in diagnosing Alzheimer's disease, a facet frequently overlooked by conventional methods. These genes demonstrate remarkable discriminatory power, underscoring the need to integrate biological relevance with statistical measures in gene prioritization. This integrative approach enhances our understanding of the molecular mechanisms in Alzheimer’s disease and provides a promising direction for identifying potential therapeutic targets.Keywords: alzheimer's disease, single-cell RNA-seq, neural networks, blood biomarkers
Procedia PDF Downloads 66308 The Impact of Artificial Intelligence on Student’s Behavior and Mind
Authors: Makarios Mosaad Thabet Ibrahim
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the existing context paper targets to give the important position of ‘scholar voice’ and the track trainer inside the study room, which contributes to greater scholar-focused song training. The goal is to consciousness at the capabilities of the scholar voice via the tune spectrum, which has been born in the music school room, and the instructor’s methodologies and techniques used within the song classroom. The tune curriculum, the principles of pupil-centered song schooling, and the function of students and teachers as tune ambassadors have been taken into consideration the essential song parameters of scholar voice. The scholar- voice is a well worth-mentioning factor of a scholar-focused training, and all instructors have to take into account and sell its life in their lecture room. student affairs services play a critical function in contributing to the wholistic development and success of college students as they progress through their educational careers. The examine incorporates a multifaceted examination of student affairs carrier offerings among 10 personal and three public Baghdad universities. scholar affairs administrators (thirteen) have been surveyed together with over 300 students to determine university-subsidized services and pupil pride and attention. The pupil affairs service studies findings various drastically among non-public and public establishments and people that observed a country wide and international curriculum. Universities need to persist to conform to changing demographics and technological improvements to enhance students' private and academic successes, and pupil affairs services are key to preparing graduates to thrive in a diverse international world.Keywords: college student-athletes, self-concept, use of social media training, social networking student affairs, student success, higher education, Iraq, universities, Baghdad student's voice, student-centered education, music ambassadors, music teachers
Procedia PDF Downloads 32307 Enhancing Project Success: A Case Study of Investment Strategies and Planning Practices in Rwanda’s Housing Projects Managed by Rwanda Social Security Board
Authors: Amina Umulisa
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Background: Despite efforts to enhance profitability and project planning, Rwanda has experienced a decline in project success rates, notably in housing projects managed by the Rwanda Social Security Board (RSSB). This study aims to assess the impact of investment strategies and project planning practices on the performance of pension funds projects in Rwanda, focusing on housing projects by RSSB. Methods: Using descriptive and correlational research designs, this study surveyed 109 randomly selected respondents from a pool of 148 workers. Data analysis was conducted using descriptive and inferential statistics in STATA version 18. Results: Findings revealed that 54% of respondents acknowledged the importance of personnel generation. Additionally, 61% agreed with the effectiveness of training programs, and 79% supported the cost of human resource utilization. In terms of project management practices, 65.7% could determine when a project needed adjustments, 65.7% agreed with the approved budget, and 73% supported forecasted expenses. Furthermore, 68% agreed with order placement, 76.0% with using the right materials, and 64.4% with defining project scope. The study found significant associations between order placement and project quality outcomes (r=0.711, P-value <0.001), as well as with time management (Pearson was 0.701 and sing was 0.00) and cost management (r=0.885, P-value <0.001). Moreover, project time targets were found to significantly affect quality management (Pearson was 0.798, sing was 0.000), time management, and cost management (r=0.740, P-value <0.001). Conclusion: The findings highlight the positive association between the project implementation stage and quality management, indicating effective project planning practices among senior staff. However, there is a need to enhance project team collaboration and coordination to improve the performance of constructed houses.Keywords: project success rates, investment strategies, training programs, cost management
Procedia PDF Downloads 52306 Anticancer and Anti-Apoptotic Potential of Tridham and 1,2,3,4,6-Penta-O-Galloyl-β-D-Glucose in MCF-7 Breast Cancer Cell Line
Authors: R. Stalin, D. Karthick, H. Haseena Banu, T. P. Sachidanandam, P. Shanthi
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Background: Breast cancer is emerging as one of the leading cause of cancer related deaths and hence there arises the need to look out for drugs which are more targets specific with minimal side effects. In recent times, there is a shift towards alternative medicine due to low cost and less side effects. Siddha system of medicine is one the oldest system of medicine practiced against various ailments. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio (TD) and its anticancer potential is evaluated in terms of induction of apoptosis. Objective: The present study was designed to investigate the anti proliferative effect of TD and 1,2,3,4,6-penta-O-galloyl-b-D-glucose (PGG), a pure compound isolated from TD on human mammary carcinoma cell line (MCF-7). Materials and Methods: Cell viability was studied using MTT analysis and trypan blue staining. Mitochondrial membrane potential was studied using DAPI staining. The protein and mRNA expressions of pro-apoptotic and anti- apoptotic markers namely Bax, Bad, Bcl-2 and caspases were also assessed by Western Blotting and RT PCR. Results: Viability studies of TD and PGG treated MCF-7 cells showed an inhibition in cell growth in time and dose dependent manner. The alteration in mitochondrial membrane potential was restored through treatment with TD and PGG which was confirmed by DAPI staining. The protein and mRNA expression of pro-apoptotic markers was found to be significantly increased in TD and PGG treated cells with a concomitant decrease in anti-apoptotic markers. Conclusion: The results of the study suggest that TD and PGG exhibit their anticancer effect through its membrane stabilizing property and activation of apoptotic cascade in MCF-7 cells.Keywords: apoptosis, mammary carcinoma, MCF-7, penta galloyl glucose, Tridham
Procedia PDF Downloads 312305 Authentication and Traceability of Meat Products from South Indian Market by Species-Specific Polymerase Chain Reaction
Authors: J. U. Santhosh Kumar, V. Krishna, Sebin Sebastian, G. S. Seethapathy, G. Ravikanth, R. Uma Shaanker
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Food is one of the basic needs of human beings. It requires the normal function of the body part and a healthy growth. Recently, food adulteration increases day by day to increase the quantity and make more benefit. Animal source foods can provide a variety of micronutrients that are difficult to obtain in adequate quantities from plant source foods alone. Particularly in the meat industry, products from animals are susceptible targets for fraudulent labeling due to the economic profit that results from selling cheaper meat as meat from more profitable and desirable species. This work presents an overview of the main PCR-based techniques applied to date to verify the authenticity of beef meat and meat products from beef species. We were analyzed 25 market beef samples in South India. We examined PCR methods based on the sequence of the cytochrome b gene for source species identification. We found all sample were sold as beef meat as Bos Taurus. However, interestingly Male meats are more valuable high price compare to female meat, due to this reason most of the markets samples are susceptible. We were used sex determination gene of cattle like TSPY(Y-encoded, testis-specific protein TSPY is a Y-specific gene). TSPY homologs exist in several mammalian species, including humans, horses, and cattle. This gene is Y coded testis protein genes, which only amplify the male. We used multiple PCR products form species-specific “fingerprints” on gel electrophoresis, which may be useful for meat authentication. Amplicons were obtained only by the Cattle -specific PCR. We found 13 market meat samples sold as female beef samples. These results suggest that the species-specific PCR methods established in this study would be useful for simple and easy detection of adulteration of meat products.Keywords: authentication, meat products, species-specific, TSPY
Procedia PDF Downloads 375304 Correlation of Structure and Antiviral Activity of Alkaloids of Polygonum L. Plants Growing in Kazakhstan
Authors: Dmitry Yu. Korulkin, Raissa A. Muzychkina
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Currently to treat infectious diseases bioactive substances of plant origin having fewer side effects than synthetic medicines and medicines similar to natural components of a human body by the structure and action, become very important. One of the groups of secondary metabolites of the plants - alkaloids can be related the number of the most promising sources of medicines of plant origin. Currently, the structure of more than 7500 compounds has been identified. Analyzing the scope of research in the field of chemistry, pharmacology and technology of alkaloids, we can make a conclusion about that there is no system approach during the research of relation structure-activity on different groups of these substances. It is connected not only with a complex structure of their molecules, but also with insufficient information on the nature of their effect on organs, tissues and other targets in organism. The purpose of this research was to identify pharmacophore groups in the structure of alkaloids of endemic Polygonum L. plants growing in Kazakhstan responsible for their antiviral action. To isolate alkaloids pharmacopoeian methods were used. Antiviral activity of alkaloids of Polygonum L. plants was researched in the Institute of Microbiology and Virology of the Ministry of Education and Science of the Republic of Kazakhstan. Virus-inhibiting properties of compounds were studies in experiments with ortho- and paramyxoviruses on the model of chick-embryos. Anti-viral properties were determined using ‘screening test’ method designed to neutralization of a virus at the amount of 100EID50 with set concentrations of medicines. The difference of virus titer compared to control group was deemed as the criterion of antiviral action. It has been established that Polygonum L. alkaloids has high antiviral effect to influenza and parainfluenza viruses. The analysis of correlation of the structure and antiviral activity of alkaloids allowed identifying the main pharmacophore groups, among which the most important are glycosidation, the presence of carbonyl and hydroxyl groups, molecular weight and molecular size.Keywords: alkaloids, antiviral, bioactive substances, isolation, pharmacophore groups, Polygonum L.
Procedia PDF Downloads 437303 Investigation of Online Child Sexual Abuse: An Account of Covert Police Operations Across the Globe
Authors: Shivalaxmi Arumugham
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Child sexual abuse (CSA) has taken several forms, particularly with the advent of internet technologies that provide pedophiles access to their targets anonymously at an affordable rate. To combat CSA which has far-reaching consequences on the physical and psychological health of the victims, a special act, the Protection of Children from Sexual Offences (POCSO) Act, was formulated amongst the existing laws. With its latest amendment criminalizing various online activities about child pornography also known as child sexual abuse materials in 2019, tremendous pressure is speculated on law enforcement to identify offenders online. Effective investigations of CSA cases help in not only to detect perpetrators but also in preventing the re-victimization of children. Understanding the vulnerability of the child population and that the offenders continue to develop stealthier strategies to operate, it is high time that traditional investigation, where the focus is on apprehending and prosecuting the offender, must make a paradigm shift to proactively investigate to prevent victimization at the first place. One of the proactive policing techniques involves understanding the psychology of the offenders and children and operating undercover to catch the criminals before a real child is victimized. With the fundamental descriptive approach to research, the article attempts to identify the multitude of issues associated with the investigation of child sexual abuse cases currently in practice in India. Then, the article contextualizes the various covert operations carried out by numerous law enforcement agencies across the globe. To provide this comprehensive overview, the paper examines various reports, websites, guidelines, protocols, judicial pronouncements, and research articles. Finally, the paper presents the challenges and ethical issues that are to be considered before getting into undercover operations either in the guise of a pedophile or as a child. The research hopes to contribute to the making of standard operating protocols for investigation officers and other relevant policymakers in this regard.Keywords: child sexual abuse, cybercrime against children, covert police operations, investigation of CSA
Procedia PDF Downloads 97302 The Impact of Sign Language on Generating and Maintaining a Mental Image
Authors: Yi-Shiuan Chiu
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Deaf signers have been found to have better mental image performance than hearing nonsigners. The goal of this study was to investigate the ability to generate mental images, to maintain them, and to manipulate them in deaf signers of Taiwanese Sign Language (TSL). In the visual image task, participants first memorized digits formed in a cell of 4 × 5 grids. After presenting a cue of Chinese digit character shown on the top of a blank cell, participants had to form a corresponding digit. When showing a probe, which was a grid containing a red circle, participants had to decide as quickly as possible whether the probe would have been covered by the mental image of the digit. The ISI (interstimulus interval) between cue and probe was manipulated. In experiment 1, 24 deaf signers and 24 hearing nonsigners were asked to perform image generation tasks (ISI: 200, 400 ms) and image maintenance tasks (ISI: 800, 2000 ms). The results showed that deaf signers had had an enhanced ability to generate and maintain a mental image. To explore the process of mental image, in experiment 2, 30 deaf signers and 30 hearing nonsigners were asked to do visual searching when maintaining a mental image. Between a digit image cue and a red circle probe, participants were asked to search a visual search task to see if a target triangle apex was directed to the right or left. When there was only one triangle in the searching task, the results showed that both deaf signers and hearing non-signers had similar visual searching performance in which the searching targets in the mental image locations got facilitates. However, deaf signers could maintain better and faster mental image performance than nonsigners. In experiment 3, we increased the number of triangles to 4 to raise the difficulty of the visual search task. The results showed that deaf participants performed more accurately in visual search and image maintenance tasks. The results suggested that people may use eye movements as a mnemonic strategy to maintain the mental image. And deaf signers had enhanced abilities to resist the interference of eye movements in the situation of fewer distractors. In sum, these findings suggested that deaf signers had enhanced mental image processing.Keywords: deaf signers, image maintain, mental image, visual search
Procedia PDF Downloads 154301 Radar Track-based Classification of Birds and UAVs
Authors: Altilio Rosa, Chirico Francesco, Foglia Goffredo
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In recent years, the number of Unmanned Aerial Vehicles (UAVs) has significantly increased. The rapid development of commercial and recreational drones makes them an important part of our society. Despite the growing list of their applications, these vehicles pose a huge threat to civil and military installations: detection, classification and neutralization of such flying objects become an urgent need. Radar is an effective remote sensing tool for detecting and tracking flying objects, but scenarios characterized by the presence of a high number of tracks related to flying birds make especially challenging the drone detection task: operator PPI is cluttered with a huge number of potential threats and his reaction time can be severely affected. Flying birds compared to UAVs show similar velocity, RADAR cross-section and, in general, similar characteristics. Building from the absence of a single feature that is able to distinguish UAVs and birds, this paper uses a multiple features approach where an original feature selection technique is developed to feed binary classifiers trained to distinguish birds and UAVs. RADAR tracks acquired on the field and related to different UAVs and birds performing various trajectories were used to extract specifically designed target movement-related features based on velocity, trajectory and signal strength. An optimization strategy based on a genetic algorithm is also introduced to select the optimal subset of features and to estimate the performance of several classification algorithms (Neural network, SVM, Logistic regression…) both in terms of the number of selected features and misclassification error. Results show that the proposed methods are able to reduce the dimension of the data space and to remove almost all non-drone false targets with a suitable classification accuracy (higher than 95%).Keywords: birds, classification, machine learning, UAVs
Procedia PDF Downloads 221300 River Habitat Modeling for the Entire Macroinvertebrate Community
Authors: Pinna Beatrice., Laini Alex, Negro Giovanni, Burgazzi Gemma, Viaroli Pierluigi, Vezza Paolo
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Habitat models rarely consider macroinvertebrates as ecological targets in rivers. Available approaches mainly focus on single macroinvertebrate species, not addressing the ecological needs and functionality of the entire community. This research aimed to provide an approach to model the habitat of the macroinvertebrate community. The approach is based on the recently developed Flow-T index, together with a Random Forest (RF) regression, which is employed to apply the Flow-T index at the meso-habitat scale. Using different datasets gathered from both field data collection and 2D hydrodynamic simulations, the model has been calibrated in the Trebbia river (2019 campaign), and then validated in the Trebbia, Taro, and Enza rivers (2020 campaign). The three rivers are characterized by a braiding morphology, gravel riverbeds, and summer low flows. The RF model selected 12 mesohabitat descriptors as important for the macroinvertebrate community. These descriptors belong to different frequency classes of water depth, flow velocity, substrate grain size, and connectivity to the main river channel. The cross-validation R² coefficient (R²𝒸ᵥ) of the training dataset is 0.71 for the Trebbia River (2019), whereas the R² coefficient for the validation datasets (Trebbia, Taro, and Enza Rivers 2020) is 0.63. The agreement between the simulated results and the experimental data shows sufficient accuracy and reliability. The outcomes of the study reveal that the model can identify the ecological response of the macroinvertebrate community to possible flow regime alterations and to possible river morphological modifications. Lastly, the proposed approach allows extending the MesoHABSIM methodology, widely used for the fish habitat assessment, to a different ecological target community. Further applications of the approach can be related to flow design in both perennial and non-perennial rivers, including river reaches in which fish fauna is absent.Keywords: ecological flows, macroinvertebrate community, mesohabitat, river habitat modeling
Procedia PDF Downloads 94299 The Effects of High-frequency rTMS Targeting the Mirror Neurons on Improving Social Awareness in ASD, the Preliminary Analysis of a Pilot Study
Authors: Mitra Assadi, Md. Faan
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Background: Autism Spectrum Disorder (ASD) in a common neurodevelopmental disorder with limited pharmacological interventions. Transcranial Magnetic Stimulation (rTMS) has produced promising results in ASD, although there is no consensus regarding optimal targets or stimulation paradigms. A prevailing theory in ASD attributes the core deficits to dysfunction of the mirror neurons located in the inferior parietal lobule (IPL) and inferior frontal gyrus (IFG). Methods: Thus far, 11 subjects with ASD, 10 boys and 1 girl with the mean age of 13.36 years have completed the study by receiving 10 session of high frequency rTMS to the IPL. The subjects were randomized to receive stimulation on the left or right IPL and sham stimulation to the opposite side. The outcome measures included the Social Responsiveness Scale – Second Edition (SRS-2) and Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency task. Results: None of the 11 subjects experienced any adverse effects. The rTMS did not produce any improvement in verbal fluency, nor there was any statistically significant difference between the right versus left sided stimulation. Analysis of social awareness on SRS-2 (SRS-AWR) indicated a close to significant effect of the treatment with a small to medium effect size. After removing a single subject with Level 3 ASD, we demonstrated a close to significant improvement on SRS-AWR with a large effect size. The analysis of the data 3-month post TMS demonstrated return of the SRS-AWR values to baseline. Conclusion: This preliminary analysis of the 11 subjects who have completed our study thus far shows a favorable response to high frequency rTMS stimulation of the mirror neurons/IPL on social awareness. While the decay of the response noted during the 3-month follow-up may be considered a limitation of rTMS, the presence of the improvement, especially the effect size despite the small sample size, is indicative of the efficacy of this technique.Keywords: rTMS, autism, scoial cognition, mirror neurons
Procedia PDF Downloads 69298 Artificial Intelligence Impact on Strategic Stability
Authors: Darius Jakimavicius
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Artificial intelligence is the subject of intense debate in the international arena, identified both as a technological breakthrough and as a component of the strategic stability effect. Both the kinetic and non-kinetic development of AI and its application in the national strategies of the great powers may trigger a change in the security situation. Artificial intelligence is generally faster, more capable and more efficient than humans, and there is a temptation to transfer decision-making and control responsibilities to artificial intelligence. Artificial intelligence, which, once activated, can select and act on targets without further intervention by a human operator, blurs the boundary between human or robot (machine) warfare, or perhaps human and robot together. Artificial intelligence acts as a force multiplier that speeds up decision-making and reaction times on the battlefield. The role of humans is increasingly moving away from direct decision-making and away from command and control processes involving the use of force. It is worth noting that the autonomy and precision of AI systems make the process of strategic stability more complex. Deterrence theory is currently in a phase of development in which deterrence is undergoing further strain and crisis due to the complexity of the evolving models enabled by artificial intelligence. Based on the concept of strategic stability and deterrence theory, it is appropriate to develop further research on the development and impact of AI in order to assess AI from both a scientific and technical perspective: to capture a new niche in the scientific literature and academic terminology, to clarify the conditions for deterrence, and to identify the potential uses, impacts and possibly quantities of AI. The research problem is the impact of artificial intelligence developed by great powers on strategic stability. This thesis seeks to assess the impact of AI on strategic stability and deterrence principles, with human exclusion from the decision-making and control loop as a key axis. The interaction between AI and human actions and interests can determine fundamental changes in great powers' defense and deterrence, and the development and application of AI-based great powers strategies can lead to a change in strategic stability.Keywords: artificial inteligence, strategic stability, deterrence theory, decision making loop
Procedia PDF Downloads 40297 Technology Roadmapping in Defense Industry
Authors: Sevgi Özlem Bulu, Arif Furkan Mendi, Tolga Erol, İzzet Gökhan Özbilgin
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The rapid progress of technology in today's competitive conditions has also accelerated companies' technology development activities. As a result, companies are paying more attention to R&D studies and are beginning to allocate a larger share to R&D projects. A more systematic, comprehensive, target-oriented implementation of R&D studies is crucial for the company to achieve successful results. As a consequence, Technology Roadmap (TRM) is gaining importance as a management tool. It has critical prospects for achieving medium and long term success as it contains decisions about past business, future plans, technological infrastructure. When studies on TRM are examined, projects to be placed on the roadmap are selected by many different methods. Generally preferred methods are based on multi-criteria decision making methods. Management of selected projects becomes an important point after the selection phase of the projects. At this stage, TRM are used. TRM can be created in many different ways so that each institution can prepare its own Technology Roadmap according to their strategic plan. Depending on the intended use, there can be TRM with different layers at different sizes. In the evaluation phase of the R&D projects and in the creation of the TRM, HAVELSAN, Turkey's largest defense company in the software field, carries out this process with great care and diligence. At the beginning, suggested R&D projects are evaluated by the Technology Management Board (TMB) of HAVELSAN in accordance with the company's resources, objectives, and targets. These projects are presented to the TMB periodically for evaluation within the framework of certain criteria by board members. After the necessary steps have been passed, the approved projects are added to the time-based TRM, which is composed of four layers as market, product, project and technology. The use of a four-layered roadmap provides a clearer understanding and visualization of company strategy and objectives. This study demonstrates the benefits of using TRM, four-layered Technology Roadmapping and the possibilities for the institutions in the defense industry.Keywords: technology roadmap, research and development project, project selection, research development in defense industry
Procedia PDF Downloads 179296 Sludge Densification: Emerging and Efficient Way to Look at Biological Nutrient Removal Treatment
Authors: Raj Chavan
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Currently, there are over 14,500 Water Resource Recovery Facilities (WRRFs) in the United States, with ~35% of them having some type of nutrient limits in place. These WRRFs account for about 1% of overall power demand and 2% of total greenhouse gas emissions (GHG) in the United States and contribute for 10 to 15% of the overall nutrient load to surface rivers in the United States. The evolution of densification technologies toward more compact and energy-efficient nutrient removal processes has been impacted by a number of factors. Existing facilities that require capacity expansion or biomass densification for higher treatability within the same footprint are being subjected to more stringent requirements relating to nutrient removal prior to surface water discharge. Densification of activated sludge has received recent widespread interest as a means for achieving process intensification and nutrient removal at WRRFs. At the core of the technology are the aerobic sludge granules where the biological processes occur. There is considerable interest in the prospect of producing granular sludge in continuous (or traditional) activated sludge processes (CAS) or densification of biomass by moving activated sludge flocs to a denser aggregate of biomass as a highly effective technique of intensification. This presentation will provide a fundamental understanding of densification by presenting insights and practical issues. The topics that will be discussed include methods used to generate and retain densified granules; the mechanisms that allow biological flocs to densify; the role that physical selectors play in the densification of biological flocs; some viable ways for managing biological flocs that have become densified; effects of physical selection design parameters on the retention of densified biological flocs and finally some operational solutions for customizing the flocs and granules required to meet performance and capacity targets. In addition, it will present some case studies where biological and physical parameters were used to generate aerobic granular sludge in the continuous flow system.Keywords: densification, aerobic granular sludge, nutrient removal, intensification
Procedia PDF Downloads 185295 BiFormerDTA: Structural Embedding of Protein in Drug Target Affinity Prediction Using BiFormer
Authors: Leila Baghaarabani, Parvin Razzaghi, Mennatolla Magdy Mostafa, Ahmad Albaqsami, Al Warith Al Rushaidi, Masoud Al Rawahi
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Predicting the interaction between drugs and their molecular targets is pivotal for advancing drug development processes. Due to the time and cost limitations, computational approaches have emerged as an effective approach to drug-target interaction (DTI) prediction. Most of the introduced computational based approaches utilize the drug molecule and protein sequence as input. This study does not only utilize these inputs, it also introduces a protein representation developed using a masked protein language model. In this representation, for every individual amino acid residue within the protein sequence, there exists a corresponding probability distribution that indicates the likelihood of each amino acid being present at that particular position. Then, the similarity between each pair of amino acids is computed to create a similarity matrix. To encode the knowledge of the similarity matrix, Bi-Level Routing Attention (BiFormer) is utilized, which combines aspects of transformer-based models with protein sequence analysis and represents a significant advancement in the field of drug-protein interaction prediction. BiFormer has the ability to pinpoint the most effective regions of the protein sequence that are responsible for facilitating interactions between the protein and drugs, thereby enhancing the understanding of these critical interactions. Thus, it appears promising in its ability to capture the local structural relationship of the proteins by enhancing the understanding of how it contributes to drugprotein interactions, thereby facilitating more accurate predictions. To evaluate the proposed method, it was tested on two widely recognized datasets: Davis and KIBA. A comprehensive series of experiments was conducted to illustrate its effectiveness in comparison to cutting edge techniques.Keywords: BiFormer, transformer, protein language processing, self-attention mechanism, binding affinity, drug target interaction, similarity matrix, protein masked representation, protein language model
Procedia PDF Downloads 7294 Proteomic Analysis of the Inhibition of Prolyl Oligopeptidase Induced by Z-Pro-Prolinal in Filarial Parasites
Authors: Mohit Wadhawan, Sushma Rathaur
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Lymphatic filariasis, also called elephantiasis is a tropical disease afflicting over 120 million people in 81 countries worldwide. Existing anti filarial drugs are effective against the larval stages of filarial parasites which call for an urgent need of drugs which are macrofilaricidal. Identification of molecular targets crucial for survival of filarial parasites is a prerequisite for drug designing. Prolyl oligopeptidase (POP) is one such crucial enzyme involved in the maturation and degradation of neuropeptides and peptide hormones. We have identified this peptidase in the bovine filarial parasite, Setaria cervi. Effect of inhibition of POP on the proteome profile of filarial parasite has been discussed in this study. Filarial parasites were exposed to Z-pro-prolinal (ZPP), a specific POP inhibitor for 8 h and the motility and viability of the parasites was observed. It significantly reduced the motility and viability of the parasites. To study the proteome profile, the cytosolic, endoplasmic reticulum (ER) and mitochondrial extracts of the adult female parasites were subjected to 2-dimensional electrophoresis. As analyzed by the PD-Quest software, the ZPP caused the alteration in the different subcellular proteins, and the significantly altered proteins were identified using MALDI-MS/MS spectrometry. The major proteins identified were found to play important role in diverse biological functions like signaling, redox regulation, energy metabolism, stress response, and cytoskeleton formation. Moreover, we found upregulation in the calcium binding proteins such as calreticulin, calponin, and calpain-6 suggesting that POP inhibition regulates calcium release. This relates to earlier reports that POP plays non-catalytic role in inositol 1,4,5-trisphosphate (IP3) signaling inducing release of calcium from ER. Taken together, the data demonstrated that inhibition of prolyl oligopeptidase alter the overall proteome signifying its role in survival of the filarial parasites. Thus this study provides a basis for the use of POP as a chemotherapeutic target for the treatment of lymphatic filariasis.Keywords: lymphatic filariasis, setaria cervi, prolyl oligopeptidase, proteomics
Procedia PDF Downloads 281293 Determination of Non-CO2 Greenhouse Gas Emission in Electronics Industry
Authors: Bong Jae Lee, Jeong Il Lee, Hyo Su Kim
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Both developed and developing countries have adopted the decision to join the Paris agreement to reduce greenhouse gas (GHG) emissions at the Conference of the Parties (COP) 21 meeting in Paris. As a result, the developed and developing countries have to submit the Intended Nationally Determined Contributions (INDC) by 2020, and each country will be assessed for their performance in reducing GHG. After that, they shall propose a reduction target which is higher than the previous target every five years. Therefore, an accurate method for calculating greenhouse gas emissions is essential to be presented as a rational for implementing GHG reduction measures based on the reduction targets. Non-CO2 GHGs (CF4, NF3, N2O, SF6 and so on) are being widely used in fabrication process of semiconductor manufacturing, and etching/deposition process of display manufacturing process. The Global Warming Potential (GWP) value of Non-CO2 is much higher than CO2, which means it will have greater effect on a global warming than CO2. Therefore, GHG calculation methods of the electronics industry are provided by Intergovernmental Panel on climate change (IPCC) and U.S. Environmental Protection Agency (EPA), and it will be discussed at ISO/TC 146 meeting. As discussed earlier, being precise and accurate in calculating Non-CO2 GHG is becoming more important. Thus this study aims to discuss the implications of the calculating methods through comparing the methods of IPCC and EPA. As a conclusion, after analyzing the methods of IPCC & EPA, the method of EPA is more detailed and it also provides the calculation for N2O. In case of the default emission factor (by IPCC & EPA), IPCC provides more conservative results compared to that of EPA; The factor of IPCC was developed for calculating a national GHG emission, while the factor of EPA was specifically developed for the U.S. which means it must have been developed to address the environmental issue of the US. The semiconductor factory ‘A’ measured F gas according to the EPA Destruction and Removal Efficiency (DRE) protocol and estimated their own DRE, and it was observed that their emission factor shows higher DRE compared to default DRE factor of IPCC and EPA Therefore, each country can improve their GHG emission calculation by developing its own emission factor (if possible) at the time of reporting Nationally Determined Contributions (NDC). Acknowledgements: This work was supported by the Korea Evaluation Institute of Industrial Technology (No. 10053589).Keywords: non-CO2 GHG, GHG emission, electronics industry, measuring method
Procedia PDF Downloads 288292 Zingiberaceous Plants as a Source of Anti-Bacterial Activity: Targeting Bacterial Cell Division Protein (FtsZ)
Authors: S. Reshma Reghu, Shiburaj Sugathan, T. G. Nandu, K. B. Ramesh Kumar, Mathew Dan
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Bacterial diseases are considered to be one of the most prevalent health hazards in the developing world and many bacteria are becoming resistant to existing antibiotics making the treatment ineffective. Thus, it is necessary to find novel targets and develop new antibacterial drugs with a novel mechanism of action. The process of bacterial cell division is a novel and attractive target for new antibacterial drug discovery. FtsZ, a homolog of eukaryotic tubulin, is the major protein of the bacterial cell division machinery and is considered as an important antibacterial drug target. Zingiberaceae, the Ginger family consists of aromatic herbs with creeping rhizomes. Many of these plants have antimicrobial properties.This study aimed to determine the anti-bacterial activity of selected Zingiberaceous plants by targeting bacterial cell division protein, FtsZ. Essential oils and methanol extracts of Amomum ghaticum, Alpinia galanga, Kaempferia galanga, K. rotunda, and Zingiber officinale were tested to find its antibacterial efficiency using disc diffusion method against authentic bacterial strains obtained from MTCC (India). Essential oil isolated from A.galanga and Z.officinale were further assayed for FtsZ inhibition assay following non-radioactive malachite green-phosphomolybdate assay using E. coli FtsZ protein obtained from Cytoskelton Inc., USA. Z.officinale essential oil possess FtsZ inhibitory property. A molecular docking study was conducted with the known bioactive compounds of Z. officinale as ligands with the E. coli FtsZ protein homology model. Some of the major constituents of this plant like catechin, epicatechin, and gingerol possess agreeable docking scores. The results of this study revealed that several chemical constituents in Ginger plants can be utilised as potential source of antibacterial activity and it can warrant further investigation through drug discovery studies.Keywords: antibacterial, FtsZ, zingiberaceae, docking
Procedia PDF Downloads 472291 Synergism in the Inquiry Lab: An Analysis of Time Targets and Achievement
Authors: John M. Basey, Clinton D. Francis, Maxwell B. Joseph
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After gathering data from experimental procedures, inquiry-oriented-science labs often allow students the freedom to stay and complete the write up in class or leave lab early and complete the write up later. Teachers must decide whether to allow students this freedom to self-regulate this time. Student interviews have indicated four time-target strategies that may influence how students utilize this time: grade-target-A, grade-target-C, time-limited, and proficiency. The hypothesis tested was that variability in class composition relative to the four grade-target strategies has an impact on when students leave class, which in turn may influence their overall learning as exemplified by grades. Students were divided into the four indicated groups with a survey. Class composition and the GTA teaching the class had significant impacts on how long students stayed in class with class composition having the greatest impact. A factor analysis identified two factors. Factor 1 included classes with percentages of grade-target students opposite time-limited/proficiency students and explained 43% of the variance. Factor 2 included classes with percentages of grade-target-A/proficiency students opposite grade-target-C students and explained 33% of the variance. Students who stayed longer received significantly higher grades (P = 0.008) with no significant relationships between grade and Factor 1 or Factor 2 (P > 0.05). The time students stayed in class was significantly positively related to Factor 1 (P = 0.006) and significantly negatively related to Factor 2 (P = 0.008). These results support the hypothesis and indicate that teachers may want to know the composition of student-target strategies before deciding on how to have students allocate study time at the end of inquiry-oriented labs. According to these results, ideal classes for self-regulation have a high proportion of proficiency and time-limited students and a low proportion of grade-target students, or a high proportion of grade-target-A and proficiency students and a low proportion of grade-target-C students. Non-ideal classes for self-regulation were comprised of the inverse proportions.Keywords: grades, inquiry lab design, synergism in student motivation, class composition
Procedia PDF Downloads 127290 Results of the Safety Evaluation of Cancer Vaccines Dealing with Novel Targets for Cancer Immunotherapy
Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias
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Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.Keywords: cancer vaccines, safety, toxicology, rats, non human primates
Procedia PDF Downloads 450289 Molecular Interactions between Vicia Faba L. Cultivars and Plant Growth Promoting Rhizobacteria (PGPR), Utilized as Yield Enhancing 'Plant Probiotics'
Authors: Eleni Stefanidou, Nikolaos Katsenios, Ioanna Karamichali, Aspasia Efthimiadou, Panagiotis Madesis
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The excessive use of pesticides and fertilizers has significant environmental and human health-related negative effects. In the frame of the development of sustainable agriculture practices, especially in the context of extreme environmental changes (climate change), it is important to develop alternative practices to increase productivity and biotic and abiotic stress tolerance. Beneficial bacteria, such as symbiotic bacteria in legumes (rhizobia) and symbiotic or free-living Plant Growth Promoting Rhizobacteria (PGPR), which could act as "plant probiotics", can promote plant growth and significantly increase the resistance of crops under adverse environmental conditions. In this study, we explored the symbiotic relationships between Faba bean (Vicia faba L.) cultivars with different PGPR bacteria, aiming to identify the possible influence on yield and biotic-abiotic phytoprotection benefits. Transcriptomic analysis of root and whole plant samples was executed for two Vicia faba L. cultivars (Polikarpi and Solon) treated with selected PGPR bacteria (6 treatments: B. subtilis + Rhizobium-mixture, A. chroococcum + Rhizobium-mixture, B. subtilis, A. chroococcum and Rhizobium-mixture). Preliminary results indicate a significant yield (Seed weight and Total number of pods) increase in both varieties, ranging around 25%, in comparison to the control, especially for the Solon cultivar. The increase was observed for all treatments, with the B. subtilis + Rhizobium-mixture treatment being the highest performing. The correlation of the physiological and morphological data with the transcriptome analysis revealed molecular mechanisms and molecular targets underlying the observed yield increase, opening perspectives for the use of nitrogen-fixing bacteria as a natural, more ecological enhancer of legume crop productivity.Keywords: plant probiotics, PGPR, legumes, sustainable agriculture
Procedia PDF Downloads 80288 Quality Assurances for an On-Board Imaging System of a Linear Accelerator: Five Months Data Analysis
Authors: Liyun Chang, Cheng-Hsiang Tsai
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To ensure the radiation precisely delivering to the target of cancer patients, the linear accelerator equipped with the pretreatment on-board imaging system is introduced and through it the patient setup is verified before the daily treatment. New generation radiotherapy using beam-intensity modulation, usually associated the treatment with steep dose gradients, claimed to have achieved both a higher degree of dose conformation in the targets and a further reduction of toxicity in normal tissues. However, this benefit is counterproductive if the beam is delivered imprecisely. To avoid shooting critical organs or normal tissues rather than the target, it is very important to carry out the quality assurance (QA) of this on-board imaging system. The QA of the On-Board Imager® (OBI) system of one Varian Clinac-iX linear accelerator was performed through our procedures modified from a relevant report and AAPM TG142. Two image modalities, 2D radiography and 3D cone-beam computed tomography (CBCT), of the OBI system were examined. The daily and monthly QA was executed for five months in the categories of safety, geometrical accuracy and image quality. A marker phantom and a blade calibration plate were used for the QA of geometrical accuracy, while the Leeds phantom and Catphan 504 phantom were used in the QA of radiographic and CBCT image quality, respectively. The reference images were generated through a GE LightSpeed CT simulator with an ADAC Pinnacle treatment planning system. Finally, the image quality was analyzed via an OsiriX medical imaging system. For the geometrical accuracy test, the average deviations of the OBI isocenter in each direction are less than 0.6 mm with uncertainties less than 0.2 mm, while all the other items have the displacements less than 1 mm. For radiographic image quality, the spatial resolution is 1.6 lp/cm with contrasts less than 2.2%. The spatial resolution, low contrast, and HU homogenous of CBCT are larger than 6 lp/cm, less than 1% and within 20 HU, respectively. All tests are within the criteria, except the HU value of Teflon measured with the full fan mode exceeding the suggested value that could be due to itself high HU value and needed to be rechecked. The OBI system in our facility was then demonstrated to be reliable with stable image quality. The QA of OBI system is really necessary to achieve the best treatment for a patient.Keywords: CBCT, image quality, quality assurance, OBI
Procedia PDF Downloads 298287 Development of a Novel Antibacterial to Block Growth of Pseudomonas Aeruginosa and Prevent Biofilm Formation
Authors: Clara Franch de la Cal, Christopher J Morris, Michael McArthur
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Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by abnormal transport of chloride and sodium across the lung epithelium, leading to thick and viscous secretions. Within which CF patients suffer from repeated bacterial pulmonary infections, with Pseudomonas aeru-ginosa (PA) eliciting the greatest inflammatory response, causing an irreversible loss of lung func-tion that determines morbidity and mortality. The cell wall of PA is a permeability barrier to many antibacterials and the rise of Mutli-Drug Resistant strains (MDR) is eroding the efficacy of the few remaining clinical options. In addition when PA infection becomes established it forms an antibi-otic-resistant biofilm, embedded in which are slow growing cells that are refractive to drug treat-ment. Making the development of new antibacterials a major challenge. This work describes the development of new type of nanoparticulate oligonucleotide antibacterial capable of tackling PA infections, including MDR strains. It is being developed to both block growth and prevent biofilm formation. These oligonucleotide therapeutics, Transcription Factor Decoys (TFD), act on novel genomic targets by capturing key regulatory proteins to block essential bacterial genes and defeat infection. They have been successfully transfected into a wide range of pathogenic bacteria, both in vitro and in vivo, using a proprietary delivery technology. The surfactant used self-assembles with TFD to form a nanoparticle stable in biological fluids, which protects the TFD from degradation and preferentially transfects prokaryotic membranes. Key challenges are to adapt the nanoparticle so it is active against PA in the context of biofilms and to formulate it for administration by inhalation. This would allow the drug to be delivered to the respiratory tract, thereby achieving drug concentrations sufficient to eradicate the pathogenic organisms at the site of infection.Keywords: antibacterials, transcriptional factor decoys (TFDs), pseudomonas aeruginosa
Procedia PDF Downloads 284286 Stress Hyperglycaemia and Glycaemic Control Post Cardiac Surgery: Relaxed Targets May Be Acceptable
Authors: Nicholas Bayfield, Liam Bibo, Charley Budgeon, Robert Larbalestier, Tom Briffa
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Introduction: Stress hyperglycaemia is common following cardiac surgery. Its optimal management is uncertain and may differ by diabetic status. This study assesses the in-hospital glycaemic management of cardiac surgery patients and associated postoperative outcomes. Methods: A retrospective cohort analysis of all patients undergoing cardiac surgery at Fiona Stanley Hospital from February 2015 to May 2019 was undertaken. Management and outcomes of hyperglycaemia following cardiac surgery were assessed. Follow-up was assessed to 1 year postoperatively. Multivariate regression modelling was utilised. Results: 1050 non-diabetic patients and 689 diabetic patients were included. In the non-diabetic cohort, patients with mild (peak blood sugar level [BSL] < 14.3), transient stress hyperglycaemia managed without insulin were not at an increased risk of wound-related morbidity (P=0.899) or mortality at 1 year (P=0.483). Insulin management was associated with wound-related readmission to hospital (P=0.004) and superficial sternal wound infection (P=0.047). Prolonged or severe stress hyperglycaemia was predictive of hospital re-admission (P=0.050) but not morbidity or mortality (P=0.546). Diabetes mellitus was an independent risk factor 1-year mortality (OR; 1.972 [1.041–3.736], P=0.037), graft harvest site wound infection (OR; 1.810 [1.134–2.889], P=0.013) and wound-related readmission (OR; 1.866 [1.076–3.236], P=0.026). In diabetics, postoperative peak BSL > 13.9mmol/L was predictive of graft harvest site infections (OR; 3.528 [1.724-7.217], P=0.001) and wound-related readmission OR; 3.462 [1.540-7.783], P=0.003) regardless of modality of management. A peak BSL of 10.0-13.9 did not increase the risk of morbidity/mortality compared to a peak BSL of < 10.0 (P=0.557). Diabetics with a peak BSL of 13.9 or less did not have significantly increased morbidity/mortality outcomes compared to non-diabetics (P=0.418). Conclusion: In non-diabetic patients, transient mild stress hyperglycaemia following cardiac surgery does not uniformly require treatment. In diabetic patients, postoperative hyperglycaemia with peak BSL exceeding 13.9mmol/L was associated with wound-related morbidity and hospital readmission following cardiac surgery.Keywords: cardiac surgery, pulmonary embolism, pulmonary embolectomy, cardiopulmonary bypass
Procedia PDF Downloads 162285 Healthcare-SignNet: Advanced Video Classification for Medical Sign Language Recognition Using CNN and RNN Models
Authors: Chithra A. V., Somoshree Datta, Sandeep Nithyanandan
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Sign Language Recognition (SLR) is the process of interpreting and translating sign language into spoken or written language using technological systems. It involves recognizing hand gestures, facial expressions, and body movements that makeup sign language communication. The primary goal of SLR is to facilitate communication between hearing- and speech-impaired communities and those who do not understand sign language. Due to the increased awareness and greater recognition of the rights and needs of the hearing- and speech-impaired community, sign language recognition has gained significant importance over the past 10 years. Technological advancements in the fields of Artificial Intelligence and Machine Learning have made it more practical and feasible to create accurate SLR systems. This paper presents a distinct approach to SLR by framing it as a video classification problem using Deep Learning (DL), whereby a combination of Convolutional Neural Networks (CNNs) and Recurrent Neural Networks (RNNs) has been used. This research targets the integration of sign language recognition into healthcare settings, aiming to improve communication between medical professionals and patients with hearing impairments. The spatial features from each video frame are extracted using a CNN, which captures essential elements such as hand shapes, movements, and facial expressions. These features are then fed into an RNN network that learns the temporal dependencies and patterns inherent in sign language sequences. The INCLUDE dataset has been enhanced with more videos from the healthcare domain and the model is evaluated on the same. Our model achieves 91% accuracy, representing state-of-the-art performance in this domain. The results highlight the effectiveness of treating SLR as a video classification task with the CNN-RNN architecture. This approach not only improves recognition accuracy but also offers a scalable solution for real-time SLR applications, significantly advancing the field of accessible communication technologies.Keywords: sign language recognition, deep learning, convolution neural network, recurrent neural network
Procedia PDF Downloads 26284 Nanotechnology in Construction as a Building Security
Authors: Hanan Fayez Hussein
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‘Due to increasing environmental challenges and security problems in the world such as global warming, storms, and terrorism’, humans have discovered new technologies and new materials in order to program daily life. As providing physical and psychological security is one of the primary functions of architecture, so in order to provide security, building must prevents unauthorized entry and harm to occupant and reduce the threat of attack by making building less attractive targets by new technologies such as; Nanotechnology, which has emerged as a major science and technology focus of the 21st century and will be the next industrial revolution. Nanotechnology is control of the properties of matter, and it deals with structures of the size 100 nanometers or smaller in at least one dimension and has wide application in various fields. The construction and architecture sectors were among the first to be identified as a promising application area for nanotechnology. The advantages of using nanomaterials in construction are enormous, and promises heighten building security by utilizing the strength of building materials to make our buildings more secure and get smart home. Access barriers such as wall and windows could incorporate stronger materials benefiting from nano-reinforcement utilizing nanotubes and nano composites to act as protective cover. Carbon nanotubes, as one of nanotechnology application, can be designed up to 250 times stronger than steel. Nano-enabled devices and materials offer both enhanced and, in some cases, completely new defence systems. In the addition, the small amount of carbon nanoparticles to the construction materials such as; cement, concrete, wood, glass, gypson, and steel can make these materials act as defence elements. This paper highlights the fact that nanotechnology can impact the future global security and how building’s envelop can act as a defensive cover for the building and can be resistance to any threats can attack it. Then focus on its effect on construction materials such as; Concrete can obtain by nanoadditives excellent mechanical, chemical, and physical properties with less material, which can acts as a precautionary shield to the building.Keywords: nanomaterial, global warming, building security, smart homes
Procedia PDF Downloads 82283 Constraint-Based Computational Modelling of Bioenergetic Pathway Switching in Synaptic Mitochondria from Parkinson's Disease Patients
Authors: Diana C. El Assal, Fatima Monteiro, Caroline May, Peter Barbuti, Silvia Bolognin, Averina Nicolae, Hulda Haraldsdottir, Lemmer R. P. El Assal, Swagatika Sahoo, Longfei Mao, Jens Schwamborn, Rejko Kruger, Ines Thiele, Kathrin Marcus, Ronan M. T. Fleming
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Degeneration of substantia nigra pars compacta dopaminergic neurons is one of the hallmarks of Parkinson's disease. These neurons have a highly complex axonal arborisation and a high energy demand, so any reduction in ATP synthesis could lead to an imbalance between supply and demand, thereby impeding normal neuronal bioenergetic requirements. Synaptic mitochondria exhibit increased vulnerability to dysfunction in Parkinson's disease. After biogenesis in and transport from the cell body, synaptic mitochondria become highly dependent upon oxidative phosphorylation. We applied a systems biochemistry approach to identify the metabolic pathways used by neuronal mitochondria for energy generation. The mitochondrial component of an existing manual reconstruction of human metabolism was extended with manual curation of the biochemical literature and specialised using omics data from Parkinson's disease patients and controls, to generate reconstructions of synaptic and somal mitochondrial metabolism. These reconstructions were converted into stoichiometrically- and fluxconsistent constraint-based computational models. These models predict that Parkinson's disease is accompanied by an increase in the rate of glycolysis and a decrease in the rate of oxidative phosphorylation within synaptic mitochondria. This is consistent with independent experimental reports of a compensatory switching of bioenergetic pathways in the putamen of post-mortem Parkinson's disease patients. Ongoing work, in the context of the SysMedPD project is aimed at computational prediction of mitochondrial drug targets to slow the progression of neurodegeneration in the subset of Parkinson's disease patients with overt mitochondrial dysfunction.Keywords: bioenergetics, mitochondria, Parkinson's disease, systems biochemistry
Procedia PDF Downloads 294282 Mannosidase Alpha Class 1B Member 1 Targets F Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein and Ebola Virus Glycoprotein to Endoplasmic Reticulum-To-Lysosome-Associated Degradation by Micro-Endoplasmic Reticulum-Phagy
Authors: Yong-Hui Zheng
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Viruses hijack host machineries to propagate and spread, which disrupts cellular homeostasis and activates various counteractive mechanisms. Infection of enveloped viruses is dependent on their fusion proteins, which bind to viral receptors to allow virus entry into cells. Fusion proteins are glycoproteins and expressed in the endoplasmic reticulum (ER) by hijacking the secretory pathway. Previously, we reported that Zaire ebolavirus (EBOV)-glycoprotein (GP) expression induces ER stress, and EBOV-GP is targeted by the calnexin cycle to macro-ER-phagy for degradation. We now report that expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/SARS2)-spike (S) protein also causes ER stress, and its expression is strongly downregulated by mannosidase alpha class 1B member 1 (MAN1B1), a class I α-mannosidase from the ER. MAN1B1 co-localizes with SARS2-S in the ER, and its downregulation of SARS2-S is blocked by inhibitors targeting lysosomes and autophagy, but not proteasomes, indicating SARS2-S degradation by autolysosomes. Notably, the SARS2-S degradation does not require the core autophagy machinery including ATG3, ATG5, ATG7, and phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3)/vacuolar protein sorting 34 (VPS34), and instead, it requires Beclin 1 (BECN1), a core component in the PI3KC3 complex. In addition, MAN1B1 does not trigger SARS2-S polyubiquitination, and consistently, the SARS2-S degradation does not require the autophagy receptor sequestosome 1 (SQSTM1)/p62. MAN1B1 also downregulates EBOV-GP similarly, but this degradation does not require BECN1. Collectively, we conclude that MAN1B1 downregulates viral fusions by micro-ER-phagy, and importantly, we have identified BECN1-dependent and BECN1-independent mechanisms for micro-ER-phagy.Keywords: Micro-ER-phagy, reticulophagy, fusion proteins, ER stress
Procedia PDF Downloads 69281 Policy Recommendations for Reducing CO2 Emissions in Kenya's Electricity Generation, 2015-2030
Authors: Paul Kipchumba
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Kenya is an East African Country lying at the Equator. It had a population of 46 million in 2015 with an annual growth rate of 2.7%, making a population of at least 65 million in 2030. Kenya’s GDP in 2015 was about 63 billion USD with per capita GDP of about 1400 USD. The rural population is 74%, whereas urban population is 26%. Kenya grapples with not only access to energy but also with energy security. There is direct correlation between economic growth, population growth, and energy consumption. Kenya’s energy composition is at least 74.5% from renewable energy with hydro power and geothermal forming the bulk of it; 68% from wood fuel; 22% from petroleum; 9% from electricity; and 1% from coal and other sources. Wood fuel is used by majority of rural and poor urban population. Electricity is mostly used for lighting. As of March 2015 Kenya had installed electricity capacity of 2295 MW, making a per capital electricity consumption of 0.0499 KW. The overall retail cost of electricity in 2015 was 0.009915 USD/ KWh (KES 19.85/ KWh), for installed capacity over 10MW. The actual demand for electricity in 2015 was 3400 MW and the projected demand in 2030 is 18000 MW. Kenya is working on vision 2030 that aims at making it a prosperous middle income economy and targets 23 GW of generated electricity. However, cost and non-cost factors affect generation and consumption of electricity in Kenya. Kenya does not care more about CO2 emissions than on economic growth. Carbon emissions are most likely to be paid by future costs of carbon emissions and penalties imposed on local generating companies by sheer disregard of international law on C02 emissions and climate change. The study methodology was a simulated application of carbon tax on all carbon emitting sources of electricity generation. It should cost only USD 30/tCO2 tax on all emitting sources of electricity generation to have solar as the only source of electricity generation in Kenya. The country has the best evenly distributed global horizontal irradiation. Solar potential after accounting for technology efficiencies such as 14-16% for solar PV and 15-22% for solar thermal is 143.94 GW. Therefore, the paper recommends adoption of solar power for generating all electricity in Kenya in order to attain zero carbon electricity generation in the country.Keywords: co2 emissions, cost factors, electricity generation, non-cost factors
Procedia PDF Downloads 364280 X-Ray Crystallographic Studies on BPSL2418 from Burkholderia pseudomallei
Authors: Mona Alharbi
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Melioidosis has emerged as a lethal disease. Unfortunately, the molecular mechanisms of virulence and pathogenicity of Burkholderia pseudomallei remain unknown. However, proteomics research has selected putative targets in B. pseudomallei that might play roles in the B. pseudomallei virulence. BPSL 2418 putative protein has been predicted as a free methionine sulfoxide reductase and interestingly there is a link between the level of the methionine sulfoxide in pathogen tissues and its virulence. Therefore in this work, we describe the cloning expression, purification, and crystallization of BPSL 2418 and the solution of its 3D structure using X-ray crystallography. Also, we aimed to identify the substrate binding and reduced forms of the enzyme to understand the role of BPSL 2418. The gene encoding BPSL2418 from B. pseudomallei was amplified by PCR and reclone in pETBlue-1 vector and transformed into E. coli Tuner DE3 pLacI. BPSL2418 was overexpressed using E. coli Tuner DE3 pLacI and induced by 300μM IPTG for 4h at 37°C. Then BPS2418 purified to better than 95% purity. The pure BPSL2418 was crystallized with PEG 4000 and PEG 6000 as precipitants in several conditions. Diffraction data were collected to 1.2Å resolution. The crystals belonged to space group P2 21 21 with unit-cell parameters a = 42.24Å, b = 53.48Å, c = 60.54Å, α=γ=β= 90Å. The BPSL2418 binding MES was solved by molecular replacement with the known structure 3ksf using PHASER program. The structure is composed of six antiparallel β-strands and four α-helices and two loops. BPSL2418 shows high homology with the GAF domain fRMsrs enzymes which suggest that BPSL2418 might act as methionine sulfoxide reductase. The amino acids alignment between the fRmsrs including BPSL 2418 shows that the three cysteines that thought to catalyze the reduction are fully conserved. BPSL 2418 contains the three conserved cysteines (Cys⁷⁵, Cys⁸⁵ and Cys¹⁰⁹). The active site contains the six antiparallel β-strands and two loops where the disulfide bond formed between Cys⁷⁵ and Cys¹⁰⁹. X-ray structure of free methionine sulfoxide binding and native forms of BPSL2418 were solved to increase the understanding of the BPSL2418 catalytic mechanism.Keywords: X-Ray Crystallography, BPSL2418, Burkholderia pseudomallei, Melioidosis
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