Search results for: therapeutic design
13514 Siderophore Receptor Protein from Klebsiella pneumoniae as a Promising Immunogen for Serotype-Independent Therapeutic Lead Development
Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri
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Klebsiella pneumoniae causes a wide range of infections, including urinary tract infections, sepsis, bacteremia, pneumonia, and liver abscesses. The emergence of multi-drug resistance in this bacterium led to a major setback for clinical management. WHO also endorsed a need for finding alternative therapy to antibiotics for the treatment of these infections. Development of vaccines and passive antibody therapy has been proven as a potent alternative to antibiotics in the case of MDR, XDR, and PDR Klebsiella infections. Siderophore receptors have been demonstrated to be overexpressed for the internalization of iron siderophore complexes during infections in most Gram-negative bacteria. For the present study, immune response to siderophore receptors to establish this protein as a potential immunogen for the development of therapeutic leads was explored. Clinical strains of Klebsiella pneumoniae were grown in iron-deficient conditions, and the iron-regulated outer membrane proteins were extracted and characterized through mass spectrometry for specific identification. The gene for identified protein was cloned in pET- 28a vector and expressed in E. coli. The native protein and the recombinant protein were isolated and purified and used as antigens for the generation of immune response in BALB/c mice. The native protein of Klebsiella pneumoniae grown in iron-deficient conditions was identified as FepA (Ferrienterobactin receptor) and other siderophore receptors. This 80 kDa protein generated an immune response in BALB/c mice. The antiserum from mice after subsequent booster doses was collected and showed binding with FepA protein in western blot and phagocytic uptake of the K. pneumoniae in the presence antiserum from immunized mice also observed from the animal studies after bacterial challenge post immunisation in mice have shown bacterial clearance. The antiserum from mice showed binding and clearance of the Klebsiella pneumoniae bacteria in vitro and in vivo. These antigens used for generating an active immune response in mice can further be used for therapeutic monoclonal antibody development against Klebsiella pneumoniae infections.Keywords: antiserum, FepA, Klebsiella pneumoniae, multi drug resistance, siderophore receptor
Procedia PDF Downloads 10213513 A Survey Proposal towards Holistic Management of Schizophrenia
Authors: Pronab Ganguly, Ahmed A. Moustafa
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Holistic management of schizophrenia involves mainstream pharmacological intervention, complimentary medicine intervention, therapeutic intervention and other psychosocial factors such as accommodation, education, job training, employment, relationship, friendship, exercise, overall well-being, smoking, substance abuse, suicide prevention, stigmatisation, recreation, entertainment, violent behaviour, arrangement of public trusteeship and guardianship, day-day-living skill, integration with community, and management of overweight due to medications and other health complications related to medications amongst others. Our review shows that there is no integrated survey by combining all these factors. An international web-based survey was conducted to evaluate the significance of all these factors and present them in a unified manner. It is believed this investigation will contribute positively towards holistic management of schizophrenia. There will be two surveys. In the pharmacological intervention survey, five popular drugs for schizophrenia will be chosen and their efficacy as well as harmful side effects will be evaluated on a scale of 0 -10. This survey will be done by psychiatrists. In the second survey, each element of therapeutic intervention and psychosocial factors will be evaluated according to their significance on a scale of 0 - 10. This survey will be done by care givers, psychologists, case managers and case workers. For the first survey, professional bodies of psychiatrists in English speaking countries will be contacted to request them to ask their members to participate in the survey. For the second survey, professional bodies of clinical psychologist and care givers in English speaking countries will be contacted to request them to ask their members to participate in the survey. Additionally, for both the surveys, relevant professionals will be contacted through personal contact networks. For both the surveys, mean, mode, median, standard deviation and net promoter score will be calculated for each factor and then presented in a statistically significant manner. Subsequently each factor will be ranked according to their statistical significance. Additionally, country specific variation will be highlighted to identify the variation pattern. The results of these surveys will identify the relative significance of each type of pharmacological intervention, each type of therapeutic intervention and each type of psychosocial factor. The determination of this relative importance will definitely contribute to the improvement in quality of life for individuals with schizophrenia.Keywords: schizophrenia, holistic management, antipsychotics, quality of life
Procedia PDF Downloads 15013512 Design of an Electric Arc Furnace for the Production of Metallurgical Grade Silicon
Authors: M. Barbouche, M. Hajji, H. Ezzaouia
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This project is a step to manufacture solar grade silicon. It consists in designing an electrical arc furnace in order to produce metallurgical silicon Mg-Si with mutually carbon and high purity of silica. It concerns, first, the development of a functional analysis, a mechanical design and thermodynamic study. Our study covers also, the design of the temperature control system and the design of the electric diagrams. The furnace works correctly. A Labview interface was developed to control all parameters and to supervise the operation of furnace. Characterization tests with X-ray technique and Raman spectroscopy allow us to confirm the metallurgical silicon production.Keywords: arc furnace, electrical design, silicon manufacturing, regulation, x-ray characterization
Procedia PDF Downloads 49513511 Influence of Maturity Stage on Nutritional and Therapeutic Potentialities of Solanum anguivi Lam Berries (Gnagnan) Cultivated in CôTe D'Ivoire
Authors: G. Dan Chépo, L. Ban-Koffi, N. Kouassi Kouakou, M. Dje Kouakou, J. Nemlin, A. Sahore Drogba, L. Kouame Patrice
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Solanum anguivi Lam, collectively called Gnagnan in Côte d'Ivoire is an eggplant with nutritional and therapeutic potentialities more or less known. The present study was undertaken to analyze the biochemical composition of berries at the different stages of maturity. Data showed that at the first stage of maturity (green berries), fruits are rich in ascorbic acid (34.48 ± 1.7 mg / 100 g dm), phenolic compounds (956.7 ± 71.14 mg / 100 g dm), iron (467.7 ± 1.84 mg / 100 g dm), magnesium (404.6 ± 16.25 mg / 100 g dm) and potassium (404.64 ± 16.25 mg/100 g dm). However, at the last stage of maturity (red berries), fruits are rich in proteins, cellulose, total sugars, fat and potassium with the values of 22.53 ± 2 g/100 g dm, 19.12 ± 0.35 g/100 g dm, 3.7 ± 0.2 g/100 g dm, 2.65 ± 0.19 g/100 g dm and 2290.84 ± 22.24 mg / 100 g dm, respectively. The chromatography on thin layer revealed the presence of glucose, ribose, xylose, arabinose and fructose at all the maturity stages. Except for alkaloids and gallic tannins, the phytochemical sorting revealed that Gnagnan contain many pharmacological components. According to the maturity stages, orange and red berries showed a higher content in sterols and polyterpens, flavonoids and saponins. The green berries contain most of polyphenols, catechintannins and quinons. As for the yellow berries, they are rich in polyphenols and catechintannins. These data contribute to enhance clinical researches on nutritional and pharmacological properties of S. anguivi Lam.Keywords: Gnagnan, maturity stage, chemical composition, chromatography thin layer, phytochemical sorting
Procedia PDF Downloads 49713510 Targeting Calcium Dysregulation for Treatment of Dementia in Alzheimer's Disease
Authors: Huafeng Wei
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Dementia in Alzheimer’s Disease (AD) is the number one cause of dementia internationally, without effective treatments. Increasing evidence suggest that disruption of intracellular calcium homeostasis, primarily pathological elevation of cytosol and mitochondria but reduction of endoplasmic reticulum (ER) calcium concentrations, play critical upstream roles on multiple pathologies and associated neurodegeneration, impaired neurogenesis, synapse, and cognitive dysfunction in various AD preclinical studies. The last federal drug agency (FDA) approved drug for AD dementia treatment, memantine, exert its therapeutic effects by ameliorating N-methyl-D-aspartate (NMDA) glutamate receptor overactivation and subsequent calcium dysregulation. More research works are needed to develop other drugs targeting calcium dysregulation at multiple pharmacological acting sites for future effective AD dementia treatment. Particularly, calcium channel blockers for the treatment of hypertension and dantrolene for the treatment of muscle spasm and malignant hyperthermia can be repurposed for this purpose. In our own research work, intranasal administration of dantrolene significantly increased its brain concentrations and durations, rendering it a more effective therapeutic drug with less side effects for chronic AD dementia treatment. This review summarizesthe progress of various studies repurposing drugs targeting calcium dysregulation for future effective AD dementia treatment as potentially disease-modifying drugs.Keywords: alzheimer, calcium, cognitive dysfunction, dementia, neurodegeneration, neurogenesis
Procedia PDF Downloads 18213509 Design Optimization and Thermoacoustic Analysis of Pulse Tube Cryocooler Components
Authors: K. Aravinth, C. T. Vignesh
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The usage of pulse tube cryocoolers is significantly increased mainly due to the advantage of the absence of moving parts. The underlying idea of this project is to optimize the design of pulse tube, regenerator, a resonator in cryocooler and analyzing the thermo-acoustic oscillations with respect to the design parameters. Computational Fluid Dynamic (CFD) model with time-dependent validation is done to predict its performance. The continuity, momentum, and energy equations are solved for various porous media regions. The effect of changing the geometries and orientation will be validated and investigated in performance. The pressure, temperature and velocity fields in the regenerator and pulse tube are evaluated. This optimized design performance results will be compared with the existing pulse tube cryocooler design. The sinusoidal behavior of cryocooler in acoustic streaming patterns in pulse tube cryocooler will also be evaluated.Keywords: acoustics, cryogenics, design, optimization
Procedia PDF Downloads 17513508 Muscle Relaxant Dantrolene Repurposed to Treat Alzheimer's Disease
Authors: Huafeng Wei
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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis
Procedia PDF Downloads 20813507 Design and Implementation of Remote Control Application for Elderly People Who Live Alone
Authors: Cristina Nieves Perdomo Delgado
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The study consists of the design and use of an application for cell phones called “Me Cuido” that consists of remote control of elderly people who live alone with their families. The objective of the study is to analyze the usability of the application by 40-year-olds using the Questionnaire for User Interaction Satisfaction (QUIS) method. The results highlight that the application has a design adapted to the elderly and that it is easy to use and understand.Keywords: design, assistive technology, elderly people, independence
Procedia PDF Downloads 25013506 A New Design Methodology for Partially Reconfigurable Systems-on-Chip
Authors: Roukaya Dalbouchi, Abdelkrin Zitouni
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In this paper, we propose a novel design methodology for Dynamic Partial Reconfigurable (DPR) system. This type of system has the property of being able to be modified after its design and during its execution. The suggested design methodology is generic in terms of granularity, number of modules, and reconfigurable region and suitable for any type of modern application. It is based on the interconnection between several design stages. The recommended methodology represents a guide for the design of DPR architectures that meet compromise reconfiguration/performance. To validate the proposed methodology, we use as an application a video watermarking. The comparison result shows that the proposed methodology supports all stages of DPR architecture design and characterized by a high abstraction level. It provides a dynamic/partial reconfigurable architecture; it guarantees material efficiency, the flexibility of reconfiguration, and superior performance in terms of frequency and power consumption.Keywords: dynamically reconfigurable system, block matching algorithm, partial reconfiguration, motion vectors, video watermarking
Procedia PDF Downloads 9513505 Clinical Application of Mesenchymal Stem Cells for Cancer Therapy: A Review of Registered Clinical Trials
Authors: Tuong Thi Van Thuy, Dao Van Toan, Nguyen Duc Phuc
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Mesenchymal stem cells (MSCs) were discovered in the 1970s with their unique properties of differentiation, immunomodulation, multiple secreting, and homing factors to injured organs. MSC-based therapies have emerged as a promising strategy for various diseases such as cancer, tissue regeneration, or immunologic/inflammatory-related diseases. This study evaluated the clinical application of MSCs for cancer therapy in trials registered on Clinical Trial as of July 2022. The results showed 40 clinical trials used MSCs in various cancer conditions. 62% of trials used MSCs for therapeutic purposes to minimize the side effects of cancer treatment. Besides, 38% of trials were focused on using MSCs as a therapeutic agent to treat cancer directly. Most trials (38/40) are ongoing phase I/II, and 2 are entering phase III. 84% of trials used allogeneic MSCs compared with 13% using autologous sources and 3% using both. 25/40 trials showed participants received a single dose of MSCs, while the most times were 12 times in a pancreatic cancer treatment trial. Conclusion: MSC-based therapy for cancer in clinical trials should be applied to (1) minimize the side effects of oncological treatments and (2) directly affect the tumor via selectively delivering anti-cancer payloads to tumor cells. Allogeneic MSCs are a priority selected in clinical cancer therapy.Keywords: mesenchymal stem cells, MSC-based therapy, cancer condition, cancer treatment, clinical trials
Procedia PDF Downloads 9213504 Combined Analysis of Sudoku Square Designs with Same Treatments
Authors: A. Danbaba
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Several experiments are conducted at different environments such as locations or periods (seasons) with identical treatments to each experiment purposely to study the interaction between the treatments and environments or between the treatments and periods (seasons). The commonly used designs of experiments for this purpose are randomized block design, Latin square design, balanced incomplete block design, Youden design, and one or more factor designs. The interest is to carry out a combined analysis of the data from these multi-environment experiments, instead of analyzing each experiment separately. This paper proposed combined analysis of experiments conducted via Sudoku square design of odd order with same experimental treatments.Keywords: combined analysis, sudoku design, common treatment, multi-environment experiments
Procedia PDF Downloads 34513503 Method of Visual Prosthesis Design Based on Biologically Inspired Design
Authors: Shen Jian, Hu Jie, Zhu Guo Niu, Peng Ying Hong
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There are two issues exited in the traditional visual prosthesis: lacking systematic method and the low level of humanization. To tackcle those obstacles, a visual prosthesis design method based on biologically inspired design is proposed. Firstly, a constrained FBS knowledge cell model is applied to construct the functional model of visual prosthesis in biological field. Then the clustering results of engineering domain are ob-tained with the use of the cross-domain knowledge cell clustering algorithm. Finally, a prototype system is designed to support the bio-logically inspired design where the conflict is digested by TRIZ and other tools, and the validity of the method is verified by the solution schemeKeywords: knowledge-based engineering, visual prosthesis, biologically inspired design, biomedical engineering
Procedia PDF Downloads 19213502 Targeting APP IRE mRNA to Combat Amyloid -β Protein Expression in Alzheimer’s Disease
Authors: Mateen A Khan, Taj Mohammad, Md. Imtaiyaz Hassan
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Alzheimer’s disease is characterized by the accumulation of the processing products of the amyloid beta peptide cleaved by amyloid precursor protein (APP). Iron increases the synthesis of amyloid beta peptides, which is why iron is present in Alzheimer's disease patients' amyloid plaques. Iron misregulation in the brain is linked to the overexpression of APP protein, which is directly related to amyloid-β aggregation in Alzheimer’s disease. The APP 5'-UTR region encodes a functional iron-responsive element (IRE) stem-loop that represents a potential target for modulating amyloid production. Targeted regulation of APP gene expression through the modulation of 5’-UTR sequence function represents a novel approach for the potential treatment of AD because altering APP translation can be used to improve both the protective brain iron balance and provide anti-amyloid efficacy. The molecular docking analysis of APP IRE RNA with eukaryotic translation initiation factors yields several models exhibiting substantial binding affinity. The finding revealed that the interaction involved a set of functionally active residues within the binding sites of eIF4F. Notably, APP IRE RNA and eIF4F interaction were stabilized by multiple hydrogen bonds with residues of APP IRE RNA and eIF4F. It was evident that APP IRE RNA exhibited a structural complementarity that tightly fit within binding pockets of eIF4F. The simulation studies further revealed the stability of the complexes formed between RNA and eIF4F, which is crucial for assessing the strength of these interactions and subsequent roles in the pathophysiology of Alzheimer’s disease. In addition, MD simulations would capture conformational changes in the IRE RNA and protein molecules during their interactions, illustrating the mechanism of interaction, conformational change, and unbinding events and how it may affect aggregation propensity and subsequent therapeutic implications. Our binding studies correlated well with the translation efficiency of APP mRNA. Overall, the outcome of this study suggests that the genomic modification and/or inhibiting the expression of amyloid protein by targeting APP IRE RNA can be a viable strategy to identify potential therapeutic targets for AD and subsequently be exploited for developing novel therapeutic approaches.Keywords: Alzheimer's disease, Protein-RNA interaction analysis, molecular docking simulations, conformational dynamics, binding stability, binding kinetics, protein synthesis.
Procedia PDF Downloads 6413501 Therapeutic Effects of Toll Like Receptor 9 Ligand CpG-ODN on Radiation Injury
Authors: Jianming Cai
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Exposure to ionizing radiation causes severe damage to human body and an safe and effective radioprotector is urgently required for alleviating radiation damage. In 2008, flagellin, an agonist of TLR5, was found to exert radioprotective effects on radiation injury through activating NF-kB signaling pathway. From then, the radioprotective effects of TLR ligands has shed new lights on radiation protection. CpG-ODN is an unmethylated oligonucleotide which activates TLR9 signaling pathway. In this study, we demonstrated that CpG-ODN has therapeutic effects on radiation injuries induced by γ ray and 12C6+ heavy ion particles. Our data showed that CpG-ODN increased the survival rate of mice after whole body irradiation and increased the number of leukocytes as well as the bone marrow cells. CpG-ODN also alleviated radiation damage on intestinal crypt through regulating apoptosis signaling pathway including bcl2, bax, and caspase 3 etc. By using a radiation-induced pulmonary fibrosis model, we found that CpG-ODN could alleviate structural damage, within 20 week after whole–thorax 15Gy irradiation. In this model, Th1/Th2 imbalance induced by irradiation was also reversed by CpG-ODN. We also found that TGFβ-Smad signaling pathway was regulated by CpG-ODN, which accounts for the therapeutic effects of CpG-ODN in radiation-induced pulmonary injury. On another hand, for high LET radiation protection, we investigated protective effects of CpG-ODN against 12C6+ heavy ion irradiation and found that after CpG-ODN treatment, the apoptosis and cell cycle arrest induced by 12C6+ irradiation was reduced. CpG-ODN also reduced the expression of Bax and caspase 3, while increased the level of bcl2. Then we detected the effect of CpG-ODN on heavy ion induced immune dysfunction. Our data showed that CpG-ODN increased the survival rate of mice and also the leukocytes after 12C6+ irradiation. Besides, the structural damage of immune organ such as thymus and spleen was also alleviated by CpG-ODN treatment. In conclusion, we found that TLR9 ligand, CpG-ODN reduced radiation injuries in response to γ ray and 12C6+ heavy ion irradiation. On one hand, CpG-ODN inhibited the activation of apoptosis induced by radiation through regulating bcl2, bax and caspase 3. On another hand, through activating TLR9, CpG-ODN recruit MyD88-IRAK-TRAF6 complex, activating TAK1, IRF5 and NF-kB pathway, and thus alleviates radiation damage. This study provides novel insights into protection and therapy of radiation damages.Keywords: TLR9, CpG-ODN, radiation injury, high LET radiation
Procedia PDF Downloads 48013500 Integrated Evaluation of Green Design and Green Manufacturing Processes Using a Mathematical Model
Authors: Yuan-Jye Tseng, Shin-Han Lin
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In this research, a mathematical model for integrated evaluation of green design and green manufacturing processes is presented. To design a product, there can be alternative options to design the detailed components to fulfill the same product requirement. In the design alternative cases, the components of the product can be designed with different materials and detailed specifications. If several design alternative cases are proposed, the different materials and specifications can affect the manufacturing processes. In this paper, a new concept for integrating green design and green manufacturing processes is presented. A green design can be determined based the manufacturing processes of the designed product by evaluating the green criteria including energy usage and environmental impact, in addition to the traditional criteria of manufacturing cost. With this concept, a mathematical model is developed to find the green design and the associated green manufacturing processes. In the mathematical model, the cost items include material cost, manufacturing cost, and green related cost. The green related cost items include energy cost and environmental cost. The objective is to find the decisions of green design and green manufacturing processes to achieve the minimized total cost. In practical applications, the decision-making can be made to select a good green design case and its green manufacturing processes. In this presentation, an example product is illustrated. It shows that the model is practical and useful for integrated evaluation of green design and green manufacturing processes.Keywords: supply chain management, green supply chain, green design, green manufacturing, mathematical model
Procedia PDF Downloads 80713499 Akt: Isoform-Specific Regulation of Cellular Signaling in Cancer
Authors: Bhumika Wadhwa, Fayaz Malik
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The serine/threonine protein kinase B (PKB) also known as Akt, is one of the multifaceted kinase in human kinome, existing in three isoforms. Akt plays a vital role in phosphoinositide 3-kinase (PI3K) mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. The functional significance of an individual isoform of Akt is not redundant in cancer cell proliferation and metastasis instead Akt isoforms play distinct roles during metastasis; thereby regulating EMT. This study aims to determine isoform specific functions of Akt in cancer. The results obtained suggest that Akt1 restrict tumor invasion, whereas Akt2 promotes cell migration and invasion by various techniques like MTT, wound healing and invasion assay. Similarly, qRT-PCR also revealed that Akt3 has shown promising results in promoting cancer cell migration. Contrary to pro-oncogenic properties attributed to Akt, it is to be understood how various isoforms of Akt compensates each other in the regulation of common pathways during cancer progression and drug resistance. In conclusion, this study aims to target selective isoforms which is essential to inhibit cancer. However, the question now is whether, and how much, Akt inhibition will be tolerated in the clinic remains to be answered and the experiments will have to address the question of which combinations of newly devised Akt isoform specific inhibitors exert a favourable therapeutic effect in in vivo models of cancer to provide the therapeutic window with minimal toxicity.Keywords: Akt isoforms, cancer, drug resistance, epithelial mesenchymal transition
Procedia PDF Downloads 25613498 Eradication of Mental Illness through Buddhism
Authors: Deshar Bashu Dev
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In this modern age, most people in developed and developing countries are affected by mental illness. There are many mental illnesses, and their differing symptoms impact peoples’ lives in different ways. These illnesses affect the way people think and feel, as well as how they behave with others. Mental illness results from compound interactions between the mind, body, and environment. New technologies and sciences make the world a better place. These technologies are becoming smarter and are being developed every day to help make daily life easier However, people suffer from mental illness in every part of the world. The philosophy propounded by the Buddha, Buddhism, teaches that all life is connected, from the microcosm to macrocosm. In the 2,500 years that elapsed since the death of the Buddha, his disciples have spread his teachings and developed sophisticated psycho-therapeutic methodologies. We can find many examples in Buddhist texts and in the modern age where Buddhist philosophy modern science could not solve. The Noble Eightfold Path, which is one of the main philosophies of Buddhism; it eradicates hatred and ill will and cultivates good deeds, kindness, and compassion. Buddhism, as a practice of dialectic conversation and mindfulness training, is full of rich therapeutic tools that the mental health community has adopted to help people. Similarly, Buddhist meditation is very necessary; it purifies thoughts and avoids unnecessary thinking. This research aims to study different causes of mental illness; analyzes the different approaches to eradicate mental illness problems and provides conclusions and recommendations present solutions through Buddhism in this modern age.Keywords: mental illness, Buddhism, mindfulness, Buddhist practices
Procedia PDF Downloads 25313497 Pioneering Technology of Night Photo-Stimulation of the Brain Lymphatic System: Therapy of Brain Diseases during Sleep
Authors: Semyachkina-Glushkovskaya Oxana, Fedosov Ivan, Blokhina Inna, Terskov Andrey, Evsukova Arina, Elovenko Daria, Adushkina Viktoria, Dubrovsky Alexander, Jürgen Kurths
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In modern neurobiology, sleep is considered a novel biomarker and a promising therapeutic target for brain diseases. This is due to recent discoveries of the nighttime activation of the brain lymphatic system (BLS), playing an important role in the removal of wastes and toxins from the brain and contributes neuroprotection of the central nervous system (CNS). In our review, we discuss that night stimulation of BLS might be a breakthrough strategy in a new treatment of Alzheimer’s and Parkinson’s disease, stroke, brain trauma, and oncology. Although this research is in its infancy, however, there are pioneering and promising results suggesting that night transcranial photostimulation (tPBM) stimulates more effectively lymphatic removal of amyloid-beta from mouse brain than daily tPBM that is associated with a greater improvement of the neurological status and recognition memory of animals. In our previous study, we discovered that tPBM modulates the tone and permeability of the lymphatic endothelium by stimulating NO formation, promoting lymphatic clearance of wastes and toxins from the brain tissues. We also demonstrate that tPBM can also lead to angio- and lymphangiogenesis, which is another mechanism underlying tPBM-mediated stimulation of BLS. Thus, photo-augmentation of BLS might be a promising therapeutic target for preventing or delaying brain diseases associated with BLS dysfunction. Here we present pioneering technology for simultaneous tPBM in humans and sleep monitoring for stimulation of BLS to remove toxins from CNS and modulation of brain immunity. The wireless-controlled gadget includes a flexible organic light-emitting diode (LED) source that is controlled directly by a sleep-tracking device via a mobile application. The designed autonomous LED source is capable of providing the required therapeutic dose of light radiation at a certain region of the patient’s head without disturbing of sleeping patient. To minimize patients' discomfort, advanced materials like flexible organic LEDs were used. Acknowledgment: This study was supported by RSF project No. 23-75-30001.Keywords: brain diseases, brain lymphatic system, phototherapy, sleep
Procedia PDF Downloads 7213496 FPGA Implementation of RSA Encryption Algorithm for E-Passport Application
Authors: Khaled Shehata, Hanady Hussien, Sara Yehia
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Securing the data stored on E-passport is a very important issue. RSA encryption algorithm is suitable for such application with low data size. In this paper the design and implementation of 1024 bit-key RSA encryption and decryption module on an FPGA is presented. The module is verified through comparing the result with that obtained from MATLAB tools. The design runs at a frequency of 36.3 MHz on Virtex-5 Xilinx FPGA. The key size is designed to be 1024-bit to achieve high security for the passport information. The whole design is achieved through VHDL design entry which makes it a portable design and can be directed to any hardware platform.Keywords: RSA, VHDL, FPGA, modular multiplication, modular exponential
Procedia PDF Downloads 39113495 Modern Forms and Aesthetics in Design
Authors: Chukwuma Anya, Mekwa Eme
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The term ‘’FORM’’ in design could be referred to as the combination of various shapes of different sizes and assembling them in appropriate positions to achieve a unique figure of high aesthetic value. A deduction from this definition is that forms contribute immensely to the actualization of aesthetics in a building. When these various shapes and figures are properly assembled, it may give rise to a concept in design. However some architects and other designers either misuse or abuse the use of these shapes, hence resulting to a design imbalance, lack of uniformity and expression. This academic work is designed to educate the public on the proper usage of some regular shapes like circles, rectangles, pentagons, hexagons, triangles etc, to achieve a unique form in design. By the end of this work, one should be able to assemble different shapes to express different emotions of the mind, such as peace, love, confusion, war, and unity. Some elements of design, such as balance, stability, functionality and aesthetics, will also be achieved even as the building maintains its unique form.Keywords: aesthetics, form, balance, stability
Procedia PDF Downloads 8613494 Bioinformatic Design of a Non-toxic Modified Adjuvant from the Native A1 Structure of Cholera Toxin with Membrane Synthetic Peptide of Naegleria fowleri
Authors: Frida Carrillo Morales, Maria Maricela Carrasco Yépez, Saúl Rojas Hernández
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Naegleria fowleri is the causative agent of primary amebic meningoencephalitis, this disease is acute and fulminant that affects humans. It has been reported that despite the existence of therapeutic options against this disease, its mortality rate is 97%. Therefore, the need arises to have vaccines that confer protection against this disease and, in addition to developing adjuvants to enhance the immune response. In this regard, in our work group, we obtained a peptide designed from the membrane protein MP2CL5 of Naegleria fowleri called Smp145 that was shown to be immunogenic; however, it would be of great importance to enhance its immunological response, being able to co-administer it with a non-toxic adjuvant. Therefore, the objective of this work was to carry out the bioinformatic design of a peptide of the Naegleria fowleri membrane protein MP2CL5 conjugated with a non-toxic modified adjuvant from the native A1 structure of Cholera Toxin. For which different bioinformatics tools were used to obtain a model with a modification in amino acid 61 of the A1 subunit of the CT (CTA1), to which the Smp145 peptide was added and both molecules were joined with a 13-glycine linker. As for the results obtained, the modification in CTA1 bound to the peptide produces a reduction in the toxicity of the molecule in in silico experiments, likewise, the prediction in the binding of Smp145 to the receptor of B cells suggests that the molecule is directed in specifically to the BCR receptor, decreasing its native enzymatic activity. The stereochemical evaluation showed that the generated model has a high number of adequately predicted residues. In the ERRAT test, the confidence with which it is possible to reject regions that exceed the error values was evaluated, in the generated model, a high score was obtained, which determines that the model has a good structural resolution. Therefore, the design of the conjugated peptide in this work will allow us to proceed with its chemical synthesis and subsequently be able to use it in the mouse meningitis protection model caused by N. fowleri.Keywords: immunology, vaccines, pathogens, infectious disease
Procedia PDF Downloads 9213493 The Improved Therapeutic Effect of Trans-Cinnamaldehyde on Adipose-Derived Stem Cells without Chemical Induction
Authors: Karthyayani Rajamani, Yi-Chun Lin, Tung-Chou Wen, Jeanne Hsieh, Yi-Maun Subeq, Jen-Wei Liu, Po-Cheng Lin, Horng-Jyh Harn, Shinn-Zong Lin, Tzyy-Wen Chiou
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Assuring cell quality is an essential parameter for the success of stem cell therapy, utilization of various components to improve this potential has been the primary goal of stem cell research. The aim of this study was not only to demonstrate the capacity of trans-cinnamaldehyde (TC) to reverse stress-induced senescence but also improve the therapeutic abilities of stem cells. Because of the availability and the promising application potential in regenerative medicine, adipose-derived stem cells (ADSCs) were chosen for the study. We found that H2O2 treatment resulted in the expression of senescence characteristics in the ADSCs, including decreased proliferation rate, increased senescence-associated- β-galactosidase (SA-β-gal) activity, decreased SIRT1 (silent mating type information regulation 2 homologs) expression and decreased telomerase activity. However, TC treatment was sufficient to rescue or reduce the effects of H2O2 induction, ultimately leading to an increased proliferation rate, a decrease in the percentage of SA-β-gal positive cells, upregulation of SIRT1 expression, and increased telomerase activity of the senescent ADSCs at the cellular level. Further recently it was observed that the ADSCs were treated with TC without induction of senescence, all the before said positives were observed. Moreover, a chemically induced liver fibrosis animal model was used to evaluate the functionality of these rescued cells in vivo. Liver dysfunction was established by injecting 200 mg/kg thioacetamide (TAA) intraperitoneally into Wistar rats every third day for 60 days. The experimental rats were separated into groups; normal group (rats without TAA induction), sham group (without ADSC transplantation), positive control group (transplanted with normal ADSCs); H2O2 group (transplanted with H2O2 -induced senescent ADSCs), H2O2+TC group (transplanted with ADSCs pretreated with H2O2 and then further treated with TC) and TC group (ADSC treated with TC without H2O2 treatment). In the transplantation group, 1 × 106 human ADSCs were introduced into each rat via direct liver injection. Based on the biochemical analysis and immunohistochemical staining results, it was determined that the therapeutic effects on liver fibrosis by the induced senescent ADSCs (H2O2 group) were not as significant as those exerted by the normal ADSCs (the positive control group). However, the H2O2+TC group showed significant reversal of liver damage when compared to the H2O2 group 1 week post-transplantation. Further ADSCs without H2O2 treatment but with just TC treatment performed much better than all the groups. These data confirmed that the TC treatment had the potential to improve the therapeutic effect of ADSCs. It is therefore suggested that TC has potential applications in maintaining stem cell quality and could possibly aid in the treatment of senescence-related disorders.Keywords: senescence, SIRT1, adipose derived stem cells, liver fibrosis
Procedia PDF Downloads 25813492 Investigation of FoxM1 Gene Expression in Breast Cancer and Its Relationship with miR-216B-5p Expression Level
Authors: Ramin Mehdiabadi
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Background: Breast cancer remains the most prevalent cancer diagnosis and the leading cause of cancer death among women globally, representing 11.7% of new cases and 6.9% of deaths. While the incidence and mortality of major cancers are declining in developed regions like the United States and Western Europe, underdeveloped and developing countries exhibit an increasing trend, attributed to lifestyle factors such as smoking, physical inactivity, and high-calorie diets. Objective: This study explores the intricate relationship between the mammalian transcription factor forkhead box (FoxM1) and the microRNA miR-216b-5p in various subtypes of breast cancer, aiming to deepen the understanding of their roles in tumorigenesis, metastasis, and drug resistance. Methods: Breast cancer subtypes were categorized based on key biomarkers: estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. These include luminal A, luminal B, HER2 enriched, triple-negative, and normal-like subtypes. We focused on analyzing the expression levels of FoxM1 and miR-216b-5p, given the known role of FoxM1 in cell proliferation and its implications in cancer pathologies such as lung, gastric, and breast cancers. Concurrently, miR-216b-5p's function as a tumor suppressor was evaluated to ascertain its regulatory effects on FoxM1. Results: Preliminary data indicate a nuanced interplay between FoxM1 and miR-216b-5p, suggesting a potential inverse relationship that varies across breast cancer subtypes. This relationship underscores the dual role of these biomarkers in modulating cancer progression and response to treatments. Conclusion: The findings advocate for the potential of miR-216b-5p to serve as a prognostic biomarker and a therapeutic target, particularly in subtypes where FoxM1 is prominently expressed. Understanding these molecular interactions provides crucial insights into the personalized treatment strategies and could lead to more effective therapeutic interventions in breast cancer management. Implications: The study highlights the importance of molecular profiling in breast cancer treatment and emphasizes the need for targeted therapeutic approaches in managing diverse cancer subtypes, particularly in varying global contexts where lifestyle factors significantly impact cancer dynamics.Keywords: breast cancer, gene expression, FoxM1, microRNA
Procedia PDF Downloads 5513491 Trigonella foenum-graecum Seeds Extract as Therapeutic Candidate for Treatment of Alzheimer's Disease
Authors: Mai M. Farid, Ximeng Yang, Tomoharu Kuboyama, Yuna Inada, Chihiro Tohda
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Intro: Trigonella foenum-graecum (Fenugreek), from Fabaceae family is a well-known plant traditionally used as food and medicine. Many pharmacological effects of Trigonella foenum- graecum seeds extract (TF extract) were evaluated such as anti-diabetic, anti-tumor and anti-dementia effects using in vivo models. Regarding the anti-dementia effects of TF extract, diabetic rats, aluminum chloride-induced amnesia rats and scopolamine-injected mice were used previously for evaluation, which are not well established as Alzheimer’s disease models. In addition, those previous studies, active constituents in TF extract for memory function were not identified. Method: This study aimed to clarify the effect of TF extract on Alzheimer’s disease model, 5XFAD mouse that overexpresses mutated APP and PS1 genes and determine the major active constituent in the brain after oral intake of TF extract. Results: Trigonelline was detected in the cerebral cortex of 5XFAD mice after 24 hours of oral administration of TF extract by LC-MS/MS. Oral administration of TF extract for 17 days improved object location memory in 5XFAD mice. Conclusion: These results suggest that TF extract and its active constituents could be an expected therapeutic candidate for Alzheimer’s disease.Keywords: Alzheimer's disease, LC-MS/MS, memory recovery, Trigonella foenum-graecum Seeds, 5XFAD mice
Procedia PDF Downloads 14713490 Design of Impedance Box to Study Fluid Parameters
Authors: K. AlJimaz, A. Abdullah, A. Abdulsalam, K. Ebdah, A. Abdalrasheed
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Understanding flow distribution and head losses is essential to design and calculate Thermo fluid parameters in order to reduce the pressure to a certain required pressure. This paper discusses the ways acquired in design and simulation to create and design an impedance box that reduces pressure. It's controlled by specific scientific principles such as Bernoulli’s principle and conservation of mass. In this paper, the design is made using SOLIDWORKS, and the simulation is done using ANSYS software to solve differential equations and study the parameters in the 3D model, also to understand how the design of this box reduced the pressure. The design was made so that fluid enters at a certain pressure of 3000 Pa in a single inlet; then, it exits from six outlets at a pressure of 300 Pa with respect to the conservation of mass principle. The effect of the distribution of flow and the head losses has been noticed that it has an impact on reducing the pressure since other factors, such as friction, were neglected and also the temperature, which was constant. The design showed that the increase in length and diameter of the pipe helped to reduce the pressure, and the head losses contributed significantly to reduce the pressure to 10% of the original pressure (from 3000 Pa to 300 Pa) at the outlets.Keywords: box, pressure, thermodynamics, 3D
Procedia PDF Downloads 8813489 Quality of Life of Women with Breast Cancer and Its Correlation with Depression and Anxiety
Authors: Maria Malliarou, Efrossini Lyraraki, Pavlos Sarafis, Theodosios Paralikas, Styliani Kotrotsiou, Evangelia Kotrotsiou, Mairy Gouva
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Women with breast cancer have to adapt to physical malformations, side effects of chemotherapy, emotional insecurity, and changes in social roles. Inability to recognize the co-morbidity of psychiatric conditions can have an aggravating effect on patient compliance in therapeutic interventions, resulting in treatment delays and an impact on overall survival. The purpose of this study was to identify the quality of life of breast cancer patients undergoing external radiation therapy and to correlate it with depression and anxiety. Patients were asked to respond to an anonymous questionnaire with general demographic and clinical questions, followed by the EORTCQLQ-C30 questionnaire for assessing the quality of life of patients with breast cancer. Hospital Anxiety and Depression Scale (HADS) as well as the Depression, Anxiety and Stress Scale (DASS-21) was also administered. The statistical analysis of the data was done in IBM SPSS. Results indicated that the incidence of anxiety and depression in breast cancer patients is high both in HADS (37.5 % with mild to moderate depression and 62.5 % with significant to severe depression) and DASS - 21 (39.2 % mild to moderate depression and 60.8 % significant to severe) scales. The correlation of anxiety and depression with life quality was negative for HADS (r = -, 810, p = .000) as well as for DASS-21 (r = -, 682, p = .000). The psychological impact of breast cancer on patients is important. Its correlation with the quality of life may lead to better tolerance to treatment and better effectiveness of the therapeutic approach.Keywords: anxiety, breast cancer, depression, quality of life
Procedia PDF Downloads 26713488 Value Engineering and Its Impact on Drainage Design Optimization for Penang International Airport Expansion
Authors: R.M. Asyraf, A. Norazah, S.M. Khairuddin, B. Noraziah
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Designing a system at present requires a vital, challenging task; to ensure the design philosophy is maintained in economical ways. This paper perceived the value engineering (VE) approach applied in infrastructure works, namely stormwater drainage. This method is adopted in line as consultants have completed the detailed design. Function Analysis System Technique (FAST) diagram and VE job plan, information, function analysis, creative judgement, development, and recommendation phase are used to scrutinize the initial design of stormwater drainage. An estimated cost reduction using the VE approach of 2% over the initial proposal was obtained. This cost reduction is obtained from the design optimization of the drainage foundation and structural system, where the pile design and drainage base structure are optimized. Likewise, the design of the on-site detention tank (OSD) pump was revised and contribute to the cost reduction obtained. This case study shows that the VE approach can be an important tool in optimizing the design to reduce costs.Keywords: value engineering, function analysis system technique, stormwater drainage, cost reduction
Procedia PDF Downloads 14513487 Design, Prototyping, Integration, Flight Testing of a 20 cm Span Fully Autonomous Fixed Wing Micro Air Vehicle
Authors: Vivek Paul, Abel Nelly, Shoeb A Adeel, R. Tilak, S. Maheshwaran, S. Pulikeshi, Roshan Antony, C. S. Suraj
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This paper presents the complete design and development cycle of a 20 cm span fixed wing micro air vehicle that was developed at CSIR-NAL, under the micro air vehicle development program. The design is a cropped delta flying wing MAV with a modified N22 airfoil of 12.3% thickness. The design was fabricated using the fused deposition method- RPT technique. COTS components were procured and integrated into this RPT prototype. A commercial autopilot that was proven in the earlier MAV designs was used for this MAV. The MAV was flown fully autonomous for 14mins at an open field. The flight data showed good performance as expected from the MAV design. The paper also describes about the process involved in the design of MAVs.Keywords: autopilot, autonomous mode, flight testing, MAV, RPT
Procedia PDF Downloads 51913486 Design for Error-Proofing Assembly: A Systematic Approach to Prevent Assembly Issues since Early Design Stages, an Industrial Case Study
Authors: Gabriela Estrada, Joaquim Lloveras
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Design for error-proofing assembly is a new DFX approach to prevent assembly issues since early design stages. Assembly issues that can happen during the life phases of a system such as: production, installation, operation, and replacement phases. This prevention is possible by designing the product with poka-yoke or error-proofing characteristics. This approach guide designers to make decisions based on poka-yoke assembly design requirements. As a result of applying these requirements designers are able to create solutions to prevent assembly issues for the product in development stage. This paper integrates the needs to design products in an error proofing way into the systematic approach of design process by Pahl and Beitz. A case study is presented applying this approach.Keywords: poka-yoke, error-proofing, assembly issues, design process, life phases of a system
Procedia PDF Downloads 37613485 Design for Error-Proofing Assembly: A Systematic Approach to Prevent Assembly Issues since Early Design Stages. An Industry Case Study
Authors: Gabriela Estrada, Joaquim Lloveras
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Design for error-proofing assembly is a new DFX approach to prevent assembly issues since early design stages. Assembly issues that can happen during the life phases of a system such as: production, installation, operation and replacement phases. This prevention is possible by designing the product with poka-yoke or error-proofing characteristics. This approach guide designers to make decisions based on poka-yoke assembly design requirements. As a result of applying these requirements designers are able to create solutions to prevent assembly issues for the product in development stage. This paper integrates the needs to design products in an error proofing way into the systematic approach of design process by Pahl and Beitz. A case study is presented applying this approach.Keywords: poka-yoke, error-proofing, assembly issues, design process, life phases of a system
Procedia PDF Downloads 323