Search results for: therapeutic response
6092 Peak Floor Response for Buildings with Flexible Base
Authors: Luciano Roberto Fernandez-Sola, Cesar Augusto Arredondo-Velez, Miguel Angel Jaimes-Tellez
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This paper explores the modifications on peak acceleration, velocity and displacement profiles over the structure due to dynamic soil-structure interaction (DSSI). A shear beam model is used for the structure. Soil-foundation flexibility (inertial interaction) is considered by a set of springs and dashpots at the structure base. Kinematic interaction is considered using transfer functions. Impedance functions are computed using simplified expressions for rigid foundations. The research studies the influence of the slenderness ratio on the value of the peak floor response. It is shown that the modifications of peak floor responses are not the same for acceleration, velocity and displacement. This is opposite to the hypothesis used by methods included in several building codes. Results show that modifications produced by DSSI on different response quantities are not equal.Keywords: peak floor intensities, dynamic soil-structure interaction, buildings with flexible base, kinematic and inertial interaction
Procedia PDF Downloads 4506091 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 926090 Seismic Response Analysis of Frame Structures Based on Super Joint Element Model
Authors: Li Xu, Yang Hong, T. Zhao Wen
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Experimental results of many RC beam-column subassemblage indicate that slippage of longitudinal beam rebar within the joint and the shear deformation of joint core have significant influence on seismic behavior of the subassemblage. However, rigid joint assumption has been generally used in the seismic response analysis of RC frames, in which two kinds of inelastic deformation of joint have been ignored. Based on OpenSees platform, ‘Super Joint Element Model’ with more detailed inelastic mechanism is used to simulate the inelastic response of joints. Two finite element models of typical RC plane frame, namely considering or ignoring the inelastic deformation of joint respectively, were established and analyzed under seven strong earthquake waves. The simulated global and local inelastic deformations of the RC plane frame is shown and discussed. The analyses also confirm the security of the earthquake-resistant frame designed according to Chinese codes.Keywords: frame structure, beam-column joint, longitudinal bar slippage, shear deformation, nonlinear analysis
Procedia PDF Downloads 4096089 Studying the Dynamical Response of Nano-Microelectromechanical Devices for Nanomechanical Testing of Nanostructures
Authors: Mohammad Reza Zamani Kouhpanji
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Characterizing the fatigue and fracture properties of nanostructures is one of the most challenging tasks in nanoscience and nanotechnology due to lack of a MEMS/NEMS device for generating uniform cyclic loadings at high frequencies. Here, the dynamic response of a recently proposed MEMS/NEMS device under different inputs signals is completely investigated. This MEMS/NEMS device is designed and modeled based on the electromagnetic force induced between paired parallel wires carrying electrical currents, known as Ampere’s Force Law (AFL). Since this MEMS/NEMS device only uses two paired wires for actuation part and sensing part, it represents highly sensitive and linear response for nanostructures with any stiffness and shapes (single or arrays of nanowires, nanotubes, nanosheets or nanowalls). In addition to studying the maximum gains at different resonance frequencies of the MEMS/NEMS device, its dynamical responses are investigated for different inputs and nanostructure properties to demonstrate the capability, usability, and reliability of the device for wide range of nanostructures. This MEMS/NEMS device can be readily integrated into SEM/TEM instruments to provide real time study of the fatigue and fracture properties of nanostructures as well as their softening or hardening behaviors, and initiation and/or propagation of nanocracks in them.Keywords: MEMS/NEMS devices, paired wire actuators and sensors, dynamical response, fatigue and fracture characterization, Ampere’s force law
Procedia PDF Downloads 3996088 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 646087 Examining Effects of Electronic Market Functions on Decrease in Product Unit Cost and Response Time to Customer
Authors: Maziyar Nouraee
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Electronic markets in recent decades contribute remarkably in business transactions. Many organizations consider traditional ways of trade non-economical and therefore they do trade only through electronic markets. There are different categorizations of electronic markets functions. In one classification, functions of electronic markets are categorized into classes as information, transactions, and value added. In the present paper, effects of the three classes on the two major elements of the supply chain management are measured. The two elements are decrease in the product unit cost and reduction in response time to the customer. The results of the current research show that among nine minor elements related to the three classes of electronic markets functions, six factors and three factors influence on reduction of the product unit cost and reduction of response time to the customer, respectively.Keywords: electronic commerce, electronic market, B2B trade, supply chain management
Procedia PDF Downloads 3926086 Melanoma Antigen Proteins Are Involved in DNA Damage Response
Authors: Olivier de Backer, Alexis Khelfi, Olivier Svensek, Axelle Nolmans, Dominique Desnoeck
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The SMC5-SMC6 complex helps replication and repair of DNA double-strand breaks. Nse1, Nse3 and Nse4 are non-SMC components of the complex in which Nse3 stimulates the E3 ubiquitin ligase activity of Nse1 and is required for recruiting the complex on DNA. In most eukaryotes, Nse3 is a single protein, but in eutherians (placental mammals), it belongs to a large family of proteins called MAGE (Melanoma antigen) that share a conserved domain of about 200 aa known as MHD (Mage homology domain). MAGE assembles specific RING and HECT ubiquitin ligases and determines new substrates for ubiquitination. The MHD is required for the interaction with the cognate E3 ligase. Some MAGEs (referred to as Type I) are exclusively expressed in germ cells of the testis but are often expressed ectopically in cancer cells as the result of epigenetic modifications. The 12 MAGE-A genes belong to this category. Serval MAGE-A proteins could promote tumorigenesis by targeting tumor suppressor proteins (including p53) for ubiquitination and degradation. We showed that depletion of MAGE-A proteins in melanoma cells results in impaired DNA damage response and increased double-strand breaks after exposure to camptothecin. Moreover, it was shown that other actors of the DNA Damage Response were impacted when cells were depleted of MAGEA proteins.Keywords: DNA damage response, melanoma, camptothecin, new role, MAGEA
Procedia PDF Downloads 1016085 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 2566084 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 2536083 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 726082 The Arts in Medicine and Health: A Necessity for Evidence-Based Health Systems
Authors: Alan S. Weber
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This contribution reviews the current biomedical and qualitative arts research on arts-in-health interventions to improve both individual and population health outcomes. Arts therapies–for example, music therapy with roots in Aristoxenus’s Ἁρμονικὰ στοιχεῖα and the Pythagorean sect–have long been employed in therapeutic contexts. However, the 20th century witnessed the increasing use of the visual and plastic arts (drawing, painting, sculpting), performing arts (drama and dance), and other expressive arts modalities into occupational therapy, well-being medicine, and psychological and psychiatric counselling, diagnosis, and treatment. A significant body of peer-reviewed evidence in the medical and neurological sciences on the role of arts-in-health has developed, and specifically, research on music and art therapy has led to their inclusion within the current biomedical paradigm of evidence-based practice. The arts cannot only aid in public and population health promotion (promoting healthy behaviors and lifestyles, preventing disease onset) but also in addressing psychological issues (regulation of emotion; stress, anxiety, and depression reduction), behavioural issues (basic life skills, coping), and physiological response (immune system function, hormonal regulation, homeostatis). Working as a cross-disciplinary researcher in the arts in an American medical college, the author has developed several successful arts-in-health programs at the national and international level.Keywords: arts-in-health, evidence based medicine, arts for health, expressive arts therapies
Procedia PDF Downloads 706081 Rescue Emergency Drone for Fast Response to Medical Emergencies Due to Traffic Accidents
Authors: Anders S. Kristensen, Dewan Ahsan, Saqib Mehmood, Shakeel Ahmed
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Traffic accidents are a result of the convergence of hazards, malfunctioning of vehicles and human negligence that have adverse economic and health impacts and effects. Unfortunately, avoiding them completely is very difficult, but with quick response to rescue and first aid, the mortality rate of inflicted persons can be reduced significantly. Smart and innovative technologies can play a pivotal role to respond faster to traffic crash emergencies comparing conventional means of transportation. For instance, Rescue Emergency Drone (RED) can provide faster and real-time crash site risk assessment to emergency medical services, thereby helping them to quickly and accurately assess a situation, dispatch the right equipment and assist bystanders to treat inflicted person properly. To conduct a research in this regard, the case of a traffic roundabout that is prone to frequent traffic accidents on the outskirts of Esbjerg, a town located on western coast of Denmark is hypothetically considered. Along with manual calculations, Emergency Disaster Management Simulation (EDMSIM) has been used to verify the response time of RED from a fire station of the town to the presumed crash site. The results of the study demonstrate the robustness of RED into emergency services to help save lives.Keywords: automated external defibrillator, medical emergency, response time, unmanned aerial system
Procedia PDF Downloads 2286080 Soil-Structure Interaction in Stiffness and Strength Degrading Systems
Authors: Enrique Bazan-Zurita, Sittipong Jarernprasert, Jacobo Bielak
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We study the effects of soil-structure interaction (SSI) on the inelastic seismic response of a single-degree-of-freedom system whose hysteretic behaviour exhibits stiffness and/or strength degrading characteristics. Two sets of accelerograms are used as seismic input: the first comprising 87 record from stiff to medium stiff sites in California, and the second comprising 66 records from the soft lakebed of Mexico City. This study focuses in three seismic response parameters: ductility demand, inter-story drift, and total lateral displacement. The results allow quantitative estimates of changes in such parameters in an SSI system in comparison with those corresponding to the associated fixed-base system. We found that degrading features affect significantly both the response of fixed-base structures and the impact of soil-structure interaction. We propose a procedure to incorporate the results of this and similar studies in seismic design regulations for SSI system with anticipated nonlinear degrading behaviour.Keywords: inelastic, seismic, building, foundation, interaction
Procedia PDF Downloads 2866079 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 2586078 Therapeutic Application of Light and Electromagnetic Fields to Reduce Hyper-Inflammation Triggered by COVID-19
Authors: Blanche Aguida, Marootpong Pooam, Nathalie Jourdan, Margaret Ahmad
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COVID-19-related morbidity is associated with exaggerated inflammation and cytokine production in the lungs, leading to acute respiratory failure. The cellular mechanisms underlying these so-called ‘cytokine storms’ are regulated through the Toll-like receptor 4 (TLR4) signaling pathway and by reactive oxygen species (ROS). Both light (photobiomodulation) and magnetic fields (e.g., pulsed electromagnetic field) stimulation are non-invasive therapies known to confer anti-inflammatory effects and regulate ROS signaling pathways. Here we show that daily exposure to two 10-minute intervals of moderate-intensity infra-red light significantly lowered the inflammatory response induced via the TLR4 receptor signaling pathway in human cell cultures. Anti-inflammatory effects were likewise achieved by electromagnetic field exposure of cells to daily 10-minute intervals of either pulsed electromagnetic fields (PEMF) or to low-level static magnetic fields. Because current illumination and electromagnetic field therapies have no known side effects and are already approved for some medical uses, we have here developed protocols for verification in clinical trials of COVID 19 infection. These treatments are affordable, simple to implement, and may help to resolve the acute respiratory distress of COVID 19 patients both in the home and in the hospital.Keywords: COVID 19, electromagnetic fields therapy, inflammation, photobiomodulation therapy
Procedia PDF Downloads 1446077 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 1476076 Evaluating the Efficacy of Tasquinimod in Covid-19
Authors: Raphael Udeh, Luis García De Guadiana Romualdo, Xenia Dolje-Gore
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Background: Quite disturbing is the huge public health impact of COVID-19: As at today [25th March 2021, the COVID-19 global burden shows over 123 million cases and over 2.7 million deaths worldwide. Rationale: Recent evidence shows calprotectin’s potential as a therapeutic target, stating that tasquinimod, from the Quinoline-3-Carboxamide family is capable of blocking the interaction between calprotectin and TLR4. Hence preventing the cytokine release syndrome, that heralds the functional exhaustion in COVID-19. Early preclinical studies showed that tasquinimod inhibit tumor growth and prevent angiogenesis/cytokine storm. Phase I – III clinical studies in prostate cancer showed it has a good safety profile with good radiologic progression free survival but no effect on overall survival. Rationale/hypothesis: Strategic endeavors have been amplified globally to assess new therapeutic interventions for COVID-19 management – thus the clinical and antiviral efficacy of tasquinimod in COVID-19 remains to be explored. Hence the primary objective of this trial will be to evaluate the efficacy of tasquinimod in the treatment of adult patients with severe COVID-19 infections. Therefore, I hypothesise that among adults with COVID19 infection, tasquinimod will reduce the severe respiratory distress associated with COVID-19 compared to placebo, over a 28-day study period. Method: The setting is in Europe. Design – a randomized, placebo-controlled, phase II double-blinded trial. Trial lasts for 28 days from randomization, Tasquinimod capsule given as 0.5mg daily 1st fortnight, then 1mg daily 2nd fortnight. I0 outcome - assessed using six-point ordinal scale alongside eight 20 outcomes. 125 participants to be enrolled, data collection at baseline and subsequent data points, and safety reporting monitored via serological profile. Significance: This work could potentially establish tasquinimod as an effective and safe therapeutic agent for COVID-19 by reducing the severe respiratory distress, related time to recovery, time on oxygen/admission. It will also drive future research – as in larger multi-centre RCT.Keywords: Calprotectin, COVID-19, Phase II Trial, Tasquinimod
Procedia PDF Downloads 1956075 Seismic Response and Sensitivity Analysis of Circular Shallow Tunnels
Authors: Siti Khadijah Che Osmi, Mohammed Ahmad Syed
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Underground tunnels are one of the most popular public facilities for various applications such as transportation, water transfer, network utilities and etc. Experience from the past earthquake reveals that the underground tunnels also become vulnerable components and may damage at certain percentage depending on the level of ground shaking and induced phenomena. In this paper a numerical analysis is conducted in evaluating the sensitivity of two types of circular shallow tunnel lining models to wide ranging changes in the geotechnical design parameter. Critical analysis has been presented about the current methods of analysis, structural typology, ground motion characteristics, effect of soil conditions and associated uncertainties on the tunnel integrity. The response of the tunnel is evaluated through 2D non-linear finite element analysis, which critically assesses the impact of increasing levels of seismic loads. The finding from this study offer significant information on improving methods to assess the vulnerability of underground structures.Keywords: geotechnical design parameter, seismic response, sensitivity analysis, shallow tunnel
Procedia PDF Downloads 4416074 An Investigation on Material Removal Rate of EDM Process: A Response Surface Methodology Approach
Authors: Azhar Equbal, Anoop Kumar Sood, M. Asif Equbal, M. Israr Equbal
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In the present work response surface methodology (RSM) based central composite design (CCD) is used for analyzing the electrical discharge machining (EDM) process. For experimentation, mild steel is selected as work piece and copper is used as electrode. Three machining parameters namely current (I), spark on time (Ton) and spark off time (Toff) are selected as the input variables. The output or response chosen is material removal rate (MRR) which is to be maximized. To reduce the number of runs face centered central composite design (FCCCD) was used. ANOVA was used to determine the significance of parameter and interactions. The suitability of model is tested using Anderson darling (AD) plot. The results conclude that different parameters considered i.e. current, pulse on and pulse off time; all have dominant effect on the MRR. At last, the optimized parameter setting for maximizing MRR is found through main effect plot analysis.Keywords: EDM, electrode, MRR, RSM, ANOVA
Procedia PDF Downloads 3056073 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 2676072 Comparison of Equivalent Linear and Non-Linear Site Response Model Performance in Kathmandu Valley
Authors: Sajana Suwal, Ganesh R. Nhemafuki
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Evaluation of ground response under earthquake shaking is crucial in geotechnical earthquake engineering. Damage due to seismic excitation is mainly correlated to local geological and geotechnical conditions. It is evident from the past earthquakes (e.g. 1906 San Francisco, USA, 1923 Kanto, Japan) that the local geology has strong influence on amplitude and duration of ground motions. Since then significant studies has been conducted on ground motion amplification revealing the importance of influence of local geology on ground. Observations from the damaging earthquakes (e.g. Nigata and San Francisco, 1964; Irpinia, 1980; Mexico, 1985; Kobe, 1995; L’Aquila, 2009) divulged that non-uniform damage pattern, particularly in soft fluvio-lacustrine deposit is due to the local amplification of seismic ground motion. Non-uniform damage patterns are also observed in Kathmandu Valley during 1934 Bihar Nepal earthquake and recent 2015 Gorkha earthquake seemingly due to the modification of earthquake ground motion parameters. In this study, site effects resulting from amplification of soft soil in Kathmandu are presented. A large amount of subsoil data was collected and used for defining the appropriate subsoil model for the Kathamandu valley. A comparative study of one-dimensional total-stress equivalent linear and non-linear site response is performed using four strong ground motions for six sites of Kathmandu valley. In general, one-dimensional (1D) site-response analysis involves the excitation of a soil profile using the horizontal component and calculating the response at individual soil layers. In the present study, both equivalent linear and non-linear site response analyses were conducted using the computer program DEEPSOIL. The results show that there is no significant deviation between equivalent linear and non-linear site response models until the maximum strain reaches to 0.06-0.1%. Overall, it is clearly observed from the results that non-linear site response model perform better as compared to equivalent linear model. However, the significant deviation between two models is resulted from other influencing factors such as assumptions made in 1D site response, lack of accurate values of shear wave velocity and nonlinear properties of the soil deposit. The results are also presented in terms of amplification factors which are predicted to be around four times more in case of non-linear analysis as compared to equivalent linear analysis. Hence, the nonlinear behavior of soil prevails the urgent need of study of dynamic characteristics of the soft soil deposit that can specifically represent the site-specific design spectra for the Kathmandu valley for building resilient structures from future damaging earthquakes.Keywords: deep soil, equivalent linear analysis, non-linear analysis, site response
Procedia PDF Downloads 2916071 Photo Electrical Response in Graphene Based Resistive Sensor
Authors: H. C. Woo, F. Bouanis, C. S. Cojocaur
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Graphene, which consists of a single layer of carbon atoms in a honeycomb lattice, is an interesting potential optoelectronic material because of graphene’s high carrier mobility, zero bandgap, and electron–hole symmetry. Graphene can absorb light and convert it into a photocurrent over a wide range of the electromagnetic spectrum, from the ultraviolet to visible and infrared regimes. Over the last several years, a variety of graphene-based photodetectors have been reported, such as graphene transistors, graphene-semiconductor heterojunction photodetectors, graphene based bolometers. It is also reported that there are several physical mechanisms enabling photodetection: photovoltaic effect, photo-thermoelectric effect, bolometric effect, photogating effect, and so on. In this work, we report a simple approach for the realization of graphene based resistive photo-detection devices and the measurements of their photoelectrical response. The graphene were synthesized directly on the glass substrate by novel growth method patented in our lab. Then, the metal electrodes were deposited by thermal evaporation on it, with an electrode length and width of 1.5 mm and 300 μm respectively, using Co to fabricate simple graphene based resistive photosensor. The measurements show that the graphene resistive devices exhibit a photoresponse to the illumination of visible light. The observed re-sistance response was reproducible and similar after many cycles of on and off operations. This photoelectrical response may be attributed not only to the direct photocurrent process but also to the desorption of oxygen. Our work shows that the simple graphene resistive devices have potential in photodetection applications.Keywords: graphene, resistive sensor, optoelectronics, photoresponse
Procedia PDF Downloads 2866070 Effector and Memory Immune Responses Induced by Total Extracts of Naegleria fowleri Co-Administered with Cholera Toxin
Authors: Q. B. Maria de la Luz Ortega Juárez, Saúl Rojas Hernández, Itzel Berenice Rodríguez Mera, María Maricela Carrasco Yépez, Mara Gutierrez Sánchez
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Naegleria fowleri is a free-living amoeba found mainly in temperate freshwater and is the etiologic agent of primary amebic meningoencephalitis (PAM), a fatal acute disease with a mortality rate greater than 95%. At present, there are no treatments available for MAP, and the development of effective vaccines that generate long-term immunological memory allowing protection against MAP would be of great importance. The objective of this work was to analyze the effector and memory immune response in BALB/c mice immunized with total extract of N. fowleri co-administered with cholera toxin. In this study, BALB/c mice were immunized four times intranasally with ET of N. fowleri adjuvanted with CT with or without booster at three months and were challenged or not with the lethal dose of N. fowleri, determining survival, the humoral, effector and memory response, by ELISA and flow cytometry techniques. The results obtained showed that the survival of mice immunized with booster had 60% protection compared to the group without booster, which obtained 20% protection. Evaluating the humoral response, it was found that both IgG and IgA levels were higher in sera than in nasal washes in both treatments. In the cellular response, the increase in the percentage of positive cells was found for effector T and B lymphocytes in the nasal passages (NP) in the group with boost and nasopharynx-associated lymphoid tissue (NALT) in the group without boost and lymphocytes only. B in both treatments, as well as in memory cells treatment with boost T lymphocytes in PN and NALT and without boost in cervical lymph nodes (CG) with respect to B lymphocytes, in PN, GC and NALT in treatment with boost and NALT in treatment without booster. Therefore, the involvement of the effector immune response and memory play a fundamental role for protection against N. fowleri and for the development of vaccine candidates.Keywords: immune response, immunological memory, naegleria fowleri, primary amebic meningoencephalitis
Procedia PDF Downloads 786069 Towards a Biologically Relevant Tumor-on-a-Chip: Multiplex Microfluidic Platform to Study Breast Cancer Drug Response
Authors: Soroosh Torabi, Brad Berron, Ren Xu, Christine Trinkle
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Microfluidics integrated with 3D cell culture is a powerful technology to mimic cellular environment, and can be used to study cell activities such as proliferation, migration and response to drugs. This technology has gained more attention in cancer studies over the past years, and many organ-on-a-chip systems have been developed to study cancer cell behaviors in an ex-vivo tumor microenvironment. However, there are still some barriers to adoption which include low throughput, complexity in 3D cell culture integration and limitations on non-optical analysis of cells. In this study, a user-friendly microfluidic multi-well plate was developed to mimic the in vivo tumor microenvironment. The microfluidic platform feeds multiple 3D cell culture sites at the same time which enhances the throughput of the system. The platform uses hydrophobic Cassie-Baxter surfaces created by microchannels to enable convenient loading of hydrogel/cell suspensions into the device, while providing barrier free placement of the hydrogel and cells adjacent to the fluidic path. The microchannels support convective flow and diffusion of nutrients to the cells and a removable lid is used to enable further chemical and physiological analysis on the cells. Different breast cancer cell lines were cultured in the device and then monitored to characterize nutrient delivery to the cells as well as cell invasion and proliferation. In addition, the drug response of breast cancer cell lines cultured in the device was compared to the response in xenograft models to the same drugs to analyze relevance of this platform for use in future drug-response studies.Keywords: microfluidics, multi-well 3d cell culture, tumor microenvironment, tumor-on-a-chip
Procedia PDF Downloads 2646068 Investigation of the Space in Response to the Conditions Caused by the Pandemics and Presenting Five-Scale Design Guidelines to Adapt and Prepare to Face the Pandemics
Authors: Sara Ramezanzadeh, Nashid Nabian
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Historically, pandemics in different periods have caused compulsory changes in human life. In the case of Covid-19, according to the limitations and established care instructions, spatial alignment with the conditions is important. Following the outbreak of Covid-19, the question raised in this study is how to do spatial design in five scales, namely object, space, architecture, city, and infrastructure, in response to the consequences created in the realms under study. From the beginning of the pandemic until now, some changes in the spatial realm have been created spontaneously or by space users. These transformations have been mostly applied in modifiable parts such as furniture arrangement, especially in work-related spaces. To implement other comprehensive requirements, flexibility and adaptation of space design to the conditions resulting from the pandemics are needed during and after the outbreak. Studying the effects of pandemics from the past to the present, this research covers eight major realms, including three categories of ramifications, solutions, and paradigm shifts, and analytical conclusions about the solutions that have been created in response to them. Finally, by the consideration of epidemiology as a modern discipline influencing the design, spatial solutions in the five scales mentioned (in response to the effects of the eight realms for spatial adaptation in the face of pandemics and their following conditions) are presented as a series of guidelines. Due to the unpredictability of possible pandemics in the future, the possibility of changing and updating the provided guidelines is considered.Keywords: pandemics, Covid 19, spatial design, ramifications, solutions, paradigm shifts, guidelines
Procedia PDF Downloads 826067 A Micro-Scale of Electromechanical System Micro-Sensor Resonator Based on UNO-Microcontroller for Low Magnetic Field Detection
Authors: Waddah Abdelbagi Talha, Mohammed Abdullah Elmaleeh, John Ojur Dennis
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This paper focuses on the simulation and implementation of a resonator micro-sensor for low magnetic field sensing based on a U-shaped cantilever and piezoresistive configuration, which works based on Lorentz force physical phenomena. The resonance frequency is an important parameter that depends upon the highest response and sensitivity through the frequency domain (frequency response) of any vibrated micro-scale of an electromechanical system (MEMS) device. And it is important to determine the direction of the detected magnetic field. The deflection of the cantilever is considered for vibrated mode with different frequencies in the range of (0 Hz to 7000 Hz); for the purpose of observing the frequency response. A simple electronic circuit-based polysilicon piezoresistors in Wheatstone's bridge configuration are used to transduce the response of the cantilever to electrical measurements at various voltages. Microcontroller-based Arduino program and PROTEUS electronic software are used to analyze the output signals from the sensor. The highest output voltage amplitude of about 4.7 mV is spotted at about 3 kHz of the frequency domain, indicating the highest sensitivity, which can be called resonant sensitivity. Based on the resonant frequency value, the mode of vibration is determined (up-down vibration), and based on that, the vector of the magnetic field is also determined.Keywords: resonant frequency, sensitivity, Wheatstone bridge, UNO-microcontroller
Procedia PDF Downloads 1276066 Viability of Slab Sliding System for Single Story Structure
Authors: C. Iihoshi, G. A. MacRae, G. W. Rodgers, J. G. Chase
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Slab Sliding System (SSS) with Coulomb friction interface between slab and supporting frame is a passive structural vibration control technology. The system can significantly reduce the slab acceleration and accompanied lateral force of the frame. At the same time it is expected to cause the slab displacement magnification by sliding movement. To obtain the general comprehensive seismic response of a single story structure, inelastic response spectra were computed for a large ensemble of ground motions and a practical range of structural periods and friction coefficient values. It was shown that long period structures have no trade-off relation between force reduction and displacement magnification with respect to elastic response, unlike short period structures. For structures with the majority of mass in the slab, the displacement magnification value can be predicted according to simple inelastic displacement relation for in elastically responding SDOF structures because the system behaves elastically to a SDOF structure.Keywords: earthquake, isolation, slab, sliding
Procedia PDF Downloads 2496065 Evidences for Better Recall with Compatible Items in Episodic Memory
Authors: X. Laurent, M. A. Estevez, P. Mari-Beffa
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A focus of recent research is to understand the role of our own response goals in the selection of information that will be encoded in episodic memory. For example, if we respond to a target in the presence of distractors, an important aspect under study is whether the distractor and the target share a common response (compatible) or not (incompatible). Some studies have found that compatible objects tend to be groups together and stored in episodic memory, whereas others found that targets in the presence of incompatible distractors are remembered better. Our current research seems to support both views. We used a Tulving-based definition of episodic memory to differentiate memory from episodic and non-episodic traces. In this task, participants first had to classify a blue object as human or animal (target) which appeared in the presence of a green one (distractor) that could belong to the same category of the target (compatible), to the opposite (incompatible) or to an irrelevant one (neutral). Later they had to report the identity (What), location (Where) and time (When) of both target objects (which had been previously responded to) and distractors (which had been ignored). Episodic memory was inferred when the three scene properties (identity, location and time) were correct. The measure of non-episodic memory consisted of those trials in which the identity was correctly remembered, but not the location or time. Our results showed that episodic memory for compatible stimuli is significantly superior to incompatible ones. In sharp contrast, non-episodic measures found superior memory for targets in the presence of incompatible distractors. Our results demonstrate that response compatibility affects the encoding of episodic and non-episodic memory traces in different ways.Keywords: episodic memory, action systems, compatible response, what-where-when task
Procedia PDF Downloads 1766064 Study the effect of bulk traps on Solar Blind Photodetector Based on an IZTO/β Ga2O3/ITO Schottky Diode
Authors: Laboratory of Semiconducting, Metallic Materials (LMSM) Biskra Algeria
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InZnSnO2 (IZTO)/β-Ga2O3 Schottky solar barrier photodetector (PhD) exposed to 255 nm was simulated and compared to the measurement. Numerical simulations successfully reproduced the photocurrent at reverse bias and response by taking into account several factors, such as conduction mechanisms and material parameters. By adopting reducing the density of the trap as an improvement. The effect of reducing the bulk trap densities on the photocurrent, response, and time-dependent (continuous conductivity) was studied. As the trap density decreased, the photocurrent increased. The response was 0.04 A/W for the low Ga2O3 trap density. The estimated decay time for the lowest intensity ET (0.74, 1.04 eV) is 0.05 s and is shorter at ∼0.015 s for ET (0.55 eV). This indicates that the shallow traps had the dominant effect (ET = 0.55 eV) on the continuous photoconductivity phenomenon. Furthermore, with decreasing trap densities, this PhD can be considered as a self-powered solar-blind photodiode (SBPhD).Keywords: IZTO/β-Ga2O3, self-powered solar-blind photodetector, numerical simulation, bulk traps
Procedia PDF Downloads 866063 Avoidant Restrictive Food Intake Disorder and Its Impact on Other Eating Disorders
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Avoidant Restrictive Food Intake Disorder (ARFID) was included for the first time in DSM-5, replacing the old diagnosis of DSM-4 'Early Childhood Eating Disorder'. An ARFID is characterized by a restrictive/avoidant eating pattern that can lead to severe nutritional deficiency, weight loss, nutritional supplementation dependence, and poor psychosocial functioning. This eating pattern is associated with decreased interest in food, worries about food characteristics or the act of ingestion, and lack of concern with weight or body image. This paper aims to understand the impact of this new diagnosis in other Eating Disorders (ED) prevalence, as well as to compare their therapeutic approaches. Methodology: Literature reviewed by PubMed with the following keywords: 'ARFID', 'Prevalence', and 'Eating Disorders'. We selected articles related to this theme, written since 2016. Results: In a population of children hospitalized with ED, 5% to 14% was diagnosed with ARFID, and, as outpatient treatment, the prevalence was 22%. People diagnosed with ARFID have more prevalence of other comorbidities, especially autism spectrum, are younger, and are more often male. Regarding the treatment of ARFID, it most often required nasogastric feeding, and with less suffering associated with this procedure, compared to AN. Despite these differences, 12% of patients diagnosed with ARFID transited to AN during treatment, suggesting that the first pathology may be a risk factor for the development of AN. Conclusions: The differences identified between ARFID and the other EDs are important when analyzed as differential diagnostic hypotheses and therapeutic approaches. Further study is necessary regarding its prevalence, risk factors, and treatment.Keywords: avoidant restrictive food intake disorder, ARFID, differential diagnoses, eating disorders, prevalence
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