Search results for: therapeutic design
13437 Investigation of FOXM1 Gene Expression in Breast Cancer and Its Relationship with Mir-216B-5P Expression Level
Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari
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As a pressing public health concern, breast cancer stands as the predominant oncological diagnosis and principal cause of cancer-related mortality among women globally, accounting for 11.7% of new cancer incidences and 6.9% of cancer-related deaths. The annual figures indicate that approximately 230,480 women are diagnosed with breast cancer in the United States alone, with 39,520 succumbing to the disease. While developed economies have reported a deceleration in both incidence and mortality rates across various forms of cancer, including breast cancer, emerging and low-income economies manifest a contrary escalation, largely attributable to lifestyle-mediated risk factors such as tobacco usage, physical inactivity, and high caloric intake. Breast cancer is distinctly characterized by molecular heterogeneity, manifesting in specific subtypes delineated by biomarkers—Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These subtypes, comprising Luminal A, Luminal B, HER2-enriched, triple-negative/basal-like, and normal-like, necessitate nuanced, subtype-specific therapeutic regimens, thereby challenging the applicability of generalized treatment protocols. Within this molecular complexity, the transcription factor Forkhead Box M1 (FoxM1) has garnered attention as a significant driver of cellular proliferation, tumorigenesis, metastatic progression, and treatment resistance in a spectrum of human malignancies, including breast cancer. Concurrently, microRNAs (miRs), specifically miR-216b-5p, have been identified as post-transcriptional gene expression regulators and potential tumor suppressors. The overarching objective of this academic investigation is to explicate the multifaceted interrelationship between FoxM1 and miR-216b-5p across the disparate molecular subtypes of breast cancer. Employing a methodologically rigorous, interdisciplinary research design that incorporates cutting-edge molecular biology techniques, sophisticated bioinformatics analytics, and exhaustive meta-analyses of extant clinical data, this scholarly endeavor aims to unveil novel biomarker-specific therapeutic pathways. By doing so, this research is positioned to make a seminal contribution to the advancement of personalized, efficacious, and minimally toxic treatment paradigms, thus profoundly impacting the global efforts to ameliorate the burden of breast cancer.Keywords: breast cancer, fox m1, microRNAs, mir-216b-5p, gene expression
Procedia PDF Downloads 7413436 Innovative Preparation Techniques: Boosting Oral Bioavailability of Phenylbutyric Acid Through Choline Salt-Based API-Ionic Liquids and Therapeutic Deep Eutectic Systems
Authors: Lin Po-Hsi, Sheu Ming-Thau
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Urea cycle disorders (UCD) are rare genetic metabolic disorders that compromise the body's urea cycle. Sodium phenylbutyrate (SPB) is a medication commonly administered in tablet or powder form to lower ammonia levels. Nonetheless, its high sodium content poses risks to sodium-sensitive UCD patients. This necessitates the creation of an alternative drug formulation to mitigate sodium load and optimize drug delivery for UCD patients. This study focused on crafting a novel oral drug formulation for UCD, leveraging choline bicarbonate and phenylbutyric acid. The active pharmaceutical ingredient-ionic liquids (API-ILs) and therapeutic deep eutectic systems (THEDES) were formed by combining these with choline chloride. These systems display characteristics like maintaining a liquid state at room temperature and exhibiting enhanced solubility. This in turn amplifies drug dissolution rate, permeability, and ultimately oral bioavailability. Incorporating choline-based phenylbutyric acid as a substitute for traditional SPB can effectively curtail the sodium load in UCD patients. Our in vitro dissolution experiments revealed that the ILs and DESs, synthesized using choline bicarbonate and choline chloride with phenylbutyric acid, surpassed commercial tablets in dissolution speed. Pharmacokinetic evaluations in SD rats indicated a notable uptick in the oral bioavailability of phenylbutyric acid, underscoring the efficacy of choline salt ILs in augmenting its bioavailability. Additional in vitro intestinal permeability tests on SD rats authenticated that the ILs, formulated with choline bicarbonate and phenylbutyric acid, demonstrate superior permeability compared to their sodium and acid counterparts. To conclude, choline salt ILs developed from choline bicarbonate and phenylbutyric acid present a promising avenue for UCD treatment, with the added benefit of reduced sodium load. They also hold merit in formulation engineering. The sustained-release capabilities of DESs position them favorably for drug delivery, while the low toxicity and cost-effectiveness of choline chloride signal potential in formulation engineering. Overall, this drug formulation heralds a prospective therapeutic avenue for UCD patients.Keywords: phenylbutyric acid, sodium phenylbutyrate, choline salt, ionic liquids, deep eutectic systems, oral bioavailability
Procedia PDF Downloads 11613435 Analysis of Importance of Culture in Distributed Design Based on the Case Study at the University of Strathclyde
Authors: Zixuan Yang
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This paper presents an analysis of the necessary consideration culture in distributed design through a thorough literature review and case study. The literature review has identified that the need for understanding cultural differences in product design and user evaluations is highlighted by analyzing cross-cultural influences; culture plays a significant role in distributed work, particularly in establishing team cohesion, trust, and credibility early in the project. By applying approaches of Geert Hofstede's dimensions and Fukuyama's trust analysis, a case study of a global design project, i.e., multicultural distributed teamwork solving the problem in terms of reducing the risk of deep vein thrombosis, showcases cultural dynamics, emphasizing trust-building and decision-making. The lessons learned emphasized the importance of cultural awareness, adaptability, and the utilization of scientific theories to enable effective cross-cultural collaborations in global design, providing valuable insights into navigating cultural diversity within design practices.Keywords: culture, distributed design, global design, Geert Hofstede's dimensions, Fukuyama's trust analysis
Procedia PDF Downloads 6913434 Socio-Sensorial Assessment of Nursing Homes in Singapore: Towards Integrated Enabling Design
Authors: Zdravko Trivic, John Chye Fung, Ruzica Bozovic-Stamenovic
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Within the context of rapidly ageing population in Singapore and the pressing demands on both caregivers and care providers, an integrated approach to ageing-friendly and ability-sensitive enabling environment becomes an imperative. This particularly applies to nursing home environments and their immediate surroundings, as they are becoming one of the main available options of long-term care for many senior adults who are unable to age at home. Yet, despite the considerable efforts to break the still predominant clinical approach to eldercare and to introduce more home-like design and person-centric care model, nursing homes keep being stigmatised and perceived as not so desirable environments to grow old in. The challenges are further emphasised by the associated physical, sensorial, psychological and cognitive declines that are the common consequences of ageing. Such declines have an immense impact on almost all aspects of older adults’ daily functioning, including problems with mobility and spatial orientation, difficulties in communication, withdrawal from social interaction, higher level of depression and decreased sense of independence and autonomy. However, typical nursing home designs tend to neglect the full capacities of balanced and carefully integrated multisensory stimuli as active component of care and ability building. This paper outlines part of a larger multi-disciplinary study of six nursing homes in Singapore, with overarching objectives to create new models of supportive nursing home environments that go beyond the clinical care model and encourage community integration with the nursing home settings. The paper focuses on the largely neglected aspects of sensorial comfort and multi-sensorial properties of nursing homes, including both indoor and immediate outdoor spaces (boundaries). The objective was to investigate the sensory rhythms and explore their role in nursing home users’ daily routine and therapeutic capacities. Socio-sensory rhythms were captured and analysed through a combination of on-site sensory recordings of “objective” quantitative sensory data (air temperature and humidity, sound level and luminance) using multi-function environment meter, perceived experienced data, spatial mapping, first-person observations of nursing home users’ activity patterns, and interviews. This was done in addition to employment of available assessment tools, such as Wisconsin Person Directed Care assessment tool, Dementia Quality of Life [DQoL] instrument, and Resident Environment Impact Scale [REIS], as these tools address the issues of sensorial experience insufficiently and selectively. Key findings indicate varied levels of sensory comfort, as well as diversity, intensity, and customisation of multi-sensory conditions within different nursing home spaces. Sensory stimulation is typically concentrated in communal living areas of the nursing homes or in the areas that often provide controlled or limited access, including specifically designed sensory rooms and outdoor green spaces (gardens and terraces). Opportunities for sensory stimulation are particularly limited for bed-bound senior residents and within more functional areas, such as corridors. This suggests that the capacities of nursing home designs to provide more diverse and better integrated pleasant sensory conditions as integrated “therapeutic devices” to build nursing home residents’ physical and mental abilities, encourage activity and improve wellbeing are far from exhausted.Keywords: ageing-supportive environment, enabling design, multi-sensory assessment, nursing home environment
Procedia PDF Downloads 17213433 Integration of Design Management in the Product Development Process in SME's
Authors: Vitor Carneiro, Augusto Barata Da Rocha, Barbara Rangel, Jorge Lino Alves
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In the European Union countries, Small and Medium-Sized Enterprises (SME’s) have an important contribution to economic activity and to the Gross Domestic Product (GDP). The implementation of design practices in SME’s is often a difficult task due to resources limitations. Unlike large companies, their product development and innovation processes frequentlylack adequate planning and systematic procedures. Design management interest has grown exponentially in recent years, but as it is a recent topic there is an absence of systematic methodologies to implement design management in SME’s with little or no design experience. This work presents a contribution to improve and optimize the process of design integration and management in SME’s. A review analysis is presented to select relevant articles on the subject, review and classify the main published contributions. Based on the selected articles content it was possible to identify five main themes related to the subject under analysis: Design Function Organization, Design Management Integration, Design Management Capabilities, Managing Design Projects, and Tools and Methods. Design management is discussed from different perspectives depending on the focus on which it is placed, whether in a design or management perspective, leading to different visions and definitions: from a more upstream strand at the intersection of design and the organization's strategic management (strategic design management) to a more downstream strand related to project management and design process (design management operational). The review analysis of the selected articles allowed the identification of a high level of complexity of connections and parameters in the design management during the product development process in the context of SME’s. Within each group of the five main themes, several sub-themes, directly or indirectly related, should be considered.Sub-connections also occur between sub-themes of different themes creating a complex and intricate web of connections. This complexity of connections is often the main obstacle to conduct design management and product development efficiently. This work proposes a formulation of a systematic methodological approach to optimize the integrated project and the management and control of the product development process among SME's. The implementation of this formulation will improve the integration of design management in the product development and innovation process in SME’s.Keywords: design management, product development, product innovation, SME’s.
Procedia PDF Downloads 22213432 Sustainable Nanoengineering of Copper Oxide: Harnessing Its Antimicrobial and Anticancer Capabilities
Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel
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Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.Keywords: copper oxide nanoparticles, green synthesis, nanotechnology, microbial infection
Procedia PDF Downloads 6413431 Prevailing Clinical Evidence on Medicinal Hemp (Cannabis Sativa L.)
Authors: Siti Hajar Muhamad Rosli, Xin Yi Lim, Terence Yew Chin Tan, Muhammad nor Farhan Sa’At, Syazwani Sirdar Ali, Ami Fazlin Syed Mohamed
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A growing interest on therapeutic benefits of hemp (Cannabis sativa subsp. sativa) is evident in the pharmaceutical market, attributed to its lower levels of psychoactive constituent delta-9-tetrahydronannabidiol (THC). Deemed as a legal and safer alternative to its counterpart marijuana, the use of medicinal hemp is highly debatable as current scientific evidence on the efficacy for clinical use is yet to be established This study was aimed to provide an overview of the current landscape of hemp research, through recent clinical findings specific to the pharmacological properties of the hemp plant and its derived compounds. A systematic search was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis-ScR (PRISMA) checklist on electronic databases (MEDLINE, OVID, Cochrane Library Central, and Clinicaltrials.gov) for articles published from 2009 to 2019. With predetermined inclusion criteria, all human trials with hemp intervention were included. A total of 18 human trials were identified, investigating therapeutic effects on the neuronal, gastrointestinal, musculoskeletal and immune system, with sample sizes ranging from one to 194 subjects. Three randomised controlled trials showed hempseed pills (in Traditional Chinese Medicine formulation MaZiRenWan) consumption significantly improved spontaneous bowel movement in functional constipation. The use of commercial cannabidiol (CBD) sourced from hemp suggested benefits in cannabis dependence, epilepsy, and anxiety disorders. However, there was insufficient evidence to suggest analgesic or anxiolytics effects of hemp being equivalent to marijuana. All clinical trials reviewed varied in terms of test item formulation and standardisation, which made it challenging to confirm overall efficacy for a specific disease or condition. Published efficacy data on hemp are still at a preliminary level, with limited high quality clinical evidence for any specific therapeutic indication. With multiple variants of this plant having different phytochemical and bioactive compounds, future empirical research should focus on uniformity in experimental designs to further strengthen the notion of using medicinal hemp.Keywords: cannabis, complementary medicine, hemp, herbal medicine.
Procedia PDF Downloads 11813430 Inf-γ and Il-2 Asses the Therapeutic Response in Anti-tuberculosis Patients at Jamot Hospital Yaounde, Cameroon
Authors: Alexandra Emmanuelle Membangbi, Jacky Njiki Bikoï, Esther Del-florence Moni Ndedi, Marie Joseph Nkodo Mindimi, Donatien Serge Mbaga, Elsa Nguiffo Makue, André Chris Mikangue Mbongue, Martha Mesembe, George Ikomey Mondinde, Eric Walter Perfura-yone, Sara Honorine Riwom Essama
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Background: Tuberculosis (TB) is one of the top lethal infectious diseases worldwide. In recent years, interferon-γ (INF-γ) release assays (IGRAs) have been established as routine tests for diagnosing TB infection. However, produced INF-γ assessment failed to distinguish active TB (ATB) from latent TB infection (LTBI), especially in TB epidemic areas. In addition to IFN-γ, interleukin-2 (IL-2), another cytokine secreted by activated T cells, is also involved in immune response against Mycobacterium tuberculosis. The aim of the study was to assess the capacity of IFN-γ and IL2 to evaluate the therapeutic response of patients on anti-tuberculosis treatment. Material and Methods: We conducted a cross-sectional study in the Pneumonology Departments of the Jamot Hospital in Yaoundé between May and August 2021. After signed the informed consent, the sociodemographic data, as well as 5 mL of blood, were collected in the crook of the elbow of each participant. Sixty-one subjects were selected (n= 61) and divided into 4 groups as followed: group 1: resistant tuberculosis (n=13), group 2: active tuberculosis (n=19), group 3 cured tuberculosis (n=16), and group 4: presumed healthy persons (n=13). The cytokines of interest were determined using an indirect Enzyme-linked Immuno-Sorbent Assay (ELISA) according to the manufacturer's recommendations. P-values < 0.05 were interpreted as statistically significant. All statistical calculations were performed using SPSS version 22.0 Results: The results showed that men were more 14/61 infected (31,8%) with a high presence in active and resistant TB groups. The mean age was 41.3±13.1 years with a 95% CI = [38.2-44.7], the age group with the highest infection rate was ranged between 31 and 40 years. The IL-2 and INF-γ means were respectively 327.6±160.6 pg/mL and 26.6±13.0 pg/mL in active tuberculosis patients, 251.1±30.9 pg/mL and 21.4±9.2 pg/mL in patients with resistant tuberculosis, while it was 149.3±93.3 pg/mL and 17.9±9.4 pg/mL in cured patients, 15.1±8.4 pg/mL and 5.3±2.6 pg/mL in participants presumed healthy (p <0.0001). Significant differences in IFN-γ and IL-2 rates were observed between the different groups. Conclusion: Monitoring the serum levels of INF-γ and IL-2 would be useful to evaluate the therapeutic response of anti-tuberculosis patients, particularly in the both cytokines association case, that could improve the accuracy of routine examinations.Keywords: antibiotic therapy, interferon gamma, interleukin 2, tuberculosis
Procedia PDF Downloads 11713429 Design of a Low Cost Motion Data Acquisition Setup for Mechatronic Systems
Authors: Baris Can Yalcin
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Motion sensors have been commonly used as a valuable component in mechatronic systems, however, many mechatronic designs and applications that need motion sensors cost enormous amount of money, especially high-tech systems. Design of a software for communication protocol between data acquisition card and motion sensor is another issue that has to be solved. This study presents how to design a low cost motion data acquisition setup consisting of MPU 6050 motion sensor (gyro and accelerometer in 3 axes) and Arduino Mega2560 microcontroller. Design parameters are calibration of the sensor, identification and communication between sensor and data acquisition card, interpretation of data collected by the sensor.Keywords: design, mechatronics, motion sensor, data acquisition
Procedia PDF Downloads 58813428 Study of Therapeutic Potential of Dodonaea Viscosa Against Rheumatoid Arthritis in Collagen Induced Arthritic Mouse Model
Authors: Peter John, Zainab Ali, Attya Bhatti
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Rheumatoid Arthritis (RA) is a systemic autoimmune inflammatory disease that primarily affects the joints. RA is caused in many cases by the interaction between genes and environmental factors, including tobacco, that primarily involves synovial joints. It typically starts in small peripheral joints, is usually symmetric, and progresses to involve proximal joints if left untreated. The prevalence of rheumatoid arthritis varies substantially around the globe, ranging from 0·25% to 1%.3. Rheumatoid arthritis can affect individuals of any age, with an increased incidence in people older than 40 years. Women are affected two to three times more frequently than men. The present work involved evaluating the toxicity and therapeutic potential of Dodonaea viscosa in a collagen-induced arthritic mouse model. Chemical analysis exhibited that Dodonaea viscosa has high levels of beneficial compounds, including phenols, flavonoids, and other phytochemicals. The Dodonaea viscosa showed significant antioxidant, anti-inflammatory, and anti-arthritic potential without toxic effects. Arthritic mice treated with Dodonaea viscosa showed reduced levels of rheumatoid factor and paw edema, while no significant effects on spleen indices and radiological examination of paws were found compared to control untreated arthritic mice. In summary, the Dodonaea viscosa treatment results in improvement in Arthritic Mice Model for which further studies are required.Keywords: rheumatoid arthritis, dodonaea viscisa, anti-inflammatory, anti-rheumatic
Procedia PDF Downloads 2313427 Green and Cost-Effective Biofabrication of Copper Oxide Nanoparticles: Exploring Antimicrobial and Anticancer Applications
Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel
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Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.Keywords: biological synthesis, copper oxide nanoparticles, microbial infection, nanotechnology
Procedia PDF Downloads 6213426 Flexible Design of Triboelectric Nanogenerators for Efficient Vibration Energy Harvesting
Authors: Meriam Khelifa
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In recent years, many studies have focused on the harvesting of the vibrations energy to produce electrical energy using contact separation (CS) triboelectric nanogenerators (TENG). The simplest design for a TENG consists of a capacitor comprising a single moving electrode. The conversion efficiency of vibration energy into electrical energy can, in principle, reach 100%. But to actually achieve this objective, it is necessary to optimize the parameters of the TENG, such as the dielectric constant and the thickness of the insulator, the load resistance, etc. In particular, the use of a switch which is actioned at optimal times within the TENG cycle is essential. Using numerical modeling and experimental design, we applied a methodology to find the TENG parameters which optimize the energy transfer efficiency (ETE) to almost 100% for any vibration frequency and amplitude. The rather simple design of a TENG is promising as an environment friendly device. It opens the doors for harvesting acoustic vibrations from the environment and to design effective protection against environmental noise.Keywords: vibrations, CS TENG, efficiency, design of experiments
Procedia PDF Downloads 9013425 The Design of a Phase I/II Trial of Neoadjuvant RT with Interdigitated Multiple Fractions of Lattice RT for Large High-grade Soft-Tissue Sarcoma
Authors: Georges F. Hatoum, Thomas H. Temple, Silvio Garcia, Xiaodong Wu
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Soft Tissue Sarcomas (STS) represent a diverse group of malignancies with heterogeneous clinical and pathological features. The treatment of extremity STS aims to achieve optimal local tumor control, improved survival, and preservation of limb function. The National Comprehensive Cancer Network guidelines, based on the cumulated clinical data, recommend radiation therapy (RT) in conjunction with limb-sparing surgery for large, high-grade STS measuring greater than 5 cm in size. Such treatment strategy can offer a cure for patients. However, when recurrence occurs (in nearly half of patients), the prognosis is poor, with a median survival of 12 to 15 months and with only palliative treatment options available. The spatially-fractionated-radiotherapy (SFRT), with a long history of treating bulky tumors as a non-mainstream technique, has gained new attention in recent years due to its unconventional therapeutic effects, such as bystander/abscopal effects. Combining single fraction of GRID, the original form of SFRT, with conventional RT was shown to have marginally increased the rate of pathological necrosis, which has been recognized to have a positive correlation to overall survival. In an effort to consistently increase the pathological necrosis rate over 90%, multiple fractions of Lattice RT (LRT), a newer form of 3D SFRT, interdigitated with the standard RT as neoadjuvant therapy was conducted in a preliminary clinical setting. With favorable results of over 95% of necrosis rate in a small cohort of patients, a Phase I/II clinical study was proposed to exam the safety and feasibility of this new strategy. Herein the design of the clinical study is presented. In this single-arm, two-stage phase I/II clinical trial, the primary objectives are >80% of the patients achieving >90% tumor necrosis and to evaluation the toxicity; the secondary objectives are to evaluate the local control, disease free survival and overall survival (OS), as well as the correlation between clinical response and the relevant biomarkers. The study plans to accrue patients over a span of two years. All patient will be treated with the new neoadjuvant RT regimen, in which one of every five fractions of conventional RT is replaced by a LRT fraction with vertices receiving dose ≥10Gy while keeping the tumor periphery at or close to 2 Gy per fraction. Surgical removal of the tumor is planned to occur 6 to 8 weeks following the completion of radiation therapy. The study will employ a Pocock-style early stopping boundary to ensure patient safety. The patients will be followed and monitored for a period of five years. Despite much effort, the rarity of the disease has resulted in limited novel therapeutic breakthroughs. Although a higher rate of treatment-induced tumor necrosis has been associated with improved OS, with the current techniques, only 20% of patients with large, high-grade tumors achieve a tumor necrosis rate exceeding 50%. If this new neoadjuvant strategy is proven effective, an appreciable improvement in clinical outcome without added toxicity can be anticipated. Due to the rarity of the disease, it is hoped that such study could be orchestrated in a multi-institutional setting.Keywords: lattice RT, necrosis, SFRT, soft tissue sarcoma
Procedia PDF Downloads 6013424 Identification of Potential Small Molecule Regulators of PERK Kinase
Authors: Ireneusz Majsterek, Dariusz Pytel, J. Alan Diehl
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PKR-like ER kinase (PERK) is serine/threonie endoplasmic reticulum (ER) transmembrane kinase activated during ER-stress. PERK can activate signaling pathways known as unfolded protein response (UPR). Attenuation of translation is mediated by PERK via phosphorylation of eukaryotic initiation factor 2α (eIF2α), which is necessary for translation initiation. PERK activation also directly contributes to activation of Nrf2 which regulates expression of anti-oxidant enzymes. An increased phosphorylation of eIF2α has been reported in Alzheimer disease (AD) patient hippocampus, indicating that PERK is activated in this disease. Recent data have revealed activation of PERK signaling in non-Hodgkins lymphomas. Results also revealed that loss of PERK limits mammary tumor cell growth in vitro and in vivo. Consistent with these observations, activation of UPR in vitro increases levels of the amyloid precursor protein (APP), the peptide from which beta-amyloid plaques (AB) fragments are derived. Finally, proteolytic processing of APP, including the cleavages that produce AB, largely occurs in the ER, and localization coincident with PERK activity. Thus, we expect that PERK-dependent signaling is critical for progression of many types of diseases (human cancer, neurodegenerative disease and other). Therefore, modulation of PERK activity may be a useful therapeutic target in the treatment of different diseases that fail to respond to traditional chemotherapeutic strategies, including Alzheimer’s disease. Our goal will be to developed therapeutic modalities targeting PERK activity.Keywords: PERK kinase, small molecule inhibitor, neurodegenerative disease, Alzheimer’s disease
Procedia PDF Downloads 48213423 A Resistant-Based Comparative Study between Iranian Concrete Design Code and Some Worldwide Ones
Authors: Seyed Sadegh Naseralavi, Najmeh Bemani
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The design in most counties should be inevitably carried out by their native code such as Iran. Since the Iranian concrete code does not exist in structural design software, most engineers in this country analyze the structures using commercial software but design the structural members manually. This point motivated us to make a communication between Iranian code and some other well-known ones to create facility for the engineers. Finally, this paper proposes the so-called interpretation charts which help specify the position of Iranian code in comparison of some worldwide ones.Keywords: beam, concrete code, strength, interpretation charts
Procedia PDF Downloads 52613422 Using Multi-Arm Bandits to Optimize Game Play Metrics and Effective Game Design
Authors: Kenny Raharjo, Ramon Lawrence
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Game designers have the challenging task of building games that engage players to spend their time and money on the game. There are an infinite number of game variations and design choices, and it is hard to systematically determine game design choices that will have positive experiences for players. In this work, we demonstrate how multi-arm bandits can be used to automatically explore game design variations to achieve improved player metrics. The advantage of multi-arm bandits is that they allow for continuous experimentation and variation, intrinsically converge to the best solution, and require no special infrastructure to use beyond allowing minor game variations to be deployed to users for evaluation. A user study confirms that applying multi-arm bandits was successful in determining the preferred game variation with highest play time metrics and can be a useful technique in a game designer's toolkit.Keywords: game design, multi-arm bandit, design exploration and data mining, player metric optimization and analytics
Procedia PDF Downloads 51013421 Transferring of Digital DIY Potentialities through a Co-Design Tool
Authors: Marita Canina, Carmen Bruno
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Digital Do It Yourself (DIY) is a contemporary socio-technological phenomenon, enabled by technological tools. The nature and potential long-term effects of this phenomenon have been widely studied within the framework of the EU funded project ‘Digital Do It Yourself’, in which the authors have created and experimented a specific Digital Do It Yourself (DiDIY) co-design process. The phenomenon was first studied through a literature research to understand its multiple dimensions and complexity. Therefore, co-design workshops were used to investigate the phenomenon by involving people to achieve a complete understanding of the DiDIY practices and its enabling factors. These analyses allowed the definition of the DiDIY fundamental factors that were then translated into a design tool. The objective of the tool is to shape design concepts by transferring these factors into different environments to achieve innovation. The aim of this paper is to present the ‘DiDIY Factor Stimuli’ tool, describing the research path and the findings behind it.Keywords: co-design process, digital DIY, innovation, toolkit
Procedia PDF Downloads 17813420 Design for Sentiment-ancy: Conceptual Framework to Improve User’s Well-being Through Fostering Emotional Attachment in the Use Experience with Their Assistive Devices
Authors: Seba Quqandi
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This study investigates the bond that people form using their assistive devices and the tactics applied during the product design process to help improve the user experience leading to a long-term product relationship. The aim is to develop a conceptual framework with which to describe and analyze the bond people form with their assistive devices and to integrate human emotions as a factor during the development of the product design process. The focus will be on the assistive technology market, namely, the Aid-For-Daily-Living market for situational impairments, to increase the quality of wellbeing. Findings will help us better understand the real issues of the product experience concerning people’s interaction throughout the product performance, establish awareness of the emotional effects in the daily interaction that fosters the product attachment, and help product developers and future designers create a connection between users and their assistive devices. The research concludes by discussing the implications of these findings for professionals and academics in the form of experiments in order to identify new areas that can stimulate new /or developed design directions.Keywords: experience design, interaction design, emotion, design psychology, assistive tools, customization, userentred design
Procedia PDF Downloads 23113419 Examples of RC Design with Eurocode2
Authors: Carla Ferreira, Helena Barros
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The paper termed “Design of reinforced concrete with Eurocode 2” presents the theory regarding the design of reinforced concrete sections and the development of the tables and abacuses to verify the concrete section to the ultimate limit and service limit states. This paper is a complement of it, showing how to use the previous tools. Different numerical results are shown, proving the capability of the methodology. When a section of a beam is already chosen, the computer program presents the reinforcing steel in many locations along the structure, and it is the engineer´s task to choose the layout available for the construction, considering the maximum regular kind of reinforcing bars. There are many computer programs available for this task, but the interest of the present kind of tools is the fast and easy way of making the design and choose the optimal solution. Another application of these design tools is in the definition of the section dimensions, in a way that when stresses are evaluated, the final design is acceptable. In the design offices, these are considered by the engineers a very quick and useful way of designing reinforced concrete sections, employing variable strength concrete and higher steel classes. Examples of nonlinear analyses and redistribution of the bending moment will be considered, according to the Eurocode 2 recommendations, for sections under bending moment and axial forces. Examples of the evaluation of the service limit state will be presented.Keywords: design examples, eurocode 2, reinforced concrete, section design
Procedia PDF Downloads 7213418 Dimensioning of a Solar Dryer with Application of an Experiment Design Method for Drying Food Products
Authors: B. Touati, A. Saad, B. Lips, A. Abdenbi, M. Mokhtari.
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The purpose of this study is an application of experiment design method for dimensioning of a solar drying system. NIMROD software was used to build up the matrix of experiments and to analyze the results. The software has the advantages of being easy to use and consists of a forced way, with some choices about the number and range of variation of the parameters, and the desired polynomial shape. The first design of experiments performed concern the drying with constant input characteristics of the hot air in the dryer and a second design of experiments in which the drying chamber is coupled with a solar collector. The first design of experiments allows us to study the influence of various parameters and get the studied answers in a polynomial form. The correspondence between the polynomial thus determined, and the model results were good. The results of the polynomials of the second design of experiments and those of the model are worse than the results in the case of drying with constant input conditions. This is due to the strong link between all the input parameters, especially, the surface of the sensor and the drying chamber, and the mass of the product.Keywords: solar drying, experiment design method, NIMROD, mint leaves
Procedia PDF Downloads 50313417 Development and Analysis of SFR Control Rod Design
Authors: Lenka Dujčíková, Laurent Buiron, Ján Haščík
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The study is dedicated to safety management of SFR CAPRA core with CFV design improvements. In the case of CAPRA core, demands for reactivity control are higher than for reference core. There are two possible ways how to ensure the certain amount of negative reactivity. One option is to boost control rods worth. The Greater part of the study is aimed at the proposal of appropriate control rod design. At first, the European Fast Reactor (EFR) control rod design with high-enriched boron carbide B4C as absorber material was tested. Considering costly and difficult enrichment process, usage of natural boron carbide absorbator is desired. Obviously, the use of natural boron leads to CR worth reduction. In order to increase it to required value, moderator material was inserted inside the control rod. Various materials and geometric configurations were examined to find optimal solution corresponding with EFR based CR worth value.Keywords: boron carbide, CAPRA core, control rod design, low void effect design, melting temperature, moderator material
Procedia PDF Downloads 50513416 Optimization of Three-Layer Corrugated Metal Gasket by Using Finite Element Method
Authors: I Made Gatot Karohika, Shigeyuki Haruyama, Ken Kaminishi
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In this study, we proposed a three-layer metal gasket with Al, Cu, and SUS304 as the material, respectively. A finite element method was employed to develop simulation solution and design of experiment (DOE). Taguchi method was used to analysis the effect of each parameter design and predicts optimal design of new 25A-size three layer corrugated metal gasket. The L18 orthogonal array of Taguchi method was applied to design experiment matrix for eight factors with three levels. Based on elastic mode and plastic mode, optimum design gasket is gasket with core metal SUS304, surface layer aluminum, p1 = 4.5 mm, p2 = 4.5 mm, p3 = 4 mm, Tg = 1.2 mm, R = 3.5 mm, h = 0.4 mm and Ts = 0.3 mm.Keywords: contact width, contact stress, layer, metal gasket, corrugated, simulation
Procedia PDF Downloads 31513415 Physical Verification Flow on Multiple Foundries
Authors: Rohaya Abdul Wahab, Raja Mohd Fuad Tengku Aziz, Nazaliza Othman, Sharifah Saleh, Nabihah Razali, Muhammad Al Baqir Zinal Abidin, Md Hanif Md Nasir
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This paper will discuss how we optimize our physical verification flow in our IC Design Department having various rule decks from multiple foundries. Our ultimate goal is to achieve faster time to tape-out and avoid schedule delay. Currently the physical verification runtimes and memory usage have drastically increased with the increasing number of design rules, design complexity and the size of the chips to be verified. To manage design violations, we use a number of solutions to reduce the amount of violations needed to be checked by physical verification engineers. The most important functions in physical verifications are DRC (design rule check), LVS (layout vs. schematic) and XRC (extraction). Since we have a multiple number of foundries for our design tape-outs, we need a flow that improve the overall turnaround time and ease of use of the physical verification process. The demand for fast turnaround time is even more critical since the physical design is the last stage before sending the layout to the foundries.Keywords: physical verification, DRC, LVS, XRC, flow, foundry, runset
Procedia PDF Downloads 65413414 Methods of Livable Goal-Oriented Master Urban Design: A Case Study on Zibo City
Authors: Xiaoping Zhang, Fengying Yan
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The implementation of the 'Urban Design Management Measures' requires that the master urban design should aim at creating a livable urban space. However, to our best knowledge, the existing researches and practices of master urban design not only focus less on the livable space but also face a number of problems such as paying more attention to the image of the city, ignoring the people-oriented and lacking dynamic continuity. In order to make the master urban design can better guide the construction of city. Firstly, the paper proposes the livable city hierarchy system to meet the needs of different groups of people and then constructs the framework of livable goal-oriented master urban design based on the theory of livable content and the ideological origin of people-oriented. Secondly, the paper takes the master urban design practice of Zibo as a sample and puts forward the design strategy of strengthening the pattern, improve the quality of space, shape the feature, and establish a series of action plans based on the strategy of urban space development. Finally, the paper explores the method system of livable goal-oriented master urban design from the aspects of safety pattern, morphology pattern, neighborhood scale, open space, street space, public interface, style feature, public participation and action plans.Keywords: livable, master urban design, public participation, zibo city
Procedia PDF Downloads 31713413 Systematic Literature Review of Therapeutic Use of Autonomous Sensory Meridian Response (ASMR) and Short-Term ASMR Auditory Training Trial
Authors: Christine H. Cubelo
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This study consists of 2-parts: a systematic review of current publications on the therapeutic use of autonomous sensory meridian response (ASMR) and a within-subjects auditory training trial using ASMR videos. The main intent is to explore ASMR as potentially therapeutically beneficial for those with atypical sensory processing. Many hearing-related disorders and mood or anxiety symptoms overlap with symptoms of sensory processing issues. For this reason, inclusion and exclusion criteria of the systematic review were generated in an effort to produce optimal search outcomes and avoid overly confined criteria that would limit yielded results. Criteria for inclusion in the review for Part 1 are (1) adult participants diagnosed with hearing loss or atypical sensory processing, (2) inclusion of measures related to ASMR as a treatment method, and (3) published between 2000 and 2022. A total of 1,088 publications were found in the preliminary search, and a total of 13 articles met the inclusion criteria. A total of 14 participants completed the trial and post-trial questionnaire. Of all responses, 64.29% agreed that the duration of auditory training sessions was reasonable. In addition, 71.43% agreed that the training improved their perception of music. Lastly, 64.29% agreed that the training improved their perception of a primary talker when there are other talkers or background noises present.Keywords: autonomous sensory meridian response, auditory training, atypical sensory processing, hearing loss, hearing aids
Procedia PDF Downloads 5513412 Future Sustainable Mobility for Colorado
Authors: Paolo Grazioli
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In this paper, we present the main results achieved during an eight-week international design project on Colorado Future Sustainable Mobilitycarried out at Metropolitan State University of Denver. The project was born with the intention to seize the opportunity created by the Colorado government’s plan to promote e-bikes mobility by creating a large network of dedicated tracks. The project was supported by local entrepreneurs who offered financial and professional support. The main goal of the project was to engage design students with the skills to design a user-centered, original vehicle that would satisfy the unarticulated practical and emotional needs of “Gen Z” users by creating a fun, useful, and reliablelife companion that would helps users carry out their everyday tasks in a practical and enjoyable way. The project was carried out with the intention of proving the importance of the combination of creative methods with practical design methodologies towards the creation of an innovative yet immediately manufacturable product for a more sustainable future. The final results demonstrate the students' capability to create innovative and yet manufacturable products and, especially, their ability to create a new design paradigm for future sustainable mobility products. The design solutions explored n the project include collaborative learning and human-interaction design for future mobility. The findings of the research led students to the fabrication of two working prototypes that will be tested in Colorado and developed for manufacturing in the year 2024. The project showed that collaborative design and project-based teaching improve the quality of the outcome and can lead to the creation of real life, innovative products directly from the classroom to the market.Keywords: sustainable transportation design, interface design, collaborative design, user -centered design research, design prototyping
Procedia PDF Downloads 9613411 Innovation in Sustainable Development: Sustainable Place-Making Strategies in Hong Kong
Authors: Tris Kee
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As the urban design discipline develops renewed interests in participatory design and collaborative place-making, it becomes critical to review the potential and limitations in current processes to ensure a sustainable method for future development.This paper explores how collaborative design can be a key to future sustainable urban development through two case studies from Asia.The process involves a multi-disciplinary collaboration and an innovative learning process by sharing ideas as well as careful consideration on social, economic and political circumstances among government and district stakeholders.This intrinsic proposition of innovative participatory planning implies interdisciplinary collaboration between professionals and local residents to integrate knowledge into new urban place-making thinking.Design innovation in contemporary society can manifest itself in the discourse sustainable urban development by bottom-up planning and community driven design. This paper examines the emerging design pedagogy which promotes interdisciplinary coalition of professionals and local stakeholders in community development as an innovative design rubric to create a sustainable urban approach.Through two case studies in Hong Kong, this paper reviews and critically evaluates the process of how the notion of sustainable development in contemporary urban planning theory is underpinned by the collaborative design practice.Keywords: collaborative design, design innovation, sustainable development, urban development
Procedia PDF Downloads 38613410 NUX: A Lightweight Block Cipher for Security at Wireless Sensor Node Level
Authors: Gaurav Bansod, Swapnil Sutar, Abhijit Patil, Jagdish Patil
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This paper proposes an ultra-lightweight cipher NUX. NUX is a generalized Feistel network. It supports 128/80 bit key length and block length of 64 bit. For 128 bit key length, NUX needs only 1022 GEs which is less as compared to all existing cipher design. NUX design results into less footprint area and minimal memory size. This paper presents security analysis of NUX cipher design which shows cipher’s resistance against basic attacks like Linear and Differential Cryptanalysis. Advanced attacks like Biclique attack is also mounted on NUX cipher design. Two different F function in NUX cipher design results in high diffusion mechanism which generates large number of active S-boxes in minimum number of rounds. NUX cipher has total 31 rounds. NUX design will be best-suited design for critical application like smart grid, IoT, wireless sensor network, where memory size, footprint area and the power dissipation are the major constraints.Keywords: lightweight cryptography, Feistel cipher, block cipher, IoT, encryption, embedded security, ubiquitous computing
Procedia PDF Downloads 37313409 Investigation of Maxi̇mali̇st Approaches on Furni̇ture Desi̇gn
Authors: Emi̇ne Yuksel, Murat Kiliç, Onur Ülker
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Although minimalism has been coming into being in the field of interior design for a long time, it also brought a wide range of reaction. The more simple and feeling of emptiness usage of minimalism in space and furniture design has been found extremely boring so far, as a reaction to minimalism, a movement of maximalism was emerged. Thus more extravagant, splendid, magnificent and comfortable design approach was substituted by the greatest, largest and the extreme. Thus, the philosophy of “less is bore” of minimalism was replaced by “less is more” giving rise to a new interpretation in the field of interior design. While maximalism reminded us the Victorian, Rococo, Arts and Crafts and Neoclassic styles in interior design, it drew attention to the furniture designs that covered all areas of space all in one. In this study, we search the effect of maximalist approach which was born as a reaction to minimalism in furniture. Firstly, it is explained how did the maximalism emerge and its philosophy, a literature investigation was scanned and investigated. As a research method, it is concerned with the investigation of studies undertaken by the pioneers of interior space designers and architects. The findings of this study have been evaluated in the conclusion section.Keywords: furniture design, maximalism, minimalism, texture
Procedia PDF Downloads 31413408 Fuzzy-Genetic Algorithm Multi-Objective Optimization Methodology for Cylindrical Stiffened Tanks Conceptual Design
Authors: H. Naseh, M. Mirshams, M. Mirdamadian, H. R. Fazeley
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This paper presents an extension of fuzzy-genetic algorithm multi-objective optimization methodology that could effectively be used to find the overall satisfaction of objective functions (selecting the design variables) in the early stages of design process. The coupling of objective functions due to design variables in an engineering design process will result in difficulties in design optimization problems. In many cases, decision making on design variables conflicts with more than one discipline in system design. In space launch system conceptual design, decision making on some design variable (e.g. oxidizer to fuel mass flow rate O/F) in early stages of the design process is related to objective of liquid propellant engine (specific impulse) and Tanks (structure weight). Then, the primary application of this methodology is the design of a liquid propellant engine with the maximum specific impulse and cylindrical stiffened tank with the minimum weight. To this end, the design problem is established the fuzzy rule set based on designer's expert knowledge with a holistic approach. The independent design variables in this model are oxidizer to fuel mass flow rate, thickness of stringers, thickness of rings, shell thickness. To handle the mentioned problems, a fuzzy-genetic algorithm multi-objective optimization methodology is developed based on Pareto optimal set. Consequently, this methodology is modeled with the one stage of space launch system to illustrate accuracy and efficiency of proposed methodology.Keywords: cylindrical stiffened tanks, multi-objective, genetic algorithm, fuzzy approach
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