Search results for: Nicholas F. Polizzi
12 Numerical Study of Leisure Home Chassis under Various Loads by Using Finite Element Analysis
Authors: Asem Alhnity, Nicholas Pickett
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The leisure home industry is experiencing an increase in sales due to the rise in popularity of staycations. However, there is also a demand for improvements in thermal and structural behaviour from customers. Existing standards and codes of practice outline the requirements for leisure home design. However, there is a lack of expertise in applying Finite Element Analysis (FEA) to complex structures in this industry. As a result, manufacturers rely on standardized design approaches, which often lead to excessively engineered or inadequately designed products. This study aims to address this issue by investigating the impact of the habitation structure on chassis performance in leisure homes. The aim of this research is to comprehensively analyse the impact of the habitation structure on chassis performance in leisure homes. By employing FEA on the entire unit, including both the habitation structure and the chassis, this study seeks to develop a novel framework for designing and analysing leisure homes. The objectives include material reduction, enhancing structural stability, resolving existing design issues, and developing innovative modular and wooden chassis designs. The methodology used in this research is quantitative in nature. The study utilizes FEA to analyse the performance of leisure home chassis under various loads. The analysis procedures involve running the FEA simulations on the numerical model of the leisure home chassis. Different load scenarios are applied to assess the stress and deflection performance of the chassis under various conditions. FEA is a numerical method that allows for accurate analysis of complex systems. The research utilizes flexible mesh sizing to calculate small deflections around doors and windows, with large meshes used for macro deflections. This approach aims to minimize run-time while providing meaningful stresses and deflections. Moreover, it aims to investigate the limitations and drawbacks of the popular approach of applying FEA only to the chassis and replacing the habitation structure with a distributed load. The findings of this study indicate that the popular approach of applying FEA only to the chassis and replacing the habitation structure with a distributed load overlooks the strengthening generated from the habitation structure. By employing FEA on the entire unit, it is possible to optimize stress and deflection performance while achieving material reduction and enhanced structural stability. The study also introduces innovative modular and wooden chassis designs, which show promising weight reduction compared to the existing heavily fabricated lattice chassis. In conclusion, this research provides valuable insights into the impact of the habitation structure on chassis performance in leisure homes. By employing FEA on the entire unit, the study demonstrates the importance of considering the strengthening generated from the habitation structure in chassis design. The research findings contribute to advancements in material reduction, structural stability, and overall performance optimization. The novel framework developed in this study promotes sustainability, cost-efficiency, and innovation in leisure home design.Keywords: static homes, caravans, motor homes, holiday homes, finite element analysis (FEA)
Procedia PDF Downloads 10111 Chemical and Biomolecular Detection at a Polarizable Electrical Interface
Authors: Nicholas Mavrogiannis, Francesca Crivellari, Zachary Gagnon
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Development of low-cost, rapid, sensitive and portable biosensing systems are important for the detection and prevention of disease in developing countries, biowarfare/antiterrorism applications, environmental monitoring, point-of-care diagnostic testing and for basic biological research. Currently, the most established commercially available and widespread assays for portable point of care detection and disease testing are paper-based dipstick and lateral flow test strips. These paper-based devices are often small, cheap and simple to operate. The last three decades in particular have seen an emergence in these assays in diagnostic settings for detection of pregnancy, HIV/AIDS, blood glucose, Influenza, urinary protein, cardiovascular disease, respiratory infections and blood chemistries. Such assays are widely available largely because they are inexpensive, lightweight, and portable, are simple to operate, and a few platforms are capable of multiplexed detection for a small number of sample targets. However, there is a critical need for sensitive, quantitative and multiplexed detection capabilities for point-of-care diagnostics and for the detection and prevention of disease in the developing world that cannot be satisfied by current state-of-the-art paper-based assays. For example, applications including the detection of cardiac and cancer biomarkers and biothreat applications require sensitive multiplexed detection of analytes in the nM and pM range, and cannot currently be satisfied with current inexpensive portable platforms due to their lack of sensitivity, quantitative capabilities and often unreliable performance. In this talk, inexpensive label-free biomolecular detection at liquid interfaces using a newly discovered electrokinetic phenomenon known as fluidic dielectrophoresis (fDEP) is demonstrated. The electrokinetic approach involves exploiting the electrical mismatches between two aqueous liquid streams forced to flow side-by-side in a microfluidic T-channel. In this system, one fluid stream is engineered to have a higher conductivity relative to its neighbor which has a higher permittivity. When a “low” frequency (< 1 MHz) alternating current (AC) electrical field is applied normal to this fluidic electrical interface the fluid stream with high conductivity displaces into the low conductive stream. Conversely, when a “high” frequency (20MHz) AC electric field is applied, the high permittivity stream deflects across the microfluidic channel. There is, however, a critical frequency sensitive to the electrical differences between each fluid phase – the fDEP crossover frequency – between these two events where no fluid deflection is observed, and the interface remains fixed when exposed to an external field. To perform biomolecular detection, two streams flow side-by-side in a microfluidic T-channel: one fluid stream with an analyte of choice and an adjacent stream with a specific receptor to the chosen target. The two fluid streams merge and the fDEP crossover frequency is measured at different axial positions down the resulting liquidKeywords: biodetection, fluidic dielectrophoresis, interfacial polarization, liquid interface
Procedia PDF Downloads 44610 The Greek Revolution Through the Foreign Press. The Case of the Newspaper "The London Times" In the Period 1821-1828
Authors: Euripides Antoniades
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In 1821 the Greek Revolution movement, under the political influence that arose from the French revolution, and the corresponding movements in Italy, Germany and America, requested the liberation of the nation and the establishment of an independent national state. Published topics in the British press regarding the Greek Revolution, focused on : a) the right of the Greeks to claim their freedom from Turkish domination in order to establish an independent state based on the principle of national autonomy, b) criticism regarding Turkish rule as illegal and the power of the Ottoman Sultan as arbitrary, c) the recognition of the Greek identity and its distinction from the Turkish one and d) the endorsement Greeks as the descendants of ancient Greeks. The advantage of newspaper as a media is sharing information and ideas and dealing with issues in greater depth and detail, unlike other media, such as radio or television. The London Times is a print publication that presents, in chronological or thematic order, the news, opinions or announcements about the most important events that have occurred in a place during a specified period of time. This paper employs the rich archive of The London Times archive by quoting extracts from publications of that period, to convey the British public perspective regarding the Greek Revolution from its beginning until the London Protocol of 1828. Furthermore, analyses the publications of the British newspaper in terms of the number of references to the Greek revolution, front page and editorial references as well as the size of publications on the revolution during the period 1821-1828. A combination of qualitative and quantitative content analysis was applied. An attempt was made to record Greek Revolution references along with the usage of specific words and expressions that contribute to the representation of the historical events and their exposure to the reading public. Key finds of this research reveal that a) there was a frequency of passionate daily articles concerning the events in Greece, their length, and context in The London Times, b) the British public opinion was influenced by this particular newspaper and c) the newspaper published various news about the revolution by adopting the role of animator of the Greek struggle. For instance, war events and the battles of Wallachin and Moldavia, Hydra, Crete, Psara, Mesollogi, Peloponnese were presented not only for informing the readers but for promoting the essential need for freedom and the establishment of an independent Greek state. In fact, this type of news was the main substance of the The London Times’ structure, establishing a positive image about the Greek Revolution contributing to the European diplomatic development such as the standpoint of France, - that did not wish to be detached from the conclusions regarding the English loans and the death of Alexander I of Russia and his succession by the ambitious Nicholas. These factors offered a change in the attitude of the British and Russians respectively assuming a positive approach towards Greece. The Great Powers maintained a neutral position in the Greek-Ottoman conflict, same time they engaged in Greek power increasement by offering aid.Keywords: Greece, revolution, newspaper, the London times, London, great britain, mass media
Procedia PDF Downloads 909 An Evaluation of a Prototype System for Harvesting Energy from Pressurized Pipeline Networks
Authors: Nicholas Aerne, John P. Parmigiani
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There is an increasing desire for renewable and sustainable energy sources to replace fossil fuels. This desire is the result of several factors. First, is the role of fossil fuels in climate change. Scientific data clearly shows that global warming is occurring. It has also been concluded that it is highly likely human activity; specifically, the combustion of fossil fuels, is a major cause of this warming. Second, despite the current surplus of petroleum, fossil fuels are a finite resource and will eventually become scarce and alternatives, such as clean or renewable energy will be needed. Third, operations to obtain fossil fuels such as fracking, off-shore oil drilling, and strip mining are expensive and harmful to the environment. Given these environmental impacts, there is a need to replace fossil fuels with renewable energy sources as a primary energy source. Various sources of renewable energy exist. Many familiar sources obtain renewable energy from the sun and natural environments of the earth. Common examples include solar, hydropower, geothermal heat, ocean waves and tides, and wind energy. Often obtaining significant energy from these sources requires physically-large, sophisticated, and expensive equipment (e.g., wind turbines, dams, solar panels, etc.). Other sources of renewable energy are from the man-made environment. An example is municipal water distribution systems. The movement of water through the pipelines of these systems typically requires the reduction of hydraulic pressure through the use of pressure reducing valves. These valves are needed to reduce upstream supply-line pressures to levels suitable downstream users. The energy associated with this reduction of pressure is significant but is currently not harvested and is simply lost. While the integrity of municipal water supplies is of paramount importance, one can certainly envision means by which this lost energy source could be safely accessed. This paper provides a technical description and analysis of one such means by the technology company InPipe Energy to generate hydroelectricity by harvesting energy from municipal water distribution pressure reducing valve stations. Specifically, InPipe Energy proposes to install hydropower turbines in parallel with existing pressure reducing valves in municipal water distribution systems. InPipe Energy in partnership with Oregon State University has evaluated this approach and built a prototype system at the O. H. Hinsdale Wave Research Lab. The Oregon State University evaluation showed that the prototype system rapidly and safely initiates, maintains, and ceases power production as directed. The outgoing water pressure remained constant at the specified set point throughout all testing. The system replicates the functionality of the pressure reducing valve and ensures accurate control of down-stream pressure. At a typical water-distribution-system pressure drop of 60 psi the prototype, operating at an efficiency 64%, produced approximately 5 kW of electricity. Based on the results of this study, this proposed method appears to offer a viable means of producing significant amounts of clean renewable energy from existing pressure reducing valves.Keywords: pressure reducing valve, renewable energy, sustainable energy, water supply
Procedia PDF Downloads 2048 To Smile or Not to Smile: How Engendered Facial Cues affect Hiring Decisions
Authors: Sabrina S. W. Chan, Emily Schwartzman, Nicholas O. Rule
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Past literature showed mixed findings on how smiling affects a person’s chance of getting hired. On one hand, smiling suggests enthusiasm, cooperativeness, and enthusiasm, which can elicit positive impressions. On the other hand, smiling can suggest weaker professionalism or a filler to hide nervousness, which can lower a candidate’s perceived competence. Emotion expressions can also be perceived differently depending on the person’s gender and can activate certain gender stereotypes. Women especially face a double bind with respect to hiring decisions and smiling. Because women are socially expected to smile more, those who do not smile will be considered stereotype incongruent. This becomes a noisy signal to employers and may lower their chance of being hired. However, women’s smiling as a formality may also be an obstacle. They are more likely to put on fake smiles; but if they do, they are also likely to be perceived as inauthentic and over-expressive. This paper sought to investigate how smiling affects hiring decisions, and whether this relationship is moderated by gender. In Study 1, participants were shown a series of smiling and emotionally neutral face images, incorporated into fabricated LinkedIn profiles. Participants were asked to rate how hireable they thought that candidate was. Results showed that participants rated smiling candidates as more hireable than nonsmiling candidates, and that there was no difference in gender. Moreover, individuals who did not study business were more biased in their perceptions than those who did. Since results showed a trending favoritism over female targets, in suspect of desirability bias, a second study was conducted to collect implicit measures behind the decision-making process. In Study 2, a mouse-tracking design was adopted to explore whether participants’ implicit attitudes were different from their explicit responses on hiring. Participants asked to respond whether they would offer an interview to a candidate. Findings from Study 1 was replicated in that smiling candidates received more offers than neutral-faced candidates. Results also showed that female candidates received significantly more offers than male candidates but was associated with higher attractiveness ratings. There were no significant findings in reaction time or change of decisions. However, stronger hesitation was detected for responses made towards neutral targets when participants perceived the given position as masculine, implying a conscious attempt of making situational judgments (e.g., considering candidate’s personality and job fit) to override automatic processing (evaluations based on attractiveness). Future studies would look at how these findings differ for positions which are stereotypically masculine (e.g., surgeons) and stereotypically feminine (e.g., kindergarten teachers). Current findings have strong implications for developing bias-free hiring policies in workplace, especially for organizations who maintain online/hybrid working arrangements in the post-pandemic era. This also bridges the literature gap between face perception and gender discrimination, highlighting how engendered facial cues can affect individual’s career development and organization’s success in diversity and inclusion.Keywords: engendered facial cues, face perception, gender stereotypes, hiring decisions, smiling, workplace discrimination
Procedia PDF Downloads 1337 Understanding New Zealand’s 19th Century Timber Churches: Techniques in Extracting and Applying Underlying Procedural Rules
Authors: Samuel McLennan, Tane Moleta, Andre Brown, Marc Aurel Schnabel
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The development of Ecclesiastical buildings within New Zealand has produced some unique design characteristics that take influence from both international styles and local building methods. What this research looks at is how procedural modelling can be used to define such common characteristics and understand how they are shared and developed within different examples of a similar architectural style. This will be achieved through the creation of procedural digital reconstructions of the various timber Gothic Churches built during the 19th century in the city of Wellington, New Zealand. ‘Procedural modelling’ is a digital modelling technique that has been growing in popularity, particularly within the game and film industry, as well as other fields such as industrial design and architecture. Such a design method entails the creation of a parametric ‘ruleset’ that can be easily adjusted to produce many variations of geometry, rather than a single geometry as is typically found in traditional CAD software. Key precedents within this area of digital heritage includes work by Haegler, Müller, and Gool, Nicholas Webb and Andre Brown, and most notably Mark Burry. What these precedents all share is how the forms of the reconstructed architecture have been generated using computational rules and an understanding of the architects’ geometric reasoning. This is also true within this research as Gothic architecture makes use of only a select range of forms (such as the pointed arch) that can be accurately replicated using the same standard geometric techniques originally used by the architect. The methodology of this research involves firstly establishing a sample group of similar buildings, documenting the existing samples, researching any lost samples to find evidence such as architectural plans, photos, and written descriptions, and then culminating all the findings into a single 3D procedural asset within the software ‘Houdini’. The end result will be an adjustable digital model that contains all the architectural components of the sample group, such as the various naves, buttresses, and windows. These components can then be selected and arranged to create visualisations of the sample group. Because timber gothic churches in New Zealand share many details between designs, the created collection of architectural components can also be used to approximate similar designs not included in the sample group, such as designs found beyond the Wellington Region. This creates an initial library of architectural components that can be further expanded on to encapsulate as wide of a sample size as desired. Such a methodology greatly improves upon the efficiency and adjustability of digital modelling compared to current practices found in digital heritage reconstruction. It also gives greater accuracy to speculative design, as a lack of evidence for lost structures can be approximated using components from still existing or better-documented examples. This research will also bring attention to the cultural significance these types of buildings have within the local area, addressing the public’s general unawareness of architectural history that is identified in the Wellington based research ‘Moving Images in Digital Heritage’ by Serdar Aydin et al.Keywords: digital forensics, digital heritage, gothic architecture, Houdini, procedural modelling
Procedia PDF Downloads 1316 A Study on Economic Impacts of Entrepreneurial Firms and Self-Employment: Minority Ethnics in Putatan, Penampang, Inanam, Menggatal, Uitm, Tongod, Sabah, Malaysia
Authors: Lizinis Cassendra Frederick Dony, Jirom Jeremy Frederick Dony, Andrew Nicholas, Dewi Binti Tajuddin
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Starting and surviving a business is influenced by various entrepreneurship socio-economics activities. The study revealed that some of the entrepreneurs are not registered under SME but running own business as an intermediary with the private organization entrusted as “Self-Employed.” SME is known as “Small Medium Enterprise” contributes growth in Malaysia. Therefore, the entrepreneurialism business interest and entrepreneurial intention enhancing new spurring production, expanding employment opportunities, increasing productivity, promoting exports, stimulating innovation and providing new avenue in the business market place. This study has identified the unique contribution to the full understanding of complex mechanisms through entrepreneurship obstacles and education impacts on happiness and well-being to society. Moreover, “Ethnic” term has defined as a curious meaning refers to a classification of a large group of people customs implies to ancestral, racial, national, tribal, religious, linguistic and cultural origins. It is a social phenomenon.1 According to Sabah data population is amounting to 2,389,494 showed the predominant ethnic group being the Kadazan Dusun (18.4%) followed by Bajau (17.3%) and Malays (15.3%). For the year 2010, data statistic immigrants population report showed the amount to 239,765 people which cover 4% of the Sabahan’s population.2 Sabah has numerous group of talented entrepreneurs. The business environment among the minority ethnics are influenced with the business sentiment competition. The literature on ethnic entrepreneurship recognizes two main type entrepreneurships: the middleman and enclave entrepreneurs. According to Adam Smith,3 there are evidently some principles disposition to admire and maintain the distinction business rank status and cause most universal business sentiments. Due to credit barriers competition, the minority ethnics are losing the business market and since 2014, many illegal immigrants have been found to be using permits of the locals to operate businesses in Malaysia.4 The development of small business entrepreneurship among the minority ethnics in Sabah evidenced based variety of complex perception and differences concepts. The studies also confirmed the effects of heterogeneity on group decision and thinking caused partly by excessive pre-occupation with maintaining cohesiveness and the presence of cultural diversity in groups should reduce its probability.5 The researchers proposed that there are seven success determinants particularly to determine the involvement of minority ethnics comparing to the involvement of the immigrants in Sabah. Although, (SMEs) have always been considered the backbone of the economy development, the minority ethnics are often categorized it as the “second-choice.’ The study showed that illegal immigrants entrepreneur imposed a burden on Sabahan social programs as well as the prison, court and health care systems. The tension between the need for cheap labor and the impulse to protect Malaysian in Sabah workers, entrepreneurs and taxpayers, among the subjects discussed in this study. This is clearly can be advantages and disadvantages to the Sabah economic development.Keywords: entrepreneurial firms, self-employed, immigrants, minority ethnic, economic impacts
Procedia PDF Downloads 4125 Colloid-Based Biodetection at Aqueous Electrical Interfaces Using Fluidic Dielectrophoresis
Authors: Francesca Crivellari, Nicholas Mavrogiannis, Zachary Gagnon
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Portable diagnostic methods have become increasingly important for a number of different purposes: point-of-care screening in developing nations, environmental contamination studies, bio/chemical warfare agent detection, and end-user use for commercial health monitoring. The cheapest and most portable methods currently available are paper-based – lateral flow and dipstick methods are widely available in drug stores for use in pregnancy detection and blood glucose monitoring. These tests are successful because they are cheap to produce, easy to use, and require minimally invasive sampling. While adequate for their intended uses, in the realm of blood-borne pathogens and numerous cancers, these paper-based methods become unreliable, as they lack the nM/pM sensitivity currently achieved by clinical diagnostic methods. Clinical diagnostics, however, utilize techniques involving surface plasmon resonance (SPR) and enzyme-linked immunosorbent assays (ELISAs), which are expensive and unfeasible in terms of portability. To develop a better, competitive biosensor, we must reduce the cost of one, or increase the sensitivity of the other. Electric fields are commonly utilized in microfluidic devices to manipulate particles, biomolecules, and cells. Applications in this area, however, are primarily limited to interfaces formed between immiscible interfaces. Miscible, liquid-liquid interfaces are common in microfluidic devices, and are easily reproduced with simple geometries. Here, we demonstrate the use of electrical fields at liquid-liquid electrical interfaces, known as fluidic dielectrophoresis, (fDEP) for biodetection in a microfluidic device. In this work, we apply an AC electric field across concurrent laminar streams with differing conductivities and permittivities to polarize the interface and induce a discernible, near-immediate, frequency-dependent interfacial tilt. We design this aqueous electrical interface, which becomes the biosensing “substrate,” to be intelligent – it “moves” only when a target of interest is present. This motion requires neither labels nor expensive electrical equipment, so the biosensor is inexpensive and portable, yet still capable of sensitive detection. Nanoparticles, due to their high surface-area-to-volume ratio, are often incorporated to enhance detection capabilities of schemes like SPR and fluorimetric assays. Most studies currently investigate binding at an immobilized solid-liquid or solid-gas interface, where particles are adsorbed onto a planar surface, functionalized with a receptor to create a reactive substrate, and subsequently flushed with a fluid or gas with the relevant analyte. These typically involve many preparation and rinsing steps, and are susceptible to surface fouling. Our microfluidic device is continuously flowing and renewing the “substrate,” and is thus not subject to fouling. In this work, we demonstrate the ability to electrokinetically detect biomolecules binding to functionalized nanoparticles at liquid-liquid interfaces using fDEP. In biotin-streptavidin experiments, we report binding detection limits on the order of 1-10 pM, without amplifying signals or concentrating samples. We also demonstrate the ability to detect this interfacial motion, and thus the presence of binding, using impedance spectroscopy, allowing this scheme to become non-optical, in addition to being label-free.Keywords: biodetection, dielectrophoresis, microfluidics, nanoparticles
Procedia PDF Downloads 3884 A Report on the Elearning Programme of the Irish College of General Practitioners Which Can Address Continuing Education Needs of Primary Care Physicians
Authors: Nicholas P. Fenlon, Aisling Lavelle, David Mclean, Margaret O'riordan
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Background: The case for continuing professional development has been well made, and was formalized in Ireland in recent years through the enactment of the Medical Practitioner’s Act, which requires registered medical practitioners to complete a minimum of 50 hours CPD each year. The ICGP, who have been providing CPD opportunities to its members for many years, have responded to this need by developing a series of evidence-based, high-quality, multimedia modules across a range of clinical and non-clinical areas. (More traditional education opportunities are still being provided by the college also). Overview of Programme: The first module was released in September 2011, since when the eLearning program has grown steadily, and there are currently almost 20 modules available, with a further 5 in production. Each module contains three to six 10-minute video lessons, which use a combination of graphics, images, text, voice-over and clinical clips. These are supported by supplementary videos of expert pieces-to-camera, Q&As with content experts, clinical scenarios, external links and relevant documentation and other resources. Successful completion of MCQs will result in a Certificate of Completion, which can be printed or stored in Professional Competence portfolio. The Medical Practitioner’s Act requires doctors to gather CPD credits across 8 domains of practice, and various eLearning modules have been developed to address each. For instance, modules with a strong clinical content would include Management of Hypertension, Management of COPD, and Management of Asthma. Other modules focus on health promotion such as Promoting Smoking Cessation, Promoting Physical Activity, and Addressing Childhood Obesity. Modules where communication skills are keys include modules on Suicide Prevention and Management of Depression. Other modules, currently in development include non-clinical topics around risk management, including Confidentiality, Consent etc. Each module is developed by a core group, which includes where possible, a GP with a special interest in the area, and a content expert(s). The college works closely with a medical education consultant and a production company in developing and producing the modules. Modules can be accessed (with password) through the ICGP website and are available free to all ICGP members. Summary of Evaluation: There are over 1700 registered users to date (over 55% of College membership). The program was evaluated using an online survey in 2013 (N = 144/950 – 12%) and results were very positive overall but provided material for the further improvement of the program also. Future Plans: While knowledge can be imparted well through eLearning, skills and attitudes are more difficult to influence through an online environment. The college is now developing a series of linked workshops, which will lead to ICGP Professional Competence Awards. The first pilot workshop is scheduled for February 2015 and is Cardiology-themed. Participants will be required to complete the following 4 modules in advance of attending – Management of Hypertension, Management of Heart Failure, Promoting Smoking Cessation, and Promoting Physical Activity. The workshop will be case-based and interactive, addressing ECG Interpretation in General Practice. Conclusions: The ICGP have responded to members needs for high-quality evidence-based education delivered in a way that suits GPs.Keywords: CPD opportunities, evidence-based, high quality, multimedia modules across a range of clinical and non-clinical areas, medical practitioner’s act
Procedia PDF Downloads 5993 Targeting TACI Signaling Enhances Immune Function and Halts Chronic Lymphocytic Leukemia Progression
Authors: Yong H Sheng, Beatriz Garcillán, Eden Whitlock, Yukli Freedman, SiLing Yang, M Arifur Rahman, Nicholas Weber, Fabienne Mackay
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Chronic lymphocytic leukemia (CLL) is closely associated with immune dysfunction, yet the mechanisms underlying this immune deficiency remain poorly understood. Transmembrane Activator and CAML Interactor (TACI), a receptor known for its role in IL-10 regulation and autoimmunity, to the best of our knowledge has not been investigated in the context of anti-tumor immunity or its impact on CLL progression. This study addresses the gap by exploring the role of TACI in regulating CLL cells within the tumor microenvironment and its broader effects on disease progression and immune competence. We utilized the Eµ-TCL1 mouse model to generate CLL mice deficient in TACI and examined the consequences of TACI loss in adoptive transfer models over a five-week period. Comprehensive transcriptomic analysis, including RNA sequencing and microarray, was employed to determine TACI’s influence on the CLL gene expression profile. Additionally, we studied TACI’s direct role in CLL cell migration and immune modulation using patient-derived CLL cells in culture and Patient-Derived Xenograph (PDX) models. Our findings demonstrate that TACI signaling plays a pivotal role in promoting CLL progression and immune suppression. Loss of TACI signaling significantly inhibited CLL development and enhanced immune functionality. When TACI+/+ or TACI-/- TCL1 CLL cells were transferred into wild-type recipient mice, those receiving TACI-deficient cells showed reduced disease progression and lower incidence of CLL. Mice with TACI-/- CLL cells exhibited normalized serum levels of pro-inflammatory cytokines IL-6 and IL-10, restored proportions of T-cell subsets, and improved immune compartment function compared to counterparts with TACI+/+ CLL cells. Mechanistically, TACI-deficient CLL cells expressed significantly lower levels of IL-10, TNF, and inhibitory receptors such as PD-L1 and PD-L2. These cells also display restored circulating immunoglobulin levels and responses to T cell-dependent antigens, highlighting a recovery of immune competence. Further mechanistic studies revealed that TACI signaling drives CLL cell migration and homing to the spleen, where these cells actively establish an immunosuppressive microenvironment that supports immune evasion and tumor growth. Patient-derived CLL cells and PDX models confirmed TACI’s direct role in enhancing CLL cell migration and fostering immune suppression, emphasizing its critical function in the tumor microenvironment. By disrupting TACI signaling, we observed a reduction in CLL-associated immune suppression and tumor progression, offering a promising therapeutic avenue. This study establishes, for the first time, that targeting TACI disrupts key mechanisms underlying CLL progression while preserving vital immune functions. Unlike existing treatments that often impair immunity and lead to infection-related complications, TACI inhibition offers the dual benefit of controlling disease and maintaining immune homeostasis. These findings provide a strong rationale for developing therapeutic strategies that inhibit TACI as a means to improve outcomes in CLL patients. Beyond its implications for CLL, this research underscores the broader importance of TACI in regulating immune-tumor interactions, paving the way for future studies into its role in other malignancies.Keywords: chronic lymphocytic leukemia, TACI, IL-10, immune suppression
Procedia PDF Downloads 52 Braille Lab: A New Design Approach for Social Entrepreneurship and Innovation in Assistive Tools for the Visually Impaired
Authors: Claudio Loconsole, Daniele Leonardis, Antonio Brunetti, Gianpaolo Francesco Trotta, Nicholas Caporusso, Vitoantonio Bevilacqua
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Unfortunately, many people still do not have access to communication, with specific regard to reading and writing. Among them, people who are blind or visually impaired, have several difficulties in getting access to the world, compared to the sighted. Indeed, despite technology advancement and cost reduction, nowadays assistive devices are still expensive such as Braille-based input/output systems which enable reading and writing texts (e.g., personal notes, documents). As a consequence, assistive technology affordability is fundamental in supporting the visually impaired in communication, learning, and social inclusion. This, in turn, has serious consequences in terms of equal access to opportunities, freedom of expression, and actual and independent participation to a society designed for the sighted. Moreover, the visually impaired experience difficulties in recognizing objects and interacting with devices in any activities of daily living. It is not a case that Braille indications are commonly reported only on medicine boxes and elevator keypads. Several software applications for the automatic translation of written text into speech (e.g., Text-To-Speech - TTS) enable reading pieces of documents. However, apart from simple tasks, in many circumstances TTS software is not suitable for understanding very complicated pieces of text requiring to dwell more on specific portions (e.g., mathematical formulas or Greek text). In addition, the experience of reading\writing text is completely different both in terms of engagement, and from an educational perspective. Statistics on the employment rate of blind people show that learning to read and write provides the visually impaired with up to 80% more opportunities of finding a job. Especially in higher educational levels, where the ability to digest very complex text is key, accessibility and availability of Braille plays a fundamental role in reducing drop-out rate of the visually impaired, thus affecting the effectiveness of the constitutional right to get access to education. In this context, the Braille Lab project aims at overcoming these social needs by including affordability in designing and developing assistive tools for visually impaired people. In detail, our awarded project focuses on a technology innovation of the operation principle of existing assistive tools for the visually impaired leaving the Human-Machine Interface unchanged. This can result in a significant reduction of the production costs and consequently of tool selling prices, thus representing an important opportunity for social entrepreneurship. The first two assistive tools designed within the Braille Lab project following the proposed approach aims to provide the possibility to personally print documents and handouts and to read texts written in Braille using refreshable Braille display, respectively. The former, named ‘Braille Cartridge’, represents an alternative solution for printing in Braille and consists in the realization of an electronic-controlled dispenser printing (cartridge) which can be integrated within traditional ink-jet printers, in order to leverage the efficiency and cost of the device mechanical structure which are already being used. The latter, named ‘Braille Cursor’, is an innovative Braille display featuring a substantial technology innovation by means of a unique cursor virtualizing Braille cells, thus limiting the number of active pins needed for Braille characters.Keywords: Human rights, social challenges and technology innovations, visually impaired, affordability, assistive tools
Procedia PDF Downloads 2731 Restoring Total Form and Function in Patients with Lower Limb Bony Defects Utilizing Patient-Specific Fused Deposition Modelling- A Neoteric Multidisciplinary Reconstructive Approach
Authors: Divya SY. Ang, Mark B. Tan, Nicholas EM. Yeo, Siti RB. Sudirman, Khong Yik Chew
Abstract:
Introduction: The importance of the amalgamation of technological and engineering advances with surgical principles of reconstruction cannot be overemphasized. With earlier detection of cancer, consequences of high-speed living and neglect, like traumatic injuries and infection, resulting in increasingly younger patients with bone defects. This may result in malformations and suboptimal function that is more noticeable and palpable in the younger, active demographic. Our team proposes a technique that encapsulates a mesh of multidisciplinary effort, tissue engineering and reconstructive principles. Methods/Materials: Our patient was a young competitive footballer in his early 30s who was diagnosed with submandibular adenoid cystic carcinoma with bony involvement. He was thus counselled for a right hemi mandibulectomy, the floor of mouth resection, right selective neck dissection, tracheostomy, and free fibular flap reconstruction of his mandible and required post-operative radiotherapy. Being young and in his prime sportsman years, he was unable to accept the morbidities associated with using his fibula to reconstruct his mandible despite it being the gold standard reconstructive option. The fibula is an ideal vascularized bone flap because it’s reliable and easily shaped with relatively minimal impact on functional outcomes. The fibula contributes to 30% of weightbearing and is the attachment for the lateral compartment muscles; it is stronger in footballers concerning lateral bending. When harvesting the fibula, the distal 6-8cm and up to 10% of the total length is preserved to maintain the ankle’s stability, thus, minimizing the impact on daily activities. There are studies that have noted gait variability post-operatively. Therefore, returning to a premorbid competitive level may be doubtful. To improve his functional outcomes, the decision was made to try and restore the fibula's form and function. Using the concept of Fused Deposition Modelling (FDM), our team comprising of Plastics, Otolaryngology, Orthopedics and Radiology, worked with Osteopore to design a 3D bioresorbable implant to regenerate the fibula defect (14.5cm). Bone marrow was harvested via reaming the contralateral hip prior to the wide resection. 30mls of his blood was obtained for extracting platelet rich plasma. These were packed into the Osteopore 3D-printed bone scaffold. This was then secured into the fibula defect with titanium plates and screws. The flexor hallucis longus and soleus were anchored along the construct and intraosseous membrane, done in a single setting. Results: He was reviewed closely as an outpatient over 10 months post operatively. He reported no discernable loss or difference in ankle function. He is satisfied and back in training and our team has video and photographs that substantiate his progress. Conclusion: FDM allows regeneration of long bone defects. However, we aimed to also restore his eversion and inversion that is imperative for footballers and hence reattached his previously dissected muscles along the length of the Osteopore implant. We believe that the reattachment of the muscle stabilizes not only the construct but allows optimum muscle tensioning when moving his ankle. This is a simple but effective technique in restoring complete function and form in a young patient whose minute muscle control is imperative to life.Keywords: fused deposition modelling, functional reconstruction, lower limb bony defects, regenerative surgery, 3D printing, tissue engineering
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