Search results for: complex urban geometry
2411 Effect of Ultrasound-Assisted Pretreatment on Saccharification of Spent Coffee Grounds
Authors: Shady S. Hassan, Brijesh K. Tiwari, Gwilym A. Williams, Amit K. Jaiswal
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EU is known as the destination with the highest rate of the coffee consumption per capita in the world. Spent coffee grounds (SCG) are the main by-product of coffee brewing. SCG is either disposed as a solid waste or employed as compost, although the polysaccharides from such lignocellulosic biomass might be used as feedstock for fermentation processes. However, SCG as a lignocellulose have a complex structure and pretreatment process is required to facilitate an efficient enzymatic hydrolysis of carbohydrates. However, commonly used pretreatment methods, such as chemical, physico-chemical and biological techniques are still insufficient to meet optimal industrial production requirements in a sustainable way. Ultrasound is a promising candidate as a sustainable green pretreatment solution for lignocellulosic biomass utilization in a large scale biorefinery. Thus, ultrasound pretreatment of SCG without adding harsh chemicals investigated as a green technology to enhance enzyme hydrolysis. In the present work, ultrasound pretreatment experiments were conducted on SCG using different ultrasound frequencies (25, 35, 45, 130, and 950 kHz) for 60 min. Regardless of ultrasound power, low ultrasound frequency is more effective than high ultrasound frequency in pretreatment of biomass. Ultrasound pretreatment of SCG (at ultrasound frequency of 25 kHz for 60 min) followed by enzymatic hydrolysis resulted in total reducing sugars of 56.1 ± 2.8 mg/g of biomass. Fourier transform Infrared Spectroscopy (FTIR) was employed to investigate changes in functional groups of biomass after pretreatment, while high-performance liquid chromatography (HPLC) was employed for determination of glucose. Pretreatment of lignocellulose by low frequency ultrasound in water only was found to be an effective green approach for SCG to improve saccharification and glucose yield compared to native biomass. Pretreatment conditions will be optimized, and the enzyme hydrolysate will be used as media component substitute for the production of ethanol.Keywords: lignocellulose, ultrasound, pretreatment, spent coffee grounds
Procedia PDF Downloads 3262410 A Critical Reflection of Ableist Methodologies: Approaching Interviews and Go-Along Interviews
Authors: Hana Porkertová, Pavel Doboš
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Based on a research project studying the experience of visually disabled people with urban space in the Czech Republic, the conference contribution discusses the limits of social-science methodologies used in sociology and human geography. It draws on actor-network theory, assuming that science does not describe reality but produces it. Methodology connects theory, research questions, ways to answer them (methods), and results. A research design utilizing ableist methodologies can produce ableist realities. Therefore, it was necessary to adjust the methods so that they could mediate blind experience to the scientific community without reproducing ableism. The researchers faced multiple challenges, ranging from questionable validity to how to research experience that differs from that of the researchers who are able-bodied. Finding a suitable theory that could be used as an analytical tool that would demonstrate space and blind experience as multiple, dynamic, and mutually constructed was the first step that could offer a range of potentially productive methods and research questions, as well as bring critically reflected results. Poststructural theory, mainly Deleuze-Guattarian philosophy, was chosen, and two methods were used: interviews and go-along interviews that had to be adjusted to be able to explore blind experience. In spite of a thorough preparation of these methods, new difficulties kept emerging, which exposed the ableist character of scientific knowledge. From the beginning of data collecting, there was an agreement to work in teams with slightly different roles of each of the researchers, which was significant especially during go-along interviews. In some cases, the anticipations of the researchers and participants differed, which led to unexpected and potentially dangerous situations. These were not caused only by the differences between scientific and lay communities but also between able-bodied and disabled people. Researchers were sometimes assigned to the assistants’ roles, and this new position – doing research together – required further negotiations, which also opened various ethical questions.Keywords: ableist methodology, blind experience, go-along interviews, research ethics, scientific knowledge
Procedia PDF Downloads 1652409 For Post-traumatic Stress Disorder Counselors in China, the United States, and around the Globe, Cultural Beliefs Offer Challenges and Opportunities
Authors: Anne Giles
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Trauma is generally defined as an experience, or multiple experiences, overwhelming a person's ability to cope. Over time, many people recover from the neurobiological, physical, and emotional effects of trauma on their own. For some people, however, troubling symptoms develop over time that can result in distress and disability. This cluster of symptoms is classified as Post-traumatic Stress Disorder (PTSD). People who meet the criteria for PTSD and other trauma-related disorder diagnoses often hold a set of understandable but unfounded beliefs about traumatic events that cause undue suffering. Becoming aware of unhelpful beliefs—termed "cognitive distortions"—and challenging them is the realm of Cognitive Behavior Therapy (CBT). A form of CBT found by researchers to be especially effective for PTSD is Cognitive Processing Therapy (CPT). Through the compassionate use of CPT, people identify, examine, challenge, and relinquish unhelpful beliefs, thereby reducing symptoms and suffering. Widely-held cultural beliefs can interfere with the progress of recovery from trauma-related disorders. Although highly revered, largely unquestioned, and often stabilizing, cultural beliefs can be founded in simplistic, dichotomous thinking, i.e., things are all right, or all wrong, all good, or all bad. The reality, however, is nuanced and complex. After studying examples of cultural beliefs from China and the United States and how these might interfere with trauma recovery, trauma counselors can help clients derive criteria for preserving helpful beliefs, discover, examine, and jettison unhelpful beliefs, reduce trauma symptoms, and live their lives more freely and fully.Keywords: cognitive processing therapy (CPT), cultural beliefs, post-traumatic stress disorder (PTSD), trauma recovery
Procedia PDF Downloads 2502408 Reduction of Cooling Demands in a Subtropical Humid Climate Zone: A Study on Roofs of Existing Residential Building Using Passive
Authors: Megha Jain, K. K. Pathak
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In sub-tropical humid climates, it is estimated most of the urban peak load of energy consumption is used to satisfy air-conditioning or air-coolers cooling demand in summer time. As the urbanization rate in developing nation – like the case in India is rising rapidly, the pressure placed on energy resources to satisfy inhabitants’ indoor comfort requirements is consequently increasing too. This paper introduces passive cooling through roof as a means of reducing energy cooling loads for satisfying human comfort requirements in a sub-tropical climate. Experiments were performed by applying different insulators which are locally available solar reflective materials to insulate the roofs of five rooms of 4 case buildings; three rooms having RCC (Reinforced Cement Concrete) roof and two having Asbestos sheet roof of existing buildings. The results are verified by computer simulation using Computational Fluid Dynamics tools with FLUENT software. The result of using solar reflective paint with high albedo coating shows a fall of 4.8⁰C in peak hours and saves 303 kWh considering energy load with air conditioner during the summer season in comparison to non insulated flat roof energy load of residential buildings in Bhopal. An optimum solution of insulator for both types of roofs is presented. It is recommended that the selected cool roof solution be combined with insulation on other elements of envelope, to increase the indoor thermal comfort. The application is intended for low cost residential buildings in composite and warm climate like Bhopal.Keywords: cool roof, computational fluid dynamics, energy loads, insulators, passive cooling, subtropical climate, thermal performance
Procedia PDF Downloads 1702407 Understanding Profit Shifting by Multinationals in the Context of Cross-Border M&A: A Methodological Exploration
Authors: Michal Friedrich
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Cross-border investment has never been easier than in today’s global economy. Despite recent initiatives tightening the international tax landscape, profit shifting and tax optimization by multinational entities (MNEs) in the context of cross-border M&A remain persistent and complex phenomena that warrant in-depth exploration. By synthesizing the outcomes of existing research, this study aims to first provide a methodological framework for identifying MNEs’ profit-shifting behavior and quantifying its fiscal impacts via various macroeconomic and microeconomic approaches. The study also proposes additional methods and qualitative/quantitative measures for extracting insight into the profit shifting behavior of MNEs in the context of their M&A activities at industry and entity levels. To develop the proposed methods, this study applies the knowledge of international tax laws and known profit shifting conduits (incl. dividends, interest, and royalties) on several model cases/types of cross-border acquisitions and post-acquisition integration activities by MNEs and highlights important factors that encourage or discourage tax optimization. Follow-up research is envisaged to apply the methods outlined in this study on published data on real-world M&A transactions to gain practical country-by-country, industry and entity-level insights. In conclusion, this study seeks to contribute to the ongoing discourse on profit shifting by providing a methodological toolkit for exploring profit shifting tendencies MNEs in connection with their M&A activities and to serve as a backbone for further research. The study is expected to provide valuable insight to policymakers, tax authorities, and tax professionals alike.Keywords: BEPS, cross-border M&A, international taxation, profit shifting, tax optimization
Procedia PDF Downloads 692406 Water Quality, Risk, Management and Distribution in Abeokuta, Ogun State
Authors: Ayedun Hassan, Ayadi Odunayo Peter
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The ancient city of Abeokuta has been supplied with pipe borne water since 1911, yet, a continuous increase in population and unplanned city expansion makes water a very precious and scarce commodity. The government reserved areas (GRA’s) are well planned, and public water supply is available; however, the sub-urban areas consist of scattered structures with individuals trying to source water by digging wells and boreholes. The geology of the city consists of basement rock which makes digging wells and boreholes very difficult. The present study was conducted to assess the risk arising from the consumption of toxic elements in the groundwater of Abeokuta, Ogun State, Nigeria. Forty-five groundwater samples were collected from nine different areas of Abeokuta and analyzed for physicochemical parameters and toxic elements. The physicochemical parameters were determined using standard methods, while the toxic elements were determined using Inductively Coupled Plasma-Mass Spectrometer (ICP/MS). Ninety-six percent (96%) of the water sample has pH < 6.5, and 11% has conductivity > 250 µSCm⁻¹ limits in drinking water as recommended by WHO. Seven percent (7%) of the samples have Pb concentration >10 µgL⁻¹ while 75% have Al concentration >200 µgL⁻¹ recommended by WHO. The order for risk of cancer from different area of Abeokuta are Cd²⁺ > As³⁺ > Pb²⁺ > Cr⁶⁺ for Funaab, Camp and Obantoko; As³⁺ > Cd²⁺ > Pb²⁺ > Cr⁶⁺ for Ita Osin, Isale Igbein, Ake and Itoku; Cd²⁺ >As > Cr⁶⁺ > Pb²⁺ for Totoro; Pb²⁺ > Cd²⁺ > As³⁺ > Cr⁶⁺ for Idiaba. The order of non-cancer hazard index (HI) calculated for groundwater of Abeokuta City are Cd²⁺ > As³⁺ > Mn²⁺ > Pb²⁺ > Ni²⁺ and were all greater than one, which implies susceptibility to other illnesses. The sources of these elements are the rock and inappropriate waste disposal method, which leached the elements into the groundwater. A combination of sources from food will accumulate these elements in the human body system. Treatment to remove Al and Pb is necessary, while the method of water distribution should be reviewed to ensure access to potable water by the residents.Keywords: Abeokuta, groundwater, Nigeria, risk
Procedia PDF Downloads 942405 The Use of Whatsapp Platform in Spreading Fake News among Mass Communication Students of Abdu Gusau Polytechnic, Talata Mafara
Authors: Aliyu Damri
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In every educational institution, students of mass communication receive training to report events and issues accurately and objectively in accordance with official controls. However, the complex nature of society today made it possible to use WhatsApp platform that revolutionizes the means of sharing information, ideas, and experiences. This paper examined how students in the Department of Mass Communication, Abdu Gusau Polytechnic, Talata Mafara used WhatsApp platform in spreading fake news. It used in depth interview techniques and focus group discussion with students as well as the use of published materials to gather related and relevant data. Also, the paper used procedures involved to analyze long interview content. This procedure includes observation of a useful utterance, development of expanded observation, examination of interconnection of observed comments, collective scrutiny of observation for patterns and themes, and review and analysis of the themes across all interviews for development of thesis. The result indicated that inadequate and absent of official controls guiding the conduct of online information sharing, inaccuracies and poor source verification, lack of gate keeping procedures to ensure ethical and legal provisions, bringing users into the process, sharing all information, availability of misinformation, disinformation and rumor and problem of conversation strongly encouraged the emergence of fake news. Surprisingly, the idea of information as a commodity has increased, and transparency of a source as new ethics emerged.Keywords: disinformation, fake news, group, mass communication, misinformation, WhatsApp
Procedia PDF Downloads 1432404 Collective Potential: A Network of Acupuncture Interventions for Flood Resilience
Authors: Sachini Wickramanayaka
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The occurrence of natural disasters has increased in an alarming rate in recent times due to escalating effects of climate change. One such natural disaster that has continued to grow in frequency and intensity is ‘flooding’, adversely affecting communities around the globe. This is an exploration on how architecture can intervene and facilitate in preserving communities in the face of disaster, specifically in battling floods. ‘Resilience’ is one of the concepts that have been brought forward to be instilled in vulnerable communities to lower the impact from such disasters as a preventative and coping mechanism. While there are number of ways to achieve resilience in the built environment, this paper aims to create a synthesis between resilience and ‘urban acupuncture’. It will consider strengthening communities from within, by layering a network of relatively small-scale, fast phased interventions on pre-existing conventional flood preventative large-scale engineering infrastructure.By investigating ‘The Woodlands’, a planned neighborhood as a case study, this paper will argue that large-scale water management solutions while extremely important will not suffice as a single solution particularly during a time of frequent and extreme weather events. The different projects will try to synthesize non-architectural aspects such as neighborhood aspirations, requirements, potential and awareness into a network of architectural forms that would collectively increase neighborhood resiliency to floods. A mapping study of the selected study area will identify the problematic areas that flood in the neighborhood while the empirical data from previously implemented case studies will assess the success of each solution.If successful the different solutions for each of the identified problem areas will exhibithow flooding and water management can be integrated as part and parcel of daily life.Keywords: acupuncture, architecture, resiliency, micro-interventions, neighborhood
Procedia PDF Downloads 1702403 Experimental Research of Smoke Impact on the Performance of Cylindrical Eight Channel Cyclone
Authors: Pranas Baltrėnas, Dainius Paliulis
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Cyclones are widely used for separating particles from gas in energy production objects. Efficiency of normal centrifugal air cleaning devices ranges from 85 to 90%, but weakness of many cyclones is low collection efficiency of particles less than 10 μm in diameter. Many factors have impact on cyclone efficiency – humidity, temperature, gas (air) composition, airflow velocity and etc. Many scientists evaluated only effect of origin and size of PM on cyclone efficiency. Effect of gas (air) composition and temperature on cyclone efficiency still demands contributions. Complex experimental research on efficiency of cylindrical eight-channel system with adjustable half-rings for removing fine dispersive particles (< 20 μm) was carried out. The impact of gaseous smoke components on removal of wood ashes was analyzed. Gaseous components, present in the smoke mixture, with the dynamic viscosity lower than that of same temperature air, decrease the d50 value, simultaneously increasing the overall particulate matter removal efficiency in the cyclone, i.e. this effect is attributed to CO2 and CO, while O2 and NO have the opposite effect. Air temperature influences the d50 value, an increase in air temperature yields an increase in d50 value, i.e. the overall particulate matter removal efficiency declines, the reason for this being an increasing dynamic air viscosity. At 120 °C temperature the d50 value is approximately 11.8 % higher than at air temperature of 20 °C. With an increase in smoke (gas) temperature from 20 °C to 50 °C, the aerodynamic resistance in a 1-tier eight-channel cylindrical cyclone drops from 1605 to 1380 Pa, from 1660 to 1420 Pa in a 2-tier eight-channel cylindrical cyclone, from 1715 to 1450 Pa in a 3-tier eight-channel cylindrical cyclone. The reason for a decline in aerodynamic resistance is the declining gas density. The aim of the paper is to analyze the impact of gaseous smoke components on the eight–channel cyclone with tangential inlet.Keywords: cyclone, adjustable half-rings, particulate matter, efficiency, gaseous compounds, smoke
Procedia PDF Downloads 2892402 Dialectics of Modern Law: Perspectives and Strategies of Resistance from the Margins
Authors: Nisar Alungal Chungath
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“No human being is illegal" has become a dictum strongly upheld in the context of global immigration and migration, highlighting the ethical and moral dimensions of how societies and governments treat individuals and communities who have crossed political borders or are living in a country without legal authorization. It seeks to shift the focus from categorizing human beings as illegal immigrants to recognizing their inherent human rights and the complexities of their circumstances. As a complex social phenomenon, law has been a crucial instrument in shaping, regulating and governing human societies and vice versa. The law has now become a humongous political project of the modern majoritarian regimes to democratically illegitimize and illegalize the unpopular sections and minorities. Drawing from the theoretical frameworks of dialectics, the paper explores the philosophical underpinnings of the historical evolution and dynamic nature of modern law. The paper employs a phenomenological approach to analyze the dialectical relations between individuals, societies, and legal systems, aiming to shed light on the ethical and political implications of these interactions. By examining the historical essence of law, its relationship with social and cultural norms, and the role of power dynamics, this article argues for constantly maintaining the dialectics of law—the dynamic interplay between legal norms, social practices, cultural values, and historical contexts through a philosophical and phenomenological lens, in order to bridge the gap between universal principles and particular contexts. The paper will shed light to the dialectics of the law in the context of instances of the legal persecutions of the modern secular democracies such as Citizenship Amendment Act-2019, India.Keywords: phenomenology, dialectic, modern law, politics, resistance, margins
Procedia PDF Downloads 562401 Influence of Internal Topologies on Components Produced by Selective Laser Melting: Numerical Analysis
Authors: C. Malça, P. Gonçalves, N. Alves, A. Mateus
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Regardless of the manufacturing process used, subtractive or additive, material, purpose and application, produced components are conventionally solid mass with more or less complex shape depending on the production technology selected. Aspects such as reducing the weight of components, associated with the low volume of material required and the almost non-existent material waste, speed and flexibility of production and, primarily, a high mechanical strength combined with high structural performance, are competitive advantages in any industrial sector, from automotive, molds, aviation, aerospace, construction, pharmaceuticals, medicine and more recently in human tissue engineering. Such features, properties and functionalities are attained in metal components produced using the additive technique of Rapid Prototyping from metal powders commonly known as Selective Laser Melting (SLM), with optimized internal topologies and varying densities. In order to produce components with high strength and high structural and functional performance, regardless of the type of application, three different internal topologies were developed and analyzed using numerical computational tools. The developed topologies were numerically submitted to mechanical compression and four point bending testing. Finite Element Analysis results demonstrate how different internal topologies can contribute to improve mechanical properties, even with a high degree of porosity relatively to fully dense components. Results are very promising not only from the point of view of mechanical resistance, but especially through the achievement of considerable variation in density without loss of structural and functional high performance.Keywords: additive manufacturing, internal topologies, porosity, rapid prototyping, selective laser melting
Procedia PDF Downloads 3312400 Vehicle Activity Characterization Approach to Quantify On-Road Mobile Source Emissions
Authors: Hatem Abou-Senna, Essam Radwan
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Transportation agencies and researchers in the past have estimated emissions using one average speed and volume on a long stretch of roadway. Other methods provided better accuracy utilizing annual average estimates. Travel demand models provided an intermediate level of detail through average daily volumes. Currently, higher accuracy can be established utilizing microscopic analyses by splitting the network links into sub-links and utilizing second-by-second trajectories to calculate emissions. The need to accurately quantify transportation-related emissions from vehicles is essential. This paper presents an examination of four different approaches to capture the environmental impacts of vehicular operations on a 10-mile stretch of Interstate 4 (I-4), an urban limited access highway in Orlando, Florida. First, (at the most basic level), emissions were estimated for the entire 10-mile section 'by hand' using one average traffic volume and average speed. Then, three advanced levels of detail were studied using VISSIM/MOVES to analyze smaller links: average speeds and volumes (AVG), second-by-second link drive schedules (LDS), and second-by-second operating mode distributions (OPMODE). This paper analyzes how the various approaches affect predicted emissions of CO, NOx, PM2.5, PM10, and CO2. The results demonstrate that obtaining precise and comprehensive operating mode distributions on a second-by-second basis provides more accurate emission estimates. Specifically, emission rates are highly sensitive to stop-and-go traffic and the associated driving cycles of acceleration, deceleration, and idling. Using the AVG or LDS approach may overestimate or underestimate emissions, respectively, compared to an operating mode distribution approach.Keywords: limited access highways, MOVES, operating mode distribution (OPMODE), transportation emissions, vehicle specific power (VSP)
Procedia PDF Downloads 3392399 Judging Restoration Success of Kamisaigo River Japan
Authors: Rita Lopa, Yukihiro Shimatani
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The focus of this research is 880m extension development along the Kamisaigo River. The river is flowing tributary of grade 2 rivers Fukutsu City, Fukuoka Prefecture. This river is a small-scale urban river and the river was formerly a straight concrete sea wall construction. The river runs through National Highway No. 3 from the confluence of Saigo River. The study covers the river basin about 326 ha with a catchment area of 20.63 ha and 4,700 m3 capacity regulating pond. The river is not wide, shallow, and has a straight alignment with active (un-vegetated) river channel sinuosity (ratio of river length to valley length) ranging between 1 and 1.3. However, the alignment of the low-flow river channel does have meandering or sinuous characteristics. Flooding is likely to occur. It has become difficult to live in the environment for organisms of the river. Hydrophilic is very low (children cannot play). There is little connection with the local community. Overall, the Kamisaigo River watershed is heavily urbanized and from a morphological, biological and habitat perspective, Kamisaigo River functions marginally not well. For river improvement and maintenance of the Kamisaigo River, the workshop was conducted in the form of planning for the proposed model is presented by the Watershed Management Laboratory. This workshop showed the relationship between citizens, City Government, and University of mutual trust has been established, that have been made landscape, environment, usage, etc.: retaining wall maintenance, hydrophilic zone, landscape zone, nature walks zone: adjacent medical facilities and adjacent to large commercial facilities. Propose of Nature walks zone with point of the design: provide slope that the wheelchair can access and walking paths to enjoy the scenery, and summary of the Kamisaigo River workshop: creating a multi-model study and creation of natural rivers.Keywords: river restoration, river improvement, natural rivers, Saigo River
Procedia PDF Downloads 3572398 Structural Characterization of TIR Domains Interaction
Authors: Sara Przetocka, Krzysztof Żak, Grzegorz Dubin, Tadeusz Holak
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Toll-like receptors (TLRs) play central role in the innate immune response and inflammation by recognizing pathogen-associated molecular patterns (PAMPs). A fundamental basis of TLR signalling is dependent upon the recruitment and association of adaptor molecules that contain the structurally conserved Toll/interleukin-1 receptor (TIR) domain. MyD88 (myeloid differentiation primary response gene 88) is the universal adaptor for TLRs and cooperates with Mal (MyD88 adapter-like protein, also known as TIRAP) in TLR4 response which is predominantly used in inflammation, host defence and carcinogenesis. Up to date two possible models of MyD88, Mal and TLR4 interactions have been proposed. The aim of our studies is to confirm or abolish presented models and accomplish the full structural characterisation of TIR domains interaction. Using molecular cloning methods we obtained several construct of MyD88 and Mal TIR domain with GST or 6xHis tag. Gel filtration method as well as pull-down analysis confirmed that recombinant TIR domains from MyD88 and Mal are binding in complexes. To examine whether obtained complexes are homo- or heterodimers we carried out cross-linking reaction of TIR domains with BS3 compound combined with mass spectrometry. To investigate which amino acid residues are involved in this interaction the NMR titration experiments were performed. 15N MyD88-TIR solution was complemented with non-labelled Mal-TIR. The results undoubtedly indicate that MyD88-TIR interact with Mal-TIR. Moreover 2D spectra demonstrated that simultaneously Mal-TIR self-dimerization occurs which is necessary to create proper scaffold for Mal-TIR and MyD88-TIR interaction. Final step of this study will be crystallization of MyD88 and Mal TIR domains complex. This crystal structure and characterisation of its interface will have an impact in understanding the TLR signalling pathway and possibly will be used in development of new anti-cancer treatment.Keywords: cancer, MyD88, TIR domains, Toll-like receptors
Procedia PDF Downloads 2962397 Applications of Multivariate Statistical Methods on Geochemical Data to Evaluate the Hydrocarbons Source Rocks and Oils from Ghadames Basin, NW Libya
Authors: Mohamed Hrouda
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The Principal Component Analysis (PCA) was performed on a dataset comprising 41 biomarker concentrations from twenty-three core source rocks samples and seven oil samples from different location, with the objective of establishing the major sources of variance within the steranes, tricyclic terpanes, hopanes, and triaromatic steroid. This type of analysis can be used as an aid when deciding which molecular biomarker maturity, source facies or depositional environment parameters should be plotted, because the principal component loadings plots tend to extract the biomarker variables related to maturity, source facies or depositional environment controls. Facies characterization of the source rock samples separate the Silurian and Devonian source rock samples into three groups. Maturity evaluation of source rock samples based on biomarker and aromatic hydrocarbon distributions indicates that not all the samples are strongly affected by maturity, the Upper Devonian samples from wells located in the northern part of the basin are immature, whereas the other samples which have been selected from the Lower Silurian are mature and have reached the main stage of the oil window, the Lower Silurian source rock strata revealed a trend of increasing maturity towards the south and southwestern part of Ghadames Basin. Most of the facies-based parameters employed in this project using biomarker distributions clearly separate the oil samples into three groups. Group I contain oil samples from wells within Al-Wafa oil field Located in the south western part of the basin, Group II contains oil samples collected from Al-Hamada oil field complex in the south and the third group contains oil samples collected from oil fields located in the northKeywords: Ghadamis basin, geochemistry, silurian, devonian
Procedia PDF Downloads 622396 Food Insecurity and Mental Health among Adolescents in Southwest Ethiopia: Structural Equation Modeling Analysis
Authors: Mulusew G. Jebena, David Lindstrom, Tefera Belachew, Craig Hadley, Carl Lachat, Patrick Kolsteren
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Background: The biological and psychosocial consequence of food insecurity on physical health and nutritional status has been reported. But, its effect on mental health during adolescence remains unexplored. Thus, the main aim of this analysis is to examine the mechanism by which food insecurity is linked to mental health among adolescents living in Jimma, Southwest Ethiopia. Methods: We used data from third round observation of Jimma Longitudinal Family and Youth Survey (JLFSY). A total of 1,521 adolescents included for the main analysis. Food insecurity was measured using 5-items scale and The Self Reporting Questionnaire (SRQ-20) was used to measure mental distress. Structural equation modeling analysis was done using maximum likelihood estimation method. Model diagnostics test was reported. All p values were two tailed and P value ≤ 0.05 was used to determine statistical significance. Results: The prevalence of mental distress was 20.8%, 95% CI: (18.8, 22.9). After adjusted for covariates, the final model depicts food insecurity was associated with adolescent mental distress (β=.324). This analysis showed 94.1% of the effect of food insecurity on mental distress is direct. By contrast, 5.9% of the food insecurity effect is mediated by physical health. In addition, Self-rated health (β=.356), socioeconomic status (β=-.078) parental educational (β= .170), living in urban (β= .193) and female headed household (β=.205) were associated with adolescent mental distress. Conclusions: This finding highlights the direct effect of food insecurity on adolescent mental distress. Therefore, any intervention aimed to improve mental distress of adolescents should consider strategies to improve access to sufficient, safe, and nutritious food. Beside this, prevention of underlying factors such as psychosomatic health illness and improving socio economic status is also very critical. Furthermore longitudinal relationship of the long term effect of food insecurity on mental health should be investigated.Keywords: adolescent, Ethiopia, food insecurity, mental health
Procedia PDF Downloads 5962395 Making Permanent Supportive Housing Work for Vulnerable Populations
Authors: Olayinka Ariba, Abe Oudshoorn, Steve Rolfe, Carrie Anne Marshall, Deanna Befus, Jason Gilliland, Miranda Crockett, Susana Caxaj, Sarah McLean, Amy Van Berkum, Natasha Thuemler
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Background: Secure housing is a platform for health and well-being. Those who struggle with housing stability have complex life and health histories and often require some support services such as the provision of permanent supportive housing. Poor access to supportive resources creates an exacerbation of chronic homelessness, particularly affecting individuals who need immediate access to mental health and addiction supports. This paper presents the first phase of a three-part study examining how on-site support impacts housing stability for recently-re-housed persons. Method: This study utilized a community-based participatory research methodology. Twenty in-depth interviews were conducted with permanent supportive housing residents from a single-site dwelling. Interpretative description analysis was used to draw common themes and understand the experiences and challenges of housing support. Results: Three interconnected themes were identified: 1) Available and timely supports; 2) Affordability; and 3) Community, but with independence as desired. These interconnected components are helping residents transition from homelessness or long-term mental health inpatient care to live in the community. Despite some participant concerns about resident conflicts, staff availability, and affordability, this has been a welcome and successful move for most. Conclusion: Supportive housing is essential for successful tenancies as a platform for health and well-being among Canada’s most vulnerable and, from the perspective of persons recently re-housed, permanent supportive housing is a worthwhile investment.Keywords: homelessness, supportive housing, rehoused, housing stability
Procedia PDF Downloads 1062394 Mapping Iron Content in the Brain with Magnetic Resonance Imaging and Machine Learning
Authors: Gabrielle Robertson, Matthew Downs, Joseph Dagher
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Iron deposition in the brain has been linked with a host of neurological disorders such as Alzheimer’s, Parkinson’s, and Multiple Sclerosis. While some treatment options exist, there are no objective measurement tools that allow for the monitoring of iron levels in the brain in vivo. An emerging Magnetic Resonance Imaging (MRI) method has been recently proposed to deduce iron concentration through quantitative measurement of magnetic susceptibility. This is a multi-step process that involves repeated modeling of physical processes via approximate numerical solutions. For example, the last two steps of this Quantitative Susceptibility Mapping (QSM) method involve I) mapping magnetic field into magnetic susceptibility and II) mapping magnetic susceptibility into iron concentration. Process I involves solving an ill-posed inverse problem by using regularization via injection of prior belief. The end result from Process II highly depends on the model used to describe the molecular content of each voxel (type of iron, water fraction, etc.) Due to these factors, the accuracy and repeatability of QSM have been an active area of research in the MRI and medical imaging community. This work aims to estimate iron concentration in the brain via a single step. A synthetic numerical model of the human head was created by automatically and manually segmenting the human head on a high-resolution grid (640x640x640, 0.4mm³) yielding detailed structures such as microvasculature and subcortical regions as well as bone, soft tissue, Cerebral Spinal Fluid, sinuses, arteries, and eyes. Each segmented region was then assigned tissue properties such as relaxation rates, proton density, electromagnetic tissue properties and iron concentration. These tissue property values were randomly selected from a Probability Distribution Function derived from a thorough literature review. In addition to having unique tissue property values, different synthetic head realizations also possess unique structural geometry created by morphing the boundary regions of different areas within normal physical constraints. This model of the human brain is then used to create synthetic MRI measurements. This is repeated thousands of times, for different head shapes, volume, tissue properties and noise realizations. Collectively, this constitutes a training-set that is similar to in vivo data, but larger than datasets available from clinical measurements. This 3D convolutional U-Net neural network architecture was used to train data-driven Deep Learning models to solve for iron concentrations from raw MRI measurements. The performance was then tested on both synthetic data not used in training as well as real in vivo data. Results showed that the model trained on synthetic MRI measurements is able to directly learn iron concentrations in areas of interest more effectively than other existing QSM reconstruction methods. For comparison, models trained on random geometric shapes (as proposed in the Deep QSM method) are less effective than models trained on realistic synthetic head models. Such an accurate method for the quantitative measurement of iron deposits in the brain would be of important value in clinical studies aiming to understand the role of iron in neurological disease.Keywords: magnetic resonance imaging, MRI, iron deposition, machine learning, quantitative susceptibility mapping
Procedia PDF Downloads 1372393 Impact of Maternal Nutrition on Newborn Anthropometry and Hemoglobin
Authors: Vinay Mishra, Meena Malkani
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Objectives: To study the effect of physical maternal nutritional markers (viz. weight, height, gestational weight gain, BMI) and third-trimester haemoglobin concentration on anthropometry and cord blood haemoglobin of their newborn. Methods: Study area: Post-natal ward of a tertiary care hospital in an urban area. Study population: All post-partum women and their newborns. Sample size: 100. Maternal and neonatal data and anthropometric measurements were recorded in semi-structured case proforma. Data analysis: The data obtained was analysed using SPSS 20 software.The comparison between the groups was done using One-Way Analysis of Variance for two groups. For more than two groups comparisons further posthoc analysis was done using Tukey test. Pearson correlation coefficient was used for correlating the variables. A P value less than 0.05 was considered significant. Results: 1. Out of the 100 studied mothers, 52% were anaemic. 2. Cord blood haemoglobin values decreased significantly with the order of birth. 3. Cord blood haemoglobin of normal-weight newborns is significantly higher as compared to that of LBW newborns. 4. Cord blood haemoglobin has strong statistical significance with maternal anaemia. 5. Pre-pregnancy weight and gestational weight gain significantly influence the neonates anthropometry. Conclusions: 1. Birth order has a prominent inverse effect on the cord blood haemoglobin. 2. Majority of the expectant mothers are anaemic and give birth to LBW babies with reduced anthropometric markers. 3. Pre-pregnancy weight, height and gestational weight gain has a very significant impact on the neonatal anthropometry. 4. Thus, maternal nutrition during gestation and during the crucial periods of growth in the pre-child bearing age group has a very significant impact on foetal development.Keywords: maternal nutrition, anthropometry, cord blood hemoglobin, newborn
Procedia PDF Downloads 3922392 Holistic Approach to Assess the Potential of Using Traditional and Advance Insulation Materials for Energy Retrofit of Office Buildings
Authors: Marco Picco, Mahmood Alam
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Improving the energy performance of existing buildings can be challenging, particularly when facades cannot be modified, and the only available option is internal insulation. In such cases, the choice of the most suitable material becomes increasingly complex, as in addition to thermal transmittance and capital cost, the designer needs to account for the impact of the intervention on the internal spaces, and in particular the loss of usable space due to the additional layers of materials installed. This paper explores this issue by analysing a case study of an average office building needing to go through a refurbishment in order to reach the limits imposed by current regulations to achieve energy efficiency in buildings. The building is simulated through dynamic performance simulation under three different climate conditions in order to evaluate its energy needs. The use of Vacuum Insulated Panels as an option for energy refurbishment is compared to traditional insulation materials (XPS, Mineral Wool). For each scenario, energy consumptions are calculated and, in combination with their expected capital costs, used to perform a financial feasibility analysis. A holistic approach is proposed, taking into account the impact of the intervention on internal space by quantifying the value of the lost usable space and used in the financial feasibility analysis. The proposed approach highlights how taking into account different drivers will lead to the choice of different insulation materials, showing how accounting for the economic value of space can make VIPs an attractive solution for energy retrofitting under various climate conditions.Keywords: vacuum insulated panels, building performance simulation, payback period, building energy retrofit
Procedia PDF Downloads 1542391 Unpacking the Summarising Event in Trauma Emergencies: The Case of Pre-briefings
Authors: Professor Jo Angouri, Polina Mesinioti, Chris Turner
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In order for a group of ad-hoc professional to perform as a team, a shared understanding of the problem at hand and an agreed action plan are necessary components. This is particularly significant in complex, time sensitive professional settings such as in trauma emergencies. In this context, team briefings prior to the patient arrival (pre-briefings) constitute a critical event for the performance of the team; they provide the necessary space for co-constructing a shared understanding of the situation through summarising information available to the team: yet the act of summarising is widely assumed in medical practice but not systematically researched. In the vast teamwork literature, terms such as ‘shared mental model’, ‘mental space’ and ‘cognate labelling’ are used extensively, and loosely, to denote the outcome of the summarising process, but how exactly this is done interactionally remains under researched. This paper reports on the forms and functions of pre-briefings in a major trauma centre in the UK. Taking an interactional approach, we draw on 30 simulated and real-life trauma emergencies (15 from each dataset) and zoom in on the use of pre-briefings, which we consider focal points in the management of trauma emergencies. We show how ad hoc teams negotiate sharedness of future orientation through summarising, synthesising information, and establishing common understanding of the situation. We illustrate the role, characteristics, and structure of pre-briefing sequences that have been evaluated as ‘efficient’ in our data and the impact (in)effective pre-briefings have on teamwork. Our work shows that the key roles in the event own the act of summarising and we problematise the implications for leadership in trauma emergencies. We close the paper with a model for pre-briefing and provide recommendations for clinical practice, arguing that effective pre-briefing practice is teachable.Keywords: summarising, medical emergencies, interaction analysis, shared/mental models
Procedia PDF Downloads 942390 The Aesthetics of Time in Thus Spoke Zarathustra: A Reappraisal of the Eternal Recurrence of the Same
Authors: Melanie Tang
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According to Nietzsche, the eternal recurrence is his most important idea. However, it is perhaps his most cryptic and difficult to interpret. Early readings considered it as a cosmological hypothesis about the cyclic nature of time. However, following Nehamas’s ‘Life as Literature’ (1985), it has become a widespread interpretation that the eternal recurrence never really had any theoretical dimensions, and is not actually a philosophy of time, but a practical thought experiment intended to measure the extent to which we have mastered and perfected our lives. This paper endeavours to challenge this line of thought becoming scholarly consensus, and to carry out a more complex analysis of the eternal recurrence as it is presented in Thus Spoke Zarathustra. In its wider scope, this research proposes that Thus Spoke Zarathustra — as opposed to The Birth of Tragedy — be taken as the primary source for a study of Nietzsche’s Aesthetics, due to its more intrinsic aesthetic qualities and expressive devices. The eternal recurrence is the central philosophy of a work that communicates its ideas in unprecedentedly experimental and aesthetic terms, and a more in-depth understanding of why Nietzsche chooses to present his conception of time in aesthetic terms is warranted. Through hermeneutical analysis of Thus Spoke Zarathustra and engagement with secondary sources such as those by Nehamas, Karl Löwith, and Jill Marsden, the present analysis challenges the ethics of self-perfection upon which current interpretations of the recurrence are based, as well as their reliance upon a linear conception of time. Instead, it finds the recurrence to be a cyclic interplay between the self and the world, rather than a metric pertaining solely to the self. In this interpretation, time is found to be composed of an intertemporal rather than linear multitude of will to power, which structures itself through tensional cycles into an experience of circular time that can be seen to have aesthetic dimensions. In putting forth this understanding of the eternal recurrence, this research hopes to reopen debate on this key concept in the field of Nietzsche studies.Keywords: Nietzsche, eternal recurrence, Zarathustra, aesthetics, time
Procedia PDF Downloads 1502389 Culture and Mental Health in Nigeria: A Qualitative Study of Berom, Hausa, Yoruba and Igbo Cultural Beliefs
Authors: Dung Jidong, Rachel Tribe, Poul Rohlerder, Aneta Tunariu
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Cultural understandings of mental health problems are frequently overshadowed by the western conceptualizations. Research on culture and mental health in the Nigerian context seems to be lacking. This study examined the linguistic understandings and cultural beliefs that have implications for mental health among the Berom, Hausa, Yoruba and Igbo people of Nigeria. A purposive sample of 53 participants underwent semi-structured interviews that lasted approximately 55 minutes each. Of the N=53 participants, n=26 were psychology-aligned practitioners and n=27 ‘laypersons’. Participants were recruited from four states in Nigeria, Plateau, Kaduna, Ekiti, and Enugu. All participants were self-identified as members of their ethnic groups who speak and understand their native-languages, cultural beliefs, and also are domiciled within their ethnic communities. Thematic analysis using socio-constructionism from a critical-realist position was employed to explore the participants’ beliefs about mental health, and the clash between western trained practitioners’ views and the cultural beliefs of the ‘laypersons’. Data analysis found three main themes that re-emerged across the four ethnic samples: (i) beliefs about mental health problems as a spiritual curse (ii) traditional and religious healing are used more often than western mental health care (iii) low levels of mental health awareness. In addition, the Nigerian traditional and religious healing are also revealed to be helpful as the practice gives prominence to the native-languages, religious and cultural values. However, participants described the role of ‘false’ traditional or religious healers in communities as being potentially harmful. Finally, due to the current lack of knowledge about mental health problems, awareness creation and re-orientation may be beneficial for both rural and urban Nigerian communities.Keywords: beliefs cultures, health mental, languages religions, values
Procedia PDF Downloads 2842388 Drawing Building Blocks in Existing Neighborhoods: An Automated Pilot Tool for an Initial Approach Using GIS and Python
Authors: Konstantinos Pikos, Dimitrios Kaimaris
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Although designing building blocks is a procedure used by many planners around the world, there isn’t an automated tool that will help planners and designers achieve their goals with lesser effort. The difficulty of the subject lies in the repeating process of manually drawing lines, while not only it is mandatory to maintain the desirable offset but to also achieve a lesser impact to the existing building stock. In this paper, using Geographical Information Systems (GIS) and the Python programming language, an automated tool integrated into ArcGIS PRO, is being presented. Despite its simplistic enviroment and the lack of specialized building legislation due to the complex state of the field, a planner who is aware of such technical information can use the tool to draw an initial approach of the final building blocks in an area with pre-existing buildings in an attempt to organize the usually sprawling suburbs of a city or any continuously developing area. The tool uses ESRI’s ArcPy library to handle the spatial data, while interactions with the user is made throught Tkinter. The main process consists of a modification of building edgescoordinates, using NumPy library, in an effort to draw the line of best fit, so the user can get the optimal results per block’s side. Finally, after the tool runs successfully, a table of primary planning information is shown, such as the area of the building block and its coverage rate. Regardless of the primary stage of the tool’s development, it is a solid base where potential planners with programming skills could invest, so they can make the tool adapt to their individual needs. An example of the entire procedure in a test area is provided, highlighting both the strengths and weaknesses of the final results.Keywords: arcPy, GIS, python, building blocks
Procedia PDF Downloads 1792387 Evaluating the Impact of Future Scenarios on Water Availability and Demand Based on Stakeholders Prioritized Water Management Options in the Upper Awash Basin, Ethiopia
Authors: Adey Nigatu Mersha, Ilyas Masih, Charlotte de Fraiture, Tena Alamirew
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Conflicts over water are increasing mainly as a result of water scarcity in response to higher water demand and climatic variability. There is often not enough water to meet all demands for different uses. Thus, decisions have to be made as to how the available resources can be managed and utilized. Correspondingly water allocation goals, practically national water policy goals, need to be revised accordingly as the pressure on water increases from time to time. A case study is conducted in the Upper Awash Basin, Ethiopia, to assess and evaluate prioritized comprehensive water demand management options based on the framework of integrated water resources management in account of stakeholders’ knowledge and preferences as well as practical prominence within the Upper Awash Basin. Two categories of alternative management options based on policy analysis and stakeholders' consultation were evaluated against the business-as-usual scenario by using WEAP21 model as an analytical tool. Strong effects on future (unmet) demands are observed with major socio-economic assumptions and forthcoming water development plans. Water management within the basin will get more complex with further abstraction which may lead to an irreversible damage to the ecosystem. It is further confirmed through this particular study that efforts to maintain users’ preferences alone cannot insure economically viable and environmentally sound development and vice versa. There is always a tradeoff between these factors. Hence, all of these facets must be analyzed separately, related with each other in equal footing, and ultimately taken up in decision making in order for the whole system to function properly.Keywords: water demand, water availability, WEAP21, scenarios
Procedia PDF Downloads 2812386 The Role of Institutions in Community Wildlife Conservation in Zimbabwe
Authors: Herbert Ntuli, Edwin Muchapondwa
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This study used a sample of 336 households and community level data from 30 communities around the Gonarezhou National Park in Zimbabwe to analyse the association between ability to self-organize or cooperation and institutions on one hand and the relationship between success of biodiversity outcomes and cooperation on the other hand. Using both the ordinary least squares and instrumental variables estimation with heteroskedasticity-based instruments, our results confirmed that sound institutions are indeed an important ingredient for cooperation in the respective communities and cooperation positively and significantly affects biodiversity outcomes. Group size, community level trust, the number of stakeholders and punishment were found to be important variables explaining cooperation. From a policy perspective, our results show that external enforcement of rules and regulations does not necessarily translate into sound ecological outcomes but better outcomes are attainable when punishment is rather endogenized by local communities. This seems to suggest that communities should rather be supported in such a way that robust institutions that are tailor made to suit the needs of local condition will emerge that will in turn facilitate good environmental husbandry. Cooperation, training, benefits, distance from the nearest urban canter, distance from the fence, social capital average age of household head, fence and information sharing were found to be very important variables explaining the success of biodiversity outcomes ceteris paribus. Government programmes should target capacity building in terms of institutional capacity and skills development in order to have a positive impact on biodiversity. Hence, the role of stakeholders (e.g., NGOs) in capacity building and government effort should complement each other to ensure that the necessary resources are mobilized and all communities receive the necessary training and resources.Keywords: institutions, self-organize, common pool resources, wildlife, conservation, Zimbabwe
Procedia PDF Downloads 2812385 Dynamic Analysis of Mono-Pile: Spectral Element Method
Authors: Rishab Das, Arnab Banerjee, Bappaditya Manna
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Mono-pile foundations are often used in soft soils in order to support heavy mega-structures, whereby often these deep footings may undergo dynamic excitation due to many causes like earthquake, wind or wave loads acting on the superstructure, blasting, and unbalanced machines, etc. A comprehensive analytical study is performed to study the dynamics of the mono-pile system embedded in cohesion-less soil. The soil is considered homogeneous and visco-elastic in nature and is analytically modeled using complex springs. Considering the N number of the elements of the pile, the final global stiffness matrix is obtained by using the theories of the spectral element matrix method. Further, statically condensing the intermediate internal nodes of the global stiffness matrix results to a smaller sub matrix containing the nodes experiencing the external translation and rotation, and the stiffness and damping functions (impedance functions) of the embedded piles are determined. Proper plots showing the variation of the real and imaginary parts of these impedance functions with the dimensionless frequency parameter are obtained. The plots obtained from this study are validated by that provided by Novak,1974. Further, the dynamic analysis of the resonator impregnated pile is proposed within this study. Moreover, with the aid of Wood's 1g laboratory scaling law, a proper scaled-down resonator-pile model is 3D printed using PLA material. Dynamic analysis of the scaled model is carried out in the time domain, whereby the lateral loads are imposed on the pile head. The response obtained from the sensors through the LabView software is compared with the proposed theoretical data.Keywords: mono-pile, visco-elastic, impedance, LabView
Procedia PDF Downloads 1182384 Free Vibration Analysis of Timoshenko Beams at Higher Modes with Central Concentrated Mass Using Coupled Displacement Field Method
Authors: K. Meera Saheb, K. Krishna Bhaskar
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Complex structures used in many fields of engineering are made up of simple structural elements like beams, plates etc. These structural elements, sometimes carry concentrated masses at discrete points, and when subjected to severe dynamic environment tend to vibrate with large amplitudes. The frequency amplitude relationship is very much essential in determining the response of these structural elements subjected to the dynamic loads. For Timoshenko beams, the effects of shear deformation and rotary inertia are to be considered to evaluate the fundamental linear and nonlinear frequencies. A commonly used method for solving vibration problem is energy method, or a finite element analogue of the same. In the present Coupled Displacement Field method the number of undetermined coefficients is reduced to half when compared to the famous Rayleigh Ritz method, which significantly simplifies the procedure to solve the vibration problem. This is accomplished by using a coupling equation derived from the static equilibrium of the shear flexible structural element. The prime objective of the present paper here is to study, in detail, the effect of a central concentrated mass on the large amplitude free vibrations of uniform shear flexible beams. Accurate closed form expressions for linear frequency parameter for uniform shear flexible beams with a central concentrated mass was developed and the results are presented in digital form.Keywords: coupled displacement field, coupling equation, large amplitude vibrations, moderately thick plates
Procedia PDF Downloads 2262383 The Effect of Incorporating Animal Assisted Interventions with Trauma Focused Cognitive Behavioral Therapy
Authors: Kayla Renteria
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This study explored the role animal-assisted psychotherapy (AAP) can play in treating Post-Traumatic Stress Disorder (PTSD) when incorporated into Trauma-informed cognitive behavioral therapy (TF-CBT). A review of the literature was performed to show how incorporating AAP could benefit TF-CBT since this treatment model often presents difficulties, such as client motivation and avoidance of the exposure element of the intervention. In addition, the fluidity of treatment goals during complex trauma cases was explored, as this issue arose in the case study. This study follows the course of treatment of a 12-year-old female presenting with symptoms of PTSD. Treatment consisted of traditional components of the TF-CBT model, with the added elements of AAP to address typical treatment obstacles in TF-CBT. A registered therapy dog worked with the subject in all sessions throughout her treatment. The therapy dog was incorporated into components such as relaxation and coping techniques, narrative therapy techniques, and psychoeducation on the cognitive triangle. Throughout the study, the client’s situation and clinical needs required the therapist to switch goals to focus on current safety and stability. The therapy dog provided support and neurophysiological benefits to the client through AAP during this shift in treatment. The client was assessed quantitatively using the Child PTSD Symptom Scale Self Report for DSM-5 (CPSS-SR-5) before and after therapy and qualitatively through a feedback form given after treatment. The participant showed improvement in CPSS-SR-V scores, and she reported that the incorporation of the therapy animal improved her therapy. The results of this study show how the use of AAP provided the client a solid, consistent relationship with the therapy dog that supported her through processing various types of traumas. Implications of the results of treatment and for future research are discussed.Keywords: animal-assisted therapy, trauma-focused cognitive behavioral therapy, PTSD in children, trauma treatment
Procedia PDF Downloads 2182382 Library Screening and Evaluation of Mycobacterium tuberculosis Ketol-Acid Reductoisomerase Inhibitors
Authors: Vagolu S. Krishna, Shan Zheng, Estharla M. Rekha, Luke W. Guddat, Dharmarajan Sriram
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Tuberculosis (TB) remains a major threat to human health. This due to the fact that current drug treatments are less than optimal as well as the rising occurrence of multi drug-resistant and extensively drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mt). Given the wide-spread significance of this disease, we have undertaken a design and evaluation program to discover new anti-TB drug leads. Here, our attention is focused on ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. Importantly, this enzyme is present in bacteria but not in humans, making it an attractive proposition for drug discovery. In the present work, we used high-throughput virtual screening to identify seventeen potential inhibitors of KARI using the Birla Institute of Technology and Science in-house database. Compounds were selected based on high docking scores, which were assigned as the result of favourable interactions between the compound and the active site of KARI. The Ki values for two leads, compounds 14 and 16 are 3.71 and 3.06 µM, respectively for Mt KARI. To assess the mode of binding, 100 ns molecular dynamics simulations for these two compounds in association with Mt KARI were performed and showed that the complex was stable with an average RMSD of less than 2.5 Å for all atoms. Compound 16 showed an MIC of 2.06 ± 0.91 µM and a 1.9 fold logarithmic reduction in the growth of Mt in an infected macrophage model. The two compounds exhibited low toxicity against murine macrophage RAW 264.7 cell lines. Thus, both compounds are promising candidates for development as an anti-TB drug leads.Keywords: ketol-acid reductoisomerase, macrophage, molecular docking and dynamics, tuberculosis
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