Search results for: William Selvamurthy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 203

Search results for: William Selvamurthy

83 Sleep Disturbance in Indonesian School-Aged Children and Its Relationship to Nutritional Aspect

Authors: William Cheng, Rini Sekartini

Abstract:

Background: Sleep is essential for children because it provides enhancement for the neural system activities that give physiologic effects for the body to support growth and development. One of the modifiable factors that relates with sleep is nutrition, which includes nutritional status, iron intake, and magnesium intake. Nutritional status represents the balance between nutritional intake and expenditure, while iron and magnesium are micronutrients that are related to sleep regulation. The aim of this study is to identify prevalence of sleep disturbance among Indonesian children and to evaluate its relation with aspect to nutrition. Methods : A cross-sectional study involving children aged 5 to 7-years-old in an urban primary health care between 2012 and 2013 was carried out. Related data includes anthropometric status, iron intake, and magnesium intake. Iron and magnesium intake was obtained by 24-hours food recall procedure. Sleep Disturbance Scale for Children (SDSC) was used as the diagnostic tool for sleep disturbance, with score under 39 indicating presence of problem. Results: Out of 128 school-aged children included in this study, 28 (23,1%) of them were found to have sleep disturbance. The majority of children had good nutritional status, with only 15,7% that were severely underweight or underweight, and 12,4% that were identified as stunted. On the contrary, 99 children (81,8%) were identified to have inadequate magnesium intake and 56 children (46,3%) with inadequate iron intake. Our analysis showed there was no significant relation between all of the nutritional status indicators and sleep disturbance (p>0,05%). Moreover, inadequate iron and magnesium intake also failed to prove significant relation with sleep disturbance in this population. Conclusion: Almost fourth of school-aged children in Indonesia were found to have sleep disturbance and further study are needed to overcome this problem. According to our finding, there is no correlation between nutritional status, iron intake, magnesium intake, and sleep disturbance.

Keywords: iron intake, magnesium intake, nutritional status, school-aged children, sleep disturbance

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82 A Rapid Prototyping Tool for Suspended Biofilm Growth Media

Authors: Erifyli Tsagkari, Stephanie Connelly, Zhaowei Liu, Andrew McBride, William Sloan

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Biofilms play an essential role in treating water in biofiltration systems. The biofilm morphology and function are inextricably linked to the hydrodynamics of flow through a filter, and yet engineers rarely explicitly engineer this interaction. We develop a system that links computer simulation and 3-D printing to optimize and rapidly prototype filter media to optimize biofilm function with the hypothesis that biofilm function is intimately linked to the flow passing through the filter. A computational model that numerically solves the incompressible time-dependent Navier Stokes equations coupled to a model for biofilm growth and function is developed. The model is imbedded in an optimization algorithm that allows the model domain to adapt until criteria on biofilm functioning are met. This is applied to optimize the shape of filter media in a simple flow channel to promote biofilm formation. The computer code links directly to a 3-D printer, and this allows us to prototype the design rapidly. Its validity is tested in flow visualization experiments and by microscopy. As proof of concept, the code was constrained to explore a small range of potential filter media, where the medium acts as an obstacle in the flow that sheds a von Karman vortex street that was found to enhance the deposition of bacteria on surfaces downstream. The flow visualization and microscopy in the 3-D printed realization of the flow channel validated the predictions of the model and hence its potential as a design tool. Overall, it is shown that the combination of our computational model and the 3-D printing can be effectively used as a design tool to prototype filter media to optimize biofilm formation.

Keywords: biofilm, biofilter, computational model, von karman vortices, 3-D printing.

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81 Bionaut™: A Microrobotic Drug-Device Platform for the Local Treatment of Brainstem Gliomas

Authors: Alex Kiselyov, Suehyun Cho, Darrell Harrington; Florent Cros, Olin Palmer, John Caputo, Michael Kardosh, Eran Oren, William Loudon, Michael Shpigelmacher

Abstract:

Despite the most aggressive surgical and adjuvant therapeutic strategies, treatment of both pediatric and adult brainstem tumors remains problematic. Novel strategies, including targeted biologics, immunotherapy, and specialized delivery systems such as convection-enhanced delivery (CED), have been proposed. While some of these novel treatments are entering phase I trials, the field is still in need of treatment(s) that exhibits dramatically enhanced potency with optimal therapeutic ratio. Bionaut Labs has developed a modular microrobotic platform for performing localized delivery of diverse therapeutics in vivo. Our biocompatible particles (Bionauts™) are externally propelled and visualized in real-time. Bionauts™ are specifically designed to enhance the effect of radiation therapy via anatomically precise delivery of a radiosensitizing agent, as exemplified by temozolomide (TMZ) and Avastin™ to the brainstem gliomas of diverse origin. The treatment protocol is designed to furnish a better therapeutic outcome due to the localized (vs systemic) delivery of the drug to the neoplastic lesion(s) for use as a synergistic combination of radiation and radiosensitizing agent. In addition, the procedure is minimally invasive and is expected to be appropriate for both adult and pediatric patients. Current progress, including platform optimization, selection of the lead radiosensitizer as well as in vivo safety studies of the Bionauts™ in large animals, specifically the spine and the brain of porcine and ovine models, will be discussed.

Keywords: Bionaut, brainstem, glioma, local delivery, micro-robot, radiosensitizer

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80 MAGNI Dynamics: A Vision-Based Kinematic and Dynamic Upper-Limb Model for Intelligent Robotic Rehabilitation

Authors: Alexandros Lioulemes, Michail Theofanidis, Varun Kanal, Konstantinos Tsiakas, Maher Abujelala, Chris Collander, William B. Townsend, Angie Boisselle, Fillia Makedon

Abstract:

This paper presents a home-based robot-rehabilitation instrument, called ”MAGNI Dynamics”, that utilized a vision-based kinematic/dynamic module and an adaptive haptic feedback controller. The system is expected to provide personalized rehabilitation by adjusting its resistive and supportive behavior according to a fuzzy intelligence controller that acts as an inference system, which correlates the user’s performance to different stiffness factors. The vision module uses the Kinect’s skeletal tracking to monitor the user’s effort in an unobtrusive and safe way, by estimating the torque that affects the user’s arm. The system’s torque estimations are justified by capturing electromyographic data from primitive hand motions (Shoulder Abduction and Shoulder Forward Flexion). Moreover, we present and analyze how the Barrett WAM generates a force-field with a haptic controller to support or challenge the users. Experiments show that by shifting the proportional value, that corresponds to different stiffness factors of the haptic path, can potentially help the user to improve his/her motor skills. Finally, potential areas for future research are discussed, that address how a rehabilitation robotic framework may include multisensing data, to improve the user’s recovery process.

Keywords: human-robot interaction, kinect, kinematics, dynamics, haptic control, rehabilitation robotics, artificial intelligence

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79 Alignment and Antagonism in Flux: A Diachronic Sentiment Analysis of Attitudes towards the Chinese Mainland in the Hong Kong Press

Authors: William Feng, Qingyu Gao

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Despite the extensive discussions about Hong Kong’s sentiments towards the Chinese Mainland since the sovereignty transfer in 1997, there has been no large-scale empirical analysis of the changing attitudes in the mainstream media, which both reflect and shape sentiments in the society. To address this gap, the present study uses an optimised semantic-based automatic sentiment analysis method to examine a corpus of news about China from 1997 to 2020 in three main Chinese-language newspapers in Hong Kong, namely Apple Daily, Ming Pao, and Oriental Daily News. The analysis shows that although the Hong Kong press had a positive emotional tone toward China in general, the overall trend of sentiment was becoming increasingly negative. Meanwhile, the alignment and antagonism toward China have both increased, providing empirical evidence of attitudinal polarisation in the Hong Kong society. Specifically, Apple Daily’s depictions of China have become increasingly negative, though with some positive turns before 2008, whilst Oriental Daily News has consistently expressed more favourable sentiments. Ming Pao maintained an impartial stance toward China through an increased but balanced representation of positive and negative sentiments, with its subjectivity and sentiment intensity growing to an industry-standard level. The results provide new insights into the complexity of sentiments towards China in the Hong Kong press and media attitudes in general in terms of the “us” and “them” positioning by explicating the cross-newspaper and cross-period variations using an enhanced sentiment analysis method which incorporates sentiment-oriented and semantic role analysis techniques.

Keywords: media attitude, sentiment analysis, Hong Kong press, one country two systems

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78 A Structure-Switching Electrochemical Aptasensor for Rapid, Reagentless and Single-Step, Nanomolar Detection of C-Reactive Protein

Authors: William L. Whitehouse, Louisa H. Y. Lo, Andrew B. Kinghorn, Simon C. C. Shiu, Julian. A. Tanner

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C-reactive protein (CRP) is an acute-phase reactant and sensitive indicator for sepsis and other life-threatening pathologies, including systemic inflammatory response syndrome (SIRS). Currently, clinical turn-around times for established CRP detection methods take between 30 minutes to hours or even days from centralized laboratories. Here, we report the development of an electrochemical biosensor using redox probe-tagged DNA aptamers functionalized onto cheap, commercially available screen-printed electrodes. Binding-induced conformational switching of the CRP-targeting aptamer induces a specific and selective signal-ON event, which enables single-step and reagentless detection of CRP in as little as 1 minute. The aptasensor dynamic range spans 5-1000nM (R=0.97) or 5-500nM (R=0.99) in 50% diluted human serum, with a LOD of 3nM, corresponding to 2-orders of magnitude sensitivity under the clinically relevant cut-off for CRP. The sensor is stable for up to one week and can be reused numerous times, as judged from repeated real-time dosing and dose-response assays. By decoupling binding events from the signal induction mechanism, structure-switching electrochemical aptamer-based sensors (SS-EABs) provide considerable advantages over their adsorption-based counterparts. Our work expands on the retinue of such sensors reported in the literature and is the first instance of an SS-EAB for reagentless CRP detection. We hope this study can inspire further investigations into the suitability of SS-EABs for diagnostics, which will aid translational R&D toward fully realized devices aimed at point-of-care applications or for use more broadly by the public.

Keywords: structure-switching, C-reactive protein, electrochemical, biosensor, aptasensor.

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77 Teaching Critical Thinking in Post-Conflict Countries: The University of Liberia

Authors: Kamille Beye

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Critical thinking is a topic that has been disputed in the field of education for decades, but many resulting debates have centered around strengthening critical thinking capabilities in the societies, workforces, and educational centers of the global north. In contrast, this paper provides an analysis of the teaching of critical thinking in Liberia, which has been ravaged by years of war and a recent Ebola outbreak. These crises have decimated the Liberian education sector, leading to a loss of teaching capacities that are essential to providing critical thinking education. Until recently, critical thinking had no seat at the table when the future needs of the country were discussed by the government and non-governmental agencies. Now, the University of Liberia has a bold goal to become one of the top twenty universities in West Africa in the next seven years, which has led to a focus on teaching critical thinking skills to improve learning. This paper argues that critical thinking is essential to strengthening not only the Liberian education system, but for promoting peace amongst community members, and yet it suggests that commitments to the teaching of critical thinking in Liberia have hitherto been overly superficial. Based on an initial scoping study, this paper will examine the potential impacts of teaching critical thinking skills to undergraduate students in the William V. S. Tubman School of Education at the University of Liberia on continued peacebuilding and reconstruction efforts of the country. The research contends that if critical thinking skills are taught, practiced and continually utilized, teachers and students will have the ability to engage with information and negotiate challenges to solutions in ways that are beneficial to the communities in which they live. The research will use a variety of methods, that include the California Critical Thinking Disposition Inventory. This research will demonstrate that critical thinking skills are not only needed for entering the workforce, but necessary for negotiating and expressing the needs and desires of local communities in a peaceful way.

Keywords: critical thinking, higher education, Liberia, peacebuilding, post-conflict

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76 High-Risk Gene Variant Profiling Models Ethnic Disparities in Diabetes Vulnerability

Authors: Jianhua Zhang, Weiping Chen, Guanjie Chen, Jason Flannick, Emma Fikse, Glenda Smerin, Yanqin Yang, Yulong Li, John A. Hanover, William F. Simonds

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Ethnic disparities in many diseases are well recognized and reflect the consequences of genetic, behavior, and environmental factors. However, direct scientific evidence connecting the ethnic genetic variations and the disease disparities has been elusive, which may have led to the ethnic inequalities in large scale genetic studies. Through the genome-wide analysis of data representing 185,934 subjects, including 14,955 from our own studies of the African America Diabetes Mellitus, we discovered sets of genetic variants either unique to or conserved in all ethnicities. We further developed a quantitative gene function-based high-risk variant index (hrVI) of 20,428 genes to establish profiles that strongly correlate with the subjects' self-identified ethnicities. With respect to the ability to detect human essential and pathogenic genes, the hrVI analysis method is both comparable with and complementary to the well-known genetic analysis methods, pLI and VIRlof. Application of the ethnicity-specific hrVI analysis to the type 2 diabetes mellitus (T2DM) national repository, containing 20,791 cases and 24,440 controls, identified 114 candidate T2DM-associated genes, 8.8-fold greater than that of ethnicity-blind analysis. All the genes identified are defined as either pathogenic or likely-pathogenic in ClinVar database, with 33.3% diabetes-associated and 54.4% obesity-associated genes. These results demonstrate the utility of hrVI analysis and provide the first genetic evidence by clustering patterns of how genetic variations among ethnicities may impede the discovery of diabetes and foreseeably other disease-associated genes.

Keywords: diabetes-associated genes, ethnic health disparities, high-risk variant index, hrVI, T2DM

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75 Accuracy of Peak Demand Estimates for Office Buildings Using Quick Energy Simulation Tool

Authors: Mahdiyeh Zafaranchi, Ethan S. Cantor, William T. Riddell, Jess W. Everett

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The New Jersey Department of Military and Veteran’s Affairs (NJ DMAVA) operates over 50 facilities throughout the state of New Jersey, U.S. NJDMAVA is under a mandate to move toward decarbonization, which will eventually include eliminating the use of natural gas and other fossil fuels for heating. At the same time, the organization requires increased resiliency regarding electric grid disruption. These competing goals necessitate adopting the use of on-site renewables such as photovoltaic and geothermal power, as well as implementing power control strategies through microgrids. Planning for these changes requires a detailed understanding of current and future electricity use on yearly, monthly, and shorter time scales, as well as a breakdown of consumption by heating, ventilation, and air conditioning (HVAC) equipment. This paper discusses case studies of two buildings that were simulated using the QUick Energy Simulation Tool (eQUEST). Both buildings use electricity from the grid and photovoltaics. One building also uses natural gas. While electricity use data are available in hourly intervals and natural gas data are available in monthly intervals, the simulations were developed using monthly and yearly totals. This approach was chosen to reflect the information available for most NJ DMAVA facilities. Once completed, simulation results are compared to metrics recommended by several organizations to validate energy use simulations. In addition to yearly and monthly totals, the simulated peak demands are compared to actual monthly peak demand values. The simulations resulted in monthly peak demand values that were within 30% of the measured values. These benchmarks will help to assess future energy planning efforts for NJ DMAVA.

Keywords: building energy modeling, eQUEST, peak demand, smart meters

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74 Digital Self-Identity and the Role of Interactivity in Psychiatric Assessment and Treatment

Authors: Kevin William Taylor

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This work draws upon research in the fields of games development and mental health treatments to assess the influence that interactive entertainment has on the populous, and the potential of technology to affect areas of psychiatric assessment and treatment. It will use studies to establish the evolving direction of interactive media in the development of ‘digital self-identity,’ and how this can be incorporated into treatment to the benefit of psychiatry. It will determine that this approach will require collaborative production between developers and psychiatrists in order to ensure precise goals are met, improving the success of serious gaming for psychiatric assessment and treatment. Analysis documents the reach of video games across a growing global community of gamers, highlighting cases of the positives and negatives of video game usage. The games industry is largely oblivious to the psychological negatives, with psychiatrists encountering new conditions such as gaming addiction, which is now recognized by the World Health Organization. With an increasing amount of gamers worldwide, and an additional time per day invested in online gaming and character development, the concept of virtual identity as a means of expressing the id needs further study to ensure successful treatment. In conclusion, the assessment and treatment of game-related conditions are currently reactionary, and while some mental health professionals have begun utilizing interactive technologies to assist with the assessment and treatment of conditions, this study will determine how the success of these products can be enhanced. This will include collaboration between software developers and psychiatrists, allowing new avenues of skill-sharing in interactive design and development. Outlining how to innovate approaches to engagement will reap greater rewards in future interactive products developed for psychiatric assessment and treatment.

Keywords: virtual reality, virtual identity, interactivity, psychiatry

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73 How to Incorporate Vernacular Architecture into Practice for Sustainable Development: Case Studies from Kashmir and Kerala, India

Authors: Debanjana Chatterjee

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Vernacular settlements in India often take the form that is dictated by the climate they are in. India, with its vast cultural diversity and various climatic regions, offers a wide range of vernacular architecture. This paper focuses on two main geographical regions: Kashmir and Kerala. They bring together myriad challenges of climatic and social characteristics to incorporate into their vernacular architectures, which are still relevant despite the advent of globalization and modernization. Scholars like William Wurster and Catherine Bauer even claimed that all the traditional buildings in these places have the kind of urbanity, which is dignified and elegant but also lively and human that every architect would like to achieve if they knew how. With modernization, and with a greater ease of construction, a reduction in labor, and the apparent robustness of contemporary construction techniques, people have, however, become increasingly tentative in respect of vernacular architecture. And yet modern architecture has typically led to energize intensive structures without much consideration to the location and surroundings of the structure itself. In contrary, Laurie Baker, the British-born Indian architect, had shown us the way to integrate the knowledge of vernacular when he developed his designs based on the traditional architecture of Kerala, respecting the local climate and environment. This paper also explores his technical creativity in his design of Center for Development Studies (CDS) in Trivandrum. Hence, in order to protect and conserve our rich cultural and architectural heritage, the elements of vernacular should be incorporated into the contemporary planning and architecture for sustainable building design. The provision should be made to incorporate vernacular architecture and traditional knowledge in the policies. Ultimately, the policymakers, planners, and architects should consider this incorporation of traditional vernacular and contemporary sustainability in their work for the betterment of society now.

Keywords: vernacular, architecture, sustainable development, Kashmir and Kerala, climate, Laurie Baker

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72 Death of the Author and Birth of the Adapter in a Literary Work

Authors: Slwa Al-Hammad

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Adaptation studies have been closely aligned to translation studies as both deal with the process of rendering the meaning from one culture to another. These two disciplines are related to each other, but the theories are still being developed. This research aims to fill this gap and provide a contribution to the growing discipline of adaptation studies through a theoretical perspective while investigating how different cultural interpretations of adaptation influence the final literary product. This research focuses on the theoretical concepts of Barthes’s death of the author and Benjamin’s afterlife of the text in translation, which is believed to lead to the birth of the adapter in a literary work. That is, in adaptation, the ‘death’ of the author allows for the ‘birth’ of the adapter, offering them all the creative possibilities of authorship. It also explores the differences between the meanings of adaptation in the West and the Arab world through the analysis of adapted texts in Arabic initially deriving from the European and American literature of the 19th and 20th centuries. The methodology of this thesis is based upon qualitative literary analysis, in which original and adapted works are compared and contrasted, with the additional insights of literary and adaptation theories and prior scholarship. The main works discussed are the Arabic adaptations of William Faulkner’s novels. The analysis is guided by theories of adaptation studies to help in explaining the concepts of relocating, recreating, and rewriting in the process of adaptation. It draws on scholarship on adaptations to inquire into the status of the adapted texts in relation to the original texts. Also, these theories prove that adaptation is the process that is used to transfer text from source to adapted text, not some other analytical practice. Through the textual analysis, concepts of the death of the author and the birth of the adapter will be illustrated, as will the roles of the adapter and the task of rendering works for a different culture, and the understanding of adaptation and Arabization in Arabic literature.

Keywords: adaptation, Arabization, authorship, recreating, relocating

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71 Diplomatic Assurances in International Law

Authors: William Thomas Worster

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Diplomatic assurances issued by states declaring that they will not mistreat individuals returned to them occupy a strange middle ground between being legal and non-legal obligations. States assert that they are non-binding, yet at other times that they are binding. However, this assertion may not be the end of the discussion. The International Court of Justice and other tribunals have concluded that similar instruments were binding, states have disagreed that certain similar instruments were binding, and the Vienna Convention on the Law of Treaties and its travaux prépératoires do not appear to contemplate non-binding instruments. This paper is a case study of diplomatic assurances but, by necessity, touches on the delicate question of whether certain texts are treaties, promises, or non-binding political statements. International law, and law in general, requires a binary approach to obligation. All communications must be binding or not, even if the fit is not precise. Through this study, we will find that some of the obligations in certain assurances can be understood as legal and some not. We will attempt to state the current methodology for determining which obligations are legal under the law of treaties and law on binding unilateral promises. The paper begins with some background of the legal environment of diplomatic assurances and their use in cases of expulsion. The paper then turns to discuss the legal nature of diplomatic assurances, proceeding to address various possibilities for legal value as treaties and as binding unilateral statements. This paper will not examine the legal value of diplomatic assurances solely under customary international law other than the way in which customary international law might further refine the treaty definition. In order to identify whether any assurances are contained in legal acts, this study identifies a pool of relevant assurances and qualitatively analyzes whether any of those are contained in treaties or binding unilateral statements. To the author’s best knowledge, this study is the first large-scale, qualitative qualitative analysis of assurances as a group of instruments that accounts for their heterogenous nature. It is also the first study to identify the indicators of whether an instrument is a treaty or promise.

Keywords: diplomatic assurances, deportation, extradition, expulsion, non-refoulement, torture, persecution, death penalty, human rights, memorandum of understanding, promises, secret, monitoring, compliance, enforcement

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70 Water Droplet Impact on Vibrating Rigid Superhydrophobic Surfaces

Authors: Jingcheng Ma, Patricia B. Weisensee, Young H. Shin, Yujin Chang, Junjiao Tian, William P. King, Nenad Miljkovic

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Water droplet impact on surfaces is a ubiquitous phenomenon in both nature and industry. The transfer of mass, momentum and energy can be influenced by the time of contact between droplet and surface. In order to reduce the contact time, we study the influence of substrate motion prior to impact on the dynamics of droplet recoil. Using optical high speed imaging, we investigated the impact dynamics of macroscopic water droplets (~ 2mm) on rigid nanostructured superhydrophobic surfaces vibrating at 60 – 300 Hz and amplitudes of 0 – 3 mm. In addition, we studied the influence of the phase of the substrate at the moment of impact on total contact time. We demonstrate that substrate vibration can alter droplet dynamics, and decrease total contact time by as much as 50% compared to impact on stationary rigid superhydrophobic surfaces. Impact analysis revealed that the vibration frequency mainly affected the maximum contact time, while the amplitude of vibration had little direct effect on the contact time. Through mathematical modeling, we show that the oscillation amplitude influences the possibility density function of droplet impact at a given phase, and thus indirectly influences the average contact time. We also observed more vigorous droplet splashing and breakup during impact at larger amplitudes. Through semi-empirical mathematical modeling, we describe the relationship between contact time and vibration frequency, phase, and amplitude of the substrate. We also show that the maximum acceleration during the impact process is better suited as a threshold parameter for the onset of splashing than a Weber-number criterion. This study not only provides new insights into droplet impact physics on vibrating surfaces, but develops guidelines for the rational design of surfaces to achieve controllable droplet wetting in applications utilizing vibration.

Keywords: contact time, impact dynamics, oscillation, pear-shape droplet

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69 Identification of the Microalgae Species in a Wild Mix Culture Acclimated to Landfill Leachate and Ammonia Removal Performances in a Microbubble Assisted Photobioreactor

Authors: Neslihan Ozman Say, Jim Gilmour, Pratik Desai, William Zimmerman

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Landfill leachate treatment has been attracting researchers recently for various environmental and economical reasons. Leachate discharge to receiving waterbodies without treatment causes serious detrimental effects including partial oxygen depletion due to high biological oxygen demand (BOD) and chemical oxygen demand (COD) concentrations besides toxicity of heavy metals it contains and high ammonia concentrations. In this study, it is aimed to show microalgal ammonia removal performances of a wild microalgae consortia as an alternative treatment method and determine the dominant leachate tolerant species for this consortia. For the microalgae species identification experiments a microalgal consortium which has been isolated from a local pond in Sheffield inoculated in %5 diluted raw landfill leachate and acclimated to the leachate by batch feeding for a month. In order to determine the most tolerant microalgal consortium, four different untreated landfill leachate samples have been used as diluted in four different ratios as 5%, 10%, 20%, and 40%. Microalgae cell samples have been collected from all experiment sets and have been examined by using 18S rDNA sequencing and specialised gel electrophoresis which are adapted molecular biodiversity methods. The best leachate tolerant algal consortium is being used in order to determine ammonia removal performances of the culture in a microbubble assisted photobioreactor (PBR). A porous microbubble diffuser which is supported by a fluidic oscillator is being used for dosing CO₂ and air mixture in the PBR. It is known that high mass transfer performance of microbubble technology provides a better removal efficiency and a better mixing in the photobioreactor. Ammonia concentrations and microalgal growth are being monitored for PBR currently. It is aimed to present all the results of the study in final paper submission.

Keywords: ammonia removal from leachate, landfill leachate treatment, microalgae species identification, microbubble assisted photobioreactors

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68 Public Health Infrastructure Resilience in the Face of Natural Disasters in Rwanda

Authors: Jessy Rugeyo, William Donner

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This research delves into the resilience of Rwanda's public health infrastructure amidst natural disasters, a critical issue given that the Northern Province alone has witnessed no fewer than 1500 cases of disaster ranging from floods and landslides in the last five years, with more than 200 people killed and thousands of homes destroyed, according to MINEMA. In an era where climate change escalates the frequency and intensity of such disasters, fortifying the resilience of public health systems is paramount. This study offers a comprehensive analysis of the existing state of Rwanda's public health infrastructure and its ability to manage such crises. Employing a mix of literature review, case studies, and policy analysis, the study discerns key vulnerabilities and brings to light the intricacies of disaster management in Rwanda. Case studies centered around past natural disasters in Rwanda provide critical insights into the strengths and weaknesses of the existing disaster response mechanisms. A thorough critique of related disaster management and public health infrastructure policies reveals areas of commendable practice, along with gaps calling for policy enhancements. Findings guide the proposition of targeted strategies to bolster the resilience of Rwanda's public health infrastructure. This research serves as a significant contribution to the domains of disaster studies and public health, offering valuable insights for policymakers, public health and disaster management professionals in Rwanda and similar contexts. It presents actionable recommendations for improvement, underscoring the potential for enhancing Rwanda's disaster management capacity. By advocating for the strengthening of public health infrastructure resilience, the research highlights the potential for improved public health outcomes following natural disasters, thereby showcasing significant implications for public health and disaster management in the country, particularly in the face of a changing climate.

Keywords: public health infrastructure, disaster resilience, natural disaster, disaster management, emergency preparedness, health policy

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67 Analyzing Doctors’ Knowledge of the United Kingdom Chief Medical Officer's Guidelines for Physical Activity: Survey of Secondary Care Doctors in a District General Hospital

Authors: Alexandra Von Guionneau, William Sloper, Charlotte Burford

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The benefits of exercise for the prevention and management of chronic disease are well established and the importance of primary care practitioners in promoting exercise is becoming increasingly recognized. However, those with severe manifestations of the chronic disease are managed in a secondary care setting. Secondary care practitioners, therefore, have a role to play in promoting physical activity. Methods: In order to assess secondary care doctors’ knowledge of the Chief Medical Officer’s guidelines for physical activity, a 12-question survey was administered to staff working in a district general hospital in South England during team and unit meetings. Questions related to knowledge of the current guidelines for both 19 - 64 year olds and older adults (65 years and above), barriers to exercise discussion or prescription and doctors’ own exercise habits. Responses were collected anonymously and analyzed using SPSS Version 24.0. Results: 96 responses were collected. Doctors taking part in the survey ranged from foundation years (26%) to consultants (40%). 17.7% of participants knew the guidelines for moderate intensity activity for 19 - 64 year olds. Only one participant knew all of the guidance for both 19 - 64 year olds and older adults. While 71.6% of doctors felt they were adequately informed about how to exercise, only 45.6% met the minimum recommended guidance for moderate intensity activity. Conclusion: More work is needed to promote the physical activity guidelines and exercise prescription to doctors working within a secondary care setting. In addition, doctors require more support to personally meet the recommended minimum level of physical activity.

Keywords: exercise is medicine, exercise prescription, physical activity guidelines, exercise habits

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66 Applying Cognitive Psychology to Education: Translational Educational Science

Authors: Hammache Nadir

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The scientific study of human learning and memory is now more than 125 years old. Psychologists have conducted thousands of experiments, correlational analyses, and field studies during this time, in addition to other research conducted by those from neighboring fields. A huge knowledge base has been carefully built up over the decades. Given this backdrop, we may ask ourselves: What great changes in education have resulted from this huge research base? How has the scientific study of learning and memory changed practices in education from those of, say, a century ago? Have we succeeded in building a translational educational science to rival medical science (in which biological knowledge is translated into medical practice) or types of engineering (in which, e.g., basic knowledge in chemistry is translated into products through chemical engineering)? The answer, I am afraid, is rather mixed. Psychologists and psychological research have influenced educational practice, but in fits and starts. After all, some of the great founders of American psychology—William James, Edward L. Thorndike, John Dewey, and others—are also revered as important figures in the history of education. And some psychological research and ideas have made their way into education—for instance, computer-based cognitive tutors for some specific topics have been developed in recent years—and in years past, such practices as teaching machines, programmed learning, and, in higher education, the Keller Plan were all important. These older practices have not been sustained. Was that because they failed or because of a lack of systematic research showing they were effective? At any rate, in 2012, we cannot point to a well-developed translational educational science in which research about learning and memory, thinking and reasoning, and related topics is moved from the lab into controlled field trials (like clinical trials in medicine) and the tested techniques, if they succeed, are introduced into broad educational practice. We are just not there yet, and one question that arises is how we could achieve a translational educational science.

Keywords: affective, education, cognition, pshychology

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65 Ideas About Varroa Destructor Reproduction in the Honey Bees (Hymenoptera: Apidae)

Authors: William Ramirez-Benavides

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The mite Varroa destructor Anderson & Trueman (Mesostigmata: Varroidae), is an exclusive hematophagous parasite of the Apis honey bees (Apidae: Hymenoptera). The early phoretic female mites have multiple small inactivated oocytes. Consequently, for the initial growth and vitellogenesis of the oocytes, the mother mite must feed on the hemolymph of the host, as a unique food source, by taking intermittently variable number of blood meals: 1. During the phoretic phase, to initiate vitellogenesis of the terminal oocyte, 2. From a freshly capped bee cell with a bee larva, up to the apolysis stage, to complete vitellogenesis and embryogenesis of the terminal oocyte, and 3. From all pupal stages, up to the imago stage, to induce oogenesis and vitellogenesis of the would-be nonembryonic female eggs. Additionally, oogenesis and vitellogenesis expressions in Varroa destructor and other Varroidae varies according to environmental conditions, e.g., chemical attractions produced by the adult bee and larvae, race of bees, sex of the larva, developmental period of the bee larva, food quality and quantity, and superparasitism (several cofoundressess). Also, the feeding stimuli obtained from the host hemolymph, indirectly regulate the reproductive physiology of the mite, by inducing different vitellogenin expressions, the production of a male egg first in the sequence followed by vitellogenesis of the would-be female eggs during the pupal stages. Furthermore, the different uptakes of hemolymph from the host, also indirectly induce the production of the male egg first in the sequence, local mate competition (LMC) and variable adaptive female sex ratios in the broods, especially when superparasitism occurs. Consequently, reproduction in Varroa destructor, and probably in other Varroidae, depends exclusively on feeding in the hemolymph of the bee host, even during the phoretic phase, the prepupal stages and during the pupal stages; and that, the feeding factors are common syndromes in other Varroidae.

Keywords: oogenesis, sex determination, varroa destructor, vitellogenesis

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64 An Analytical Study on the Politics of Defection in India

Authors: Diya Sarkar, Prafulla C. Mishra

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In a parliamentary system, party discipline is the impulse; when it falls short, the government usually falls. Conceivably, the platform of Indian politics suffers with innumerous practical disorders. The politics of defection is one such specie entailing gross miscarriage of fair conduct turning politics into a game of thrones (powers). This practice of political nomaditude can trace its seed in the womb of British House of Commons. Therein, if a legislator was found to cross the floor, the party considered him disloyal. In other words, the legislator lost his allegiance to his former party by joining another party. This very phenomenon, in practice has a two way traffic i.e. ruling party to the opposition party or vice versa. The democracies like USA, Australia and Canada were also aware of this fashion of swapping loyalties. There have been several instances of great politicians changing party allegiance, for example Winston Churchill, Ramsay McDonald, William Gladstone etc. Nevertheless, it is interesting to cite that irrespective of such practice of changing party allegiance, none of the democracies in the west ever desired or felt the need to legislatively ban defections. But, exceptionally India can be traced to have passed anti-defection laws. The politics of defection had been a unique popular phenomenon on the floor of Indian Parliamentary system gradually gulping the democratic essence and synchronization of the Federation. This study is both analytical and doctrinal, which tries to examine whether representative democracy has lost its essence due to political nomadism. The present study also analyzes the classical as well as contemporary pulse of floor crossing amidst dynastic politics in a representative democracy. It will briefly discuss the panorama of defections under the Indian federal structure in the light of the anti-defection law and an attempt has been made to add valuable suggestions to streamline remedy for the still prevalent political defections.

Keywords: constitutional law, defection, democracy, polarization, political anti-trust

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63 Ecocriticism and Sustainable Development: A Study of Kamila Shamsie's a God in Every Stone

Authors: Shaista Maseeh

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English Literature from the beginning itself has had psychological, social and environment concerns. Virgil, Shakespeare, John Milton, William Wordsworth to the most current Robert Hass have shown and proved their environmental and ecological interests as well as distress related to its loss. Pastoral literature is also one such genre that links literature with environment. Thanks to the contemporary literary theories that they successfully are relating Literature formally to the subjects other than written text. One of such literary theory is 'Ecocriticism.' It stands under the umbrella of the Economics term, Sustainable Development,' or it can also be understood as an ecological extension of it. Ecocriticism helps the reader to study the dynamic relation between literature and our degrading environment. It draws attention towards the ravaged condition of nature and animals, that how nature is exploited by human beings for their own benefit leaving nature at a repairable loss. For instance, deforestation is reducing the size of forest every year, injuring permanently flora, fauna and also the habitat of animals. This paper will study the ecological and environmental concerns in the latest novel by Pakistani British writer Kamila Shamsie, A God in every Stone (2014). The book is not only a literary masterpiece in elegant prose, but also a novel posing a lot of questions about 'nature and environment' in general and 'animals' in particular. It gives the glimpses of the interesting history of Temple of Zeus in Greece and Ancient Caria, and covers many episodes of history the Indian freedom struggle. In course of novel's narrative Kamila Shamsie poses disturbing question about environmental abuse, about how human beings are more 'beasts' than so call beasts, poor animals. She also glorifies the simplicity of past. The novel has enough instances to prove Shamsie's positive stand on saving the earth that is being more abused than used by human beings. This paper will provide an ecocritical approach to study A God in Every Stone (2014).

Keywords: animals, ecocriticism, environment, nature

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62 A Leader-Follower Kinematic-Based Control System for a Cable-Driven Hyper-Redundant Manipulator

Authors: Abolfazl Zaraki, Yoshikatsu Hayashi, Harry Thorpe, Vincent Strong, Gisle-Andre Larsen, William Holderbaum

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Thanks to the high maneuverability of the cable-driven hyper-redundant manipulators (HRMs), this class of robots has shown a superior capability in highly confined and unstructured space applications. Although the large number of degrees of freedom (DOF) of HRMs enhances the motion flexibility and the robot’s reachability range, it highly increases the complexity of the kinematic configuration which makes the kinematic control problem very challenging or even impossible to solve. This paper presents our current progress achieved on the development of a kinematic-based leader-follower control system which is designed to control not only the robot’s body posture but also to control the trajectory of the robot’s movement in a semi-autonomous manner (the human operator is retained in the robot’s control loop). To obtain the forward kinematic model, the coordinate frames are established by the classical Denavit–Hartenburg (D-H) convention for a hyper-redundant serial manipulator which has a controlled cables-driven mechanism. To solve the inverse kinematics of the robot, unlike the conventional methods, a leader-follower mechanism, based on the sequential inverse kinematic, is followed. Using this mechanism, the inverse kinematic problem is solved for all sequential joints starting from the head joint to the base joint of the robot. To verify the kinematic design and simulate the robot motion, the MATLAB robotic toolbox is used. The simulation result demonstrated the promising capability of the proposed leader-follower control system in controlling the robot motion and trajectory in our confined space application.

Keywords: hyper-redundant robots, kinematic analysis, semi-autonomous control, serial manipulators

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61 Mechanisms of Action in Mindfulness-Based Cognitive Therapy (MBCT) and Mindfulness-Based Stress Reduction (MBSR) in People with Physical and/or Psychological Conditions: A Systematic Review

Authors: Modi Alsubaie, Willem Kuyken, Rebecca Abbott, Barnaby Dunn, Chris Dickens, Tina Keil, William Henley

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Background: Recently, there has been an increased interest in studying the effects of mindfulness-based interventions for people with psychological and physical problems. However, the mechanisms of action in these interventions that lead to beneficial physical and psychological outcomes have yet to be clearly identified. Purpose: The aim of this paper is to review, systematically, the evidence to date on the mechanisms of action in mindfulness interventions in populations with physical and/or psychological conditions. Method: Searches of seven databases (PsycINFO, Medline (Ovid), Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, AMED, ClinicalTrials.gov) were undertaken in June 2014 and July 2015. We evaluated to what extent the studies we identified met the criteria suggested by Kazdin for establishing mechanisms of action within a psychological treatment (2007, 2009). Results: We identified four trials examining mechanisms of mindfulness interventions in those with comorbid psychological and physical health problems and 14 in those with psychological conditions. These studies examined a diverse range of potential mechanisms, including mindfulness and rumination. Of these candidate mechanisms, the most consistent finding was that greater self-reported change in mindfulness mediated superior clinical outcomes. However, very few studies fully met the Kazdin criteria for examining treatment mechanisms. Conclusion: There was evidence that global changes in mindfulness are linked to better outcomes. This evidence pertained more to interventions targeting psychological rather than physical health conditions. While there is promising evidence that MBCT/MBSR intervention effects are mediated by hypothesised mechanisms, there is a lack of methodological rigour in the field of testing mechanisms of action for both MBCT and MBSR, which precludes definitive conclusions.

Keywords: MBCT, MBSR, mechanisms, physical conditions, psychological conditions, systematic review

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60 As a Little-Known Side a Passionate Statistician: Florence Nightingale

Authors: Gülcan Taşkıran, Ayla Bayık Temel

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Background: Florence Nightingale, the modern founder of the nursing, is most famous for her role as a nurse. But not so much known about her contributions as a mathematician and statistician. Aim: In this conceptual article it is aimed to examine Florence Nightingale's statistics education, how she used her passion for statistics and applied statistical data in nursing care and her scientific contributions to statistical science. Design: Literature review method was used in the study. The databases of Istanbul University Library Search Engine, Turkish Medical Directory, Thesis Scanning Center of Higher Education Council, PubMed, Google Scholar, EBSCO Host, Web of Science were scanned to reach the studies. The keywords 'statistics' and 'Florence Nightingale' have been used in Turkish and English while being screened. As a result of the screening, totally 41 studies were examined from the national and international literature. Results: Florence Nightingale has interested in mathematics and statistics at her early ages and has received various training in these subjects. Lessons learned by Nightingale in a cultured family environment, her talent in mathematics and numbers, and her religious beliefs played a crucial role in the direction of the statistics. She was influenced by Quetelet's ideas in the formation of the statistical philosophy and received support from William Farr in her statistical studies. During the Crimean War, she applied statistical knowledge to nursing care, developed many statistical methods and graphics, so that she made revolutionary reforms in the health field. Conclusions: Nightingale's interest in statistics, her broad vision, the statistical ideas fused with religious beliefs, the innovative graphics she has developed and the extraordinary statistical projects that she carried out has been influential on the basis of her professional achievements. Florence Nightingale has also become a model for women in statistics. Today, using and teaching of statistics and research in nursing care practices and education programs continues with the light she gave.

Keywords: Crimean war, Florence Nightingale, nursing, statistics

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59 Simulation of Soil-Pile Interaction of Steel Batter Piles Penetrated in Sandy Soil Subjected to Pull-Out Loads

Authors: Ameer A. Jebur, William Atherton, Rafid M. Alkhaddar, Edward Loffill

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Superstructures like offshore platforms, tall buildings, transition towers, skyscrapers and bridges are normally designed to resist compression, uplift and lateral forces from wind waves, negative skin friction, ship impact and other applied loads. Better understanding and the precise simulation of the response of batter piles under the action of independent uplift loads is a vital topic and an area of active research in the field of geotechnical engineering. This paper investigates the use of finite element code (FEC) to examine the behaviour of model batter piles penetrated in dense sand, subjected to pull-out pressure by means of numerical modelling. The concept of the Winkler Model (beam on elastic foundation) has been used in which the interaction between the pile embedded depth and adjacent soil in the bearing zone is simulated by nonlinear p-y curves. The analysis was conducted on different pile slenderness ratios (lc⁄d) ranging from 7.5, 15.22 and 30 respectively. In addition, the optimum batter angle for a model steel pile penetrated in dense sand has been chosen to be 20° as this is the best angle for this simulation as demonstrated by other researcher published in literature. In this numerical analysis, the soil response is idealized as elasto-plastic and the model piles are described as elastic materials for the purpose of simulation. The results revealed that the applied loads affect the pullout pile capacity as well as the lateral pile response for dense sand together with varying shear strength parameters linked to the pile critical depth. Furthermore, the pile pull-out capacity increases with increasing the pile aspect ratios.

Keywords: slenderness ratio, soil-pile interaction, winkler model (beam on elastic foundation), pull-out capacity

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58 Evaluating the Effect of Spatial Qualities, Openness and Complexity, on Human Cognitive Performance within Virtual Reality

Authors: Pierre F. Gerard, Frederic F. Leymarie, William Latham

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Architects have developed a series of objective evaluations, using spatial analysis tools such as Isovist, that show how certain spatial qualities are beneficial to specific human activities hosted in the built environments. In return, they can build more adapted environments by tuning those spatial qualities in their design. In parallel, virtual reality technologies have been developed by engineers with the dream of creating a system that immerses users in a new form of spatial experiences. They already have demonstrated a useful range of benefits not only in simulating critical events to assist people in acquiring new skills, but also to enhance memory retention, to name just a few. This paper investigates the effects of two spatial qualities, openness, and complexity, on cognitive performance within immersive virtual environments. Isovist measure is used to design a series of room settings with different levels of each spatial qualities. In an empirical study, each room was then used by every participant to solve a navigational puzzle game and give a rating of their spatial experience. They were then asked to fill in a questionnaire before solving the visual-spatial memory quiz, which addressed how well they remembered the different rooms. Findings suggest that those spatial qualities have an effect on some of the measures, including navigation performance and memory retention. In particular, there is an order effect for the navigation puzzle game. Participants tended to spend a longer time in the complex room settings. Moreover, there is an interaction effect while with more open settings, participants tended to perform better when in a simple setting; however, with more closed settings, participants tended to perform better in a more complex setting. For the visual-spatial memory quiz, participants performed significantly better within the more open rooms. We believe this is a first step in using virtual environments to enhance participant cognitive performances through better use of specific spatial qualities.

Keywords: architecture, navigation, spatial cognition, virtual reality

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57 Design of an Active Compression System for Treating Vascular Disease Using a Series of Silicone Based Inflatable Mini Bladders

Authors: Gayani K. Nandasiri, Tilak Dias, William Hurley

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Venous disease of human lower limb could range from minor asymptomatic incompetence of venous valves to chronic venous ulceration. The sheer prevalence of varicose veins and its associated significant costs of treating late complications such as chronic ulcers contribute to a higher burden on health care resources. In most of western countries with developed health care systems, treatment costs associated with Venous disease accounts for a considerable portion of their total health care budget, and it has become a high-cost burden to National Health Service (NHS), UK. The established gold standard of treatment for the venous disease is the graduated compression, where the pressure at the ankle being highest and decreasing towards the knee and thigh. Currently, medical practitioners use two main methods to treat venous disease; i.e. compression bandaging and compression stockings. Both these systems have their own disadvantages which lead to the current programme of research. The aim of the present study is to revolutionize the compression therapy by using a novel active compression system to deliver a controllable and more accurate pressure profiles using a series of inflatable mini bladders. Two types of commercially available silicones were tested for the application. The mini bladders were designed with a special fabrication procedure to provide required pressure profiles, and a series of experiments were conducted to characterise the mini bladders. The inflation/deflation heights of these mini bladders were investigated experimentally and using a finite element model (FEM), and the experimental data were compared to the results obtained from FEM simulations, which showed 70-80% agreement. Finally, the mini bladders were tested for its pressure transmittance characteristics, and the results showed a 70-80% of inlet air pressure transmitted onto the treated surface.

Keywords: finite element analysis, graduated compression, inflatable bladders, venous disease

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56 Pilgrimage: Between Culture and Religion Case study of Pilgrimage in Shia tradition in Indonesia, Traditional Philosophy approach of Seyyed Hosein Nasr and Religious Experience of William James

Authors: Ma'ruf

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Pilgrimage has a universal value, founded in every religion. No exception to Islam, has a ritual value, and became part of the religion, as well as the procession of a social culture in nature. The tradition of pilgrimage, especially in Indonesia, rooted in the society, because the Islam that entered into the archipelago through Sufism (tasawuf). In the Sufi tradition, the interconnecty of the human spirit (ruh) to the spirit (ruh) of God, must go through a guardian (wasilah) appointed by God himself ,the prophet Muhammad and wali. In the process of pilgrimage rituals usually by reading the prayer to praise God, the prophet and wali, then convey intent (hajat). In the pilgrimage procession, usually not only done in the house, but aslo completed the process by direct pilgrimage visiting the tombs of saints. The tradition of pilgrimage, especially in Indonesia continues to be maintained, and still attached to the traditions in Nahdiyin (NU followers). The relationship with God manifested in wasilah prayer to God, the prophet Muhammad, the best companions of the Prophet and Nine wali (Songo), who had been influential in spreading Islam in Java. The tradition of pilgrimage in Indonesia is also linked to the Shia community in Indonesia, along with a growing number of followers of the Shia in Indonesia, especially after the Islamic revolution of Iran after the 1979. Pilgrimage in the Shia community, Likewise NU members also pray with supplication of tawasul to the Prophet and Shia Imams. If NU members to make improvements pilgrimage to visit the tomb wali Songo in Java, residents Shia pilgrimage rituals abroad, usually one package with umrah trip, with a pilgrimage to the tomb of the prophet, proceed to the tomb of the Imam Shia, in Iran and Iraq. Trends of pilgrimage as a ritual in the Indonesian Shia tradition, together with the growing number of Shia residents increased, followed by increasing the awareness (syi’isme) - bond with the Imam, Shia. In every certain months (arbaeen, asyuro) Shia pilgrims routinely perform pilgrimage, along with increasing number spiritual travel.

Keywords: traditional approach, religious experience, culture, religion, pilgrimage, Syria

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55 An Investigation of the Pharmacomechanisms of Shang-Han Lun Formulas as Elucidated in the Qing Dynasty Classic 'Ben-Jing Shu-Zheng'

Authors: William Ceurvels, Dong-Di Zhang

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The true nature of the mechanism by which the pharmaceuticals of the Shang-Han Lun act has been a topic of debate since Wuji Cheng published the first commentary during the Northern Song. Subsequent commentaries employed a number of methodologies in their analysis of pharmaceutical mechanisms, but no commentator was able to garner universal acceptance. During the Qing Dynasty, the proliferation and development of Neo-Confucian scholarship produced a new generation of scholars possessed of rigorous and inventive research methods, one of whom was the famed materia medica scholar, Run-an Zou. Run-an Zou and his successor Zhou Yan advocated analyzing the mechanism of Treatise pharmaceuticals based upon the understanding of those pharmaceuticals during the time period in which the Treatise was written and thereby focused on the Han Dynasty materia medica tract Shen-nong Ben-cao Jing (The Divine Husbandman’s Herbal Foundation Canon). Zou Run-an’s commentary, Ben-jing Shu-zheng won nearly universal praise among materia medica scholars for its scholastic rigor and innovative research methods. However, because Ben-jing Shu-zheng only focuses on individual herbs, as opposed to formulas, its value in analyzing the Shang-Han Lun has limitations. The purpose of this study is to combine Zou Run-an’s single-pharmaceutical commentaries to generate theoretical full formula analyses to gain a fuller picture of Zou’s understanding of the healing mechanism of Shang-Han Lun formulas. Commentaries were gathered from Ben-jing Shu-zheng and Zhou Yan’s Ben-cao Si-bian Lun and combined to produce theoretical full formula model mechanisms of Treatise formulas. Through this study, a new picture of the mechanistic basis of Shang-han formulas emerges, which is based on qi-xue changes as opposed to organ or meridian theory. The author hopes that this modest research study will be of service to scholars of the Shang-han and clinical doctors alike in their pursuit of the true pharmacomechanisms of this great Han dynasty tome.

Keywords: Materia medica, Shang-han Lun, Shen-nong Ben-cao Jing, neo-Confucian scholarship

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54 De Novo Design of Functional Metalloproteins for Biocatalytic Reactions

Authors: Ketaki D. Belsare, Nicholas F. Polizzi, Lior Shtayer, William F. DeGrado

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Nature utilizes metalloproteins to perform chemical transformations with activities and selectivities that have long been the inspiration for design principles in synthetic and biological systems. The chemical reactivities of metalloproteins are directly linked to local environment effects produced by the protein matrix around the metal cofactor. A complete understanding of how the protein matrix provides these interactions would allow for the design of functional metalloproteins. The de novo computational design of proteins have been successfully used in design of active sites that bind metals like di-iron, zinc, copper containing cofactors; however, precisely designing active sites that can bind small molecule ligands (e.g., substrates) along with metal cofactors is still a challenge in the field. The de novo computational design of a functional metalloprotein that contains a purposefully designed substrate binding site would allow for precise control of chemical function and reactivity. Our research strategy seeks to elucidate the design features necessary to bind the cofactor protoporphyrin IX (hemin) in close proximity to a substrate binding pocket in a four helix bundle. First- and second-shell interactions are computationally designed to control orientation, electronic structure, and reaction pathway of the cofactor and substrate. The design began with a parameterized helical backbone that positioned a single histidine residue (as an axial ligand) to receive a second-shell H-bond from a Threonine on the neighboring helix. The metallo-cofactor, hemin was then manually placed in the binding site. A structural feature, pi-bulge was introduced to give substrate access to the protoporphyrin IX. These de novo metalloproteins are currently being tested for their activity towards hydroxylation and epoxidation. The de novo designed protein shows hydroxylation of aniline to 4-aminophenol. This study will help provide structural information of utmost importance in understanding de novo computational design variables impacting the functional activities of a protein.

Keywords: metalloproteins, protein design, de novo protein, biocatalysis

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