Search results for: Functional mechanism
Commenced in January 2007
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Paper Count: 5706

Search results for: Functional mechanism

456 Fashion Utopias: The Role of Fashion Exhibitions and Fashion Archives to Defining (and Stimulating) Possible Future Fashion Landscapes

Authors: Vittorio Linfante

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Utopìa is a term that, since its first appearance in 1516, in Tommaso Moro’s work, has taken on different meanings and forms in various fields: social studies, politics, art, creativity, and design. The utopias, although of short duration and in their apparent impossibility, have been able to give a shape to the future, laying the foundations for our present and the future of the next generations. The Twentieth century was the historical period crossed by many changes, and it saw the most significant number of utopias not only social, political, and scientific but also artistic, architectural, in design, communication, and, last but not least, in fashion. Over the years, fashion has been able to interpret various utopistic impulses giving form to the most futuristic visions. From the Manifesto del Vestito by Giacomo Balla, through the functional experiments that led to the Tuta by Thayath and the Varst by Aleksandr Rodčenko and Varvara Stepanova, through the Space Age visions of Rudi Gernreich, Paco Rabanne and Pierre Cardin, and the Archizoom’s political actions and their fashion project Vestirsi è facile. Experiments that have continued to the present days through the (sometimes) excessive visions of Hussein Chalayan, Alexander McQueen, and Gareth Pugh or those that are more anchored to the market (but no fewer innovative and visionaries) by Prada, Chanel, and Raf Simmons. If, as Bauman states, it is true that we have entered in a phase of Retrotopia characterized by the inability to think about new forms of the future; it is necessary, more than ever, to redefine the role of history, of its narration and its mise en scène, within the contemporary creative process. A process that increasingly requires an in-depth knowledge of the past for the definition of a renewed discourse about design processes. A discourse in which words like archive, exhibition, curating, revival, vintage, and costume take on new meanings. The paper aims to investigate–through case studies, research, and professional projects–the renewed role of curating and preserving fashion artefacts. A renewed role that–in an era of Retrotopia–museums, exhibitions, and archives can (and must) assume, to contribute to the definition of new design paradigms, capable of overcoming the traditional categories of revival or costume in favour of a more contemporary “mash-up” approach. Mash-up in which past and present, craftsmanship and new technologies, revival and experimentation merge seamlessly. In this perspective, dresses (as well as fashion accessories) should be considered not only as finished products but as artefacts capable of talking about the past and of producing unpublished new stories at the same time. Archives, exhibitions (academic and not), and museums thus become powerful sources of inspiration for fashion: places and projects capable of generating innovation, becoming active protagonists of the contemporary fashion design processes.

Keywords: heritage, history, costume and fashion interface, performance, language, design research

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455 A Galectin from Rock Bream Oplegnathus fasciatus: Molecular Characterization and Immunological Properties

Authors: W. S. Thulasitha, N. Umasuthan, G. I. Godahewa, Jehee Lee

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In fish, innate immune defense is the first immune response against microbial pathogens which consists of several antimicrobial components. Galectins are one of the carbohydrate binding lectins that have the ability to identify pathogen by recognition of pathogen associated molecular patterns. Galectins play a vital role in the regulation of innate and adaptive immune responses. Rock bream Oplegnathus fasciatus is one of the most important cultured species in Korea and Japan. Considering the losses due to microbial pathogens, present study was carried out to understand the molecular and functional characteristics of a galectin in normal and pathogenic conditions, which could help to establish an understanding about immunological components of rock bream. Complete cDNA of rock bream galectin like protein B (rbGal like B) was identified from the cDNA library, and the in silico analysis was carried out using bioinformatic tools. Genomic structure was derived from the BAC library by sequencing a specific clone and using Spidey. Full length of rbGal like B (contig14775) cDNA containing 517 nucleotides was identified from the cDNA library which comprised of 435 bp in the open reading frame encoding a deduced protein composed of 145 amino acids. The molecular mass of putative protein was predicted as 16.14 kDa with an isoelectric point of 8.55. A characteristic conserved galactose binding domain was located from 12 to 145 amino acids. Genomic structure of rbGal like B consisted of 4 exons and 3 introns. Moreover, pairwise alignment showed that rock bream rbGal like B shares highest similarity (95.9 %) and identity (91 %) with Takifugu rubripes galectin related protein B like and lowest similarity (55.5 %) and identity (32.4 %) with Homo sapiens. Multiple sequence alignment demonstrated that the galectin related protein B was conserved among vertebrates. A phylogenetic analysis revealed that rbGal like B protein clustered together with other fish homologs in fish clade. It showed closer evolutionary link with Takifugu rubripes. Tissue distribution and expression patterns of rbGal like B upon immune challenges were performed using qRT-PCR assays. Among all tested tissues, level of rbGal like B expression was significantly high in gill tissue followed by kidney, intestine, heart and spleen. Upon immune challenges, it showed an up-regulated pattern of expression with Edwardsiella tarda, rock bream irido virus and poly I:C up to 6 h post injection and up to 24 h with LPS. However, In the presence of Streptococcus iniae rbGal like B showed an up and down pattern of expression with the peak at 6 - 12 h. Results from the present study revealed the phylogenetic position and role of rbGal like B in response to microbial infection in rock bream.

Keywords: galectin like protein B, immune response, Oplegnathus fasciatus, molecular characterization

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454 Precursor Synthesis of Carbon Materials with Different Aggregates Morphologies

Authors: Nikolai A. Khlebnikov, Vladimir N. Krasilnikov, Evgenii V. Polyakov, Anastasia A. Maltceva

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Carbon materials with advanced surfaces are widely used both in modern industry and in environmental protection. The physical-chemical nature of these materials is determined by the morphology of primary atomic and molecular carbon structures, which are the basis for synthesizing the following materials: zero-dimensional (fullerenes), one-dimensional (fiber, tubes), two-dimensional (graphene) carbon nanostructures, three-dimensional (multi-layer graphene, graphite, foams) with unique physical-chemical and functional properties. Experience shows that the microscopic morphological level is the basis for the creation of the next mesoscopic morphological level. The dependence of the morphology on the chemical way and process prehistory (crystallization, colloids formation, liquid crystal state and other) is the peculiarity of the last called level. These factors determine the consumer properties of carbon materials, such as specific surface area, porosity, chemical resistance in corrosive environments, catalytic and adsorption activities. Based on the developed ideology of thin precursor synthesis, the authors discuss one of the approaches of the porosity control of carbon-containing materials with a given aggregates morphology. The low-temperature thermolysis of precursors in a gas environment of a given composition is the basis of the above-mentioned idea. The processes of carbothermic precursor synthesis of two different compounds: tungsten carbide WC:nC and zinc oxide ZnO:nC containing an impurity phase in the form of free carbon were selected as subjects of the research. In the first case, the transition metal (tungsten) forming carbides was the object of the synthesis. In the second case, there was selected zinc that does not form carbides. The synthesis of both kinds of transition metals compounds was conducted by the method of precursor carbothermic synthesis from the organic solution. ZnO:nC composites were obtained by thermolysis of succinate Zn(OO(CH2)2OO), formate glycolate Zn(HCOO)(OCH2CH2O)1/2, glycerolate Zn(OCH2CHOCH2OH), and tartrate Zn(OOCCH(OH)CH(OH)COO). WC:nC composite was synthesized from ammonium paratungstate and glycerol. In all cases, carbon structures that are specific for diamond- like carbon forms appeared on the surface of WC and ZnO particles after the heat treatment. Tungsten carbide and zinc oxide were removed from the composites by selective chemical dissolution preserving the amorphous carbon phase. This work presents the results of investigating WC:nC and ZnO:nC composites and carbon nanopowders with tubular, tape, plate and onion morphologies of aggregates that are separated by chemical dissolution of WC and ZnO from the composites by the following methods: SEM, TEM, XPA, Raman spectroscopy, and BET. The connection between the carbon morphology under the conditions of synthesis and chemical nature of the precursor and the possibility of regulation of the morphology with the specific surface area up to 1700-2000 m2/g of carbon-structured materials are discussed.

Keywords: carbon morphology, composite materials, precursor synthesis, tungsten carbide, zinc oxide

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453 Evidence-Based Health System Strengthening in Urban India: Drawing Insights from Rapid Assessment Study

Authors: Anisur Rahman, Sabyasachi Behera, Pawan Pathak, Benazir Patil, Rajesh Khanna

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Background: Nearly half of India’s population is expected to reside in urban areas by 2030. The extent to which India's health system can provide for this large and growing city-based population will determine the country's success in achieving universal health coverage and improved national health indices. National Urban Health Mission (NUHM) strive for improving access to primary health care in urban areas. Implementation of NUHM solicits sensitive, effective and sustainable strategies to strengthen the service delivery mechanisms. The Challenge Initiative for Healthy Cities (TCIHC) is working with the Government of India and three provincial states to develop effective service delivery mechanisms for reproductive, maternal, newborn and child health (RMNCH) through a health systems approach for the urban poor. Method: A rapid assessment study was conceptualized and executed to generate evidence in order to address the challenges impeding in functioning of urban health facilities to deliver effective, efficient and equitable health care services in 7 cities spread across two project States viz. Madhya Pradesh and Odisha. Results: The findings of the assessment reflect: 1. The overall ecosystem pertaining to planning and management of public health interventions is not conducive. 2. The challenges regarding population dynamics like migration keeps on influencing the demand-supply-enabling environment triangle for both public and private service providers. 3. Lack of norms for planning and benchmark for service delivery further impedes urban health system as a whole. 4. Operationalization of primary level services have enough potential to meet the demand of slum dwellers at large. 5. Lack of policy driven strategies on how to integrate the NUHM with other thematic areas of Maternal, Newborn & Child Health (MNCH) and Family Planning (FP). 5. The inappropriate capacity building and acute shortage of Human Resources has huge implication on service provisioning and adherence to the service delivery protocols. Conclusion: The findings from rapid assessment are aimed to inform pertinent stakeholders to develop a multiyear city health action plan to strengthen the health systems in order to improve the efficacy of service delivery mechanism in urban settings.

Keywords: city health plan, health system, rapid assessment, urban mission

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452 Gold Nano Particle as a Colorimetric Sensor of HbA0 Glycation Products

Authors: Ranjita Ghoshmoulick, Aswathi Madhavan, Subhavna Juneja, Prasenjit Sen, Jaydeep Bhattacharya

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Type 2 diabetes mellitus (T2DM) is a very complex and multifactorial metabolic disease where the blood sugar level goes up. One of the major consequence of this elevated blood sugar is the formation of AGE (Advance Glycation Endproducts), from a series of chemical or biochemical reactions. AGE are detrimental because it leads to severe pathogenic complications. They are a group of structurally diverse chemical compounds formed from nonenzymatic reactions between the free amino groups (-NH2) of proteins and carbonyl groups (>C=O) of reducing sugars. The reaction is known as Maillard Reaction. It starts with the formation of reversible schiff’s base linkage which after sometime rearranges itself to form Amadori Product along with dicarbonyl compounds. Amadori products are very unstable hence rearrangement goes on until stable products are formed. During the course of the reaction a lot of chemically unknown intermediates and reactive byproducts are formed that can be termed as Early Glycation Products. And when the reaction completes, structurally stable chemical compounds are formed which is termed as Advanced Glycation Endproducts. Though all glycation products have not been characterized well, some fluorescence compounds e.g pentosidine, Malondialdehyde (MDA) or carboxymethyllysine (CML) etc as AGE and α-dicarbonyls or oxoaldehydes such as 3-deoxyglucosone (3-DG) etc as the intermediates have been identified. In this work Gold NanoParticle (GNP) was used as an optical indicator of glycation products. To achieve faster glycation kinetics and high AGE accumulation, fructose was used instead of glucose. Hemoglobin A0 (HbA0) was fructosylated by in-vitro method. AGE formation was measured fluorimetrically by recording emission at 450nm upon excitation at 350nm. Thereafter this fructosylated HbA0 was fractionated by column chromatography. Fractionation separated the proteinaceous substance from the AGEs. Presence of protein part in the fractions was confirmed by measuring the intrinsic protein fluorescence and Bradford reaction. GNPs were synthesized using the templates of chromatographically separated fractions of fructosylated HbA0. Each fractions gave rise to GNPs of varying color, indicating the presence of distinct set of glycation products differing structurally and chemically. Clear solution appeared due to settling down of particles in some vials. The reactive groups of the intermediates kept the GNP formation mechanism on and did not lead to a stable particle formation till Day 10. Whereas SPR of GNP showed monotonous colour for the fractions collected in case of non fructosylated HbA0. Our findings accentuate the use of GNPs as a simple colorimetric sensing platform for the identification of intermediates of glycation reaction which could be implicated in the prognosis of the associated health risk due to T2DM and others.

Keywords: advance glycation endproducts, glycation, gold nano particle, sensor

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451 A Fermatean Fuzzy MAIRCA Approach for Maintenance Strategy Selection of Process Plant Gearbox Using Sustainability Criteria

Authors: Soumava Boral, Sanjay K. Chaturvedi, Ian Howard, Kristoffer McKee, V. N. A. Naikan

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Due to strict regulations from government to enhance the possibilities of sustainability practices in industries, and noting the advances in sustainable manufacturing practices, it is necessary that the associated processes are also sustainable. Maintenance of large scale and complex machines is a pivotal task to maintain the uninterrupted flow of manufacturing processes. Appropriate maintenance practices can prolong the lifetime of machines, and prevent associated breakdowns, which subsequently reduces different cost heads. Selection of the best maintenance strategies for such machines are considered as a burdensome task, as they require the consideration of multiple technical criteria, complex mathematical calculations, previous fault data, maintenance records, etc. In the era of the fourth industrial revolution, organizations are rapidly changing their way of business, and they are giving their utmost importance to sensor technologies, artificial intelligence, data analytics, automations, etc. In this work, the effectiveness of several maintenance strategies (e.g., preventive, failure-based, reliability centered, condition based, total productive maintenance, etc.) related to a large scale and complex gearbox, operating in a steel processing plant is evaluated in terms of economic, social, environmental and technical criteria. As it is not possible to obtain/describe some criteria by exact numerical values, these criteria are evaluated linguistically by cross-functional experts. Fuzzy sets are potential soft-computing technique, which has been useful to deal with linguistic data and to provide inferences in many complex situations. To prioritize different maintenance practices based on the identified sustainable criteria, multi-criteria decision making (MCDM) approaches can be considered as potential tools. Multi-Attributive Ideal Real Comparative Analysis (MAIRCA) is a recent addition in the MCDM family and has proven its superiority over some well-known MCDM approaches, like TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) and ELECTRE (ELimination Et Choix Traduisant la REalité). It has a simple but robust mathematical approach, which is easy to comprehend. On the other side, due to some inherent drawbacks of Intuitionistic Fuzzy Sets (IFS) and Pythagorean Fuzzy Sets (PFS), recently, the use of Fermatean Fuzzy Sets (FFSs) has been proposed. In this work, we propose the novel concept of FF-MAIRCA. We obtain the weights of the criteria by experts’ evaluation and use them to prioritize the different maintenance practices according to their suitability by FF-MAIRCA approach. Finally, a sensitivity analysis is carried out to highlight the robustness of the approach.

Keywords: Fermatean fuzzy sets, Fermatean fuzzy MAIRCA, maintenance strategy selection, sustainable manufacturing, MCDM

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450 Evidence-Based Policy Making to Improve Human Security in Pakistan

Authors: Ayesha Akbar

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Pakistan is moving from a security state to a welfare state despite several security challenges both internal and external. Human security signifies a varied approach in different regions depending upon the leadership and policy priorities. The link between human development and economic growth is not automatic. It has to be created consciously by forward-looking policies and strategies by national governments. There are seven components or categories of human security these include: Economic Security, Personal Security, Health Security, Environmental Security, Food Security, Community Security and Political Security. The increasing interest of the international community to clearly understand the dimensions of human security provided the grounds to Pakistani scholars as well to ponder on the issue and delineate lines of human security. A great deal of work has been either done or in process to evaluate human security indicators in Pakistan. Notwithstanding, after having been done a great deal of work the human security in Pakistan is not satisfactory. A range of deteriorating indicators of human development that lies under the domain of human security leaves certain inquiries to be answered. What are the dimensions of human security in Pakistan? And how are they being dealt from the perspective of policy and institution in terms of its operationalization in Pakistan? Is the human security discourse reflects evidence-based policy changes. The methodology is broadly based on qualitative methods that include interviews, content analysis of policy documents. Pakistan is among the most populous countries in the world and faces high vulnerability to climate change. Literacy rate has gone down with the surge of youth bulge to accommodate in the job market. Increasing population is creating food problems as the resources have not been able to compete with the raising demands of food and other social amenities of life. Majority of the people are facing acute poverty. Health outcomes are also not satisfactory with the high infant and maternal mortality rate. Pakistan is on the verge of facing water crisis as the water resources are depleting so fast with the high demand in agriculture and energy sector. Pakistan is striving hard to deal with the declining state of human security but the dilemma is lack of resources that hinders in meeting up with the emerging demands. The government requires to bring about more change with scaling-up economic growth avenues with enhancing the capacity of human resources. A modern performance drive culture with the integration of technology is required to deliver efficient and effective service delivery. On an already fast track process of reforms; e-governance and evidence based policy mechanism is being instilled in the government process for better governance and evidence based decisions.

Keywords: governance, human development index, human security, Pakistan, policy

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449 Atypical Retinoid ST1926 Nanoparticle Formulation Development and Therapeutic Potential in Colorectal Cancer

Authors: Sara Assi, Berthe Hayar, Claudio Pisano, Nadine Darwiche, Walid Saad

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Nanomedicine, the application of nanotechnology to medicine, is an emerging discipline that has gained significant attention in recent years. Current breakthroughs in nanomedicine have paved the way to develop effective drug delivery systems that can be used to target cancer. The use of nanotechnology provides effective drug delivery, enhanced stability, bioavailability, and permeability, thereby minimizing drug dosage and toxicity. As such, the use of nanoparticle (NP) formulations in drug delivery has been applied in various cancer models and have shown to improve the ability of drugs to reach specific targeted sites in a controlled manner. Cancer is one of the major causes of death worldwide; in particular, colorectal cancer (CRC) is the third most common type of cancer diagnosed amongst men and women and the second leading cause of cancer related deaths, highlighting the need for novel therapies. Retinoids, consisting of natural and synthetic derivatives, are a class of chemical compounds that have shown promise in preclinical and clinical cancer settings. However, retinoids are limited by their toxicity and resistance to treatment. To overcome this resistance, various synthetic retinoids have been developed, including the adamantyl retinoid ST1926, which is a potent anti-cancer agent. However, due to its limited bioavailability, the development of ST1926 has been restricted in phase I clinical trials. We have previously investigated the preclinical efficacy of ST1926 in CRC models. ST1926 displayed potent inhibitory and apoptotic effects in CRC cell lines by inducing early DNA damage and apoptosis. ST1926 significantly reduced the tumor doubling time and tumor burden in a xenograft CRC model. Therefore, we developed ST1926-NPs and assessed their efficacy in CRC models. ST1926-NPs were produced using Flash NanoPrecipitation with the amphiphilic diblock copolymer polystyrene-b-ethylene oxide and cholesterol as a co-stabilizer. ST1926 was formulated into NPs with a drug to polymer mass ratio of 1:2, providing a stable formulation for one week. The contin ST1926-NP diameter was 100 nm, with a polydispersity index of 0.245. Using the MTT cell viability assay, ST1926-NP exhibited potent anti-growth activities as naked ST1926 in HCT116 cells, at pharmacologically achievable concentrations. Future studies will be performed to study the anti-tumor activities and mechanism of action of ST1926-NPs in a xenograft mouse model and to detect the compound and its glucuroconjugated form in the plasma of mice. Ultimately, our studies will support the use of ST1926-NP formulations in enhancing the stability and bioavailability of ST1926 in CRC.

Keywords: nanoparticles, drug delivery, colorectal cancer, retinoids

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448 An Appraisal of Mitigation and Adaptation Measures under Paris Agreement 2015: Developing Nations' Pie

Authors: Olubisi Friday Oluduro

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The Paris Agreement 2015, the result of negotiations under the United Nations Framework Convention on Climate Change (UNFCCC), after Kyoto Protocol expiration, sets a long-term goal of limiting the increase in the global average temperature to well below 2 degrees Celsius above pre-industrial levels, and of pursuing efforts to limiting this temperature increase to 1.5 degrees Celsius. An advancement on the erstwhile Kyoto Protocol which sets commitments to only a limited number of Parties to reduce their greenhouse gas (GHGs) emissions, it includes the goal to increase the ability to adapt to the adverse impacts of climate change and to make finance flows consistent with a pathway towards low GHGs emissions. For it achieve these goals, the Agreement requires all Parties to undertake efforts towards reaching global peaking of GHG emissions as soon as possible and towards achieving a balance between anthropogenic emissions by sources and removals by sinks in the second half of the twenty-first century. In addition to climate change mitigation, the Agreement aims at enhancing adaptive capacity, strengthening resilience and reducing the vulnerability to climate change in different parts of the world. It acknowledges the importance of addressing loss and damage associated with the adverse of climate change. The Agreement also contains comprehensive provisions on support to be provided to developing countries, which includes finance, technology transfer and capacity building. To ensure that such supports and actions are transparent, the Agreement contains a number reporting provisions, requiring parties to choose the efforts and measures that mostly suit them (Nationally Determined Contributions), providing for a mechanism of assessing progress and increasing global ambition over time by a regular global stocktake. Despite the somewhat global look of the Agreement, it has been fraught with manifold limitations threatening its very existential capability to produce any meaningful result. Considering these obvious limitations some of which were the very cause of the failure of its predecessor—the Kyoto Protocol—such as the non-participation of the United States, non-payment of funds into the various coffers for appropriate strategic purposes, among others. These have left the developing countries largely threatened eve the more, being more vulnerable than the developed countries, which are really responsible for the climate change scourge. The paper seeks to examine the mitigation and adaptation measures under the Paris Agreement 2015, appraise the present situation since the Agreement was concluded and ascertain whether the developing countries have been better or worse off since the Agreement was concluded, and examine why and how, while projecting a way forward in the present circumstance. It would conclude with recommendations towards ameliorating the situation.

Keywords: mitigation, adaptation, climate change, Paris agreement 2015, framework

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447 Impact of Experiential Learning on Executive Function, Language Development, and Quality of Life for Adults with Intellectual and Developmental Disabilities (IDD)

Authors: Mary Deyo, Zmara Harrison

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This study reports the outcomes of an 8-week experiential learning program for 6 adults with Intellectual and Developmental Disabilities (IDD) at a day habilitation program. The intervention foci for this program include executive function, language learning in the domains of expressive, receptive, and pragmatic language, and quality of life. The interprofessional collaboration aimed at supporting adults with IDD to reach person-centered, functional goals across skill domains is critical. This study is a significant addition to the speech-language pathology literature in that it examines a therapy method that potentially meets this need while targeting domains within the speech-language pathology scope of practice. Communication therapy was provided during highly valued and meaningful hands-on learning experiences, referred to as the Garden Club, which incorporated all aspects of planting and caring for a garden as well as related journaling, sensory, cooking, art, and technology-based activities. Direct care staff and an undergraduate research assistant were trained by SLP to be impactful language guides during their interactions with participants in the Garden Club. SLP also provided direct therapy and modeling during Garden Club. Research methods used in this study included a mixed methods analysis of a literature review, a quasi-experimental implementation of communication therapy in the context of experiential learning activities, Quality of Life participant surveys, quantitative pre- post- data collection and linear mixed model analysis, qualitative data collection with qualitative content analysis and coding for themes. Outcomes indicated overall positive changes in expressive vocabulary, following multi-step directions, sequencing, problem-solving, planning, skills for building and maintaining meaningful social relationships, and participant perception of the Garden Project’s impact on their own quality of life. Implementation of this project also highlighted supports and barriers that must be taken into consideration when planning similar projects. Overall findings support the use of experiential learning projects in day habilitation programs for adults with IDD, as well as additional research to deepen understanding of best practices, supports, and barriers for implementation of experiential learning with this population. This research provides an important contribution to research in the fields of speech-language pathology and other professions serving adults with IDD by describing an interprofessional experiential learning program with positive outcomes for executive function, language learning, and quality of life.

Keywords: experiential learning, adults, intellectual and developmental disabilities, expressive language, receptive language, pragmatic language, executive function, communication therapy, day habilitation, interprofessionalism, quality of life

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446 Frailty and Quality of Life among Older Adults: A Study of Six LMICs Using SAGE Data

Authors: Mamta Jat

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Background: The increased longevity has resulted in the increase in the percentage of the global population aged 60 years or over. With this “demographic transition” towards ageing, “epidemiologic transition” is also taking place characterised by growing share of non-communicable diseases in the overall disease burden. So, many of the older adults are ageing with chronic disease and high levels of frailty which often results in lower levels of quality of life. Although frailty may be increasingly common in older adults, prevention or, at least, delay the onset of late-life adverse health outcomes and disability is necessary to maintain the health and functional status of the ageing population. This is an effort using SAGE data to assess levels of frailty and its socio-demographic correlates and its relation with quality of life in LMICs of India, China, Ghana, Mexico, Russia and South Africa in a comparative perspective. Methods: The data comes from multi-country Study on Global AGEing and Adult Health (SAGE), consists of nationally representative samples of older adults in six low and middle-income countries (LMICs): China, Ghana, India, Mexico, the Russian Federation and South Africa. For our study purpose, we will consider only 50+ year’s respondents. The logistic regression model has been used to assess the correlates of frailty. Multinomial logistic regression has been used to study the effect of frailty on QOL (quality of life), controlling for the effect of socio-economic and demographic correlates. Results: Among all the countries India is having highest mean frailty in males (0.22) and females (0.26) and China with the lowest mean frailty in males (0.12) and females (0.14). The odds of being frail are more likely with the increase in age across all the countries. In India, China and Russia the chances of frailty are more among rural older adults; whereas, in Ghana, South Africa and Mexico rural residence is protecting against frailty. Among all countries china has high percentage (71.46) of frail people in low QOL; whereas Mexico has lowest percentage (36.13) of frail people in low QOL.s The risk of having low and middle QOL is significantly (p<0.001) higher among frail elderly as compared to non–frail elderly across all countries with controlling socio-demographic correlates. Conclusion: Women and older age groups are having higher frailty levels than men and younger aged adults in LMICs. The mean frailty scores demonstrated a strong inverse relationship with education and income gradients, while lower levels of education and wealth are showing higher levels of frailty. These patterns are consistent across all LMICs. These data support a significant role of frailty with all other influences controlled, in having low QOL as measured by WHOQOL index. Future research needs to be built on this evolving concept of frailty in an effort to improve quality of life for frail elderly population, in LMICs setting.

Keywords: Keywords: Ageing, elderly, frailty, quality of life

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445 Mirna Expression Profile is Different in Human Amniotic Mesenchymal Stem Cells Isolated from Obese Respect to Normal Weight Women

Authors: Carmela Nardelli, Laura Iaffaldano, Valentina Capobianco, Antonietta Tafuto, Maddalena Ferrigno, Angela Capone, Giuseppe Maria Maruotti, Maddalena Raia, Rosa Di Noto, Luigi Del Vecchio, Pasquale Martinelli, Lucio Pastore, Lucia Sacchetti

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Maternal obesity and nutrient excess in utero increase the risk of future metabolic diseases in the adult life. The mechanisms underlying this process are probably based on genetic, epigenetic alterations and changes in foetal nutrient supply. In mammals, the placenta is the main interface between foetus and mother, it regulates intrauterine development, modulates adaptive responses to sub optimal in uterus conditions and it is also an important source of human amniotic mesenchymal stem cells (hA-MSCs). We previously highlighted a specific microRNA (miRNA) profiling in amnion from obese (Ob) pregnant women, here we compared the miRNA expression profile of hA-MSCs isolated from (Ob) and control (Co) women, aimed to search for any alterations in metabolic pathways that could predispose the new-born to the obese phenotype. Methods: We isolated, at delivery, hA-MSCs from amnion of 16 Ob- and 7 Co-women with pre-pregnancy body mass index (mean/SEM) 40.3/1.8 and 22.4/1.0 kg/m2, respectively. hA-MSCs were phenotyped by flow cytometry. Globally, 384 miRNAs were evaluated by the TaqMan Array Human MicroRNA Panel v 1.0 (Applied Biosystems). By the TargetScan program we selected the target genes of the miRNAs differently expressed in Ob- vs Co-hA-MSCs; further, by KEGG database, we selected the statistical significant biological pathways. Results: The immunophenotype characterization confirmed the mesenchymal origin of the isolated hA-MSCs. A large percentage of the tested miRNAs, about 61.4% (232/378), was expressed in hA-MSCs, whereas 38.6% (146/378) was not. Most of the expressed miRNAs (89.2%, 207/232) did not differ between Ob- and Co-hA-MSCs and were not further investigated. Conversely, 4.8% of miRNAs (11/232) was higher and 6.0% (14/232) was lower in Ob- vs Co-hA-MSCs. Interestingly, 7/232 miRNAs were obesity-specific, being expressed only in hA-MSCs isolated from obese women. Bioinformatics showed that these miRNAs significantly regulated (P<0.001) genes belonging to several metabolic pathways, i.e. MAPK signalling, actin cytoskeleton, focal adhesion, axon guidance, insulin signaling, etc. Conclusions: Our preliminary data highlight an altered miRNA profile in Ob- vs Co-hA-MSCs and suggest that an epigenetic miRNA-based mechanism of gene regulation could affect pathways involved in placental growth and function, thereby potentially increasing the newborn’s risk of metabolic diseases in the adult life.

Keywords: hA-MSCs, obesity, miRNA, biosystem

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444 Impact of Helicobacter pylori Infection on Colorectal Adenoma-Colorectal Carcinoma Sequence

Authors: Jannis Kountouras, Nikolaos Kapetanakis, Stergios A. Polyzos, Apostolis Papaeftymiou, Panagiotis Katsinelos, Ioannis Venizelos, Christina Nikolaidou, Christos Zavos, Iordanis Romiopoulos, Elena Tsiaousi, Evangelos Kazakos, Michael Doulberis

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Background & Aims: Helicobacter pylori infection (Hp-I) has been recognized as a substantial risk agent involved in gastrointestinal (GI) tract oncogenesis by stimulating cancer stem cells (CSCs), oncogenes, immune surveillance processes, and triggering GI microbiota dysbiosis. We aimed to investigate the possible involvement of active Hp-I in the sequence: chronic inflammation–adenoma–colorectal cancer (CRC) development. Methods: Four pillars were investigated: (i) endoscopic and conventional histological examinations of patients with CRC, colorectal adenomas (CRA) versus controls to detect the presence of active Hp-I; (ii) immunohistochemical determination of the presence of Hp; expression of CD44, an indicator of CSCs and/or bone marrow-derived stem cells (BMDSCs); expressions of oncogene Ki67 and anti-apoptotic Bcl-2 protein; (iii) expression of CD45, indicator of immune surveillance locally (assessing mainly T and B lymphocytes locally); and (iv) correlation of the studied parameters with the presence or absence of Hp-I. Results: Among 50 patients with CRC, 25 with CRA, and 10 controls, a significantly higher presence of Hp-I in the CRA (68%) and CRC group (84%) were found compared with controls (30%). The presence of Hp-I with accompanying immunohistochemical expression of CD44 in biopsy specimens was revealed in a high proportion of patients with CRA associated with moderate/severe dysplasia (88%) and CRC patients with moderate/severe degree of malignancy (91%). Comparable results were also obtained for Ki67, Bcl-2, and CD45 immunohistochemical expressions. Concluding Remarks: Hp-I seems to be involved in the sequence: CRA – dysplasia – CRC, similarly to the upper GI tract oncogenesis, by several pathways such as the following: Beyond Hp-I associated insulin resistance, the major underlying mechanism responsible for the metabolic syndrome (MetS) that increase the risk of colorectal neoplasms, as implied by other Hp-I related MetS pathologies, such as non-alcoholic fatty liver disease and upper GI cancer, the disturbance of the normal GI microbiota (i.e., dysbiosis) and the formation of an irritative biofilm could contribute to a perpetual inflammatory upper GIT and colon mucosal damage, stimulating CSCs or recruiting BMDSCs and affecting oncogenes and immune surveillance processes. Further large-scale relative studies with a pathophysiological perspective are necessary to demonstrate in-depth this relationship.

Keywords: Helicobacter pylori, colorectal cancer, colorectal adenomas, gastrointestinal oncogenesis

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443 Deforestation, Vulnerability and Adaptation Strategies of Rural Farmers: The Case of Central Rift Valley Region of Ethiopia

Authors: Dembel Bonta Gebeyehu

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In the study area, the impacts of deforestation for environmental degradation and livelihood of farmers manifest in different faces. They are more vulnerable as they depend on rain-fed agriculture and immediate natural forests. On the other hand, after planting seedling, waste disposal and management system of the plastic cover is poorly practiced and administered in the country in general and in the study area in particular. If this situation continues, the plastic waste would also accentuate land degradation. Besides, there is the absence of empirical studies conducted comprehensively on the research under study the case. The results of the study could suffice to inform any intervention schemes or to contribute to the existing knowledge on these issues. The study employed a qualitative approach based on intensive fieldwork data collected via various tools namely open-ended interviews, focus group discussion, key-informant interview and non-participant observation. The collected data was duly transcribed and latter categorized into different labels based on pre-determined themes to make further analysis. The major causes of deforestation were the expansion of agricultural land, poor administration, population growth, and the absence of conservation methods. The farmers are vulnerable to soil erosion and soil infertility culminating in low agricultural production; loss of grazing land and decline of livestock production; climate change; and deterioration of social capital. Their adaptation and coping strategies include natural conservation measures, diversification of income sources, safety-net program, and migration. Due to participatory natural resource conservation measures, soil erosion has been decreased and protected, indigenous woodlands started to regenerate. These brought farmers’ attitudinal change. The existing forestation program has many flaws. Especially, after planting seedlings, there is no mechanism for the plastic waste disposal and management. It was also found out organizational challenges among the mandated offices In the studied area, deforestation is aggravated by a number of factors, which made the farmers vulnerable. The current forestation programs are not well-planned, implemented, and coordinated. Sustainable and efficient seedling plastic cover collection and reuse methods should be devised. This is possible through creating awareness, organizing micro and small enterprises to reuse, and generate income from the collected plastic etc.

Keywords: land-cover and land-dynamics, vulnerability, adaptation strategy, mitigation strategies, sustainable plastic waste management

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442 Screening Tools and Its Accuracy for Common Soccer Injuries: A Systematic Review

Authors: R. Christopher, C. Brandt, N. Damons

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Background: The sequence of prevention model states that by constant assessment of injury, injury mechanisms and risk factors are identified, highlighting that collecting and recording of data is a core approach for preventing injuries. Several screening tools are available for use in the clinical setting. These screening techniques only recently received research attention, hence there is a dearth of inconsistent and controversial data regarding their applicability, validity, and reliability. Several systematic reviews related to common soccer injuries have been conducted; however, none of them addressed the screening tools for common soccer injuries. Objectives: The purpose of this study was to conduct a review of screening tools and their accuracy for common injuries in soccer. Methods: A systematic scoping review was performed based on the Joanna Briggs Institute procedure for conducting systematic reviews. Databases such as SPORT Discus, Cinahl, Medline, Science Direct, PubMed, and grey literature were used to access suitable studies. Some of the key search terms included: injury screening, screening, screening tool accuracy, injury prevalence, injury prediction, accuracy, validity, specificity, reliability, sensitivity. All types of English studies dating back to the year 2000 were included. Two blind independent reviewers selected and appraised articles on a 9-point scale for inclusion as well as for the risk of bias with the ACROBAT-NRSI tool. Data were extracted and summarized in tables. Plot data analysis was done, and sensitivity and specificity were analyzed with their respective 95% confidence intervals. I² statistic was used to determine the proportion of variation across studies. Results: The initial search yielded 95 studies, of which 21 were duplicates, and 54 excluded. A total of 10 observational studies were included for the analysis: 3 studies were analysed quantitatively while the remaining 7 were analysed qualitatively. Seven studies were graded low and three studies high risk of bias. Only high methodological studies (score > 9) were included for analysis. The pooled studies investigated tools such as the Functional Movement Screening (FMS™), the Landing Error Scoring System (LESS), the Tuck Jump Assessment, the Soccer Injury Movement Screening (SIMS), and the conventional hamstrings to quadriceps ratio. The accuracy of screening tools was of high reliability, sensitivity and specificity (calculated as ICC 0.68, 95% CI: 52-0.84; and 0.64, 95% CI: 0.61-0.66 respectively; I² = 13.2%, P=0.316). Conclusion: Based on the pooled results from the included studies, the FMS™ has a good inter-rater and intra-rater reliability. FMS™ is a screening tool capable of screening for common soccer injuries, and individual FMS™ scores are a better determinant of performance in comparison with the overall FMS™ score. Although meta-analysis could not be done for all the included screening tools, qualitative analysis also indicated good sensitivity and specificity of the individual tools. Higher levels of evidence are, however, needed for implication in evidence-based practice.

Keywords: accuracy, screening tools, sensitivity, soccer injuries, specificity

Procedia PDF Downloads 158
441 Functional Analysis of Variants Implicated in Hearing Loss in a Cohort from Argentina: From Molecular Diagnosis to Pre-Clinical Research

Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

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Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

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440 Combined Treatment of Estrogen-Receptor Positive Breast Microtumors with 4-Hydroxytamoxifen and Novel Non-Steroidal Diethyl Stilbestrol-Like Analog Produces Enhanced Preclinical Treatment Response and Decreased Drug Resistance

Authors: Sarah Crawford, Gerry Lesley

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This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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439 From Preoccupied Attachment Pattern to Depression: Serial Mediation Model on the Female Sample

Authors: Tatjana Stefanovic Stanojevic, Milica Tosic Radev, Aleksandra Bogdanovic

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Depression is considered to be a leading cause of death and disability in the female population, and that is the reason why understanding the dynamics of the onset of depressive symptomatology is important. A review of the literature indicates the relationship between depressive symptoms and insecure attachment patterns, but very few studies have examined the mechanism underlying this relation. The aim of the study was to examine the pathway from the preoccupied attachment pattern to depressive symptomatology, as well as to test the mediation effect of mentalization, social anxiety and rumination in this relationship using a serial mediation model. The research was carried out on a geographical cluster sample from the general population of Serbia included within the project ‘Indicators and models of family and work roles harmonization’ funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia. This research was carried out on a subsample of 791 working-age female adults from 37 urban and rural locations distributed through 20 administrative districts of Serbia. The respondents filled in a battery of instruments, including Relationship Questionnaire - Clinical Version (RQ - CV), The Mentalization Scale (MentS), Scale of Social Anxiety (SA), Patient Ruminative Thought Style Questionnaire (RTSQ), Health Questionnaire (PHQ-9). The results confirm our assumption that the total indirect effect of the preoccupied attachment pattern to depressive symptoms is significant across all mediators separately. More importantly, this effect is still present in a model with a sequential mediator relationship, where social anxiety, rumination, and mentalization were perceived as serial mediators of a relationship between preoccupied attachment and depressive symptoms (estimated indirect effect=0.004, boot-strapped 95% CI=0.002 to 0.007). Our findings suggest that there is a significant specific indirect effect of the preoccupied attachment pattern to depressive symptoms, occurring through mentalization, social anxiety and rumination, indicating that preoccupied attachment cause decrease of a self related mentalization, which in turn causes increasing of social anxiety and rumination, concluding in depressive symptoms as a final consequence. The finding that the path from the preoccupied attachment pattern to depressive symptoms is typical in women is understandable from the perspective of both evolutionary and culturally conditioned gender differences. The practical implications of the study are reflected in the recommendations for the prevention and forehand psychotherapy response among preoccupied women with depressive symptomatology. Treatment of this specific group of depressed patients should be focused on strengthening mentalization, learning to accept and to understand herself better, reducing anxiety in situations where mistakes are visible to others, and replacing the rumination strategy with more constructive coping strategies.

Keywords: preoccupied attachment, depression, serial mediation model, mentalization, rumination

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438 Urban Planning Patterns after (COVID-19): An Assessment toward Resiliency

Authors: Mohammed AL-Hasani

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The Pandemic COVID-19 altered the daily habits and affected the functional performance of the cities after this crisis leaving remarkable impacts on many metropolises worldwide. It is so obvious that having more densification in the city leads to more threats altering this main approach that was called for achieving sustainable development. The main goal to achieve resiliency in the cities, especially in forcing risks, is to deal with a planning system that is able to resist, absorb, accommodate and recover from the impacts that had been affected. Many Cities in London, Wuhan, New York, and others worldwide carried different planning approaches and varied in reaction to safeguard the impacts of the pandemic. The cities globally varied from the radiant pattern predicted by Le Corbusier, or having multi urban centers more like the approach of Frank Lloyd Wright’s Broadacre City, or having linear growth or gridiron expansion that was common by Doxiadis, compact pattern, and many other hygiene patterns. These urban patterns shape the spatial distribution and Identify both open and natural spaces with gentrified and gentrifying areas. This crisis paid attention to reassess many planning approaches and examine the existing urban patterns focusing more on the aim of continuity and resiliency in managing the crises within the rapid transformation and the power of market forces. According to that, this paper hypothesized that those urban planning patterns determine the method of reaction in assuring quarantine for the inhabitance and the performance of public services and need to be updated through carrying out an innovative urban management system and adopt further resilience patterns in prospective urban planning approaches. This paper investigates the adaptivity and resiliency of variant urban planning patterns regarding selected cities worldwide that affected by COVID-19 and their role in applying certain management strategies in controlling the pandemic spread, finding out the main potentials that should be included in prospective planning approaches. The examination encompasses the spatial arrangement, blocks definition, plots arrangement, and urban space typologies. This paper aims to investigate the urban patterns to deliberate also the debate between densification as one of the more sustainable planning approaches and disaggregation tendency that was followed after the pandemic by restructuring and managing its application according to the assessment of the spatial distribution and urban patterns. The biggest long-term threat to dense cities proves the need to shift to online working and telecommuting, creating a mixture between using cyber and urban spaces to remobilize the city. Reassessing spatial design and growth, open spaces, urban population density, and public awareness are the main solutions that should be carried out to face the outbreak in our current cities that should be managed from global to tertiary levels and could develop criteria for designing the prospective cities

Keywords: COVID-19, densification, resiliency, urban patterns

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437 Teaching Timber: The Role of the Architectural Student and Studio Course within an Interdisciplinary Research Project

Authors: Catherine Sunter, Marius Nygaard, Lars Hamran, Børre Skodvin, Ute Groba

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Globally, the construction and operation of buildings contribute up to 30% of annual green house gas emissions. In addition, the building sector is responsible for approximately a third of global waste. In this context, the utilization of renewable resources in buildings, especially materials that store carbon, will play a significant role in the growing city. These are two reasons for introducing wood as a building material with a growing relevance. A third is the potential economic value in countries with a forest industry that is not currently used to capacity. In 2013, a four-year interdisciplinary research project titled “Wood Be Better” was created, with the principle goal to produce and publicise knowledge that would facilitate increased use of wood in buildings in urban areas. The research team consisted of architects, engineers, wood technologists and mycologists, both from research institutions and industrial organisations. Five structured work packages were included in the initial research proposal. Work package 2 was titled “Design-based research” and proposed using architecture master courses as laboratories for systematic architectural exploration. The aim was twofold: to provide students with an interdisciplinary team of experts from consultancies and producers, as well as teachers and researchers, that could offer the latest information on wood technologies; whilst at the same time having the studio course test the effects of the use of wood on the functional, technical and tectonic quality within different architectural projects on an urban scale, providing results that could be fed back into the research material. The aim of this article is to examine the successes and failures of this pedagogical approach in an architecture school, as well as the opportunities for greater integration between academic research projects, industry experts and studio courses in the future. This will be done through a set of qualitative interviews with researchers, teaching staff and students of the studio courses held each semester since spring 2013. These will investigate the value of the various experts of the course; the different themes of each course; the response to the urban scale, architectural form and construction detail; the effect of working with the goals of a research project; and the value of the studio projects to the research. In addition, six sample projects will be presented as case studies. These will show how the projects related to the research and could be collected and further analysed, innovative solutions that were developed during the course, different architectural expressions that were enabled by timber, and how projects were used as an interdisciplinary testing ground for integrated architectural and engineering solutions between the participating institutions. The conclusion will reflect on the original intentions of the studio courses, the opportunities and challenges faced by students, researchers and teachers, the educational implications, and on the transparent and inclusive discourse between the architectural researcher, the architecture student and the interdisciplinary experts.

Keywords: architecture, interdisciplinary, research, studio, students, wood

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436 Dys-Regulation of Immune and Inflammatory Response in in vitro Fertilization Implantation Failure Patients under Ovarian Stimulation

Authors: Amruta D. S. Pathare, Indira Hinduja, Kusum Zaveri

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Implantation failure (IF) even after the good-quality embryo transfer (ET) in the physiologically normal endometrium is the main obstacle in in vitro fertilization (IVF). Various microarray studies have been performed worldwide to elucidate the genes requisite for endometrial receptivity. These studies have included the population based on different phases of menstrual cycle during natural cycle and stimulated cycle in normal fertile women. Additionally, the literature is also available in recurrent implantation failure patients versus oocyte donors in natural cycle. However, for the first time, we aim to study the genomics of endometrial receptivity in IF patients under controlled ovarian stimulation (COS) during which ET is generally practised in IVF. Endometrial gene expression profiling in IF patients (n=10) and oocyte donors (n=8) were compared during window of implantation under COS by whole genome microarray (using Illumina platform). Enrichment analysis of microarray data was performed to determine dys-regulated biological functions and pathways using Database for Annotation, Visualization and Integrated Discovery, v6.8 (DAVID). The enrichment mapping was performed with the help of Cytoscape software. Microarray results were validated by real-time PCR. Localization of genes related to immune response (Progestagen-Associated Endometrial Protein (PAEP), Leukaemia Inhibitory Factor (LIF), Interleukin-6 Signal Transducer (IL6ST) was detected by immunohistochemistry. The study revealed 418 genes downregulated and 519 genes upregulated in IF patients compared to healthy fertile controls. The gene ontology, pathway analysis and enrichment mapping revealed significant downregulation in activation and regulation of immune and inflammation response in IF patients under COS. The lower expression of Progestagen Associated Endometrial Protein (PAEP), Leukemia Inhibitory Factor (LIF) and Interleukin 6 Signal Transducer (IL6ST) in cases compared to controls by real time and immunohistochemistry suggests the functional importance of these genes. The study was proved useful to uncover the probable reason of implantation failure being imbalance of immune and inflammatory regulation in our group of subjects. Based on the present study findings, a panel of significant dysregulated genes related to immune and inflammatory pathways needs to be further substantiated in larger cohort in natural as well as stimulated cycle. Upon which these genes could be screened in IF patients during window of implantation (WOI) before going for embryo transfer or any other immunological treatment. This would help to estimate the regulation of specific immune response during WOI in a patient. The appropriate treatment of either activation of immune response or suppression of immune response can be then attempted in IF patients to enhance the receptivity of endometrium.

Keywords: endometrial receptivity, immune and inflammatory response, gene expression microarray, window of implantation

Procedia PDF Downloads 127
435 De-Densifying Congested Cores of Cities and Their Emerging Design Opportunities

Authors: Faith Abdul Rasak Asharaf

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Every city has a threshold known as urban carrying capacity based on which it can withstand a particular density of people, above which the city might need to resort to measures like expanding its boundaries or growing vertically. As a result of this circumstance, the number of squatter communities is growing, as is the claustrophobic feeling of being confined inside a "concrete jungle." The expansion of suburbs, commercial areas, and industrial real estate in the areas surrounding medium-sized cities has resulted in changes to their landscapes and urban forms, as well as a systematic shift in their role in the urban hierarchy when functional endowment and connections to other territories are considered. The urban carrying capacity idea provides crucial guidance for city administrators and planners in better managing, designing, planning, constructing, and distributing urban resources to satisfy the huge demands of an evergrowing urban population. An ecological footprint is a criterion of urban carrying capacity, which is the amount of land required to provide humanity with renewable resources and absorb its trash. However, as each piece of land has its unique carrying capacity, including ecological, social, and economic considerations, these metropolitan areas begin to reach a saturation point over time. Various city models have been tried throughout the years to meet the increasing urban population density by moving the zones of work, life, and leisure to achieve maximum sustainable growth. The current scenario is that of a vertical city and compact city concept, in which the maximum density of people is attempted to fit into a definite area using efficient land use and a variety of other strategies, but this has proven to be a very unsustainable method of growth, as evidenced by the COVID-19 period. Due to a shortage of housing and basic infrastructure, densely populated cities gave rise to massive squatter communities, unable to accommodate the overflowing migrants. To achieve optimum carrying capacity, planning measures such as polycentric city and diffuse city concepts can be implemented, which will help to relieve the congested city core by relocating certain sectors of the town to the city periphery, which will help to create newer spaces for design in terms of public space, transportation, and housing, which is a major concern in the current scenario. The study's goal is focused on suggesting design options and solutions in terms of placemaking for better urban quality and urban life for the citizens once city centres have been de-densified based on urban carrying capacity and ecological footprint, taking the case of Kochi as an apt example of a highly densified city core, focusing on Edappally, which is an agglomeration of many urban factors.

Keywords: urban carrying capacity, urbanization, urban sprawl, ecological footprint

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434 Evolutionary Advantages of Loneliness with an Agent-Based Model

Authors: David Gottlieb, Jason Yoder

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The feeling of loneliness is not uncommon in modern society, and yet, there is a fundamental lack of understanding in its origins and purpose in nature. One interpretation of loneliness is that it is a subjective experience that punishes a lack of social behavior, and thus its emergence in human evolution is seemingly tied to the survival of early human tribes. Still, a common counterintuitive response to loneliness is a state of hypervigilance, resulting in social withdrawal, which may appear maladaptive to modern society. So far, no computational model of loneliness’ effect during evolution yet exists; however, agent-based models (ABM) can be used to investigate social behavior, and applying evolution to agents’ behaviors can demonstrate selective advantages for particular behaviors. We propose an ABM where each agent contains four social behaviors, and one goal-seeking behavior, letting evolution select the best behavioral patterns for resource allocation. In our paper, we use an algorithm similar to the boid model to guide the behavior of agents, but expand the set of rules that govern their behavior. While we use cohesion, separation, and alignment for simple social movement, our expanded model adds goal-oriented behavior, which is inspired by particle swarm optimization, such that agents move relative to their personal best position. Since agents are given the ability to form connections by interacting with each other, our final behavior guides agent movement toward its social connections. Finally, we introduce a mechanism to represent a state of loneliness, which engages when an agent's perceived social involvement does not meet its expected social involvement. This enables us to investigate a minimal model of loneliness, and using evolution we attempt to elucidate its value in human survival. Agents are placed in an environment in which they must acquire resources, as their fitness is based on the total resource collected. With these rules in place, we are able to run evolution under various conditions, including resource-rich environments, and when disease is present. Our simulations indicate that there is strong selection pressure for social behavior under circumstances where there is a clear discrepancy between initial resource locations, and against social behavior when disease is present, mirroring hypervigilance. This not only provides an explanation for the emergence of loneliness, but also reflects the diversity of response to loneliness in the real world. In addition, there is evidence of a richness of social behavior when loneliness was present. By introducing just two resource locations, we observed a divergence in social motivation after agents became lonely, where one agent learned to move to the other, who was in a better resource position. The results and ongoing work from this project show that it is possible to glean insight into the evolutionary advantages of even simple mechanisms of loneliness. The model we developed has produced unexpected results and has led to more questions, such as the impact loneliness would have at a larger scale, or the effect of creating a set of rules governing interaction beyond adjacency.

Keywords: agent-based, behavior, evolution, loneliness, social

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433 Effects of Soil Neutron Irradiation in Soil Carbon Neutron Gamma Analysis

Authors: Aleksandr Kavetskiy, Galina Yakubova, Nikolay Sargsyan, Stephen A. Prior, H. Allen Torbert

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The carbon sequestration question of modern times requires the development of an in-situ method of measuring soil carbon over large landmasses. Traditional chemical analytical methods used to evaluate large land areas require extensive soil sampling prior to processing for laboratory analysis; collectively, this is labor-intensive and time-consuming. An alternative method is to apply nuclear physics analysis, primarily in the form of pulsed fast-thermal neutron-gamma soil carbon analysis. This method is based on measuring the gamma-ray response that appears upon neutron irradiation of soil. Specific gamma lines with energies of 4.438 MeV appearing from neutron irradiation can be attributed to soil carbon nuclei. Based on measuring gamma line intensity, assessments of soil carbon concentration can be made. This method can be done directly in the field using a specially developed pulsed fast-thermal neutron-gamma system (PFTNA system). This system conducts in-situ analysis in a scanning mode coupled with GPS, which provides soil carbon concentration and distribution over large fields. The system has radiation shielding to minimize the dose rate (within radiation safety guidelines) for safe operator usage. Questions concerning the effect of neutron irradiation on soil health will be addressed. Information regarding absorbed neutron and gamma dose received by soil and its distribution with depth will be discussed in this study. This information was generated based on Monte-Carlo simulations (MCNP6.2 code) of neutron and gamma propagation in soil. Received data were used for the analysis of possible induced irradiation effects. The physical, chemical and biological effects of neutron soil irradiation were considered. From a physical aspect, we considered neutron (produced by the PFTNA system) induction of new isotopes and estimated the possibility of increasing the post-irradiation gamma background by comparisons to the natural background. An insignificant increase in gamma background appeared immediately after irradiation but returned to original values after several minutes due to the decay of short-lived new isotopes. From a chemical aspect, possible radiolysis of water (presented in soil) was considered. Based on stimulations of radiolysis of water, we concluded that the gamma dose rate used cannot produce gamma rays of notable rates. Possible effects of neutron irradiation (by the PFTNA system) on soil biota were also assessed experimentally. No notable changes were noted at the taxonomic level, nor was functional soil diversity affected. Our assessment suggested that the use of a PFTNA system with a neutron flux of 1e7 n/s for soil carbon analysis does not notably affect soil properties or soil health.

Keywords: carbon sequestration, neutron gamma analysis, radiation effect on soil, Monte-Carlo simulation

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432 An Approach to Determine the in Transit Vibration to Fresh Produce Using Long Range Radio (LORA) Wireless Transducers

Authors: Indika Fernando, Jiangang Fei, Roger Stanely, Hossein Enshaei

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Ever increasing demand for quality fresh produce by the consumers, had increased the gravity on the post-harvest supply chains in multi-fold in the recent years. Mechanical injury to fresh produce was a critical factor for produce wastage, especially with the expansion of supply chains, physically extending to thousands of miles. The impact of vibration damages in transit was identified as a specific area of focus which results in wastage of significant portion of the fresh produce, at times ranging from 10% to 40% in some countries. Several studies were concentrated on quantifying the impact of vibration to fresh produce, and it was a challenge to collect vibration impact data continuously due to the limitations in battery life or the memory capacity in the devices. Therefore, the study samples were limited to a stretch of the transit passage or a limited time of the journey. This may or may not give an accurate understanding of the vibration impacts encountered throughout the transit passage, which limits the accuracy of the results. Consequently, an approach which can extend the capacity and ability of determining vibration signals in the transit passage would contribute to accurately analyze the vibration damage along the post-harvest supply chain. A mechanism was developed to address this challenge, which is capable of measuring the in transit vibration continuously through the transit passage subject to a minimum acceleration threshold (0.1g). A system, consisting six tri-axel vibration transducers installed in different locations inside the cargo (produce) pallets in the truck, transmits vibration signals through LORA (Long Range Radio) technology to a central device installed inside the container. The central device processes and records the vibration signals transmitted by the portable transducers, along with the GPS location. This method enables to utilize power consumption for the portable transducers to maximize the capability of measuring the vibration impacts in the transit passage extending to days in the distribution process. The trial tests conducted using the approach reveals that it is a reliable method to measure and quantify the in transit vibrations along the supply chain. The GPS capability enables to identify the locations in the supply chain where the significant vibration impacts were encountered. This method contributes to determining the causes, susceptibility and intensity of vibration impact damages to fresh produce in the post-harvest supply chain. Extensively, the approach could be used to determine the vibration impacts not limiting to fresh produce, but for products in supply chains, which may extend from few hours to several days in transit.

Keywords: post-harvest, supply chain, wireless transducers, LORA, fresh produce

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431 Bioactive Substances-Loaded Water-in-Oil/Oil-in-Water Emulsions for Dietary Supplementation in the Elderly

Authors: Agnieszka Markowska-Radomska, Ewa Dluska

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Maintaining a bioactive substances dense diet is important for the elderly, especially to prevent diseases and to support healthy ageing. Adequate bioactive substances intake can reduce the risk of developing chronic diseases (e.g. cardiovascular, osteoporosis, neurodegenerative syndromes, diseases of the oral cavity, gastrointestinal (GI) disorders, diabetes, and cancer). This can be achieved by introducing a comprehensive supplementation of components necessary for the proper functioning of the ageing body. The paper proposes the multiple emulsions of the W1/O/W2 (water-in-oil-in-water) type as carriers for effective co-encapsulation and co-delivery of bioactive substances in supplementation of the elderly. Multiple emulsions are complex structured systems ("drops in drops"). The functional structure of the W1/O/W2 emulsion enables (i) incorporation of one or more bioactive components (lipophilic and hydrophilic); (ii) enhancement of stability and bioavailability of encapsulated substances; (iii) prevention of interactions between substances, as well as with the external environment, delivery to a specific location; and (iv) release in a controlled manner. The multiple emulsions were prepared by a one-step method in the Couette-Taylor flow (CTF) contactor in a continuous manner. In general, a two-step emulsification process is used to obtain multiple emulsions. The paper contains a proposal of emulsion functionalization by introducing pH-responsive biopolymer—carboxymethylcellulose sodium salt (CMC-Na) to the external phase, which made it possible to achieve a release of components controlled by the pH of the gastrointestinal environment. The membrane phase of emulsions was soybean oil. The W1/O/W2 emulsions were evaluated for their characteristics (drops size/drop size distribution, volume packing fraction), encapsulation efficiency and stability during storage (to 30 days) at 4ºC and 25ºC. Also, the in vitro multi-substance co-release process were investigated in a simulated gastrointestinal environment (different pH and composition of release medium). Three groups of stable multiple emulsions were obtained: emulsions I with co-encapsulated vitamins B12, B6 and resveratrol; emulsions II with vitamin A and β-carotene; and emulsions III with vitamins C, E and D3. The substances were encapsulated in the appropriate emulsion phases depending on the solubility. For all emulsions, high encapsulation efficience (over 95%) and high volume packing fraction of internal droplets (0.54-0.76) were reached. In addition, due to the presence of a polymer (CMC-Na) with adhesive properties, high encapsulation stability during emulsions storage were achieved. The co-release study of encapsulated bioactive substances confirmed the possibility to modify the release profiles. It was found that the releasing process can be controlled through the composition, structure, physicochemical parameters of emulsions and pH of the release medium. The results showed that the obtained multiple emulsions might be used as potential liquid complex carriers for controlled/modified/site-specific co-delivery of bioactive substances in dietary supplementation in the elderly.

Keywords: bioactive substance co-release, co-encapsulation, elderly supplementation, multiple emulsion

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430 The Effect of Mindfulness-Based Interventions for Individuals with Tourette Syndrome: A Scoping Review

Authors: Ilana Singer, Anastasia Lučić, Julie Leclerc

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Introduction: Tics, characterized by repetitive, sudden, non-voluntary motor movements or vocalizations, are prevalent in chronic tic disorder (CT) and Tourette Syndrome (TS). These neurodevelopmental disorders often coexist with various psychiatric conditions, leading to challenges and reduced quality of life. While medication in conjunction with behavioral interventions, such as Habit Reversal Training (HRT), Exposure Response Prevention (ERP), and Comprehensive Behavioral Intervention for Tics (CBIT), has shown efficacy, a significant proportion of patients experience persistent tics. Thus, innovative treatment approaches are necessary to improve therapeutic outcomes, such as mindfulness-based approaches. Nonetheless, the effectiveness of mindfulness-based interventions in the context of CT and TS remains understudied. Objective: The objective of this scoping review is to provide an overview of the current state of research on mindfulness-based interventions for CT and TS, identify knowledge and evidence gaps, discuss the effectiveness of mindfulness-based interventions with other treatment options, and discuss implications for clinical practice and policy development. Method: Using guidelines from Peters (2020) and the PRISMA-ScR, a scoping review was conducted. Multiple electronic databases were searched from inception until June 2023, including MEDLINE, EMBASE, PsychInfo, Global Health, PubMed, Web of Science, and Érudit. Inclusion criteria were applied to select relevant studies, and data extraction was independently performed by two reviewers. Results: Five papers were included in the study. Firstly, we found that mindfulness interventions were found to be effective in reducing anxiety and depression while enhancing overall well-being in individuals with tics. Furthermore, the review highlighted the potential role of mindfulness in enhancing functional connectivity within the Default Mode Network (DMN) as a compensatory function in TS patients. This suggests that mindfulness interventions may complement and support traditional therapeutic approaches, particularly HRT, by positively influencing brain networks associated with tic regulation and control. Conclusion: This scoping review contributes to the understanding of the effectiveness of mindfulness-based interventions in managing CT and TS. By identifying research gaps, this review can guide future investigations and interventions to improve outcomes for individuals with CT or TS. Overall, these findings emphasize the potential benefits of incorporating mindfulness-based interventions as a smaller subset within comprehensive treatment strategies. However, it is essential to acknowledge the limitations of this scoping review, such as the exclusion of a pre-established protocol and the limited number of studies available for inclusion. Further research and clinical exploration are necessary to better understand the specific mechanisms and optimal integration of mindfulness-based interventions with existing behavioral interventions for this population.

Keywords: scoping reviews, Tourette Syndrome, tics, mindfulness-based, therapy, intervention

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429 Crosslinked Porous 3-Dimensional Cellulose Nanofibers/Gelatin Based Biocomposite Aerogels for Tissue Engineering Application

Authors: Ali Mirtaghavi, Andy Baldwin, Rajendarn Muthuraj, Jack Luo

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Recent advances in biomaterials have led to utilizing biopolymers to develop 3D scaffolds in tissue regeneration. One of the major challenges of designing biomaterials for 3D scaffolds is to mimic the building blocks similar to the extracellular matrix (ECM) of the native tissues. Biopolymer based aerogels obtained by freeze-drying have shown to provide structural similarities to the ECM owing to their 3D format and a highly porous structure with interconnected pores, similar to the ECM. Gelatin (GEL) is known to be a promising biomaterial with inherent regenerative characteristics owing to its chemical similarities to the ECM in native tissue, biocompatibility abundance, cost-effectiveness and accessible functional groups, which makes it facile for chemical modifications with other biomaterials to form biocomposites. Despite such advantages, gelatin offers poor mechanical properties, sensitive enzymatic degradation and high viscosity at room temperature which limits its application and encourages its use to develop biocomposites. Hydrophilic biomass-based cellulose nanofibrous (CNF) has been explored to use as suspension for biocomposite aerogels for the development of 3D porous structures with excellent mechanical properties, biocompatibility and slow enzymatic degradation. In this work, CNF biocomposite aerogels with various ratios of CNF:GEL) (90:10, 70:30 and 50:50) were prepared by freeze-drying technique, and their properties were investigated in terms of physicochemical, mechanical and biological characteristics. Epichlorohydrin (EPH) was used to investigate the effect of chemical crosslinking on the molecular interaction of CNF: GEL, and its effects on physicochemical, mechanical and biological properties of the biocomposite aerogels. Ultimately, chemical crosslinking helped to improve the mechanical resilience of the resulting aerogels. Amongst all the CNF-GEL composites, the crosslinked CNF: GEL (70:30) biocomposite was found to be favourable for cell attachment and viability. It possessed highly porous structure (porosity of ~93%) with pore sizes ranging from 16-110 µm, adequate mechanical properties (compression modulus of ~47 kPa) and optimal biocompatibility both in-vitro and in-vivo, as well as controlled enzymatic biodegradation, high water penetration, which could be considered a suitable option for wound healing application. In-vivo experiments showed improvement on inflammation and foreign giant body cell reaction for the crosslinked CNF: GEL (70:30) compared to the other samples. This could be due to the superior interaction of CNF with gelatin through chemical crosslinking, resulting in more optimal in-vivo improvement. In-vitro cell culture investigation on human dermal fibroblasts showed satisfactory 3D cell attachment over time. Overall, it has been observed that the developed CNF: GEL aerogel can be considered as a potential scaffold for soft tissue regeneration application.

Keywords: 3D scaffolds, aerogels, Biocomposites , tissue engineering

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428 Malaysia as a Case Study for Climate Policy Integration into Energy Policy

Authors: Marcus Lee

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The energy sector is the largest contributor of greenhouse gas emissions in Malaysia, which induces climate change. The climate change problem is therefore an energy sector problem. Tackling climate change issues successfully is contingent on actions taken in the energy sector. The researcher propounds that ‘Climate Policy Integration’ (CPI) into energy policy is a viable and insufficiently developed strategy in Malaysia that promotes the synergies between climate change and energy objectives, in order to achieve the targets found in both climate change and energy policies. In exploring this hypothesis, this paper presentation will focus on two particular aspects. Firstly, the meaning of CPI as an approach and as a concept will be explored. As an approach, CPI into energy policy means the integration of climate change objectives into the energy policy area. Its subject matter focuses on establishing the functional interrelations between climate change and energy objectives, by promoting their synergies and minimising their contradictions. However, its conceptual underpinnings are less than straightforward. Drawing from the ‘principle of integration’ found in international treaties and declarations such as the Stockholm Declaration 1972, the Rio Declaration 1992 and the United Nations Framework on Climate Change 1992 (‘UNFCCC’), this paper presentation will explore the contradictions in international standards on how the sustainable development tenets of environmental sustainability, social development and economic development are to be balanced and its relevance to CPI. Further, the researcher will consider whether authority may be derived from international treaties and declarations in order to argue for the prioritisation of environmental sustainability over the other sustainable development tenets through CPI. Secondly, this paper presentation will also explore the degree to which CPI into energy policy has been achieved and pursued in Malaysia. In particular, the strength of the conceptual framework with regard to CPI in Malaysian governance will be considered by assessing Malaysia’s National Policy on Climate Change (2009) (‘NPCC 2009’). The development (or the lack of) of CPI as an approach since the publication of the NPCC 2009 will also be assessed based on official government documents and policies that may have a climate change and/or energy agenda. Malaysia’s National Renewable Energy Policy and Action Plan (2010), draft National Energy Efficiency Action Plan (2014), Intended Nationally Determined Contributions (2015) in relation to the Paris Agreement, 11th Malaysia Plan (2015) and Biennial Update Report to the UNFCCC (2015) will be discussed. These documents will be assessed for the presence of CPI based on the language/drafting of the documents as well as the degree of subject matter regarding CPI expressed in the documents. Based on the analysis, the researcher will propose solutions on how to improve Malaysia’s climate change and energy governance. The theory of reflexive governance will be applied to CPI. The concluding remarks will be about whether CPI reflects reflexive governance by demonstrating how the governance process can be the object of shaping outcomes.

Keywords: climate policy integration, mainstreaming, policy coherence, Malaysian energy governance

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427 Modulation of Receptor-Activation Due to Hydrogen Bond Formation

Authors: Sourav Ray, Christoph Stein, Marcus Weber

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A new class of drug candidates, initially derived from mathematical modeling of ligand-receptor interactions, activate the μ-opioid receptor (MOR) preferentially at acidic extracellular pH-levels, as present in injured tissues. This is of commercial interest because it may preclude the adverse effects of conventional MOR agonists like fentanyl, which include but are not limited to addiction, constipation, sedation, and apnea. Animal studies indicate the importance of taking the pH value of the chemical environment of MOR into account when designing new drugs. Hydrogen bonds (HBs) play a crucial role in stabilizing protein secondary structure and molecular interaction, such as ligand-protein interaction. These bonds may depend on the pH value of the chemical environment. For the MOR, antagonist naloxone and agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) form HBs with ionizable residue HIS 297 at physiological pH to modulate signaling. However, such interactions were markedly reduced at acidic pH. Although fentanyl-induced signaling is also diminished at acidic pH, HBs with HIS 297 residue are not observed at either acidic or physiological pH for this strong agonist of the MOR. Molecular dynamics (MD) simulations can provide greater insight into the interaction between the ligand of interest and the HIS 297 residue. Amino acid protonation states are adjusted to the model difference in system acidity. Unbiased and unrestrained MD simulations were performed, with the ligand in the proximity of the HIS 297 residue. Ligand-receptor complexes were embedded in 1-palmitoyl-2-oleoyl-sn glycero-3-phosphatidylcholine (POPC) bilayer to mimic the membrane environment. The occurrence of HBs between the different ligands and the HIS 297 residue of MOR at acidic and physiological pH values were tracked across the various simulation trajectories. No HB formation was observed between fentanyl and HIS 297 residue at either acidic or physiological pH. Naloxone formed some HBs with HIS 297 at pH 5, but no such HBs were noted at pH 7. Interestingly, DAMGO displayed an opposite yet more pronounced HB formation trend compared to naloxone. Whereas a marginal number of HBs could be observed at even pH 5, HBs with HIS 297 were more stable and widely present at pH 7. The HB formation plays no and marginal role in the interaction of fentanyl and naloxone, respectively, with the HIS 297 residue of MOR. However, HBs play a significant role in the DAMGO and HIS 297 interaction. Post DAMGO administration, these HBs might be crucial for the remediation of opioid tolerance and restoration of opioid sensitivity. Although experimental studies concur with our observations regarding the influence of HB formation on the fentanyl and DAMGO interaction with HIS 297, the same could not be conclusively stated for naloxone. Therefore, some other supplementary interactions might be responsible for the modulation of the MOR activity by naloxone binding at pH 7 but not at pH 5. Further elucidation of the mechanism of naloxone action on the MOR could assist in the formulation of cost-effective naloxone-based treatment of opioid overdose or opioid-induced side effects.

Keywords: effect of system acidity, hydrogen bond formation, opioid action, receptor activation

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