Search results for: bloodstream expression site
Commenced in January 2007
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Edition: International
Paper Count: 4436

Search results for: bloodstream expression site

386 The Importance of Development Evaluation to Preterm Children in Remote Area

Authors: Chung-Yuan Wang, Min Hsu, Bo-Ya Juan, Hsiv Ching Lin, Hsveh Min Lin, Hsiu-Fang Yeh

Abstract:

The success of Taiwan's National Health Insurance (NHI) system attracts widespread praise from the international society. However, the availability of medical care in a emote area is limited. Without the convenient public transportation system and mature social welfare policy, these people are difficult to regain their health and prevent disability. Preterm children have more risk to get development delay. Preterm children in a remote area have the human right to get rehabilitation resources as those in the city area. Therefore, the aim of this study was to show the importance of development screening to preterm children in a remote area and a tract the government to notice the issue. In Pingtung, children who are suspected development delay would be suggested to take a skillful screening evaluation in our hospital. Those preterm children (within 1-year-old) visited our pediatric clinic would also be referred to take the development evaluation. After the physiatrist’s systemic evaluation, the subjects would be scheduled to take the development evaluation. Gross motor, fine motor, speech comprehension/expression and mental study were included. The evaluation was in-charged by a physical therapist, occupational therapy, speech therapist and pediatric psychologist. The tools were Peabody developmental scale, Bayley Scales of Infant and Toddler Development (Bayley-III) and Wechsler Preschool & Primary Scale of Intelligence-Revised (WPPSI-R). In 2013, 459 children received the service in our hospital. Among these children, fifty-seven were noted with preterm baby history (gestation within 37 weeks). Thirty-six of these preterm children, who had never receive development evaluation, were included in this study. Thirty-six subjects (twenty-six male and ten female) were included. Nineteen subjects were found development delay. Six subjects were found suspected development delay. In gross motor, six subjects were development delay and eight were suspected development delay. In fine motor, five subjects were development delay and three were suspected development delay. In speech, sixteen subjects were development delay and six were suspected development delay. In our study, through the provision of development evaluation service, 72.2% preterm baby were found their development delay or suspected delay. They need further early intervention rehabilitation service. We made their parents realize that when development delay was recognized at the early stage, they are often reversible. No only the patients but also their families were improved their health status. The number of the subjects was limited in our study. Further study might be needed. Compared with 770 physical therapist (PT) and 370 occupational therapy (OT) in Taipei, there are only 108 PT and 54 OT in Pingtung. Further, there are much fewer therapists working on the field of pediatric rehabilitation. Living healthy is a human's right, no matter where does he live. For those development delay children in remote area, particularly preterm children, early detection, and early intervention rehabilitation service could play an important role in decreasing their disability and improving their quality of life. Through this study, we suggest the government to add more national resources on the development evaluation to preterm children in a remote area.

Keywords: development, early intervention, preterm children, rehabilitation

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385 Value Adding of Waste Biomass of Capsicum and Chilli Crops for Medical and Health Supplement Industries

Authors: Mursleen Yasin, Sunil Panchal, Michelle Mak, Zhonghua Chen

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“The use of agricultural and horticultural waste to obtain beneficial products. Thus reduce its environmental impact and help the general population.” Every year 20 billion dollars of food is wasted in the world. All the energy, resources, nutrients and metabolites are lost to the landfills as well. On farm production losses are a main issue in agriculture. Almost 25% vegetables never leave the farm because they are not considered perfect for supermarkets and treated as waste material along with the rest of the plant parts. For capsicums, this waste is 56% of the total crop. Capsicum genus is enriched with a group of compounds called capsaicinoids which are a source of spiciness of these fruits. Capsaicin and dihydrocapsaicin are the major members comprising almost 90% of this group. The major production and accumulation site is the non-edible part of fruit i.e., placenta. Other parts of the plant, like stem, leaves, pericarp and seeds, also contain these pungent compounds. Capsaicinoids are enriched with properties like analgesic, antioxidants, anti-inflammatory, antibacterial, anti-virulence anti-carcinogenic, chemo preventive, chemotherapeutic, antidiabetic etc. They are also effective in treating problems related to gastrointestinal tract, lowering cholesterol and triglycerides in obesity. The aim of the study is to develop a standardised technique for capsaicinoids extraction and to identify better nutrient treatment for fruit and capsaicinoids yield. For research 3 capsicum and 2 chilli varieties were grown in a high-tech glass house facility in Sydney, Australia. Plants were treated with three levels of nutrient treatments i.e., EC 1.8, EC 2.8 and EC 3.8 in order to check its effect on fruit yield and capsaicinoids concentration. Solvent extraction procedure is used with 75% ethanol to extract these secondary metabolites. Physiological, post-harvest and waste biomass measurement and metabolomic analysis are also performed. The results showed that EC 2.8 gave the better fruit yield of capsicums, and those fruits have the higher capsaicinoids concentration. For chillies, higher EC levels had better results than lower treatment. The UHPLC analysis is done to quantify the compounds, and a decrease in capsaicin concentration is observed with the crop maturation. The outcome of this project is a sustainable technique for extraction of capsaicinoids which can easily be adopted by farmers. In this way, farmers can help in value adding of waste by extracting and selling capsaicinoids to nutraceutical and pharmaceutical industries and also earn some secondary income from the 56% waste of capsicum crop.

Keywords: capsaicinoids, plant waste, capsicum, solvent extraction, waste biomass

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384 Aberrant Acetylation/Methylation of Homeobox (HOX) Family Genes in Cumulus Cells of Infertile Women with Polycystic Ovary Syndrome (PCOS)

Authors: P. Asiabi, M. Shahhoseini, R. Favaedi, F. Hassani, N. Nassiri, B. Movaghar, L. Karimian, P. Eftekhariyazdi

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Introduction: Polycystic Ovary Syndrome is a common gynecologic disorder. Many factors including environment, metabolism, hormones and genetics are involved in etiopathogenesis of PCOS. Of genes that have altered expression in human reproductive system disorders are HOX family genes which act as transcription factors in regulation of cell proliferation, differentiation, adhesion and migration. Since recent evidences consider epigenetic factors as causative mechanisms of PCOS, evaluation of association between known epigenetic marks of acetylation/methylation of histone 3 (H3K9ac/me) with regulatory regions of these genes can represent better insight about PCOS. In the current study, cumulus cells (CCs) which have critical roles during folliculogenesis, oocyte maturation, ovulation and fertilization were aimed to monitor epigenetic alterations of HOX genes. Material and methods: CCs were collected from 20 PCOS patients and 20 fertile women (18-36 year) with male infertility problems referred to the Royan Institute to have ICSI under GnRH antagonist protocol. Informed consents were obtained from the participants. Thirty six hours after hCG injection, ovaries were punctured and cumulus oocyte complexes were dissected. Soluble chromatin were extracted from CCs and Chromatin Immune precipitation (ChIP) coupled with Real Time PCR was performed to quantify the epigenetic marks of histone H3K9 acetylation/methylation (H3K9ac/me) on regulatory regions of 15 members of HOX genes from A-D subfamily. Results: Obtained data showed significant increase of H3K9ac epigenetic mark on regulatory regions of HOXA1, HOXB2, HOXC4, HOXD1, HOXD3 and HOXD4 (P < 0.01) and HOXC5 (P < 0.05) and also significant decrease of H3K9ac into regulatory regions of HOXA2, HOXA4, HOXA5, HOXB1 and HOXB5 (P < 0.01) and HOXB3 (P<0.05) in PCOS patients vs. control group. On the other side, there was a significant decrease in incorporation of H3K9me level on regulatory region of HOXA2, HOXA3, HOXA4, HOXA5, HOXB3 and HOXC4 (P≤0.01) and HOXB5 (P < 0.05) in PCOS patients vs. control group. This epigenetic mark (H3K9me2) has significant increase on regulatory region of HOXB1, HOXB2, HOXC5, HOXD1, HOXD3 and HOXD4 (P ≤ 0.01) and HOXB4 (P < 0.05) in patients vs. control group. There were no significant changes in acetylation/methylation levels of H3K9 on regulatory regions of the other studied genes. Conclusion: Current study suggests that epigenetic alterations of HOX genes can be correlated with PCOS and consequently female infertility. This finding might offer additional definitions of PCOS, and eventually provides insight for novel treatments with epidrugs for this disease.

Keywords: epigenetic, HOX genes, PCOS, female infertility

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383 Preliminary Result on the Impact of Anthropogenic Noise on Understory Bird Population in Primary Forest of Gaya Island

Authors: Emily A. Gilbert, Jephte Sompud, Andy R. Mojiol, Cynthia B. Sompud, Alim Biun

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Gaya Island of Sabah is known for its wildlife and marine biodiversity. It has marks itself as one of the hot destinations of tourists from all around the world. Gaya Island tourism activities have contributed to Sabah’s economy revenue with the high number of tourists visiting the island. However, it has led to the increased anthropogenic noise derived from tourism activities. This may greatly interfere with the animals such as understory birds that rely on acoustic signals as a tool for communication. Many studies in other parts of the regions reveal that anthropogenic noise does decrease species richness of avian community. However, in Malaysia, published research regarding the impact of anthropogenic noise on the understory birds is still very lacking. This study was conducted in order to fill up this gap. This study aims to investigate the anthropogenic noise’s impact towards understory bird population. There were three sites within the Primary forest of Gaya Island that were chosen to sample the level of anthropogenic noise in relation to the understory bird population. Noise mapping method was used to measure the anthropogenic noise level and identify the zone with high anthropogenic noise level (> 60dB) and zone with low anthropogenic noise level (< 60dB) based on the standard threshold of noise level. The methods that were used for this study was solely mist netting and ring banding. This method was chosen as it can determine the diversity of the understory bird population in Gaya Island. The preliminary study was conducted from 15th to 26th April and 5th to 10th May 2015 whereby there were 2 mist nets that were set up at each of the zones within the selected site. The data was analyzed by using the descriptive analysis, presence and absence analysis, diversity indices and diversity t-test. Meanwhile, PAST software was used to analyze the obtain data. The results from this study present a total of 60 individuals that consisted of 12 species from 7 families of understory birds were recorded in three of the sites in Gaya Island. The Shannon-Wiener index shows that diversity of species in high anthropogenic noise zone and low anthropogenic noise zone were 1.573 and 2.009, respectively. However, the statistical analysis shows that there was no significant difference between these zones. Nevertheless, based on the presence and absence analysis, it shows that the species at the low anthropogenic noise zone was higher as compared to the high anthropogenic noise zone. Thus, this result indicates that there is an impact of anthropogenic noise on the population diversity of understory birds. There is still an urgent need to conduct an in-depth study by increasing the sample size in the selected sites in order to fully understand the impact of anthropogenic noise towards the understory birds population so that it can then be in cooperated into the wildlife management for a sustainable environment in Gaya Island.

Keywords: anthropogenic noise, biodiversity, Gaya Island, understory bird

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382 Novel EGFR Ectodomain Mutations and Resistance to Anti-EGFR and Radiation Therapy in H&N Cancer

Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

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Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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381 Photography as a Medium Of Communication within the Campaign for Raising Awarenes of Controlled Consumption of Television Contents

Authors: Jelena Kovačević Vorgučin, Sibila Petenji Arbutina

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The postmodern age brings a rapid development of technology which inevitably leads to man's need to adapt to modern lifestyle. On the one hand, technological achievements have made human life easier, but there are numerous risks involved. Moreover, man's awareness and perception is changing and adapting unconsciously to the world we live in, while communication in the 21st century is predominantly based on the consumption of images. This paper presents sociological aspects of a community which is confined due to turbulent political-economic circumstances and its impact on the development of media literacy in Serbia. Previous researches led to the conclusion that the media culture is on an extremely low level, and that it can have a strong influence on the general development of the society, starting from the youngest segment of the population. Our aim is to use the conceptual authorial photographs inspired by the obtained research results to emphasize the importance that the impact of visual art has in delivering the message, its role in education and in raising awareness of universal social problems. The paper presents a number of stages involved in the conceptual project which is designed to last over a longer period of time in order to facilitate dissemination of information. First, a survey was carried out in several preschool institutions. This resulted in obtaining the necessary information on the habitual use of the medium of television in children and their carers-parents. The second stage focused on the relationship between the parent and the child in TV consumption. Further, an overview of the visual part of the project was made, which consisted of photographs in various dimensions, ranging from miniature to large dimensions, and following various exhibition principles in both gallery and alternative spaces. This stage of the project placed particular emphasis on the non-standard exhibiting formats and alternative exhibition principles which are increasingly present in all kinds of visual art aimed at achieving a higher level of information noticing and memorizing. The motif on the authorial photographs is children's portraits taken while they are watching different television contents, with emphasis on their emotional response. The importance of the medium of TV is particularly emphasized due to the fact that its consumption is the highest, even though there are newer and more advanced information-technological achievements. The already realized part of the project was used for an analysis of the results in the last stage of the project, which led to the conclusion that the response to the entire visual expression campaign was extremely positive, and action as such very useful indeed. The results obtained speak in favour of widening and continuation of the project, both on a greater number of sites locally as well as in other communities in Serbia with the aim of guiding people towards meaningful consumption of the television medium.

Keywords: alternative space exhibiting, children and TV, conceptual portrait photography, media literacy

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380 Molecular Docking Analysis of Flavonoids Reveal Potential of Eriodictyol for Breast Cancer Treatment

Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

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Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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379 Interface Fracture of Sandwich Composite Influenced by Multiwalled Carbon Nanotube

Authors: Alak Kumar Patra, Nilanjan Mitra

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Higher strength to weight ratio is the main advantage of sandwich composite structures. Interfacial delamination between the face sheet and core is a major problem in these structures. Many research works are devoted to improve the interfacial fracture toughness of composites majorities of which are on nano and laminated composites. Work on influence of multiwalled carbon nano-tubes (MWCNT) dispersed resin system on interface fracture of glass-epoxy PVC core sandwich composite is extremely limited. Finite element study is followed by experimental investigation on interface fracture toughness of glass-epoxy (G/E) PVC core sandwich composite with and without MWCNT. Results demonstrate an improvement in interface fracture toughness values (Gc) of samples with a certain percentages of MWCNT. In addition, dispersion of MWCNT in epoxy resin through sonication followed by mixing of hardener and vacuum resin infusion (VRI) technology used in this study is an easy and cost effective methodology in comparison to previously adopted other methods limited to laminated composites. The study also identifies the optimum weight percentage of MWCNT addition in the resin system for maximum performance gain in interfacial fracture toughness. The results agree with finite element study, high-resolution transmission electron microscope (HRTEM) analysis and fracture micrograph of field emission scanning electron microscope (FESEM) investigation. Interface fracture toughness (GC) of the DCB sandwich samples is calculated using the compliance calibration (CC) method considering the modification due to shear. Compliance (C) vs. crack length (a) data of modified sandwich DCB specimen is fitted to a power function of crack length. The calculated mean value of the exponent n from the plots of experimental results is 2.22 and is different from the value (n=3) prescribed in ASTM D5528-01for mode 1 fracture toughness of laminate composites (which is the basis for modified compliance calibration method). Differentiating C with respect to crack length (a) and substituting it in the expression GC provides its value. The research demonstrates improvement of 14.4% in peak load carrying capacity and 34.34% in interface fracture toughness GC for samples with 1.5 wt% MWCNT (weight % being taken with respect to weight of resin) in comparison to samples without MWCNT. The paper focuses on significant improvement in experimentally determined interface fracture toughness of sandwich samples with MWCNT over the samples without MWCNT using much simpler method of sonication. Good dispersion of MWCNT was observed in HRTEM with 1.5 wt% MWCNT addition in comparison to other percentages of MWCNT. FESEM studies have also demonstrated good dispersion and fiber bridging of MWCNT in resin system. Ductility is also observed to be higher for samples with MWCNT in comparison to samples without.

Keywords: carbon nanotube, epoxy resin, foam, glass fibers, interfacial fracture, sandwich composite

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378 Design, Construction, Validation And Use Of A Novel Portable Fire Effluent Sampling Analyser

Authors: Gabrielle Peck, Ryan Hayes

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Current large scale fire tests focus on flammability and heat release measurements. Smoke toxicity isn’t considered despite it being a leading cause of death and injury in unwanted fires. A key reason could be that the practical difficulties associated with quantifying individual toxic components present in a fire effluent often require specialist equipment and expertise. Fire effluent contains a mixture of unreactive and reactive gases, water, organic vapours and particulate matter, which interact with each other. This interferes with the operation of the analytical instrumentation and must be removed without changing the concentration of the target analyte. To mitigate the need for expensive equipment and time-consuming analysis, a portable gas analysis system was designed, constructed and tested for use in large-scale fire tests as a simpler and more robust alternative to online FTIR measurements. The novel equipment aimed to be easily portable and able to run on battery or mains electricity; be able to be calibrated at the test site; be capable of quantifying CO, CO2, O2, HCN, HBr, HCl, NOx and SO2 accurately and reliably; be capable of independent data logging; be capable of automated switchover of 7 bubblers; be able to withstand fire effluents; be simple to operate; allow individual bubbler times to be pre-set; be capable of being controlled remotely. To test the analysers functionality, it was used alongside the ISO/TS 19700 Steady State Tube Furnace (SSTF). A series of tests were conducted to assess the validity of the box analyser measurements and the data logging abilities of the apparatus. PMMA and PA 6.6 were used to assess the validity of the box analyser measurements. The data obtained from the bench-scale assessments showed excellent agreement. Following this, the portable analyser was used to monitor gas concentrations during large-scale testing using the ISO 9705 room corner test. The analyser was set up, calibrated and set to record smoke toxicity measurements in the doorway of the test room. The analyser was successful in operating without manual interference and successfully recorded data for 12 of the 12 tests conducted in the ISO room tests. At the end of each test, the analyser created a data file (formatted as .csv) containing the measured gas concentrations throughout the test, which do not require specialist knowledge to interpret. This validated the portable analyser’s ability to monitor fire effluent without operator intervention on both a bench and large-scale. The portable analyser is a validated and significantly more practical alternative to FTIR, proven to work for large-scale fire testing for quantification of smoke toxicity. The analyser is a cheaper, more accessible option to assess smoke toxicity, mitigating the need for expensive equipment and specialist operators.

Keywords: smoke toxicity, large-scale tests, iso 9705, analyser, novel equipment

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377 Seismic Response of Reinforced Concrete Buildings: Field Challenges and Simplified Code Formulas

Authors: Michel Soto Chalhoub

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Building code-related literature provides recommendations on normalizing approaches to the calculation of the dynamic properties of structures. Most building codes make a distinction among types of structural systems, construction material, and configuration through a numerical coefficient in the expression for the fundamental period. The period is then used in normalized response spectra to compute base shear. The typical parameter used in simplified code formulas for the fundamental period is overall building height raised to a power determined from analytical and experimental results. However, reinforced concrete buildings which constitute the majority of built space in less developed countries pose additional challenges to the ones built with homogeneous material such as steel, or with concrete under stricter quality control. In the present paper, the particularities of reinforced concrete buildings are explored and related to current methods of equivalent static analysis. A comparative study is presented between the Uniform Building Code, commonly used for buildings within and outside the USA, and data from the Middle East used to model 151 reinforced concrete buildings of varying number of bays, number of floors, overall building height, and individual story height. The fundamental period was calculated using eigenvalue matrix computation. The results were also used in a separate regression analysis where the computed period serves as dependent variable, while five building properties serve as independent variables. The statistical analysis shed light on important parameters that simplified code formulas need to account for including individual story height, overall building height, floor plan, number of bays, and concrete properties. Such inclusions are important for reinforced concrete buildings of special conditions due to the level of concrete damage, aging, or materials quality control during construction. Overall results of the present analysis show that simplified code formulas for fundamental period and base shear may be applied but they require revisions to account for multiple parameters. The conclusion above is confirmed by the analytical model where fundamental periods were computed using numerical techniques and eigenvalue solutions. This recommendation is particularly relevant to code upgrades in less developed countries where it is customary to adopt, and mildly adapt international codes. We also note the necessity of further research using empirical data from buildings in Lebanon that were subjected to severe damage due to impulse loading or accelerated aging. However, we excluded this study from the present paper and left it for future research as it has its own peculiarities and requires a different type of analysis.

Keywords: seismic behaviour, reinforced concrete, simplified code formulas, equivalent static analysis, base shear, response spectra

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376 Modeling of Foundation-Soil Interaction Problem by Using Reduced Soil Shear Modulus

Authors: Yesim Tumsek, Erkan Celebi

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In order to simulate the infinite soil medium for soil-foundation interaction problem, the essential geotechnical parameter on which the foundation stiffness depends, is the value of soil shear modulus. This parameter directly affects the site and structural response of the considered model under earthquake ground motions. Strain-dependent shear modulus under cycling loads makes difficult to estimate the accurate value in computation of foundation stiffness for the successful dynamic soil-structure interaction analysis. The aim of this study is to discuss in detail how to use the appropriate value of soil shear modulus in the computational analyses and to evaluate the effect of the variation in shear modulus with strain on the impedance functions used in the sub-structure method for idealizing the soil-foundation interaction problem. Herein, the impedance functions compose of springs and dashpots to represent the frequency-dependent stiffness and damping characteristics at the soil-foundation interface. Earthquake-induced vibration energy is dissipated into soil by both radiation and hysteretic damping. Therefore, flexible-base system damping, as well as the variability in shear strengths, should be considered in the calculation of impedance functions for achievement a more realistic dynamic soil-foundation interaction model. In this study, it has been written a Matlab code for addressing these purposes. The case-study example chosen for the analysis is considered as a 4-story reinforced concrete building structure located in Istanbul consisting of shear walls and moment resisting frames with a total height of 12m from the basement level. The foundation system composes of two different sized strip footings on clayey soil with different plasticity (Herein, PI=13 and 16). In the first stage of this study, the shear modulus reduction factor was not considered in the MATLAB algorithm. The static stiffness, dynamic stiffness modifiers and embedment correction factors of two rigid rectangular foundations measuring 2m wide by 17m long below the moment frames and 7m wide by 17m long below the shear walls are obtained for translation and rocking vibrational modes. Afterwards, the dynamic impedance functions of those have been calculated for reduced shear modulus through the developed Matlab code. The embedment effect of the foundation is also considered in these analyses. It can easy to see from the analysis results that the strain induced in soil will depend on the extent of the earthquake demand. It is clearly observed that when the strain range increases, the dynamic stiffness of the foundation medium decreases dramatically. The overall response of the structure can be affected considerably because of the degradation in soil stiffness even for a moderate earthquake. Therefore, it is very important to arrive at the corrected dynamic shear modulus for earthquake analysis including soil-structure interaction.

Keywords: clay soil, impedance functions, soil-foundation interaction, sub-structure approach, reduced shear modulus

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375 Potential Cross-Protection Roles of Chitooligosaccharide in Alleviating Cd Toxicity in Edible Rape (Brassica rapa L.)

Authors: Haiying Zong, Yi Yuan, Pengcheng Li

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Cadmium (Cd), one of the toxic heavy metals, has high solubility and mobility in agricultural soils and is readily taken up by roots and transported to the vegetative and reproductive organs which can cause deleterious effects on crop yield and quality. Excess Cd in plants can interfere with many metabolic processes, such as photosynthesis, transpiration, respiration or nutrients homeostasis. Generally, the main methods to reduce Cd accumulation in plants are to decrease the concentration of Cd in the soil solution through reduction of Cd influx into the soil system, site selection, and management practices. However, these approaches can be very costly and consume a lot of energy Therefore, it is critical to develop effective approaches to reduce the Cd concentration in plants. It is proved that chitooligosaccharide (COS) can enhance the plant's tolerance to abiotic stress including drought stress, salinity stress, and toxic metal stress. However, so far little information is known about whether foliar application with COS modulates Cd-induced toxicity in plants. The metal detoxification processes of plants treated with COS also remain unclear. In this study, edible rape (Brassica rapa L.), one of the most widely consumed leafy vegetables, was selected as an experimental mode plant. The effect of foliar application with COS on reducing Cd accumulation in edible rape was investigated. Moreover, Cd subcellular distribution pattern in response to Cd stress in the rape plant sprayed with COS was further tested in order to explore the potential detoxification mechanisms in plants. The results demonstrated that spraying COS at different concentrations (25, 50,100 and 200 mg L-1) possess diverse functions including growth-promoting,chlorophyll contents-enhancing, malondialdehyde (MDA) level-decreasing in leaves, Cd2+ concentration-decreasingin shoots and roots of edible rape under Cd stress. In addition, it was found that COS can also dramatically improve superoxide dismutase (SOD) activity, catalase (CAT) activity and peroxidase (POX) activity of edible rape leaves. The relievingeffect of COS was related to theconcentration and COS with 50-100 mg L-1 displayed the best activity. Furtherly, theexperiments results exhibitedthat COS could decrease the proportion of Cd in the organelle fraction of leaves by 40.1% while enhance the proportion of Cd in the soluble fraction by 13.2% at the concentration of 50 mg L-1. The above results showed that COS may have thepotential to improve plant resistance to Cd via promoting antioxidant enzyme activities and altering Cd subcellular distribution. All the results described here open up a new way to study the protection role of COS in alleviating Cd tolerance and lay the foundation for future research about the detoxification mechanism at subcellular level.

Keywords: chitooligosaccharide, cadmium, edible rape (Brassica rapa L.), subcellular distribution

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374 Modern Pilgrimage Narratives and India’s Heterogeneity

Authors: Alan Johnson

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This paper focuses on modern pilgrimage narratives about sites affiliated with Indian religious expressions located both within and outside India. The paper uses a multidisciplinary approach to examine poetry, personal essays, and online attestations of pilgrimage to illustrate how non-religious ideas coexist with outwardly religious ones, exemplifying a characteristically Indian form of syncretism that pre-dates Western ideas of pluralism. The paper argues that the syncretism on display in these modern creative works refutes the current exclusionary vision of India as a primordially Hindu-nationalist realm. A crucial premise of this argument is that the narrative’s intrinsic heteroglossia, so evident in India’s historically rich variety of stories and symbols, belies this reactionary version of Hindu nationalism. Equally important to this argument, therefore, is the vibrancy of Hindu sites outside India, such as the Batu Caves temple complex in Kuala Lumpur, Malaysia. The literary texts examined in this paper include, first, Arun Kolatkar’s famous 1976 collection of poems, titled Jejuri, about a visit to the pilgrimage site of the same name in Maharashtra. Here, the modern, secularized visitor from Bombay (Mumbai) contemplates the effect of the temple complex on himself and on the other, more worshipful visitors. Kolatkar’s modernist poems reflect the narrator’s typically modern-Indian ambivalence for holy ruins, for although they do not evoke a conventionally religious feeling in him, they nevertheless possess an aura of timelessness that questions the narrator’s time-conscious sensibility. The paper bookends Kolatkar’s Jejuri with considerations of an early-twentieth-century text, online accounts by visitors to the Batu Caves, and a recent, more conventional Hindu account of pilgrimage. For example, the pioneering graphic artist Mukul Chandra Dey published in 1917, My Pilgrimages to Ajanta and Bagh, in which he devotes an entire chapter to the life of the Buddha as a means of illustrating the layering of stories that is a characteristic feature of sacred sites in India. In a different but still syncretic register, Jawaharlal Nehru, India’s first prime minister, and a committed secularist proffers India’s ancient pilgrimage network as a template for national unity in his classic 1946 autobiography The Discovery of India. Narrative is the perfect vehicle for highlighting this layering of sensibilities, for a single text can juxtapose the pilgrim-narrator’s description with that of a far older pilgrimage, a juxtaposition that establishes an imaginative connection between otherwise distanced actors, and between them and the reader.

Keywords: India, literature, narrative, syncretism

Procedia PDF Downloads 154
373 The Implication of Small Group Therapy on Sexuality in Breast Cancer Survivors

Authors: Cherng-Jye Jeng, Ming-Feng Hou, Hsing-Yuan Liu, Chuan-Feng Chang, Lih-Rong Wang, Yen-Chin Lin

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Introduction: The incidence of breast cancer has gradually increased in Taiwan, and the characteristic of younger ages impact these women in their middle age, and may also cause challenges in terms of family, work, and illness. Breasts are symbols of femininity, as well as of sex. For women, breasts are important organs for the female identity and sexual expression. Losing breasts not only affects the female role, but would also affect sexual attraction and sexual desire. Thus, women with breast cancer who have need for mastectomies experience physical incompletion, which affects women’s self-confidence, physical image, and self-orientation. Purposes: 1. To understand the physical experience of women with breast cancer. 2. To explore the issue of sexual issues on the health effects of women with breast cancer. 3. To construct a domestic sex life issue group model for domestic women with breast cancer. 4. To explore the accompaniment experiences and sexual relationship adjustments of spouses when women have breast cancer. Method: After the research plan passes IRB review, participants will be recruited at breast surgery clinic in the affiliated hospital, to screen suitable subjects for entry into the group. Between March and May 2015, two sexual health and sex life consultation groups were conducted, which were (1) 10 in postoperative groups for women with cancer; (2) 4 married couples group for postoperative women with cancer. After sharing experiences and dialogue, women can achieve mutual support and growth. Data organization and analysis underwent descriptive analysis in qualitative research, and the group process was transcribed into transcripts for overall-content and category-content analysis. Results: Ten women with breast cancer believed that participating in group can help them exchange experiences, and elevate sexual health. The main issues include: (1) after breast cancer surgery, patients generally received chemotherapy or estrogen suppressants, causing early menopause; in particular, vaginal dryness can cause pain or bleeding in intercourse, reducing their desire for sexual activity; (2) breast cancer accentuates original spousal or family and friend relationships; some people have support and care from their family, and spouses emphasize health over the appearance of breasts; however, some people do not have acceptance and support from their family, and some even hear spousal sarcasm about loss of breasts; (3) women with breast cancer have polarized expressions of optimism and pessimism in regards to their emotions, beliefs, and body image regarding cancer; this is related to the women’s original personalities, attribution of causes of cancer, and extent of worry about relapse. Conclusion: The research results can be provided as a reference to medical institutions or breast cancer volunteer teams, to pay attention to maintaining the health of women with breast cancer.

Keywords: women with breast cancer, experiences of objectifying the body, quality of sex life, sexual health

Procedia PDF Downloads 319
372 A Measurement Instrument to Determine Curricula Competency of Licensure Track Graduate Psychotherapy Programs in the United States

Authors: Laith F. Gulli, Nicole M. Mallory

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We developed a novel measurement instrument to assess Knowledge of Educational Programs in Professional Psychotherapy Programs (KEP-PPP or KEP-Triple P) within the United States. The instrument was designed by a Panel of Experts (PoE) that consisted of Licensed Psychotherapists and Medical Care Providers. Licensure track psychotherapy programs are listed in the databases of the Commission on Accreditation for Marriage and Family Therapy Education (COAMFTE); American Psychological Association (APA); Council on Social Work Education (CSWE); and the Council for Accreditation of Counseling & Related Educational Programs (CACREP). A complete list of psychotherapy programs can be obtained from these professional databases, selecting search fields of (All Programs) in (All States). Each program has a Web link that electronically and directly connects to the institutional program, which can be researched using the KEP-Triple P. The 29-item KEP Triple P was designed to consist of six categorical fields; Institutional Type: Degree: Educational Delivery: Accreditation: Coursework Competency: and Special Program Considerations. The KEP-Triple P was designed to determine whether a specific course(s) is offered in licensure track psychotherapy programs. The KEP-Triple P is designed to be modified to assess any part or the entire curriculum of licensure graduate programs. We utilized the KEP-Triple P instrument to study whether a graduate course in Addictions was offered in Marriage and Family Therapy (MFT) programs. Marriage and Family Therapists are likely to commonly encounter patients with Addiction(s) due to the broad treatment scope providing psychotherapy services to individuals, couples and families of all age groups. Our study of 124 MFT programs which concluded at the end of 2016 found that we were able to assess 61 % of programs (N = 76) since 27 % (N = 34) of programs were inaccessible due to broken Web links. From the total of all MFT programs 11 % (N = 14) did not have a published curriculum on their Institutional Web site. From the sample study, we found that 66 % (N = 50) of curricula did not offer a course in Addiction Treatment and that 34 % (N =26) of curricula did require a mandatory course in Addiction Treatment. From our study sample, we determined that 15 % (N = 11) of MFT doctorate programs did not require an Addictions Treatment course and that 1 % (N = 1) did require such a course. We found that 99 % of our study sample offered a Campus based program and 1 % offered a hybrid program with both online and residential components. From the total sample studied, we determined that 84 % of programs would be able to obtain reaccreditation within a five-year period. We recommend that MFT programs initiate procedures to revise curricula to include a required course in Addiction Treatment prior to their next accreditation cycle, to improve the escalating addiction crisis in the United States. This disparity in MFT curricula raises serious ethical and legal consideration for national and Federal stakeholders as well as for patients seeking a competently trained psychotherapist.

Keywords: addiction, competency, curriculum, psychotherapy

Procedia PDF Downloads 152
371 Environmental Impact of Autoclaved Aerated Concrete in Modern Construction: A Case Study from the New Egyptian Administrative Capital

Authors: Esraa A. Khalil, Mohamed N. AbouZeid

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Building materials selection is critical for the sustainability of any project. The choice of building materials has a huge impact on the built environment and cost of projects. Building materials emit huge amount of carbon dioxide (CO2) due to the use of cement as a basic component in the manufacturing process and as a binder, which harms our environment. Energy consumption from buildings has increased in the last few years; a huge amount of energy is being wasted from using unsustainable building and finishing materials, as well as from the process of heating and cooling of buildings. In addition, the construction sector in Egypt is taking a good portion of the economy; however, there is a lack of awareness of buildings environmental impacts on the built environment. Using advanced building materials and different wall systems can help in reducing heat consumption, the project’s initial and long-term costs, and minimizing the environmental impacts. Red Bricks is one of the materials that are being used widely in Egypt. There are many other types of bricks such as Autoclaved Aerated Concrete (AAC); however, the use of Red Bricks is dominating the construction industry due to its affordability and availability. This research focuses on the New Egyptian Administrative Capital as a case study to investigate the potential of the influence of using different wall systems such as AAC on the project’s cost and the environment. The aim of this research is to conduct a comparative analysis between the traditional and most commonly used bricks in Egypt, which is Red Bricks, and AAC wall systems. Through an economic and environmental study, the difference between the two wall systems will be justified to encourage the utilization of uncommon techniques in the construction industry to build more affordable, energy efficient and sustainable buildings. The significance of this research is to show the potential of using AAC in the construction industry and its positive influences. The study analyzes the factors associated with choosing suitable building materials for different projects according to the need and criteria of each project and its nature without harming the environment and wasting materials that could be saved or recycled. The New Egyptian Administrative Capital is considered as the country’s new heart, where ideas regarding energy savings and environmental benefits are taken into consideration. Meaning that, Egypt is taking good steps to move towards more sustainable construction. According to the analysis and site visits, there is a potential in reducing the initial costs of buildings by 12.1% and saving energy by using different techniques up to 25%. Interviews with the mega structures project engineers and managers reveal that they are more open to introducing sustainable building materials that will help in saving the environment and moving towards green construction as well as to studying more effective techniques for energy conservation.

Keywords: AAC blocks, building material, environmental impact, modern construction, new Egyptian administrative capital

Procedia PDF Downloads 121
370 The Attitudes of Senior High School Students Toward Work Immersion Programs of Nazareth School of National University

Authors: Kim Katherine Castillo, Nelson John Datubatang, Terrence Phillip Dy, Norelie Hampac, Reichen Crismark Martinez, Nina Faith Pantinople, Jose Dante Santos II, Marchel Ann Santos, Sophia Abigail Santiago, Zyrill Xsar San Juan, Aira Mae Tagao, Crystal Kylla Viagedor

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The Work Immersion Program was implemented to help students gain abundant work-related experiences while on-site; additionally, the program aims to help students improve their competencies and interpersonal skills as they are given the option to join the workforce if they ever choose to do so after senior high school. The work immersion experience posed diverse challenges for students, spanning personal, financial, engagement, environmental, and equipment-related domains. These included the need for assistance in time management, transportation expenses, and procurement of materials. Furthermore, students faced difficulties in independent task completion and encountered suboptimal work environments. Addressing these multifaceted obstacles is crucial to optimize the educational outcomes of work immersion programs. In addition to the challenges, several other issues have been identified, including the absence of standardized work immersion programs across schools and industries, the challenges in securing appropriate work immersion placements, the necessity for enhanced monitoring and evaluation of program effectiveness, and the limited availability of field programs aligned with students' chosen courses. Furthermore, there is a lack of comprehensive information regarding the attitudes of Senior High School students toward work immersion programs within their respective schools. This study aims to investigate the attitudes of senior high school students at Nazareth School of National University towards work immersion programs, with a focus on identifying factors that influence their perception and participation, including collegiality and expectations. By exploring the students' attitudes, the research endeavors to enhance the school's work immersion programs and contribute to the overall educational experience of the students. This study addresses challenges related to work immersion programs, focusing on six subtopics: Work Immersion, Work Immersion in the Philippines, Students' Attitudes, Factors Affecting Students' Attitudes, Effectiveness of Work Immersion for Senior High School Students, and Students' Perception and Willingness to Participate. Using a descriptive research design, the study examines the attitudes of senior high school students at Nazareth School of National University in Manila. Data was collected from 100 students, representing different academic strands, through a 35-item researcher-made survey. Descriptive statistics, including measures of central tendency and variability, will be used to analyze the data using JASP, providing valuable insights into the students' attitudes toward work immersion.

Keywords: attitudes, challenges, educational outcomes, work immersion programs

Procedia PDF Downloads 96
369 Landslide Susceptibility Analysis in the St. Lawrence Lowlands Using High Resolution Data and Failure Plane Analysis

Authors: Kevin Potoczny, Katsuichiro Goda

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The St. Lawrence lowlands extend from Ottawa to Quebec City and are known for large deposits of sensitive Leda clay. Leda clay deposits are responsible for many large landslides, such as the 1993 Lemieux and 2010 St. Jude (4 fatalities) landslides. Due to the large extent and sensitivity of Leda clay, regional hazard analysis for landslides is an important tool in risk management. A 2018 regional study by Farzam et al. on the susceptibility of Leda clay slopes to landslide hazard uses 1 arc second topographical data. A qualitative method known as Hazus is used to estimate susceptibility by checking for various criteria in a location and determine a susceptibility rating on a scale of 0 (no susceptibility) to 10 (very high susceptibility). These criteria are slope angle, geological group, soil wetness, and distance from waterbodies. Given the flat nature of St. Lawrence lowlands, the current assessment fails to capture local slopes, such as the St. Jude site. Additionally, the data did not allow one to analyze failure planes accurately. This study majorly improves the analysis performed by Farzam et al. in two aspects. First, regional assessment with high resolution data allows for identification of local locations that may have been previously identified as low susceptibility. This then provides the opportunity to conduct a more refined analysis on the failure plane of the slope. Slopes derived from 1 arc second data are relatively gentle (0-10 degrees) across the region; however, the 1- and 2-meter resolution 2022 HRDEM provided by NRCAN shows that short, steep slopes are present. At a regional level, 1 arc second data can underestimate the susceptibility of short, steep slopes, which can be dangerous as Leda clay landslides behave retrogressively and travel upwards into flatter terrain. At the location of the St. Jude landslide, slope differences are significant. 1 arc second data shows a maximum slope of 12.80 degrees and a mean slope of 4.72 degrees, while the HRDEM data shows a maximum slope of 56.67 degrees and a mean slope of 10.72 degrees. This equates to a difference of three susceptibility levels when the soil is dry and one susceptibility level when wet. The use of GIS software is used to create a regional susceptibility map across the St. Lawrence lowlands at 1- and 2-meter resolutions. Failure planes are necessary to differentiate between small and large landslides, which have so far been ignored in regional analysis. Leda clay failures can only retrogress as far as their failure planes, so the regional analysis must be able to transition smoothly into a more robust local analysis. It is expected that slopes within the region, once previously assessed at low susceptibility scores, contain local areas of high susceptibility. The goal is to create opportunities for local failure plane analysis to be undertaken, which has not been possible before. Due to the low resolution of previous regional analyses, any slope near a waterbody could be considered hazardous. However, high-resolution regional analysis would allow for more precise determination of hazard sites.

Keywords: hazus, high-resolution DEM, leda clay, regional analysis, susceptibility

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368 MTT Assay-Guided Isolation of a Cytotoxic Lead from Hedyotis umbellata and Its Mechanism of Action against Non-Small Cell Lung Cancer A549 Cells

Authors: Kirti Hira, A. Sajeli Begum, S. Mahibalan, Poorna Chandra Rao

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Introduction: Cancer is one of the leading causes of death worldwide. Although existing therapy effectively kills cancer cells, they do affect normal growing cells leading to many undesirable side effects. Hence there is need to develop effective as well as safe drug molecules to combat cancer, which is possible through phyto-research. The currently available plant-derived blockbuster drugs are the example for this. In view of this, an investigation was done to identify cytotoxic lead molecules from Hedyotis umbellata (Family Rubiaceae), a widely distributed weed in India. Materials and Methods: The methanolic extract of the whole plant of H. umbellata (MHU), prepared through Soxhlet extraction method was further fractionated with diethyl ether and n-butanol, successively. MHU, ether fraction (EMHU) and butanol fraction (BMHU) were lyophilized and were tested for the cytotoxic effect using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay against non-small cell lung cancer (NSCLC) A549 cell lines. The potentially active EMHU was subjected to chromatographic purification using normal-phase silica columns, in order to isolate the responsible bioactive compounds. The isolated pure compounds were tested for their cytotoxic effect by MTT assay against A549 cells. Compound-3, which was found to be most active, was characterized using IR, 1H- and 13C-NMR and MS analysis. The study was further extended to decipher the mechanism of action of cytotoxicity of compound-3 against A549 cells through various in vitro cellular models. Cell cycle analysis was done using flow cytometry following PI (Propidium Iodide) staining. Protein analysis was done using Western blot technique. Results: Among MHU, EMHU, and BMHU, the non-polar fraction EMHU demonstrated a significant dose-dependent cytotoxic effect with IC50 of 67.7μg/ml. Chromatography of EMHU yielded seven compounds. MTT assay of isolated compounds explored compound-3 as potentially active one, which inhibited the growth of A549 cells with IC50value of 14.2μM. Further, compound-3 was identified as cedrelopsin, a coumarin derivative having molecular weight of 260. Results of in vitro mechanistic studies explained that cedrelopsin induced cell cycle arrest at G2/M phase and down-regulated the expression of G2/M regulatory proteins such as cyclin B1, cdc2, and cdc25C, dose dependently. This is the first report that explores the cytotoxic mechanism of cedrelopsin. Conclusion: Thus a potential small lead molecule, cedrelopsin isolated from H. umbellata, showing antiproliferative effect mediated by G2/M arrest in A549 cells was discovered. The effect of cedrelopsin against other cancer cell lines followed by in vivo studies can be performed in future to develop a new drug candidate.

Keywords: A549, cedrelopsin, G2/M phase, Hedyotis umbellata

Procedia PDF Downloads 176
367 Coping with Geological Hazards during Construction of Hydroelectric Projects in Himalaya

Authors: B. D. Patni, Ashwani Jain, Arindom Chakraborty

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The world’s highest mountain range has been forming since the collision of Indian Plate with Asian Plate 40-50 million years ago. The Indian subcontinent has been deeper and deeper in to the rest of Asia resulting upliftment of Himalaya & Tibetan Plateau. The complex domain has become a major challenge for construction of hydro electric projects. The Himalayas are geologically complex & seismically active. Shifting of Indian Plate northwardly and increasing the amount of stresses in the fragile domain which leads to deformation in the form of several fold, faults and upliftment. It is difficult to undergo extensive geological investigation to ascertain the geological problems to be encountered during construction. Inaccessibility of the terrain, high rock cover, unpredictable ground water condition etc. are the main constraints. The hydroelectric projects located in Himalayas have faced many geological and geo-hydrological problems while construction of surface and subsurface works. Based on the experience, efforts have been made to identify the expected geological problems during and after construction of the projects. These have been classified into surface and subsurface problems which include existence of inhomogeneous deep overburden in the river bed or buried valley, abrupt change in bed rock profile, Occurrences of fault zones/shear zones/fractured rock in dam foundation and slope instability in the abutments. The tunneling difficulties are many such as squeezing ground condition, popping, rock bursting, high temperature gradient, heavy ingress of water, existence of shear seams/shear zones and emission of obnoxious gases. However, these problems were mitigated by adopting suitable remedial measures as per site requirement. The support system includes shotcrete, wire mesh, rock bolts, steel ribs, fore-poling, pre-grouting, pipe-roofing, MAI anchors, toe wall, retaining walls, reinforced concrete dowels, drainage drifts, anchorage cum drainage shafts, soil nails, concrete cladding and shear keys. Controlled drilling & blasting, heading & benching, proper drainage network and ventilation system are other remedial measures adopted to overcome such adverse situations. The paper highlights the geological uncertainties and its remedial measures in Himalaya, based on the analysis and evaluation of 20 hydroelectric projects during construction.

Keywords: geological problems, shear seams, slope, drilling & blasting, shear zones

Procedia PDF Downloads 403
366 Computational Approaches to Study Lineage Plasticity in Human Pancreatic Ductal Adenocarcinoma

Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

Procedia PDF Downloads 128
365 Inhibition of Influenza Replication through the Restrictive Factors Modulation by CCR5 and CXCR4 Receptor Ligands

Authors: Thauane Silva, Gabrielle do Vale, Andre Ferreira, Marilda Siqueira, Thiago Moreno L. Souza, Milene D. Miranda

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The exposure of A(H1N1)pdm09-infected epithelial cells (HeLa) to HIV-1 viral particles, or its gp120, enhanced interferon-induced transmembrane protein (IFITM3) content, a viral restriction factor (RF), resulting in a decrease in influenza replication. The gp120 binds to CCR5 (R5) or CXCR4 (X4) cell receptors during HIV-1 infection. Then, it is possible that the endogenous ligands of these receptors also modulate the expression of IFITM3 and other cellular factors that restrict influenza virus replication. Thus, the aim of this study is to analyze the role of cellular receptors R5 and X4 in modulating RFs in order to inhibit the replication of the influenza virus. A549 cells were treated with 2x effective dose (ED50) of endogenous R5 or X4 receptor agonists, CCL3 (20 ng/ml), CCL4 (10 ng/ml), CCL5 (10 ng/ml) and CXCL12 (100 ng/mL) or exogenous agonists, gp120 Bal-R5, gp120 IIIB-X4 and its mutants (5 µg/mL). The interferon α (10 ng/mL) and oseltamivir (60 nM) were used as a control. After 24 h post agonists exposure, the cells were infected with virus influenza A(H3N2) at 2 MOI (multiplicity of infection) for 1 h. Then, 24 h post infection, the supernatant was harvested and, the viral titre was evaluated by qRT-PCR. To evaluate IFITM3 and SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) protein levels, A549 were exposed to agonists for 24 h, and the monolayer was lysed with Laemmli buffer for western blot (WB) assay or fixed for indirect immunofluorescence (IFI) assay. In addition to this, we analyzed other RFs modulation in A549, after 24 h post agonists exposure by customized RT² Profiler Polymerase Chain Reaction Array. We also performed a functional assay in which SAMHD1-knocked-down, by single-stranded RNA (siRNA), A549 cells were infected with A(H3N2). In addition, the cells were treated with guanosine to assess the regulatory role of dNTPs by SAMHD1. We found that R5 and X4 agonists inhibited influenza replication in 54 ± 9%. We observed a four-fold increase in SAMHD1 transcripts by RFs mRNA quantification panel. After 24 h post agonists exposure, we did not observe an increase in IFITM3 protein levels through WB or IFI assays, but we observed an upregulation up to three-fold in the protein content of SAMHD1, in A549 exposed to agonists. Besides this, influenza replication enhanced in 20% in cell cultures that SAMDH1 was knockdown. Guanosine treatment in cells exposed to R5 ligands further inhibited influenza virus replication, suggesting that the inhibitory mechanism may involve the activation of the SAMHD1 deoxynucleotide triphosphohydrolase activity. Thus, our data show for the first time a direct relationship of SAMHD1 and inhibition of influenza replication, and provides perspectives for new studies on the signaling modulation, through cellular receptors, to induce proteins of great importance in the control of relevant infections for public health.

Keywords: chemokine receptors, gp120, influenza, virus restriction factors

Procedia PDF Downloads 142
364 Industrial Waste Multi-Metal Ion Exchange

Authors: Thomas S. Abia II

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Intel Chandler Site has internally developed its first-of-kind (FOK) facility-scale wastewater treatment system to achieve multi-metal ion exchange. The process was carried out using a serial process train of carbon filtration, pH / ORP adjustment, and cationic exchange purification to treat dilute metal wastewater (DMW) discharged from a substrate packaging factory. Spanning a trial period of 10 months, a total of 3,271 samples were collected and statistically analyzed (average baseline + standard deviation) to evaluate the performance of a 95-gpm, multi-reactor continuous copper ion exchange treatment system that was consequently retrofitted for manganese ion exchange to meet environmental regulations. The system is also equipped with an inline acid and hot caustic regeneration system to rejuvenate exhausted IX resins and occasionally remove surface crud. Data generated from lab-scale studies was transferred to system operating modifications following multiple trial-and-error experiments. Despite the DMW treatment system failing to meet internal performance specifications for manganese output, it was observed to remove the cation notwithstanding the prevalence of copper in the waste stream. Accordingly, the average manganese output declined from 6.5 + 5.6 mg¹L⁻¹ at pre-pilot to 1.1 + 1.2 mg¹L⁻¹ post-pilot (83% baseline reduction). This milestone was achieved regardless of the average influent manganese to DMW increasing from 1.0 + 13.7 mg¹L⁻¹ at pre-pilot to 2.1 + 0.2 mg¹L⁻¹ post-pilot (110% baseline uptick). Likewise, the pre-trial and post-trial average influent copper values to DMW were 22.4 + 10.2 mg¹L⁻¹ and 32.1 + 39.1 mg¹L⁻¹, respectively (43% baseline increase). As a result, the pre-trial and post-trial average copper output values were 0.1 + 0.5 mg¹L⁻¹ and 0.4 + 1.2 mg¹L⁻¹, respectively (300% baseline uptick). Conclusively, the operating pH range upstream of treatment (between 3.5 and 5) was shown to be the largest single point of influence for optimizing manganese uptake during multi-metal ion exchange. However, the high variability of the influent copper-to-manganese ratio was observed to adversely impact the system functionality. The journal herein intends to discuss the operating parameters such as pH and oxidation-reduction potential (ORP) that were shown to influence the functional versatility of the ion exchange system significantly. The literature also proposes to discuss limitations of the treatment system such as influent copper-to-manganese ratio variations, operational configuration, waste by-product management, and system recovery requirements to provide a balanced assessment of the multi-metal ion exchange process. The take-away from this literature is intended to analyze the overall feasibility of ion exchange for metals manufacturing facilities that lack the capability to expand hardware due to real estate restrictions, aggressive schedules, or budgetary constraints.

Keywords: copper, industrial wastewater treatment, multi-metal ion exchange, manganese

Procedia PDF Downloads 143
363 Evaluation Method for Fouling Risk Using Quartz Crystal Microbalance

Authors: Natsuki Kishizawa, Keiko Nakano, Hussam Organji, Amer Shaiban, Mohammad Albeirutty

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One of the most important tasks in operating desalination plants using a reverse osmosis (RO) method is preventing RO membrane fouling caused by foulants found in seawater. Optimal design of the pre-treatment process of RO process for plants enables the reduction of foulants. Therefore, a quantitative evaluation of the fouling risk in pre-treated water, which is fed to RO, is required for optimal design. Some measurement methods for water quality such as silt density index (SDI) and total organic carbon (TOC) have been conservatively applied for evaluations. However, these methods have not been effective in some situations for evaluating the fouling risk of RO feed water. Furthermore, stable management of plants will be possible by alerts and appropriate control of the pre-treatment process by using the method if it can be applied to the inline monitoring system for the fouling risk of RO feed water. The purpose of this study is to develop a method to evaluate the fouling risk of RO feed water. We applied a quartz crystal microbalance (QCM) to measure the amount of foulants found in seawater using a sensor whose surface is coated with polyamide thin film, which is the main material of a RO membrane. The increase of the weight of the sensor after a certain length of time in which the sample water passes indicates the fouling risk of the sample directly. We classified the values as “FP: Fouling Potential”. The characteristics of the method are to measure the very small amount of substances in seawater in a short time: < 2h, and from a small volume of the sample water: < 50mL. Using some RO cell filtration units, a higher correlation between the pressure increase given by RO fouling and the FP from the method than SDI and TOC was confirmed in the laboratory-scale test. Then, to establish the correlation in the actual bench-scale RO membrane module, and to confirm the feasibility of the monitoring system as a control tool for the pre-treatment process, we have started a long-term test at an experimental desalination site by the Red Sea in Jeddah, Kingdom of Saudi Arabia. Implementing inline equipment for the method made it possible to measure FP intermittently (4 times per day) and automatically. Moreover, for two 3-month long operations, the RO operation pressure among feed water samples of different qualities was compared. The pressure increase through a RO membrane module was observed at a high FP RO unit in which feed water was treated by a cartridge filter only. On the other hand, the pressure increase was not observed at a low FP RO unit in which feed water was treated by an ultra-filter during the operation. Therefore, the correlation in an actual scale RO membrane was established in two runs of two types of feed water. The result suggested that the FP method enables the evaluation of the fouling risk of RO feed water.

Keywords: fouling, monitoring, QCM, water quality

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362 The Torah Scroll of the National Library of the Kingdom of Morocco: Parchment Support and Black Ink Analytical Study

Authors: Oubelkacem Yacine, El Bast Hassan, El Bakkali Abdelmajid, Lamhasni Taibi, Ettakni Mahmoud, Ait Lyazidi Saadia, Haddad Mustapha, Ben-Ncer Abdelouahed, El Ferrane Mohammed, Boufarra Abdelkrim

Abstract:

The present work relates to an on-site and completely non-invasive investigation of one of the most famous west Mediterranean Torah Scroll housed at the National Library of the Kingdom of Morocco. The scroll is 26 m long and consists of 143 parchment sheets of 59 cm x 19 cm, exhibiting only black writings; it is of unknown age. The artifact has been restored by the curator staff of the library. The investigation exploring separately the parchment support and the writing black ink aims at: i) the examination of the parchment conservation/degradation state, ii) the identification of the black ink and iii) the identification of the parchment handcrafting materials. For this purpose, the analyses have been based on combining all of elemental XRF and structural Raman, ATR-FT Infrared Red and Fiber Optical Reflectance spectroscopies, in addition to chroma-metric and pH measurements. pH measurements showing values around 6.5 are in concordance with the absence of any visual corrosion related to the parchment acidity. However, on the basis of the relative intensities and frequency shift of amid I (AI) and amid II (AII) vibrational bands of the collagen, ATR-FTIR spectra revealed diffuse hydrolysis and gelatinization of the parchment writing support; diffuse and non-homogeny degradation by gelatinization has been also confirmed by the IG gelatinization index deduced from the NIR bands on the FOR spectra. This IG index, defined as the ratio I (6860 cm-1) / I (6685 cm-1), ranges in the interval 0.98 – 1 and highlights collagen degradation at the molecular level. Sequentially Shifted Excitation Raman measurements (SSERS) crossed to X-ray fluorescence (XRF) ones on the black writings revealed that the black ink used is an iron-copper gall one, while FOR spectra are typical of pure metal gall inks. These later reflectance measurements exclude, thus, any intentional addition of carbon black to the ink recipe. Moreover, no lead white had been used while pre-drawing the writing lines. On another side, ATR-FTIR measurements highlighted the presence of oxalates as ink degradation products. Considering the parchment handcrafting, the combination of XRF and ATR-FTIR measurements led to the assumption that this writing support had been prepared according to ancient Middle East practices; the parchment infrared fingerprint seems identical to that of the Dead Sea scroll. The present multi-technical analyses are the first ones performed on an ancient Judaic written parchment of Morocco; it is under furthering. The investigation will be extended to other parchments belonging to the Jewish Cultural Heritage Museum of Morocco in Casablanca.

Keywords: torah scroll, parchment, black ink, non-invasive analyses, XRF/ATR-FTIR/RAMAN/FORS

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361 Frequency of Tube Feeding in Aboriginal and Non-aboriginal Head and Neck Cancer Patients and the Impact on Relapse and Survival Outcomes

Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

Abstract:

Introduction: Head and neck cancer and treatments are known for their profound effect on nutrition and tube feeding is a common requirement to maintain nutrition. Aim: We aimed to evaluate the frequency of tube feeding in Aboriginal and non-Aboriginal patients, and to examine the relapse and survival outcomes in patients who require enteral tube feeding. Methods: We performed a retrospective cohort analysis of 320 head and neck cancer patients from a single centre in Western Australia, identifying 80 Aboriginal patients and 240 non-Aboriginal patients matched on a 1:3 ratio by site, histology, rurality, and age. Data collected included patient demographics, tumour features, treatment details, and cancer and survival outcomes. Results: Aboriginal and non-Aboriginal patients required feeding tubes at similar rates (42.5% vs 46.2% respectively), however Aboriginal patients were far more likely to fail to return to oral nutrition, with 26.3% requiring long-term tube feeding versus only 15% of non-Aboriginal patients. In the overall study population, 27.5% required short-term tube feeding, 17.8% required long-term enteral tube nutrition, and 45.3% of patients did not have a feeding tube at any point. Relapse was more common in patients who required tube feeding, with relapses in 42.1% of the patients requiring long-term tube feeding, 31.8% in those requiring a short-term tube, versus 18.9% in the ‘no tube’ group. Survival outcomes for patients who required a long-term tube were also significantly poorer when compared to patients who only required a short-term tube, or not at all. Long-term tube-requiring patients were half as likely to survive (29.8%) compared to patients requiring a short-term tube (62.5%) or no tube at all (63.5%). Patients requiring a long-term tube were twice as likely to die with active disease (59.6%) as patients with no tube (28%), or a short term tube (33%). This may suggest an increased relapse risk in patients who require long-term feeding, due to consequences of malnutrition on cancer and treatment outcomes, although may simply reflect that patients with recurrent disease were more likely to have longer-term swallowing dysfunction due to recurrent disease and salvage treatments. Interestingly long-term tube patients were also more likely to die with no active disease (10.5%) (compared with short-term tube requiring patients (4.6%), or patients with no tube (8%)), which is likely reflective of the increased mortality associated with long-term aspiration and malnutrition issues. Conclusions: Requirement for tube feeding was associated with a higher rate of cancer relapse, and in particular, long-term tube feeding was associated with a higher likelihood of dying from head and neck cancer, but also a higher risk of dying from other causes without cancer relapse. This data reflects the complex effect of head and neck cancer and its treatments on swallowing and nutrition, and ultimately, the effects of malnutrition, swallowing dysfunction, and aspiration on overall cancer and survival outcomes. Tube feeding was seen at similar rates in Aboriginal and non-Aboriginal patient, however failure to return to oral intake with a requirement for a long-term feeding tube was seen far more commonly in the Aboriginal population.

Keywords: head and neck cancer, enteral tube feeding, malnutrition, survival, relapse, aboriginal patients

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360 The Rise and Effects of Social Movement on Ethnic Relations in Malaysia: The Bersih Movement as a Case Study

Authors: Nur Rafeeda Daut

Abstract:

The significance of this paper is to provide an insight on the role of social movement in building stronger ethnic relations in Malaysia. In particular, it focuses on how the BERSIH movement have been able to bring together the different ethnic groups in Malaysia to resist the present political administration that is seen to manipulate the electoral process and oppress the basic freedom of expression of Malaysians. Attention is given on how and why this group emerged and its mobilisation strategies. Malaysia which is a multi-ethnic and multi-religious society gained its independence from the British in 1957. Like many other new nations, it faces the challenges of nation building and governance. From economic issues to racial and religious tension, Malaysia is experiencing high level of corruption and income disparity among the different ethnic groups. The political parties in Malaysia are also divided along ethnic lines. BERSIH which is translated as ‘clean’ is a movement which seeks to reform the current electoral system in Malaysia to ensure equality, justice, free and fair elections. It was originally formed in 2007 as a joint committee that comprised leaders from political parties, civil society groups and NGOs. In April 2010, the coalition developed as an entirely civil society movement unaffiliated to any political party. BERSIH claimed that the electoral roll in Malaysia has been marred by fraud and other irregularities. In 2015, the BERSIH movement organised its biggest rally in Malaysia which also includes 38 other rallies held internationally. Supporters of BERSIH that participated in the demonstration were comprised of all the different ethnic groups in Malaysia. In this paper, two social movement theories are used: resource mobilization theory and political opportunity structure to explain the emergence and mobilization of the BERSIH movement in Malaysia. Based on these two theories, corruption which is believed to have contributed to the income disparity among Malaysians has generated the development of this movement. The rise of re-islamisation values propagated by certain groups in Malaysia and the shift in political leadership has also created political opportunities for this movement to emerge. In line with the political opportunity structure theory, the BERSIH movement will continue to create more opportunities for the empowerment of civil society and the unity of ethnic relations in Malaysia. Comparison is made on the degree of ethnic unity in the country before and after BERSIH was formed. This would include analysing the level of re-islamisation values and also the level of corruption in relation to economic income under the premiership of the former Prime Minister Mahathir and the present Prime Minister Najib Razak. The country has never seen such uprisings like BERSIH where ethnic groups which over the years have been divided by ethnic based political parties and economic disparity joined together with a common goal for equality and fair elections. As such, the BERSIH movement is a unique case where it illustrates the change of political landscape, ethnic relations and civil society in Malaysia.

Keywords: ethnic relations, Malaysia, political opportunity structure, resource mobilization theory and social movement

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359 Queer Anti-Urbanism: An Exploration of Queer Space Through Design

Authors: William Creighton, Jan Smitheram

Abstract:

Queer discourse has been tied to a middle-class, urban-centric, white approach to the discussion of queerness. In doing so, the multilayeredness of queer existence has been washed away in favour of palatable queer occupation. This paper uses design to explore a queer anti-urbanist approach to facilitate a more egalitarian architectural occupancy. Scott Herring’s work on queer anti-urbanism is key to this approach. Herring redeploys anti-urbanism from its historical understanding of open hostility, rejection and desire to destroy the city towards a mode of queer critique that counters normative ideals of homonormative metronormative gay lifestyles. He questions how queer identity has been closed down into a more diminutive frame where those who do not fit within this frame are subjected to persecution or silenced through their absence. We extend these ideas through design to ask how a queer anti-urbanist approach facilitates a more egalitarian architectural occupancy. Following a “design as research” methodology, the design outputs allow a vehicle to ask how we might live, otherwise, in architectural space. A design as research methodologically is a process of questioning, designing and reflecting – in a non-linear, iterative approach – establishes itself through three projects, each increasing in scale and complexity. Each of the three scales tackled a different body relationship. The project began exploring the relations between body to body, body to known others, and body to unknown others. Moving through increasing scales was not to privilege the objective, the public and the large scale; instead, ‘intra-scaling’ acts as a tool to re-think how scale reproduces normative ideas of the identity of space. There was a queering of scale. Through this approach, the results were an installation that brings two people together to co-author space where the installation distorts the sensory experience and forces a more intimate and interconnected experience challenging our socialized proxemics: knees might touch. To queer the home, the installation was used as a drawing device, a tool to study and challenge spatial perception, drawing convention, and as a way to process practical information about the site and existing house – the device became a tool to embrace the spontaneous. The final design proposal operates as a multi-scalar boundary-crossing through “private” and “public” to support kinship through communal labour, queer relationality and mooring. The resulting design works to set adrift bodies in a sea of sensations through a mix of pleasure programmes. To conclude, through three design proposals, this design research creates a relationship between queer anti-urbanism and design. It asserts that queering the design process and outcome allows a more inclusive way to consider place, space and belonging. The projects lend to a queer relationality and interdependence by making spaces that support the unsettled, out-of-place, but is it queer enough?

Keywords: queer, queer anti-urbanism, design as research, design

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358 Risk and Coping: Understanding Community Responses to Calls for Disaster Evacuation in Central Philippines

Authors: Soledad Natalia M. Dalisay, Mylene De Guzman

Abstract:

In archipelagic countries like the Philippines, many communities thrive along coastal areas. The sea is the community members’ main source of livelihood and the site of many cultural activities. For these communities, the sea is their life and livelihood. Nevertheless, the sea also poses a hazard during the rainy season when typhoons frequent their communities. Coastal communities often encounter threats from storm surges and flooding that are common when there are typhoons. During such periods, disaster evacuation programs are implemented. However, in many instances, evacuation has been the bane of local government officials implementing such programs in their communities as resistance from community members is often encountered. Such resistance is often viewed by program implementers as due to the fact that people were hard headed and ignorant of the potential impacts of living in hazard prone areas. This paper argues that it is not for these reasons that people refused to evacuate. Drawing from data collected from fieldwork done in three sites in Central Philippines affected by super typhoon Haiyan, this study aimed to provide a contextualized understanding of peoples’ refusal to heed disaster evacuation warnings. This study utilized the multi-sited ethnography approach with in-depth episodic interviews, focus group discussions, participatory risk mapping and key informant interviews in gathering data on peoples’ experiences and insights specifically on evacuation during typhoon Haiyan. This study showed that people have priorities and considerations vital in their social lives that they are protecting in their refusal to leave their homes for pre-emptive evacuation. It is not that they are not aware of the risks when the face the hazard. It is more that they had faith in the local knowledge and strategies that they have developed since the time of their ancestors as a result of living and engaging with hazards in their areas for as long as they could remember. The study also revealed that risk in encounters with hazards was gendered. Furthermore, previous engagement with local government officials and the manner in which the pre-emptive evacuation programs were implemented had cast doubt on the value of such programs in saving their lives. Life in the designated evacuation areas can be as dangerous if not more compared with living in their coastal homes. There seems to be the impression that in the evacuation program of the government, people were being moved from hazard zones to death zones. Thus, this paper ends with several recommendations that may contribute to building more responsive evacuation programs that aim to build people’s resilience while taking into consideration the local moral world in communities in identified hazard zones.

Keywords: coastal communities, disaster evacuation, disaster risk perception, social and cultural responses to hazards

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357 The Structural Alteration of DNA Native Structure of Staphylococcus aureus Bacteria by Designed Quinoxaline Small Molecules Result in Their Antibacterial Properties

Authors: Jeet Chakraborty, Sanjay Dutta

Abstract:

Antibiotic resistance by bacteria has proved to be a severe threat to mankind in recent times, and this fortifies an urgency to design and develop potent antibacterial small molecules/compounds with nonconventional mechanisms than the conventional ones. DNA carries the genetic signature of any organism, and bacteria maintain their genomic DNA inside the cell in a well-regulated compact form with the help of various nucleoid associated proteins like HU, HNS, etc. These proteins control various fundamental processes like gene expression, replication, etc., inside the cell. Alteration of the native DNA structure of bacteria can lead to severe consequences in cellular processes inside the bacterial cell that ultimately result in the death of the organism. The change in the global DNA structure by small molecules initiates a plethora of cellular responses that have not been very well investigated. Echinomycin and Triostin-A are biologically active Quinoxaline small molecules that typically consist of a quinoxaline chromophore attached with an octadepsipeptide ring. They bind to double-stranded DNA in a sequence-specific way and have high activity against a wide variety of bacteria, mainly against Gram-positive ones. To date, few synthetic quinoxaline scaffolds were synthesized, displaying antibacterial potential against a broad scale of pathogenic bacteria. QNOs (Quinoxaline N-oxides) are known to target DNA and instigate reactive oxygen species (ROS) production in bacteria, thereby exhibiting antibacterial properties. The divergent role of Quinoxaline small molecules in medicinal research qualifies them for the evaluation of their antimicrobial properties as a potential candidate. The previous study from our lab has given new insights on a 6-nitroquinoxaline derivative 1d as an intercalator of DNA, which induces conformational changes in DNA upon binding.7 The binding event observed was dependent on the presence of a crucial benzyl substituent on the quinoxaline moiety. This was associated with a large induced CD (ICD) appearing in a sigmoidal pattern upon the interaction of 1d with dsDNA. The induction of DNA superstructures by 1d at high Drug:DNA ratios was observed that ultimately led to DNA condensation. Eviction of invitro-assembled nucleosome upon treatment with a high dose of 1d was also observed. In this work, monoquinoxaline derivatives of 1d were synthesized by various modifications of the 1d scaffold. The set of synthesized 6-nitroquinoxaline derivatives along with 1d were all subjected to antibacterial evaluation across five different bacteria species. Among the compound set, 3a displayed potent antibacterial activity against Staphylococcus aureus bacteria. 3a was further subjected to various biophysical studies to check whether the DNA structural alteration potential was still intact. The biological response of S. aureus cells upon treatment with 3a was studied using various cell biology processes, which led to the conclusion that 3d can initiate DNA damage in the S. aureus cells. Finally, the potential of 3a in disrupting preformed S.aureus and S.epidermidis biofilms was also studied.

Keywords: DNA structural change, antibacterial, intercalator, DNA superstructures, biofilms

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