Search results for: minimal delamination
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 939

Search results for: minimal delamination

159 Computational Analysis of Thermal Degradation in Wind Turbine Spars' Equipotential Bonding Subjected to Lightning Strikes

Authors: Antonio A. M. Laudani, Igor O. Golosnoy, Ole T. Thomsen

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Rotor blades of large, modern wind turbines are highly susceptible to downward lightning strikes, as well as to triggering upward lightning; consequently, it is necessary to equip them with an effective lightning protection system (LPS) in order to avoid any damage. The performance of existing LPSs is affected by carbon fibre reinforced polymer (CFRP) structures, which lead to lightning-induced damage in the blades, e.g. via electrical sparks. A solution to prevent internal arcing would be to electrically bond the LPS and the composite structures such that to obtain the same electric potential. Nevertheless, elevated temperatures are achieved at the joint interfaces because of high contact resistance, which melts and vaporises some of the epoxy resin matrix around the bonding. The produced high-pressure gasses open up the bonding and can ignite thermal sparks. The objective of this paper is to predict the current density distribution and the temperature field in the adhesive joint cross-section, in order to check whether the resin pyrolysis temperature is achieved and any damage is expected. The finite element method has been employed to solve both the current and heat transfer problems, which are considered weakly coupled. The mathematical model for electric current includes Maxwell-Ampere equation for induced electric field solved together with current conservation, while the thermal field is found from heat diffusion equation. In this way, the current sub-model calculates Joule heat release for a chosen bonding configuration, whereas the thermal analysis allows to determining threshold values of voltage and current density not to be exceeded in order to maintain the temperature across the joint below the pyrolysis temperature, therefore preventing the occurrence of outgassing. In addition, it provides an indication of the minimal number of bonding points. It is worth to mention that the numerical procedures presented in this study can be tailored and applied to any type of joints other than adhesive ones for wind turbine blades. For instance, they can be applied for lightning protection of aerospace bolted joints. Furthermore, they can even be customized to predict the electromagnetic response under lightning strikes of other wind turbine systems, such as nacelle and hub components.

Keywords: carbon fibre reinforced polymer, equipotential bonding, finite element method, FEM, lightning protection system, LPS, wind turbine blades

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158 Prediction of Sound Transmission Through Framed Façade Systems

Authors: Fangliang Chen, Yihe Huang, Tejav Deganyar, Anselm Boehm, Hamid Batoul

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With growing population density and further urbanization, the average noise level in cities is increasing. Excessive noise is not only annoying but also leads to a negative impact on human health. To deal with the increasing city noise, environmental regulations bring up higher standards on acoustic comfort in buildings by mitigating the noise transmission from building envelope exterior to interior. Framed window, door and façade systems are the leading choice for modern fenestration construction, which provides demonstrated quality of weathering reliability, environmental efficiency, and installation ease. The overall sound insulation of such systems depends both on glasses and frames, where glass usually covers the majority of the exposed surfaces, thus it is the main source of sound energy transmission. While frames in modern façade systems become slimmer for aesthetic appearance, which contribute to a minimal percentage of exposed surfaces. Nevertheless, frames might provide substantial transmission paths for sound travels through because of much less mass crossing the path, thus becoming more critical in limiting the acoustic performance of the whole system. There are various methodologies and numerical programs that can accurately predict the acoustic performance of either glasses or frames. However, due to the vast variance of size and dimension between frame and glass in the same system, there is no satisfactory theoretical approach or affordable simulation tool in current practice to access the over acoustic performance of a whole façade system. For this reason, laboratory test turns out to be the only reliable source. However, laboratory test is very time consuming and high costly, moreover different lab might provide slightly different test results because of varieties of test chambers, sample mounting, and test operations, which significantly constrains the early phase design of framed façade systems. To address this dilemma, this study provides an effective analytical methodology to predict the acoustic performance of framed façade systems, based on vast amount of acoustic test results on glass, frame and the whole façade system consist of both. Further test results validate the current model is able to accurately predict the overall sound transmission loss of a framed system as long as the acoustic behavior of the frame is available. Though the presented methodology is mainly developed from façade systems with aluminum frames, it can be easily extended to systems with frames of other materials such as steel, PVC or wood.

Keywords: city noise, building facades, sound mitigation, sound transmission loss, framed façade system

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157 Modeling Diel Trends of Dissolved Oxygen for Estimating the Metabolism in Pristine Streams in the Brazilian Cerrado

Authors: Wesley A. Saltarelli, Nicolas R. Finkler, Adriana C. P. Miwa, Maria C. Calijuri, Davi G. F. Cunha

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The metabolism of the streams is an indicator of ecosystem disturbance due to the influences of the catchment on the structure of the water bodies. The study of the respiration and photosynthesis allows the estimation of energy fluxes through the food webs and the analysis of the autotrophic and heterotrophic processes. We aimed at evaluating the metabolism in streams located in the Brazilian savannah, Cerrado (Sao Carlos, SP), by determining and modeling the daily changes of dissolved oxygen (DO) in the water during one year. Three water bodies with minimal anthropogenic interference in their surroundings were selected, Espraiado (ES), Broa (BR) and Canchim (CA). Every two months, water temperature, pH and conductivity are measured with a multiparameter probe. Nitrogen and phosphorus forms are determined according to standard methods. Also, canopy cover percentages are estimated in situ with a spherical densitometer. Stream flows are quantified through the conservative tracer (NaCl) method. For the metabolism study, DO (PME-MiniDOT) and light (Odyssey Photosynthetic Active Radiation) sensors log data for at least three consecutive days every ten minutes. The reaeration coefficient (k2) is estimated through the method of the tracer gas (SF6). Finally, we model the variations in DO concentrations and calculate the rates of gross and net primary production (GPP and NPP) and respiration based on the one station method described in the literature. Three sampling were carried out in October and December 2015 and February 2016 (the next will be in April, June and August 2016). The results from the first two periods are already available. The mean water temperatures in the streams were 20.0 +/- 0.8C (Oct) and 20.7 +/- 0.5C (Dec). In general, electrical conductivity values were low (ES: 20.5 +/- 3.5uS/cm; BR 5.5 +/- 0.7uS/cm; CA 33 +/- 1.4 uS/cm). The mean pH values were 5.0 (BR), 5.7 (ES) and 6.4 (CA). The mean concentrations of total phosphorus were 8.0ug/L (BR), 66.6ug/L (ES) and 51.5ug/L (CA), whereas soluble reactive phosphorus concentrations were always below 21.0ug/L. The BR stream had the lowest concentration of total nitrogen (0.55mg/L) as compared to CA (0.77mg/L) and ES (1.57mg/L). The average discharges were 8.8 +/- 6L/s (ES), 11.4 +/- 3L/s and CA 2.4 +/- 0.5L/s. The average percentages of canopy cover were 72% (ES), 75% (BR) and 79% (CA). Significant daily changes were observed in the DO concentrations, reflecting predominantly heterotrophic conditions (respiration exceeded the gross primary production, with negative net primary production). The GPP varied from 0-0.4g/m2.d (in Oct and Dec) and the R varied from 0.9-22.7g/m2.d (Oct) and from 0.9-7g/m2.d (Dec). The predominance of heterotrophic conditions suggests increased vulnerability of the ecosystems to artificial inputs of organic matter that would demand oxygen. The investigation of the metabolism in the pristine streams can help defining natural reference conditions of trophic state.

Keywords: low-order streams, metabolism, net primary production, trophic state

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156 Assessing the Blood-Brain Barrier (BBB) Permeability in PEA-15 Mutant Cat Brain using Magnetization Transfer (MT) Effect at 7T

Authors: Sultan Z. Mahmud, Emily C. Graff, Adil Bashir

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Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) is a multifunctional adapter protein which is associated with the regulation of apoptotic cell death. Recently it has been discovered that PEA-15 is crucial in normal neurodevelopment of domestic cats, a gyrencephalic animal model, although the exact function of PEA-15 in neurodevelopment is unknown. This study investigates how PEA-15 affects the blood-brain barrier (BBB) permeability in cat brain, which can cause abnormalities in tissue metabolite and energy supplies. Severe polymicrogyria and microcephaly have been observed in cats with a loss of function PEA-15 mutation, affecting the normal neurodevelopment of the cat. This suggests that the vital role of PEA-15 in neurodevelopment is associated with gyrification. Neurodevelopment is a highly energy demanding process. The mammalian brain depends on glucose as its main energy source. PEA-15 plays a very important role in glucose uptake and utilization by interacting with phospholipase D1 (PLD1). Mitochondria also plays a critical role in bioenergetics and essential to supply adequate energy needed for neurodevelopment. Cerebral blood flow regulates adequate metabolite supply and recent findings also showed that blood plasma contains mitochondria as well. So the BBB can play a very important role in regulating metabolite and energy supply in the brain. In this study the blood-brain permeability in cat brain was measured using MRI magnetization transfer (MT) effect on the perfusion signal. Perfusion is the tissue mass normalized supply of blood to the capillary bed. Perfusion also accommodates the supply of oxygen and other metabolites to the tissue. A fraction of the arterial blood can diffuse to the tissue, which depends on the BBB permeability. This fraction is known as water extraction fraction (EF). MT is a process of saturating the macromolecules, which has an effect on the blood that has been diffused into the tissue while having minimal effect on intravascular blood water that has not been exchanged with the tissue. Measurement of perfusion signal with and without MT enables to estimate the microvascular blood flow, EF and permeability surface area product (PS) in the brain. All the experiments were performed with Siemens 7T Magnetom with 32 channel head coil. Three control cats and three PEA-15 mutant cats were used for the study. Average EF in white and gray matter was 0.9±0.1 and 0.86±0.15 respectively, perfusion in white and gray matter was 85±15 mL/100g/min and 97±20 mL/100g/min respectively, PS in white and gray matter was 201±25 mL/100g/min and 225±35 mL/100g/min respectively for control cats. For PEA-15 mutant cats, average EF in white and gray matter was 0.81±0.15 and 0.77±0.2 respectively, perfusion in white and gray matter was 140±25 mL/100g/min and 165±18 mL/100g/min respectively, PS in white and gray matter was 240±30 mL/100g/min and 259±21 mL/100g/min respectively. This results show that BBB is compromised in PEA-15 mutant cat brain, where EF is decreased and perfusion as well as PS are increased in the mutant cats compared to the control cats. This findings might further explain the function of PEA-15 in neurodevelopment.

Keywords: BBB, cat brain, magnetization transfer, PEA-15

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155 Making Beehives More 'Intelligent'- The Case of Capturing, Reducing, and Managing Bee Pest Infestation in Hives through Modification of Hive Entrance Holes and the Installation of Multiple In-Hive Bee Pest Traps

Authors: Prince Amartey

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Bees are clever creatures, thus, capturing bees implies that the hives are intelligent in the sense that they have all of the required circumstances to attract and trap the bees. If the hive goes above and beyond to keep the bees in the hive and to keep the activities of in-hive pests to a minimal in order for the bees to develop to their maximum potential, the hive is becoming or is more 'intelligent'. Some bee pests, such as tiny beehive beetles, are endemic to Africa; however, the way we now extract honey by cutting off the combs and pressing for honey prevents the spread of these bees' insect enemies. However, when we explore entering the commercialization. When freshly collected combs are returned to the hives following the adoption of the frame and other systems, there is a need to consider putting in strategies to manage the accompanying pest concerns that arise with unprotected combs.The techniques for making hives more'intelligent' are thus more important presently, given that the African apicultural business does not wish to encourage the use of pesticides in the hives. This include changing the hive's entrance holes in order to improve the bees' own mechanism for defending the entry sites, as well as collecting pests by setting exterior and in-hive traps to prevent pest infiltration into hives by any means feasible. Material and Methods: The following five (5) mechanisms are proposed to make the hives more 'intelligent.' i. The usage of modified frames with five (5) beetle traps positioned horizontally on the vertical 'legs' to catch the beetle along the combs' surfaces-multiple bee ii. Baited bioelectric frame traps, which has both vertical sections of frame covered with a 3mm mesh that allows pest entry but not bees. The pest is attracted by strips of combs of honey, open brood, pollen on metal plates inserted horizontally on the vertical ‘legs’ of the frames. An electrical ‘mine’ system in place that electrocutes the pests as they step on the wires in the trap to enter the frame trap iii. The ten rounded hive entry holes are adapted as the bees are able to police the entrance to prevent entry of pest. The holes are arranged in two rows, with one on top of the other What Are the Main Contributions of Your Research?-Results Discussions and Conclusions The techniques implemented decrease pest ingress, while in-hive traps capture those that escape entry into the hives. Furthermore, the stand alteration traps larvae and stops their growth into adults. As beekeeping commercialization grows throughout Africa, these initiatives will minimize insect infestation in hives and necessarily enhance honey output.

Keywords: bee pests, modified frames, multiple beetle trap, Baited bioelectric frame traps

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154 An Investigation on Opportunities and Obstacles on Implementation of Building Information Modelling for Pre-fabrication in Small and Medium Sized Construction Companies in Germany: A Practical Approach

Authors: Nijanthan Mohan, Rolf Gross, Fabian Theis

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The conventional method used in the construction industries often resulted in significant rework since most of the decisions were taken onsite under the pressure of project deadlines and also due to the improper information flow, which results in ineffective coordination. However, today’s architecture, engineering, and construction (AEC) stakeholders demand faster and accurate deliverables, efficient buildings, and smart processes, which turns out to be a tall order. Hence, the building information modelling (BIM) concept was developed as a solution to fulfill the above-mentioned necessities. Even though BIM is successfully implemented in most of the world, it is still in the early stages in Germany, since the stakeholders are sceptical of its reliability and efficiency. Due to the huge capital requirement, the small and medium-sized construction companies are still reluctant to implement BIM workflow in their projects. The purpose of this paper is to analyse the opportunities and obstacles to implementing BIM for prefabrication. Among all other advantages of BIM, pre-fabrication is chosen for this paper because it plays a vital role in creating an impact on time as well as cost factors of a construction project. The positive impact of prefabrication can be explicitly observed by the project stakeholders and participants, which enables the breakthrough of the skepticism factor among the small scale construction companies. The analysis consists of the development of a process workflow for implementing prefabrication in building construction, followed by a practical approach, which was executed with two case studies. The first case study represents on-site prefabrication, and the second was done for off-site prefabrication. It was planned in such a way that the first case study gives a first-hand experience for the workers at the site on the BIM model so that they can make much use of the created BIM model, which is a better representation compared to the traditional 2D plan. The main aim of the first case study is to create a belief in the implementation of BIM models, which was succeeded by the execution of offshore prefabrication in the second case study. Based on the case studies, the cost and time analysis was made, and it is inferred that the implementation of BIM for prefabrication can reduce construction time, ensures minimal or no wastes, better accuracy, less problem-solving at the construction site. It is also observed that this process requires more planning time, better communication, and coordination between different disciplines such as mechanical, electrical, plumbing, architecture, etc., which was the major obstacle for successful implementation. This paper was carried out in the perspective of small and medium-sized mechanical contracting companies for the private building sector in Germany.

Keywords: building information modelling, construction wastes, pre-fabrication, small and medium sized company

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153 Monoallelic and Biallelic Deletions of 13q14 in a Group of 36 CLL Patients Investigated by CGH Haematological Cancer and SNP Array (8x60K)

Authors: B. Grygalewicz, R. Woroniecka, J. Rygier, K. Borkowska, A. Labak, B. Nowakowska, B. Pienkowska-Grela

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Introduction: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western world. Hemizygous and or homozygous loss at 13q14 occur in more than half of cases and constitute the most frequent chromosomal abnormality in CLL. It is believed that deletions 13q14 play a role in CLL pathogenesis. Two microRNA genes miR-15a and miR- 16-1 are targets of 13q14 deletions and plays a tumor suppressor role by targeting antiapoptotic BCL2 gene. Deletion size, as a single change detected in FISH analysis, has haprognostic significance. Patients with small deletions, without RB1 gene involvement, have the best prognosis and the longest overall survival time (OS 133 months). In patients with bigger deletion region, containing RB1 gene, prognosis drops to intermediate, like in patients with normal karyotype and without changes in FISH with overall survival 111 months. Aim: Precise delineation of 13q14 deletions regions in two groups of CLL patients, with mono- and biallelic deletions and qualifications of their prognostic significance. Methods: Detection of 13q14 deletions was performed by FISH analysis with CLL probe panel (D13S319, LAMP1, TP53, ATM, CEP-12). Accurate deletion size detection was performed by CGH Haematological Cancer and SNP array (8x60K). Results: Our investigated group of CLL patients with the 13q14 deletion, detected by FISH analysis, comprised two groups: 18 patients with monoallelic deletions and 18 patients with biallelic deletions. In FISH analysis, in the monoallelic group the range of cells with deletion, was 43% to 97%, while in biallelic group deletion was detected in 11% to 94% of cells. Microarray analysis revealed precise deletion regions. In the monoallelic group, the range of size was 348,12 Kb to 34,82 Mb, with median deletion size 7,93 Mb. In biallelic group discrepancy of total deletions, size was 135,27 Kb to 33,33 Mb, with median deletion size 2,52 Mb. The median size of smaller deletion regions on one copy chromosome 13 was 1,08 Mb while the average region of bigger deletion on the second chromosome 13 was 4,04 Mb. In the monoallelic group, in 8/18 deletion region covered RB1 gene. In the biallelic group, in 4/18 cases, revealed deletion on one copy of biallelic deletion and in 2/18 showed deletion of RB1 gene on both deleted 13q14 regions. All minimal deleted regions included miR-15a and miR-16-1 genes. Genetic results will be correlated with clinical data. Conclusions: Application of CGH microarrays technique in CLL allows accurately delineate the size of 13q14 deletion regions, what have a prognostic value. All deleted regions included miR15a and miR-16-1, what confirms the essential role of these genes in CLL pathogenesis. In our investigated groups of CLL patients with mono- and biallelic 13q14 deletions, patients with biallelic deletion presented smaller deletion sizes (2,52 Mb vs 7,93 Mb), what is connected with better prognosis.

Keywords: CLL, deletion 13q14, CGH microarrays, SNP array

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152 Diurnal Circle of Rainfall and Convective Properties over West and Central Africa

Authors: Balogun R. Ayodeji, Adefisan E. Adesanya, Adeyewa Z. Debo, E. C. Okogbue

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The need to investigate diurnal weather circles in West Africa is coined in the fact that complex interactions often results from diurnal weather patterns. This study investigates diurnal circles of wind, rainfall and convective properties using six (6) hour interval data from the ERA-Interim and the Tropical Rainfall Measurement Mission (TRMM). The seven distinct zones, used in this work and classified as rainforest (west-coast, dry, Nigeria-Cameroon), Savannah (Nigeria, and Central Africa and South Sudan (CASS)), Sudano-Sahel, and Sahel, were clearly indicated by the rainfall pattern in each zones. Results showed that the land‐ocean warming contrast was more strongly sensitive to seasonal cycle and has been very weak during March-May (MAM) but clearly spelt out during June-September (JJAS). Dipoles of wind convergence/divergence and wet/dry precipitation, between CASS and Nigeria Savannah zones, were identified in morning and evening hours of MAM, whereas distinct night and day anomaly, in the same location of CASS, were found to be consistent during the JJAS season. Diurnal variation of convective properties showed that stratiform precipitation, due to the extremely low occurrence of flashcount climatology, was dominant during morning hours for both MAM and JJAS than other periods of the day. On the other hand, diurnal variation of the system sizes showed that small system sizes were most dominant during the day time periods for both MAM and JJAS, whereas larger system sizes were frequent during the evening, night, and morning hours. The locations of flashcount and system sizes agreed with earlier results that morning and day-time hours were dominated by stratiform precipitation and small system sizes respectively. Most results clearly showed that the eastern locations of Sudano and Sahel were consistently dry because rainfall and precipitation features were predominantly few. System sizes greater than or equal to 800 km² were found in the western axis of the Sudano and Sahel zones, whereas the eastern axis, particularly in the Sahel zone, had minimal occurrences of small/large system sizes. From the results of locations of extreme systems, flashcount greater than 275 in one single system was never observed during the morning (6Z) diurnal, whereas, the evening (18Z) diurnal had the most frequent cases (at least 8) of flashcount exceeding 275 in one single system. Results presented had shown the importance of diurnal variation in understanding precipitation, flashcount, system sizes patterns at diurnal scales, and understanding land-ocean contrast, precipitation, and wind field anomaly at diurnal scales.

Keywords: convective properties, diurnal circle, flashcount, system sizes

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151 Hydrological Challenges and Solutions in the Nashik Region: A Multi Tracer and Geochemistry Approach to Groundwater Management

Authors: Gokul Prasad, Pennan Chinnasamy

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The degradation of groundwater resources, attributed to factors such as excessive abstraction and contamination, has emerged as a global concern. This study delves into the stable isotopes of water) in a hard-rock aquifer situated in the Upper Godavari watershed, an agriculturally rich region in India underlain by Basalt. The higher groundwater draft (> 90%) poses significant risks; comprehending groundwater sources, flow patterns, and their environmental impacts is pivotal for researchers and water managers. The region has faced five droughts in the past 20 years; four are categorized as medium. The recharge rates are variable and show a very minimum contribution to groundwater. The rainfall pattern shows vast variability, with the region receiving seasonal monsoon rainfall for just four months and the rest of the year experiencing minimal rainfall. This research closely monitored monsoon precipitation inputs and examined spatial and temporal fluctuations in δ18O and δ2H in both groundwater and precipitation. By discerning individual recharge events during monsoons, it became possible to identify periods when evaporation led to groundwater quality deterioration, characterized by elevated salinity and stable isotope values in the return flow. The locally derived meteoric water line (LMWL) (δ2H = 6.72 * δ18O + 1.53, r² = 0.6) provided valuable insights into the groundwater system. The leftward shift of the Nashik LMWL in relation to the GMWL and LMWL indicated groundwater evaporation (-33 ‰), supported by spatial variations in electrical conductivity (EC) data. Groundwater in the eastern and northern watershed areas exhibited higher salinity > 3000uS/cm, expanding > 40% of the area compared to the western and southern regions due to geological disparities (alluvium vs basalt). The findings emphasize meteoric precipitation as the primary groundwater source in the watershed. However, spatial variations in isotope values and chemical constituents indicate other contributing factors, including evaporation, groundwater source type, and natural or anthropogenic (specifically agricultural and industrial) contaminants. Therefore, the study recommends focused hydro geochemistry and isotope analysis in areas with strong agricultural and industrial influence for the development of holistic groundwater management plans for protecting the groundwater aquifers' quantity and quality.

Keywords: groundwater quality, stable isotopes, salinity, groundwater management, hard-rock aquifer

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150 Rehabilitation Team after Brain Damages as Complex System Integrating Consciousness

Authors: Olga Maksakova

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A work with unconscious patients after acute brain damages besides special knowledge and practical skills of all the participants requires a very specific organization. A lot of said about team approach in neurorehabilitation, usually as for outpatient mode. Rehabilitologists deal with fixed patient problems or deficits (motion, speech, cognitive or emotional disorder). Team-building means superficial paradigm of management psychology. Linear mode of teamwork fits casual relationships there. Cases with deep altered states of consciousness (vegetative states, coma, and confusion) require non-linear mode of teamwork: recovery of consciousness might not be the goal due to phenomenon uncertainty. Rehabilitation team as Semi-open Complex System includes the patient as a part. Patient's response pattern becomes formed not only with brain deficits but questions-stimuli, context, and inquiring person. Teamwork is sourcing of phenomenology knowledge of patient's processes as Third-person approach is replaced with Second- and after First-person approaches. Here is a chance for real-time change. Patient’s contacts with his own body and outward things create a basement for restoration of consciousness. The most important condition is systematic feedbacks to any minimal movement or vegetative signal of the patient. Up to now, recovery work with the most severe contingent is carried out in the mode of passive physical interventions, while an effective rehabilitation team should include specially trained psychologists and psychotherapists. It is they who are able to create a network of feedbacks with the patient and inter-professional ones building up the team. Characteristics of ‘Team-Patient’ system (TPS) are energy, entropy, and complexity. Impairment of consciousness as the absence of linear contact appears together with a loss of essential functions (low energy), vegetative-visceral fits (excessive energy and low order), motor agitation (excessive energy and excessive order), etc. Techniques of teamwork are different in these cases for resulting optimization of the system condition. Directed regulation of the system complexity is one of the recovery tools. Different signs of awareness appear as a result of system self-organization. Joint meetings are an important part of teamwork. Regular or event-related discussions form the language of inter-professional communication, as well as the patient's shared mental model. Analysis of complex communication process in TPS may be useful for creation of the general theory of consciousness.

Keywords: rehabilitation team, urgent rehabilitation, severe brain damage, consciousness disorders, complex system theory

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149 The Beneficial Effects of Inhibition of Hepatic Adaptor Protein Phosphotyrosine Interacting with PH Domain and Leucine Zipper 2 on Glucose and Cholesterol Homeostasis

Authors: Xi Chen, King-Yip Cheng

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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

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148 Experimental Analysis of the Performance of a System for Freezing Fish Products Equipped with a Modulating Vapour Injection Scroll Compressor

Authors: Domenico Panno, Antonino D’amico, Hamed Jafargholi

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This paper presents an experimental analysis of the performance of a system for freezing fish products equipped with a modulating vapour injection scroll compressor operating with R448A refrigerant. Freezing is a critical process for the preservation of seafood products, as it influences quality, food safety, and environmental sustainability. The use of a modulating scroll compressor with vapour injection, associated with the R448A refrigerant, is proposed as a solution to optimize the performance of the system, reducing energy consumption and mitigating the environmental impact. The steam injection modulating scroll compressor represents an advanced technology that allows you to adjust the compressor capacity based on the actual cooling needs of the system. Vapour injection allows the optimization of the refrigeration cycle, reducing the evaporation temperature and improving the overall efficiency of the system. The use of R448A refrigerant, with a low global warming potential (GWP), is part of an environmental sustainability perspective, helping to reduce the climate impact of the system. The aim of this research was to evaluate the performance of the system through a series of experiments conducted on a pilot plant for the freezing of fish products. Several operational variables were monitored and recorded, including evaporation temperature, condensation temperature, energy consumption, and freezing time of seafood products. The results of the experimental analysis highlighted the benefits deriving from the use of the modulating vapour injection scroll compressor with the R448A refrigerant. In particular, a significant reduction in energy consumption was recorded compared to conventional systems. The modulating capacity of the compressor made it possible to adapt the cold production to variations in the thermal load, ensuring optimal operation of the system and reducing energy waste. Furthermore, the use of an electronic expansion valve highlighted greater precision in the control of the evaporation temperature, with minimal deviation from the desired set point. This helped ensure better quality of the final product, reducing the risk of damage due to temperature changes and ensuring uniform freezing of the fish products. The freezing time of seafood has been significantly reduced thanks to the configuration of the entire system, allowing for faster production and greater production capacity of the plant. In conclusion, the use of a modulating vapour injection scroll compressor operating with R448A refrigerant has proven effective in improving the performance of a system for freezing fish products. This technology offers an optimal balance between energy efficiency, temperature control, and environmental sustainability, making it an advantageous choice for food industries.

Keywords: freezing, scroll compressor, energy efficiency, vapour injection

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147 Oscillating Water Column Wave Energy Converter with Deep Water Reactance

Authors: William C. Alexander

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The oscillating water column (OSC) wave energy converter (WEC) with deep water reactance (DWR) consists of a large hollow sphere filled with seawater at the base, referred to as the ‘stabilizer’, a hollow cylinder at the top of the device, with a said cylinder having a bottom open to the sea and a sealed top save for an orifice which leads to an air turbine, and a long, narrow rod connecting said stabilizer with said cylinder. A small amount of ballast at the bottom of the stabilizer and a small amount of floatation in the cylinder keeps the device upright in the sea. The floatation is set such that the mean water level is nominally halfway up the cylinder. The entire device is loosely moored to the seabed to keep it from drifting away. In the presence of ocean waves, seawater will move up and down within the cylinder, producing the ‘oscillating water column’. This gives rise to air pressure within the cylinder alternating between positive and negative gauge pressure, which in turn causes air to alternately leave and enter the cylinder through said top-cover situated orifice. An air turbine situated within or immediately adjacent to said orifice converts the oscillating airflow into electric power for transport to shore or elsewhere by electric power cable. Said oscillating air pressure produces large up and down forces on the cylinder. Said large forces are opposed through the rod to the large mass of water retained within the stabilizer, which is located deep enough to be mostly free of any wave influence and which provides the deepwater reactance. The cylinder and stabilizer form a spring-mass system which has a vertical (heave) resonant frequency. The diameter of the cylinder largely determines the power rating of the device, while the size (and water mass within) of the stabilizer determines said resonant frequency. Said frequency is chosen to be on the lower end of the wave frequency spectrum to maximize the average power output of the device over a large span of time (such as a year). The upper portion of the device (the cylinder) moves laterally (surge) with the waves. This motion is accommodated with minimal loading on the said rod by having the stabilizer shaped like a sphere, allowing the entire device to rotate about the center of the stabilizer without rotating the seawater within the stabilizer. A full-scale device of this type may have the following dimensions. The cylinder may be 16 meters in diameter and 30 meters high, the stabilizer 25 meters in diameter, and the rod 55 meters long. Simulations predict that this will produce 1,400 kW in waves of 3.5-meter height and 12 second period, with a relatively flat power curve between 5 and 16 second wave periods, as will be suitable for an open-ocean location. This is nominally 10 times higher power than similar-sized WEC spar buoys as reported in the literature, and the device is projected to have only 5% of the mass per unit power of other OWC converters.

Keywords: oscillating water column, wave energy converter, spar bouy, stabilizer

Procedia PDF Downloads 96
146 Crash and Injury Characteristics of Riders in Motorcycle-Passenger Vehicle Crashes

Authors: Z. A. Ahmad Noor Syukri, A. J. Nawal Aswan, S. V. Wong

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The motorcycle has become one of the most common type of vehicles used on the road, particularly in the Asia region, including Malaysia, due to its size-convenience and affordable price. This study focuses only on crashes involving motorcycles with passenger cars consisting 43 real world crashes obtained from in-depth crash investigation process from June 2016 till July 2017. The study collected and analyzed vehicle and site parameters obtained during crash investigation and injury information acquired from the patient-treating hospital. The investigation team, consisting of two personnel, is stationed at the Emergency Department of the treatment facility, and was dispatched to the crash scene once receiving notification of the related crashes. The injury information retrieved was coded according to the level of severity using the Abbreviated Injury Scale (AIS) and classified into different body regions. The data revealed that weekend crashes were significantly higher for the night time period and the crash occurrence was the highest during morning hours (commuting to work period) for weekdays. Bad weather conditions play a minimal effect towards the occurrence of motorcycle – passenger vehicle crashes and nearly 90% involved motorcycles with single riders. Riders up to 25 years old are heavily involved in crashes with passenger vehicles (60%), followed by 26-55 year age group with 35%. Male riders were dominant in each of the age segments. The majority of the crashes involved side impacts, followed by rear impacts and cars outnumbered the rest of the passenger vehicle types in terms of crash involvement with motorcycles. The investigation data also revealed that passenger vehicles were the most at-fault counterpart (62%) when involved in crashes with motorcycles and most of the crashes involved situations whereby both of the vehicles are travelling in the same direction and one of the vehicles is in a turning maneuver. More than 80% of the involved motorcycle riders had sustained yellow severity level during triage process. The study also found that nearly 30% of the riders sustained injuries to the lower extremities, while MAIS level 3 injuries were recorded for all body regions except for thorax region. The result showed that crashes in which the motorcycles were found to be at fault were more likely to occur during night and raining conditions. These types of crashes were also found to be more likely to involve other types of passenger vehicles rather than cars and possess higher likelihood in resulting higher ISS (>6) value to the involved rider. To reduce motorcycle fatalities, it first has to understand the characteristics concerned and focus may be given on crashes involving passenger vehicles as the most dominant crash partner on Malaysian roads.

Keywords: motorcycle crash, passenger vehicle, in-depth crash investigation, injury mechanism

Procedia PDF Downloads 310
145 Molecular Detection of mRNA bcr-abl and Circulating Leukemic Stem Cells CD34+ in Patients with Acute Lymphoblastic Leukemia and Chronic Myeloid Leukemia and Its Association with Clinical Parameters

Authors: B. Gonzalez-Yebra, H. Barajas, P. Palomares, M. Hernandez, O. Torres, M. Ayala, A. L. González, G. Vazquez-Ortiz, M. L. Guzman

Abstract:

Leukemia arises by molecular alterations of the normal hematopoietic stem cell (HSC) transforming it into a leukemic stem cell (LSC) with high cell proliferation, self-renewal, and cell differentiation. Chronic myeloid leukemia (CML) originates from an LSC-leading to elevated proliferation of myeloid cells and acute lymphoblastic leukemia (ALL) originates from an LSC development leading to elevated proliferation of lymphoid cells. In both cases, LSC can be identified by multicolor flow cytometry using several antibodies. However, to date, LSC levels in peripheral blood (PB) are not established well enough in ALL and CML patients. On the other hand, the detection of the minimal residue disease (MRD) in leukemia is mainly based on the identification of the mRNA bcr-abl gene in CML patients and some other genes in ALL patients. There is no a properly biomarker to detect MDR in both types of leukemia. The objective of this study was to determine mRNA bcr-abl and the percentage of LSC in peripheral blood of patients with CML and ALL and identify a possible association between the amount of LSC in PB and clinical data. We included in this study 19 patients with Leukemia. A PB sample was collected per patient and leukocytes were obtained by Ficoll gradient. The immunophenotype for LSC CD34+ was done by flow cytometry analysis with CD33, CD2, CD14, CD16, CD64, HLA-DR, CD13, CD15, CD19, CD10, CD20, CD34, CD38, CD71, CD90, CD117, CD123 monoclonal antibodies. In addition, to identify the presence of the mRNA bcr-abl by RT-PCR, the RNA was isolated using TRIZOL reagent. Molecular (presence of mRNA bcr-abl and LSC CD34+) and clinical results were analyzed with descriptive statistics and a multiple regression analysis was performed to determine statistically significant association. In total, 19 patients (8 patients with ALL and 11 patients with CML) were analyzed, 9 patients with de novo leukemia (ALL = 6 and CML = 3) and 10 under treatment (ALL = 5 and CML = 5). The overall frequency of mRNA bcr-abl was 31% (6/19), and it was negative in ALL patients and positive in 80% in CML patients. On the other hand, LSC was determined in 16/19 leukemia patients (%LSC= 0.02-17.3). The Novo patients had higher percentage of LSC (0.26 to 17.3%) than patients under treatment (0 to 5.93%). The amount of LSC was significantly associated with the amount of LSC were: absence of treatment, the absence of splenomegaly, and a lower number of leukocytes, negative association for the clinical variables age, sex, blasts, and mRNA bcr-abl. In conclusion, patients with de novo leukemia had a higher percentage of circulating LSC than patients under treatment, and it was associated with clinical parameters as lack of treatment, absence of splenomegaly and a lower number of leukocytes. The mRNA bcr-abl detection was only possible in the series of patients with CML, and molecular detection of LSC could be identified in the peripheral blood of all leukemia patients, we believe the identification of circulating LSC may be used as biomarker for the detection of the MRD in leukemia patients.

Keywords: stem cells, leukemia, biomarkers, flow cytometry

Procedia PDF Downloads 341
144 Challenges of Strategies for Improving Sustainability in Urban Historical Context in Developing Countries: The Case of Shiraz Bein Al-Haramein

Authors: Amir Hossein Ashari, Sedighe Erfan Manesh

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One of the problems in developing countries is renovating the historical context and inducing behaviors appropriate to modern life to such a context. This study was conducted using field and library methods in 2012. Similar cases carried out in Iran and developing countries were compared to unveil the strengths and weaknesses of these projects. At present, in the historical context of Shiraz, the distance between two religious shrines of Shahcheragh (Ahmad ibn Musa) and Astaneh (Sayed Alaa al-Din Hossein), which are significant places in religious, cultural, social, and economic terms, is an area full of historic places called Bein Al-Haramein. Unfortunately, some of these places have been worn out and are not appropriate for common uses. The basic strategy of Bein Al-Haramein was to improve social development of Shiraz, to enhance the vitality and dynamism of the historical context of Bein Al-Haramein and to create tourist attractions in order to boost the city's economic and social stability. To this end, the project includes the huge Bein Al-Haramein Commercial Complex which is under construction now. To construct the complex, officials have decided to demolish places of historical value which can lead to irreparable consequences. Iranian urban design has always been based on three elements of bazaars, mosques and government facilities with bazaars being the organic connector of the other elements. Therefore, the best strategy in the above case is to provide for a commercial connection between the two poles. Although this strategy is included in the project, lack of attention to renovation principles in this area and complete destruction of the context will lead to its irreversible damage and will destroy its cultural and historical identity. In urban planning of this project, some important issues have been neglected including: preserving valuable buildings and special old features of the city, rebuilding worn buildings and context to attract trust and confidence of the people, developing new models according to changes, improving the structural position of old context with minimal degradation, attracting partnerships of residents and protecting their rights and finally using potential facilities of the old context. The best strategy for achieving sustainability in Bein Al-Haramein can be the one used in the distance between Santa Maria Novella and Santa Maria Del Fiore churches in historical context where while protecting the historic context and constructions, old buildings were renovated and given different commercial and service uses making them sustainable and dynamic places. Similarly, in Bein Al-Haramein, renovating old constructions and monuments and giving different commercial and other uses to them can help improve the economic and social sustainability of the area.

Keywords: Bein Al-Haramein, sustainability, historical context, historical context

Procedia PDF Downloads 431
143 Detailed Quantum Circuit Design and Evaluation of Grover's Algorithm for the Bounded Degree Traveling Salesman Problem Using the Q# Language

Authors: Wenjun Hou, Marek Perkowski

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The Traveling Salesman problem is famous in computing and graph theory. In short, it asks for the Hamiltonian cycle of the least total weight in a given graph with N nodes. All variations on this problem, such as those with K-bounded-degree nodes, are classified as NP-complete in classical computing. Although several papers propose theoretical high-level designs of quantum algorithms for the Traveling Salesman Problem, no quantum circuit implementation of these algorithms has been created up to our best knowledge. In contrast to previous papers, the goal of this paper is not to optimize some abstract complexity measures based on the number of oracle iterations, but to be able to evaluate the real circuit and time costs of the quantum computer. Using the emerging quantum programming language Q# developed by Microsoft, which runs quantum circuits in a quantum computer simulation, an implementation of the bounded-degree problem and its respective quantum circuit were created. To apply Grover’s algorithm to this problem, a quantum oracle was designed, evaluating the cost of a particular set of edges in the graph as well as its validity as a Hamiltonian cycle. Repeating the Grover algorithm with an oracle that finds successively lower cost each time allows to transform the decision problem to an optimization problem, finding the minimum cost of Hamiltonian cycles. N log₂ K qubits are put into an equiprobablistic superposition by applying the Hadamard gate on each qubit. Within these N log₂ K qubits, the method uses an encoding in which every node is mapped to a set of its encoded edges. The oracle consists of several blocks of circuits: a custom-written edge weight adder, node index calculator, uniqueness checker, and comparator, which were all created using only quantum Toffoli gates, including its special forms, which are Feynman and Pauli X. The oracle begins by using the edge encodings specified by the qubits to calculate each node that this path visits and adding up the edge weights along the way. Next, the oracle uses the calculated nodes from the previous step and check that all the nodes are unique. Finally, the oracle checks that the calculated cost is less than the previously-calculated cost. By performing the oracle an optimal number of times, a correct answer can be generated with very high probability. The oracle of the Grover Algorithm is modified using the recalculated minimum cost value, and this procedure is repeated until the cost cannot be further reduced. This algorithm and circuit design have been verified, using several datasets, to generate correct outputs.

Keywords: quantum computing, quantum circuit optimization, quantum algorithms, hybrid quantum algorithms, quantum programming, Grover’s algorithm, traveling salesman problem, bounded-degree TSP, minimal cost, Q# language

Procedia PDF Downloads 172
142 Using Fractal Architectures for Enhancing the Thermal-Fluid Transport

Authors: Surupa Shaw, Debjyoti Banerjee

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Enhancing heat transfer in compact volumes is a challenge when constrained by cost issues, especially those associated with requirements for minimizing pumping power consumption. This is particularly acute for electronic chip cooling applications. Technological advancements in microelectronics have led to development of chip architectures that involve increased power consumption. As a consequence packaging, technologies are saddled with needs for higher rates of power dissipation in smaller form factors. The increasing circuit density, higher heat flux values for dissipation and the significant decrease in the size of the electronic devices are posing thermal management challenges that need to be addressed with a better design of the cooling system. Maximizing surface area for heat exchanging surfaces (e.g., extended surfaces or “fins”) can enable dissipation of higher levels of heat flux. Fractal structures have been shown to maximize surface area in compact volumes. Self-replicating structures at multiple length scales are called “Fractals” (i.e., objects with fractional dimensions; unlike regular geometric objects, such as spheres or cubes whose volumes and surface area values scale as integer values of the length scale dimensions). Fractal structures are expected to provide an appropriate technology solution to meet these challenges for enhanced heat transfer in the microelectronic devices by maximizing surface area available for heat exchanging fluids within compact volumes. In this study, the effect of different fractal micro-channel architectures and flow structures on the enhancement of transport phenomena in heat exchangers is explored by parametric variation of fractal dimension. This study proposes a model that would enable cost-effective solutions for thermal-fluid transport for energy applications. The objective of this study is to ascertain the sensitivity of various parameters (such as heat flux and pressure gradient as well as pumping power) to variation in fractal dimension. The role of the fractal parameters will be instrumental in establishing the most effective design for the optimum cooling of microelectronic devices. This can help establish the requirement of minimal pumping power for enhancement of heat transfer during cooling. Results obtained in this study show that the proposed models for fractal architectures of microchannels significantly enhanced heat transfer due to augmentation of surface area in the branching networks of varying length-scales.

Keywords: fractals, microelectronics, constructal theory, heat transfer enhancement, pumping power enhancement

Procedia PDF Downloads 308
141 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

Abstract:

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

Procedia PDF Downloads 77
140 Combination Therapies Targeting Apoptosis Pathways in Pediatric Acute Myeloid Leukemia (AML)

Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

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Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

Procedia PDF Downloads 187
139 Cross-Sectoral Energy Demand Prediction for Germany with a 100% Renewable Energy Production in 2050

Authors: Ali Hashemifarzad, Jens Zum Hingst

Abstract:

The structure of the world’s energy systems has changed significantly over the past years. One of the most important challenges in the 21st century in Germany (and also worldwide) is the energy transition. This transition aims to comply with the recent international climate agreements from the United Nations Climate Change Conference (COP21) to ensure sustainable energy supply with minimal use of fossil fuels. Germany aims for complete decarbonization of the energy sector by 2050 according to the federal climate protection plan. One of the stipulations of the Renewable Energy Sources Act 2017 for the expansion of energy production from renewable sources in Germany is that they cover at least 80% of the electricity requirement in 2050; The Gross end energy consumption is targeted for at least 60%. This means that by 2050, the energy supply system would have to be almost completely converted to renewable energy. An essential basis for the development of such a sustainable energy supply from 100% renewable energies is to predict the energy requirement by 2050. This study presents two scenarios for the final energy demand in Germany in 2050. In the first scenario, the targets for energy efficiency increase and demand reduction are set very ambitiously. To build a comparison basis, the second scenario provides results with less ambitious assumptions. For this purpose, first, the relevant framework conditions (following CUTEC 2016) were examined, such as the predicted population development and economic growth, which were in the past a significant driver for the increase in energy demand. Also, the potential for energy demand reduction and efficiency increase (on the demand side) was investigated. In particular, current and future technological developments in energy consumption sectors and possible options for energy substitution (namely the electrification rate in the transport sector and the building renovation rate) were included. Here, in addition to the traditional electricity sector, the areas of heat, and fuel-based consumptions in different sectors such as households, commercial, industrial and transport are taken into account, supporting the idea that for a 100% supply from renewable energies, the areas currently based on (fossil) fuels must be almost completely be electricity-based by 2050. The results show that in the very ambitious scenario a final energy demand of 1,362 TWh/a is required, which is composed of 818 TWh/a electricity, 229 TWh/a ambient heat for electric heat pumps and approx. 315 TWh/a non-electric energy (raw materials for non-electrifiable processes). In the less ambitious scenario, in which the targets are not fully achieved by 2050, the final energy demand will need a higher electricity part of almost 1,138 TWh/a (from the total: 1,682 TWh/a). It has also been estimated that 50% of the electricity revenue must be saved to compensate for fluctuations in the daily and annual flows. Due to conversion and storage losses (about 50%), this would mean that the electricity requirement for the very ambitious scenario would increase to 1,227 TWh / a.

Keywords: energy demand, energy transition, German Energiewende, 100% renewable energy production

Procedia PDF Downloads 122
138 In vitro Antioxidant, Anti-Diabetic and Nutritional Properties of Breynia retusa

Authors: Parimelazhagan Thangaraj

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Natural products serves human kind as a source of all drugs and higher plants provide most of these therapeutic agents. These products are widely recognized in the pharmaceutical industry for their broad structural diversity as well as their wide range of pharmacological activities. Euphorbiaceae is one of the important families with significant pharmacological activities, of which many species has been used traditionally for the treatment of various ailments. Breynia retusa belongs to the family Euphorbiaceae is used to cure ailments like body pain, skin inflammation, hyperglycaemia, diarrhoea, dysentery and toothache. Flowers and young leaves of B. retusa are cooked and eaten, roots are used for meningitis. The juice of the stem is used in conjunctivtis and leaves as poultice to hasten suppuration. Based on the strong evidences of traditional uses of Breynia retusa, the present study was focused on neutraceuticals evaluation of the species with special reference to oxidative stress and diabetes. Both leaves and stem of B. retusa were extracted with different solvents and analyzed for radical scavenging ability wherein ABTS.+ (8396.95±1529.01 µM TEAC/g extract), phosphomolybdenum (17.34±0.08 g AAE/100 g extract) and FRAP (6075.66±414.28 µM Fe (II) E/mg extract) assays showed good radical scavenging activity in stem. Furthermore, leaf extracts showed good radical inhibition in DPPH (2.4 µg/mL), metal ion (27.44±0.09 mg EDTAE/g extract) scavenging methods. The α-amylase and α-glucosidase inhibitors are currently used for diabetic treatment as oral hypoglycemic agents. The inhibitory effects of the B. retusa leaf and stem ethyl acetate extracts showed good inhibition on α-amylase (96.25% and 95.69 respectively) and α-glucosidase (54.50% and 50.87% respectively) enzymes compared to standard acarbose. The proximate composition analysis of B. retusa leaves contains higher amount of total carbohydrates (14.08 g Glucose equivalents/100 g sample), ash (19.04 %) and crude fibre (0.52 %). The examination of mineral profile explored that the leaves was rich in calcium (1891 ppm), sulphur (1406 ppm), copper (2600 ppm) and magnesium (778 ppm). Leaves sample revealed very minimal amount of anti-nutrient contents like trypsin (14.08±0.03 TIU/mg protein) and tannin (0.011±0.001 mg TAE/g sample). The low anti nutritional factors may not pose any serious nutritional problems when these leaves are consumed. In conclusion, it is very clear that dietary compounds from B. retusa are suitable and promising for the development of safe food products and natural additives. Based on the studies, it may be concluded that nutritional composition, antioxidant and anti-diabetic activities this species can be used as future therapeutic medicine.

Keywords: Breynia retusa, nutraceuticals, antioxidant, anti diabetic

Procedia PDF Downloads 318
137 Comparative Evaluation of Ultrasound Guided Internal Jugular Vein Cannulation Using Measured Guided Needle and Conventional Size Needle for Success and Complication of Cannulation

Authors: Devendra Gupta, Vikash Arya, Prabhat K. Singh

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Background: Ultrasound guidance could be beneficial in placing central venous catheters by improving the success rate, reducing the number of needle passes, and decreasing complications. Central venous cannulation set has a single puncture needle of a fixed length of 6.4 cm. However, the average distance of midpoint of IJV to the skin is around 1 cm to 2 cm. The long length needle has tendency to go in depth more than required and this is very common during learning period of any individual. Therefore, we devised a long needle with a guard which can be adjusted according to the required length. Methods: After approval from the institute ethics committee and patient’s written informed consent, a prospective, randomized, single-blinded controlled study was conducted. Adult patient aged of both sexes with ASA grade 1-2 undergoing surgery requiring internal jugular venous (IJV) access was included. After intubation, the head was rotated to the contralateral side at 30 degree head rotation on the position of the right IJV. The transducer probe a 6.5 to 13-MHz linear transducer (Sonosite, USA) had been placed at the apex of triangle with minimal pressure to avoid IJV compression. The distance from skin to midpoint of the right IJV and skin to anterior wall of Common Carotid Artery (CCA) had been done using B-mode duplex sonography with a 6.5 to 13-MHz linear transducer. Depending upon the results of randomization 420 patients had been divided into two groups of equal numbers (n=210). Group 1. USG guided right sided IJV cannulation was done with conventional (6.4 cm) needle; and Group 2. USG guided right sided IJV cannulation was done with conventional (6.4 cm) needle with guard fixed to a required length (length between skin and midpoint of IJV) by an experienced anesthesiologist. Independent observer has noted the number of attempts and occurrence of complications (CCA puncture, pneumothorax or adjacent tissue damage). Results: Demographic data were similar in both the group. The groups were comparable when considered for relationship of IJV to CCA. There was no significant difference between groups as regard to distance of midpoint of IJV to the skin (p<0.05). IJV cannulation was successfully done in single attempts in 180 (85.7%), in two attempts in 27 (12.9%) and three attempts in 3 (1.4%) in group I, whereas in single attempt in 207 (98.6%) and second attempts in 3 (1.4%) in group II (p <0.000). Incidence of carotid artery puncture was significantly more in group I (7.1%) compared to group II (0%) (p<0.000). Incidence of adjacent tissue puncture was significantly more in group I (8.6%) compared to group II (0%) (p<0.000). Conclusion: Therefore IJV catheterization using guard over the needle at predefined length with the help of real-time ultrasound results in better success rates and lower immediate complications.

Keywords: ultrasound guided, internal jugular vein cannulation, measured guided needle, common carotid artery puncture

Procedia PDF Downloads 204
136 Direct Assessment of Cellular Immune Responses to Ovalbumin with a Secreted Luciferase Transgenic Reporter Mouse Strain IFNγ-Lucia

Authors: Martyna Chotomska, Aleksandra Studzinska, Marta Lisowska, Justyna Szubert, Aleksandra Tabis, Jacek Bania, Arkadiusz Miazek

Abstract:

Objectives: Assessing antigen-specific T cell responses is of utmost importance for the pre-clinical testing of prototype vaccines against intracellular pathogens and tumor antigens. Mainly two types of in vitro assays are used for this purpose 1) enzyme-linked immunospot (ELISpot) and 2) intracellular cytokine staining (ICS). Both are time-consuming, relatively expensive, and require manual dexterity. Here, we assess if a straightforward detection of luciferase activity in blood samples of transgenic reporter mice expressing a secreted Lucia luciferase under the transcriptional control of IFN-γ promoter parallels the sensitivity of IFNγ ELISpot assay. Methods: IFN-γ-LUCIA mouse strain carrying multiple copies of Lucia luciferase transgene under the transcriptional control of IFNγ minimal promoter were generated by pronuclear injection of linear DNA. The specificity of transgene expression and mobilization was assessed in vitro using transgenic splenocytes exposed to various mitogens. The IFN-γ-LUCIA mice were immunized with 50mg of ovalbumin (OVA) emulsified in incomplete Freund’s adjuvant three times every two weeks by subcutaneous injections. Blood samples were collected before and five days after each immunization. Luciferase activity was assessed in blood serum. Peripheral blood mononuclear cells were separated and assessed for frequencies of OVA-specific IFNγ-secreting T cells. Results: We show that in vitro cultured splenocytes of IFN-γ-LUCIA mice respond by 2 and 3 fold increase in secreted luciferase activity to T cell mitogens concanavalin A and phorbol myristate acetate, respectively but fail to respond to B cell-stimulating E.coli lipopolysaccharide. Immunization of IFN-γ-LUCIA mice with OVA leads to over 4 fold increase in luciferase activity in blood serum five days post-immunization with a barely detectable increase in OVA-specific, IFNγ-secreting T cells by ELISpot. Second and third immunizations, further increase the luciferase activity and coincidently also increase the frequencies of OVA-specific T cells by ELISpot. Conclusions: We conclude that minimally invasive monitoring of luciferase secretions in blood serum of IFN-γ-LUCIA mice constitutes a sensitive method for evaluating primary and memory Th1 responses to protein antigens. As such, this method may complement existing methods for rapid immunogenicity assessment of prototype vaccines.

Keywords: ELISpot, immunogenicity, interferon-gamma, reporter mice, vaccines

Procedia PDF Downloads 156
135 Efficacy of Mitomycin C in Reducing Recurrence of Anterior Urethral Stricture after Internal Optical Urethrotomy

Authors: Liaqat Ali, Ehsan, Muhammad Shahzad, Nasir Orakzai

Abstract:

Introduction: Internal optical urethrotomy is the main stay treatment modality in management of urethral stricture. Being minimal invasive with less morbidity, it is commonly performed and favored procedure by urologists across the globe. Although short-term success rate of optical urethrotomy is promising but long-term efficacy of IOU is questionable with high recurrence rate in different studies. Numerous techniques had been adopted to reduce the recurrence after IOU like prolong catheterization and self-clean intermittent catheterization with varying success. Mitomycin C has anti-fibroblast and anti-collagen properties and has been used in trabeculectomy, myringotomy and after keloid scar excision in contemporary surgical practice. Present study according to the best of our knowledge is a pioneer pilot study in Pakistan to determine the efficacy of Mitomycin C in preventing recurrence of urethral stricture after internal optical urethrotomy. Objective: To determine the efficacy of Mitomycin C in reducing the recurrence of anterior urethral stricture after internal optical urethrotomy. Methods: It is a randomized control trial conducted in department of urology, Institute of Kidney Diseases Hayatabad Medical Complex Peshawar from March 2011 till December 2013. After approval of hospital ethical committee, we included maximum of 2 cm anterior urethral stricture irrespective of etiology. Total of 140 patients were equally divided into two groups by lottery method. Group A (Case) comprising of 70 patients in whom Mitomycin C 0.1% was injected sub mucosal in stricture area at 1,11,6 and 12 O clock position using straight working channel paediatric cystoscope after conventional optical urethrotomy. Group B (Control) 70 patients in whom only optical urethrotomy was performed. SCIC was not offered in both the groups. All the patients were regularly followed on a monthly basis for 3 months then three monthly for remaining 9 months. Recurrence was diagnosed by using diagnostic tools of retrograde urethrogram and flexible urethroscopy in selected cased. Data was collected on structured Proforma and was analyzed on SPSS. Result: The mean age in Group A was 33 ±1.5 years and Group B was 35 years. External trauma was leading cause of urethral stricture in both groups 46 (65%) Group A and 50 (71.4%) Group B. In Group A. Iatrogenic urethral trauma was 2nd etiological factor in both groups. 18(25%) Group A while 15( 21.4%) in Group B. At the end of 1 year, At the end of one year, recurrence of urethral stricture was recorded in 11 (15.71%) patient in Mitomycin C Group A and it was recorded in 27 (38.5 %) patients in group B. Significant difference p=0.001 was found in favour of group A Mitomycin group. Conclusion: Recurrence of urethral stricture is high after optical urethrotomy. Mitomycin C is found highly effective in preventing recurrence of urethral stricture after IOU.

Keywords: urethral stricture, mitomycine, internal optical urethrotomy, medical and health sciences

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134 Significant Influence of Land Use Type on Earthworm Communities but Not on Soil Microbial Respiration in Selected Soils of Hungary

Authors: Tsedekech Gebremeskel Weldmichael, Tamas Szegi, Lubangakene Denish, Ravi Kumar Gangwar, Erika Micheli, Barbara Simon

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Following the 1992 Earth Summit in Rio de Janeiro, soil biodiversity has been recognized globally as a crucial player in guaranteeing the functioning of soil and a provider of several ecosystem services essential for human well-being. The microbial fraction of the soil is a vital component of soil fertility as soil microbes play key roles in soil aggregate formation, nutrient cycling, humification, and degradation of pollutants. Soil fauna, such as earthworms, have huge impacts on soil organic matter dynamics, nutrient cycling, and infiltration and distribution of water in the soil. Currently, land-use change has been a global concern as evidence accumulates that it adversely affects soil biodiversity and the associated ecosystem goods and services. In this study, we examined the patterns of soil microbial respiration (SMR) and earthworm (abundance, biomass, and species richness) across three land-use types (grassland, arable land, and forest) in Hungary. The objectives were i) to investigate whether there is a significant difference in SMR and earthworm (abundance, biomass, and species richness) among land-use types. ii) to determine the key soil properties that best predict the variation in SMR and earthworm communities. Soil samples, to a depth of 25 cm, were collected from the surrounding areas of seven soil profiles. For physicochemical parameters, soil organic matter (SOM), pH, CaCO₃, E₄/E₆, available nitrogen (NH₄⁺-N and NO₃⁻-N), potassium (K₂O), phosphorus (P₂O₅), exchangeable Ca²⁺, Mg²⁺, soil moisture content (MC) and bulk density were measured. The analysis of SMR was determined by basal respiration method, and the extraction of earthworms was carried out by hand sorting method as described by ISO guideline. The results showed that there was no statistically significant difference among land-use types in SMR (p > 0.05). However, the highest SMR was observed in grassland soils (11.77 mgCO₂ 50g⁻¹ soil 10 days⁻¹) and lowest in forest soils (8.61 mgCO₂ 50g⁻¹ soil 10 days⁻¹). SMR had strong positive correlations with exchangeable Ca²⁺ (r = 0.80), MC (r = 0.72), and exchangeable Mg²⁺(r = 0.69). We found a pronounced variation in SMR among soil texture classes (p < 0.001), where the highest value in silty clay loam soils and the lowest in sandy soils. This study provides evidence that agricultural activities can negatively influence earthworm communities, in which the arable land had significantly lower earthworm communities compared to forest and grassland respectively. Overall, in our study, land use type had minimal effects on SMR whereas, earthworm communities were profoundly influenced by land-use type particularly agricultural activities related to tillage. Exchangeable Ca²⁺, MC, and texture were found to be the key drivers of the variation in SMR.

Keywords: earthworm community, land use, soil biodiversity, soil microbial respiration, soil property

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133 Development and Characterization of Topical 5-Fluorouracil Solid Lipid Nanoparticles for the Effective Treatment of Non-Melanoma Skin Cancer

Authors: Sudhir Kumar, V. R. Sinha

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Background: The topical and systemic toxicity associated with present nonmelanoma skin cancer (NMSC) treatment therapy using 5-Fluorouracil (5-FU) make it necessary to develop a novel delivery system having lesser toxicity and better control over drug release. Solid lipid nanoparticles offer many advantages like: controlled and localized release of entrapped actives, nontoxicity, and better tolerance. Aim:-To investigate safety and efficacy of 5-FU loaded solid lipid nanoparticles as a topical delivery system for the treatment of nonmelanoma skin cancer. Method: Topical solid lipid nanoparticles of 5-FU were prepared using Compritol 888 ATO (Glyceryl behenate) as lipid component and pluronic F68 (Poloxamer 188), Tween 80 (Polysorbate 80), Tyloxapol (4-(1,1,3,3-Tetramethylbutyl) phenol polymer with formaldehyde and oxirane) as surfactants. The SLNs were prepared with emulsification method. Different formulation parameters viz. type and ratio of surfactant, ratio of lipid and ratio of surfactant:lipid were investigated on particle size and drug entrapment efficiency. Results: Characterization of SLNs like–Transmission Electron Microscopy (TEM), Differential Scannig calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Particle size determination, Polydispersity index, Entrapment efficiency, Drug loading, ex vivo skin permeation and skin retention studies, skin irritation and histopathology studies were performed. TEM results showed that shape of SLNs was spherical with size range 200-500nm. Higher encapsulation efficiency was obtained for batches having higher concentration of surfactant and lipid. It was found maximum 64.3% for SLN-6 batch with size of 400.1±9.22 nm and PDI 0.221±0.031. Optimized SLN batches and marketed 5-FU cream were compared for flux across rat skin and skin drug retention. The lesser flux and higher skin retention was obtained for SLN formulation in comparison to topical 5-FU cream, which ensures less systemic toxicity and better control of drug release across skin. Chronic skin irritation studies lacks serious erythema or inflammation and histopathology studies showed no significant change in physiology of epidermal layers of rat skin. So, these studies suggest that the optimized SLN formulation is efficient then marketed cream and safer for long term NMSC treatment regimens. Conclusion: Topical and systemic toxicity associated with long-term use of 5-FU, in the treatment of NMSC, can be minimized with its controlled release with significant drug retention with minimal flux across skin. The study may provide a better alternate for effective NMSC treatment.

Keywords: 5-FU, topical formulation, solid lipid nanoparticles, non melanoma skin cancer

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132 Use of Curcumin in Radiochemotherapy Induced Oral Mucositis Patients: A Control Trial Study

Authors: Shivayogi Charantimath

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Radiotherapy and chemotherapy are effective for treating malignancies but are associated with side effects like oral mucositis. Chlorhexidine gluconate is one of the most commonly used mouthwash in prevention of signs and symptoms of mucositis. Evidence shows that chlorhexidine gluconate has side effects in terms of colonization of bacteria, bad breadth and less healing properties. Thus, it is essential to find a suitable alternative therapy which is more effective with minimal side effects. Curcumin, an extract of turmeric is gradually being studied for its wide-ranging therapeutic properties such as antioxidant, analgesic, anti-inflammatory, antitumor, antimicrobial, antiseptic, chemo sensitizing and radio sensitizing properties. The present study was conducted to evaluate the efficacy and safety of topical curcumin gel on radio-chemotherapy induced oral mucositis in cancer patients. The aim of the study is to evaluate the efficacy and safety of curcumin gel in the management of oral mucositis in cancer patients undergoing radio chemotherapy and compare with chlorhexidine. The study was conducted in K.L.E. Society’s Belgaum cancer hospital. 40 oral cancer patients undergoing the radiochemotheraphy with oral mucositis was selected and randomly divided into two groups of 20 each. The study group A [20 patients] was advised Cure next gel for 2 weeks. The control group B [20 patients] was advised chlorhexidine gel for 2 weeks. The NRS, Oral Mucositis Assessment scale and WHO mucositis scale were used to determine the grading. The results obtained were calculated by using SPSS 20 software. The comparison of grading was done by applying Mann-Whitney U test and intergroup comparison was calculated by Wilcoxon matched pairs test. The NRS scores observed from baseline to 1st and 2nd week follow up in both the group showed significant difference. The percentage of change in erythema in respect to group A was 63.3% for first week and for second week, changes were 100.0% with p = 0.0003. The changes in Group A in respect to erythema was 34.6% for 1st week and 57.7% in second week. The intergroup comparison was significant with p value of 0.0048 and 0.0006 in relation to group A and group B respectively. The size of the ulcer score was measured which showed 35.5% [P=0.0010] of change in Group A for 1st and 2nd week showed totally reduction i.e. 103.4% [P=0.0001]. Group B showed 24.7% change from baseline to 1st week and 53.6% for 2nd week follow up. The intergroup comparison with Wilcoxon matched pair test was significant with p=0.0001 in group A. The result obtained by WHO mucositis score in respect to group A shows 29.6% [p=0.0004] change in first week and 75.0% [p=0.0180] change in second week which is highly significant in comparison to group B. Group B showed minimum changes i.e. 20.1% in 1st week and 33.3% in 2nd week. The p value with Wilcoxon was significant with 0.0025 in Group A for 1st week follow up and 0.000 for 2nd week follow up. Curcumin gel appears to an effective and safer alternative to chlorhexidine gel in treatment of oral mucositis.

Keywords: curcumin, chemotheraphy, mucositis, radiotheraphy

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131 Evolutionary Advantages of Loneliness with an Agent-Based Model

Authors: David Gottlieb, Jason Yoder

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

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

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130 Stable Time Reversed Integration of the Navier-Stokes Equation Using an Adjoint Gradient Method

Authors: Jurriaan Gillissen

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This work is concerned with stabilizing the numerical integration of the Navier-Stokes equation (NSE), backwards in time. Applications involve the detection of sources of, e.g., sound, heat, and pollutants. Stable reverse numerical integration of parabolic differential equations is also relevant for image de-blurring. While the literature addresses the reverse integration problem of the advection-diffusion equation, the problem of numerical reverse integration of the NSE has, to our knowledge, not yet been addressed. Owing to the presence of viscosity, the NSE is irreversible, i.e., when going backwards in time, the fluid behaves, as if it had a negative viscosity. As an effect, perturbations from the perfect solution, due to round off errors or discretization errors, grow exponentially in time, and reverse integration of the NSE is inherently unstable, regardless of using an implicit time integration scheme. Consequently, some sort of filtering is required, in order to achieve a stable, numerical, reversed integration. The challenge is to find a filter with a minimal adverse affect on the accuracy of the reversed integration. In the present work, we explore an adjoint gradient method (AGM) to achieve this goal, and we apply this technique to two-dimensional (2D), decaying turbulence. The AGM solves for the initial velocity field u0 at t = 0, that, when integrated forward in time, produces a final velocity field u1 at t = 1, that is as close as is feasibly possible to some specified target field v1. The initial field u0 defines a minimum of a cost-functional J, that measures the distance between u1 and v1. In the minimization procedure, the u0 is updated iteratively along the gradient of J w.r.t. u0, where the gradient is obtained by transporting J backwards in time from t = 1 to t = 0, using the adjoint NSE. The AGM thus effectively replaces the backward integration by multiple forward and backward adjoint integrations. Since the viscosity is negative in the adjoint NSE, each step of the AGM is numerically stable. Nevertheless, when applied to turbulence, the AGM develops instabilities, which limit the backward integration to small times. This is due to the exponential divergence of phase space trajectories in turbulent flow, which produces a multitude of local minima in J, when the integration time is large. As an effect, the AGM may select unphysical, noisy initial conditions. In order to improve this situation, we propose two remedies. First, we replace the integration by a sequence of smaller integrations, i.e., we divide the integration time into segments, where in each segment the target field v1 is taken as the initial field u0 from the previous segment. Second, we add an additional term (regularizer) to J, which is proportional to a high-order Laplacian of u0, and which dampens the gradients of u0. We show that suitable values for the segment size and for the regularizer, allow a stable reverse integration of 2D decaying turbulence, with accurate results for more then O(10) turbulent, integral time scales.

Keywords: time reversed integration, parabolic differential equations, adjoint gradient method, two dimensional turbulence

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