Search results for: biochemical failure
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3143

Search results for: biochemical failure

2393 Structure-Guided Optimization of Sulphonamide as Gamma–Secretase Inhibitors for the Treatment of Alzheimer’s Disease

Authors: Vaishali Patil, Neeraj Masand

Abstract:

In older people, Alzheimer’s disease (AD) is turning out to be a lethal disease. According to the amyloid hypothesis, aggregation of the amyloid β–protein (Aβ), particularly its 42-residue variant (Aβ42), plays direct role in the pathogenesis of AD. Aβ is generated through sequential cleavage of amyloid precursor protein (APP) by β–secretase (BACE) and γ–secretase (GS). Thus in the treatment of AD, γ-secretase modulators (GSMs) are potential disease-modifying as they selectively lower pathogenic Aβ42 levels by shifting the enzyme cleavage sites without inhibiting γ–secretase activity. This possibly avoids known adverse effects observed with complete inhibition of the enzyme complex. Virtual screening, via drug-like ADMET filter, QSAR and molecular docking analyses, has been utilized to identify novel γ–secretase modulators with sulphonamide nucleus. Based on QSAR analyses and docking score, some novel analogs have been synthesized. The results obtained by in silico studies have been validated by performing in vivo analysis. In the first step, behavioral assessment has been carried out using Scopolamine induced amnesia methodology. Later the same series has been evaluated for neuroprotective potential against the oxidative stress induced by Scopolamine. Biochemical estimation was performed to evaluate the changes in biochemical markers of Alzheimer’s disease such as lipid peroxidation (LPO), Glutathione reductase (GSH), and Catalase. The Scopolamine induced amnesia model has shown increased Acetylcholinesterase (AChE) levels and the inhibitory effect of test compounds in the brain AChE levels have been evaluated. In all the studies Donapezil (Dose: 50µg/kg) has been used as reference drug. The reduced AChE activity is shown by compounds 3f, 3c, and 3e. In the later stage, the most potent compounds have been evaluated for Aβ42 inhibitory profile. It can be hypothesized that this series of alkyl-aryl sulphonamides exhibit anti-AD activity by inhibition of Acetylcholinesterase (AChE) enzyme as well as inhibition of plaque formation on prolong dosage along with neuroprotection from oxidative stress.

Keywords: gamma-secretase inhibitors, Alzzheimer's disease, sulphonamides, QSAR

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2392 Seismic Assessment of a Pre-Cast Recycled Concrete Block Arch System

Authors: Amaia Martinez Martinez, Martin Turek, Carlos Ventura, Jay Drew

Abstract:

This study aims to assess the seismic performance of arch and dome structural systems made from easy to assemble precast blocks of recycled concrete. These systems have been developed by Lock Block Ltd. Company from Vancouver, Canada, as an extension of their currently used retaining wall system. The characterization of the seismic behavior of these structures is performed by a combination of experimental static and dynamic testing, and analytical modeling. For the experimental testing, several tilt tests, as well as a program of shake table testing were undertaken using small scale arch models. A suite of earthquakes with different characteristics from important past events are chosen and scaled properly for the dynamic testing. Shake table testing applying the ground motions in just one direction (in the weak direction of the arch) and in the three directions were conducted and compared. The models were tested with increasing intensity until collapse occurred; which determines the failure level for each earthquake. Since the failure intensity varied with type of earthquake, a sensitivity analysis of the different parameters was performed, being impulses the dominant factor. For all cases, the arches exhibited the typical four-hinge failure mechanism, which was also shown in the analytical model. Experimental testing was also performed reinforcing the arches using a steel band over the structures anchored at both ends of the arch. The models were tested with different pretension levels. The bands were instrumented with strain gauges to measure the force produced by the shaking. These forces were used to develop engineering guidelines for the design of the reinforcement needed for these systems. In addition, an analytical discrete element model was created using 3DEC software. The blocks were designed as rigid blocks, assigning all the properties to the joints including also the contribution of the interlocking shear key between blocks. The model is calibrated to the experimental static tests and validated with the obtained results from the dynamic tests. Then the model can be used to scale up the results to the full scale structure and expanding it to different configurations and boundary conditions.

Keywords: arch, discrete element model, seismic assessment, shake-table testing

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2391 Effect of Site Amplification on Seismic Safety Evaluation of Flyover Pier

Authors: Mohammad Raihan Mukhlis, M. Abdur Rahman Bhuiyan

Abstract:

Bangladesh is a developing country in which a lot of multi-span simply/continuous supported flyovers are being constructed in its major cities. Being situated in a seismically active region, seismic safety evaluation of flyovers is essential for seismic risk reduction. Effects of site amplification on seismic safety evaluation of flyover piers are the main concern of this study. In this regard, failure mode, lateral strength and displacement ductility of piers of a typical multi-span simply supported flyover have been evaluated by Japan Road Association (JRA) recommended guidelines, with and without considering site amplification. Ultimate flexural strengths of piers have been computed using the pushover analysis results. Shear capacity of piers has been calculated using the guidelines of JRA. Lateral strengths have been determined depending on the failure modes of the piers. Displacement ductility of piers has been computed using yield and ultimate displacements of the piers obtained from the pushover analysis results. Selected earthquake time history is used in seismic safety evaluation of the flyover piers. Finally, the ductility design method is used to conduct the seismic safety evaluation of the piers with and without considering site amplification. From the numerical results, it has been revealed that the effects of site amplification on seismic safety evaluation of bridge structures should be carefully taken into account.

Keywords: displacement ductility, flyover pier, lateral strength, safety evaluation, site amplification

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2390 Inversion of PROSPECT+SAIL Model for Estimating Vegetation Parameters from Hyperspectral Measurements with Application to Drought-Induced Impacts Detection

Authors: Bagher Bayat, Wouter Verhoef, Behnaz Arabi, Christiaan Van der Tol

Abstract:

The aim of this study was to follow the canopy reflectance patterns in response to soil water deficit and to detect trends of changes in biophysical and biochemical parameters of grass (Poa pratensis species). We used visual interpretation, imaging spectroscopy and radiative transfer model inversion to monitor the gradual manifestation of water stress effects in a laboratory setting. Plots of 21 cm x 14.5 cm surface area with Poa pratensis plants that formed a closed canopy were subjected to water stress for 50 days. In a regular weekly schedule, canopy reflectance was measured. In addition, Leaf Area Index (LAI), Chlorophyll (a+b) content (Cab) and Leaf Water Content (Cw) were measured at regular time intervals. The 1-D bidirectional canopy reflectance model SAIL, coupled with the leaf optical properties model PROSPECT, was inverted using hyperspectral measurements by means of an iterative optimization method to retrieve vegetation biophysical and biochemical parameters. The relationships between retrieved LAI, Cab, Cw, and Cs (Senescent material) with soil moisture content were established in two separated groups; stress and non-stressed. To differentiate the water stress condition from the non-stressed condition, a threshold was defined that was based on the laboratory produced Soil Water Characteristic (SWC) curve. All parameters retrieved by model inversion using canopy spectral data showed good correlation with soil water content in the water stress condition. These parameters co-varied with soil moisture content under the stress condition (Chl: R2= 0.91, Cw: R2= 0.97, Cs: R2= 0.88 and LAI: R2=0.48) at the canopy level. To validate the results, the relationship between vegetation parameters that were measured in the laboratory and soil moisture content was established. The results were totally in agreement with the modeling outputs and confirmed the results produced by radiative transfer model inversion and spectroscopy. Since water stress changes all parts of the spectrum, we concluded that analysis of the reflectance spectrum in the VIS-NIR-MIR region is a promising tool for monitoring water stress impacts on vegetation.

Keywords: hyperspectral remote sensing, model inversion, vegetation responses, water stress

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2389 Successful Cesarean Delivery with Veno-Venous Extracorporeal Membrane Oxygenation Support in a Pregnant Woman with Severe Acute Respiratory Distress Syndrome and Heart Failure Complicated by a Rare Condition of Pre-B Cell Acute Lymphoblastic Leukemia in P

Authors: Kristel Dame Bañez Sumagaysay, Marie Victoria Cruz-javier

Abstract:

The current subject is a case of a 21 year-old woman at 29 1/7 weeks of gestation with Pre-B cell Acute Lymphoblastic Leukemia who was admitted to the coronary care unit (CCU) of the St. Luke’s Medical Center-Global City for Severe Acute Respiratory Distress Syndrome (ARDS) secondary to hospital-acquired pneumonia secondary to pneumocystis jiroveci; central line-associated bloodstream infection (E. aerogenes). She presented with chronic hypoxemia caused by Pulmonary edema, probably secondary to heart failure secondary to cardiomyopathy chemotherapy-induced. Due to worsening feto-maternal status, extracorporeal membrane oxygenation (ECMO) for respiratory support was instituted, and an elective cesarean section was done due to multiple maternal factors and deteriorating health status under total intravenous anesthesia assisted by veno-venous extracorporeal membrane oxygenation. She delivered a live preterm newborn male, APGAR Score: 1, 0, 0, birth weight 985 grams, birth length: 40.5cm, small for gestational age.

Keywords: extracorporeal membrane oxygenation, pre-b cell acute lymphoblastic leukemia, severe acute respiratory distress syndrome, ethical dilemmas

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2388 High Rise Building Vibration Control Using Tuned Mass Damper

Authors: T. Vikneshvaran, A. Aminudin, U. Alyaa Hashim, Waziralilah N. Fathiah, D. Shakirah Shukor

Abstract:

This paper presents the experimental study conducted on a structure of three-floor height building model. Most vibrations are undesirable and can cause damages to the buildings, machines and people all around us. The vibration wave from earthquakes, construction and winds have high potential to bring damage to the buildings. Excessive vibrations can result in structural and machinery failures. This failure is related to the human life and environment around it. The effect of vibration which causes failure and damage to the high rise buildings can be controlled in real life by implementing tuned mass damper (TMD) into the structure of the buildings. This research aims to study the effect and performance improvement achieved by applying TMD into the building structure. A structure model of three degrees of freedom (3DOF) is designed to demonstrate the performance of TMD to the designed model. The model designed is the physical representation of actual building structure in real life. It is constructed at a reduced scale and will be used for the experiment. Thus, the result obtained will be more accurate to compared with the real life effect. Based on the result from experimental study, by applying TMD to the structure model, the forces of vibration and the displacement mode of the building reduced. Thus, the reduced in vibration of the building helps to maintain the good condition of the building.

Keywords: degrees-of-freedom, displacement mode, natural frequency, tuned mass damper

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2387 Assessing the Impact of Antiretroviral Mediated Drug-Drug Interactions on Piperaquine Antimalarial Treatment in Pregnant Women Using Physiologically Based Pharmacokinetic Modelling

Authors: Olusola Omolola Olafuyi, Michael Coleman, Raj Kumar Singh Badhan

Abstract:

Introduction: Malaria in pregnancy has morbidity and mortality implication on both mother and unborn child. Piperaquine (PQ) based antimalarial treatment is emerging as a choice antimalarial for pregnant women in the face of resistance to current antimalarial treatment recommendation in pregnancy. Physiological and biochemical changes in pregnant women may affect the pharmacokinetics of the antimalarial drug in these. In malaria endemic regions other infectious diseases like HIV/AIDs are prevalent. Pregnant women who are co-infected with malaria and HIV/AID are at even more greater risk of death not only due to complications of the diseases but also due to drug-drug interactions (DDIs) between antimalarials (AMT) and antiretroviral (ARVs). In this study, physiologically based pharmacokinetic (PBPK) modelling was used to investigate the effect of physiological and biochemical changes on the impact of ARV mediated DDIs in pregnant women in three countries. Method: A PBPK model for PQ was developed on SimCYP® using published physicochemical and pharmacokinetic data of PQ from literature, this was validated in three customized population groups from Thailand, Sudan and Papua New Guinea with clinical data. Validation of PQ model was also done in presence of interaction with efavirenz (pre-validated on SimCYP®). Different albumin levels and pregnancy stages was simulated in the presence of interaction with standard doses of efavirenz and ritonavir. PQ day 7 concentration of 30ng/ml was used as the efficacy endpoint for PQ treatment.. Results: The median day 7 concentration of PQ remained virtually consistent throughout pregnancy and were satisfactory across the three population groups ranging from 26-34.1ng/ml; this implied the efficacy of PQ throughout pregnancy. DDI interaction with ritonavir and efavirenz resulted in modest effect on the day 7 concentrations of PQ with AUCratio ranging from 0.56-0.8 and 1.64-1.79 for efavirenz and ritonavir respectively over 10-40 gestational weeks, however, a reduction in human serum albumin level reflective of severe malaria resulted in significantly reduced the number of subjects attaining the PQ day 7 concentration in the presence of both DDIs. The model demonstrated that the DDI between PQ and ARV in pregnant women with different malaria severities can alter the pharmacokinetic of PQ.

Keywords: antiretroviral, malaria, piperaquine, pregnancy, physiologically-based pharmacokinetics

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2386 Contributing Factors to Building Failures and Defects in the Nigerian Construction Industry

Authors: Ndibarafinia Tobin

Abstract:

Building defect and failure are common phenomena in the Nigerian construction industry. The activities of the inexperienced labor force in the Nigerian construction industry have tarnished the image of practicing construction professionals in recent past. Defects and collapse can cause unnecessary expenditure, delays, loss of lives, property and left many people injured. They are also generating controversies among parties involved. Also, if this situation is left unanswered and untreated, it will lead to more serious problems in the future upcoming construction projects in Nigeria. Quite a number of factors are responsible for collapse of high-rise, reinforced concrete buildings in Nigeria. Government, professional bodies and stakeholders are asking countless questions as to who should be responsible and how solutions could be proffered. Therefore this study is aimed to identify the contributing factors to high-rise buildings defects and failures in Nigeria, which frequently occur in construction project in order to minimize time and cost and also the roles of professionals and other participants play in the industry in terms of the use of building materials, placement and curing of concrete, modification in the use of a building, collapse of building induced by fire and other causes. The data is collected from questionnaire from various players in construction industry in Nigeria. This study is succeeds in identifying the causes of building failure and also suggesting possible measures to be taken by government and other regulatory bodies in the building industry to avert this and also improve the effectiveness of managing appraisal process of failures and defects in the future.

Keywords: building defects, building failures, Nigerian construction industry, professionals

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2385 Hybrid Polymer Microfluidic Platform for Studying Endothelial Cell Response to Micro Mechanical Environment

Authors: Mitesh Rathod, Jungho Ahn, Noo Li Jeon, Junghoon Lee

Abstract:

Endothelial cells respond to cues from both biochemical as well as micro mechanical environment. Significant effort has been directed to understand the effects of biochemical signaling, however, relatively little is known about regulation of endothelial cell biology by the micro mechanical environment. Numerous studies have been performed to understand how physical forces regulate endothelial cell behavior. In this regard, past studies have majorly focused on exploring how fluid shear stress governs endothelial cell behavior. Parallel plate flow chambers and rectangular microchannels are routinely employed for applying fluid shear force on endothelial cells. However, these studies fall short in mimicking the in vivo like micro environment from topological aspects. Few studies have only used circular microchannels to replicate in vivo like condition. Seldom efforts have been directed to elucidate the combined effect of topology, substrate rigidity and fluid shear stress on endothelial cell response. In this regard, we demonstrate a facile fabrication process to develop a hybrid polydimethylsiloxane microfluidic platform to study endothelial cell biology. On a single chip microchannels with different cross sections i.e., circular, rectangular and square have been fabricated. In addition, our fabrication approach allows variation in the substrate rigidity along the channel length. Two different variants of polydimethylsiloxane, namely Sylgard 184 and Sylgard 527, were utilized to achieve the variation in rigidity. Moreover, our approach also enables in creating Y bifurcation circular microchannels. Our microfluidic platform thus facilitates for conducting studies pertaining to endothelial cell morphology with respect to change in topology, substrate rigidity and fluid flow on a single chip. The hybrid platform was tested by culturing Human Umbilical Vein Endothelial Cells in circular microchannels with varying substrate rigidity, and exposed to fluid shear stress of 12 dynes/cm² and static conditions. Results indicate the cell area response to flow induced shear stress was governed by the underlying substrate mechanics.

Keywords: hybrid, microfluidic platform, PDMS, shear flow, substrate rigidity

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2384 Parameter Estimation in Dynamical Systems Based on Latent Variables

Authors: Arcady Ponosov

Abstract:

A novel mathematical approach is suggested, which facilitates a compressed representation and efficient validation of parameter-rich ordinary differential equation models describing the dynamics of complex, especially biology-related, systems and which is based on identification of the system's latent variables. In particular, an efficient parameter estimation method for the compressed non-linear dynamical systems is developed. The method is applied to the so-called 'power-law systems' being non-linear differential equations typically used in Biochemical System Theory.

Keywords: generalized law of mass action, metamodels, principal components, synergetic systems

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2383 FEM Based Numerical Simulation and Analysis of a Landslide Triggered by the Fluctuations of Ground-Water Levels

Authors: Deepak Raj Bhat, Akihiko Wakai, Shigeru Ogita, Yorihiro Tanaka, Kazushige Hayashi, Shinro Abe

Abstract:

In this study, the newly developed finite element methods are used for numerical analysis ofa landslide triggered by the fluctuations of ground-water levels in different cases I-IV. In case I, the ground-water level is fixed in such a way that the overall factor of safety (Fs) would be greater or equal to 1 (i.e., stable condition). Then, the ground-water level is gradually increased up to 1.0 m for, making the overall factor of safety (Fs) less than one (i.e., stable or moving condition). Then, the newly developed finite element model is applied for numerical simulation of the slope for each case. Based on the numerical analysis results of each Cases I-IV, the details of the deformation pattern and shear strain pattern are compared to each other. Moreover, the change in mobilized shear strength and local factor of safety along the slip surface of the landslide for each case are discussed to understand the triggering behaviors of a landslide due to the increased in ground water level. It is expected that this study will help to better understand the role of groundwater fluctuation for triggering of a landslide or slope failure disasters, and it would be also helpful for the judgment of the countermeasure works for the prevention and mitigation of landslide and slope failure disasters in near future.

Keywords: finite element method, ground water fluctuations, constitutive model, landslides, long-term disaster management system

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2382 Experimental Investigation on Cold-Formed Steel Foamed Concrete Composite Wall under Compression

Authors: Zhifeng Xu, Zhongfan Chen

Abstract:

A series of tests on cold-formed steel foamed concrete (CSFC) composite walls subjected to axial load were proposed. The primary purpose of the experiments was to study the mechanical behavior and identify the failure modes of CSFC composite walls. Two main factors were considered in this study: 1) specimen with pouring foamed concrete or without and 2) different foamed concrete density ranks (corresponding to different foamed concrete strength). The interior space between two pieces of straw board of the specimen W-2 and W-3 were poured foamed concrete, and the specimen W-1 does not have foamed concrete core. The foamed concrete density rank of the specimen W-2 was A05 grade, and that of the specimen W-3 was A07 grade. Results showed that the failure mode of CSFC composite wall without foamed concrete was distortional buckling of cold-formed steel (CFS) column, and that poured foamed concrete includes the local crushing of foamed concrete and local buckling of CFS column, but the former prior to the later. Compared with CSFC composite wall without foamed concrete, the ultimate bearing capacity of spec imens poured A05 grade and A07 grade foamed concrete increased 1.6 times and 2.2 times respectively, and specimen poured foamed concrete had a low vertical deformation. According to these results, the simplified calculation formula for the CSFC wall subjected to axial load was proposed, and the calculated results from this formula are in very good agreement with the test results.

Keywords: cold-formed steel, composite wall, foamed concrete, axial behavior test

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2381 Chemical, Biochemical and Sensory Evaluation of a Quadrimix Complementary Food Developed from Sorghum, Groundnut, Crayfish and Pawpaw Blends

Authors: Ogechi Nzeagwu, Assumpta Osuagwu, Charlse Nkwoala

Abstract:

Malnutrition in infants due to poverty, poor feeding practices, and high cost of commercial complementary foods among others is a concern in developing countries. The study evaluated the proximate, vitamin and mineral compositions, antinutrients and functional properties, biochemical, haematological and sensory evaluation of complementary food made from sorghum, groundnut, crayfish and paw-paw flour blends using standard procedures. The blends were formulated on protein requirement of infants (18 g/day) using Nutrisurvey linear programming software in ratio of sorghum(S), groundnut(G), crayfish(C) and pawpaw(P) flours as 50:25:10:15(SGCP1), 60:20:10:10 (SGCP2), 60:15:15:10 (SGCP3) and 60:10:20:10 (SGCP4). Plain-pap (fermented maize flour)(TCF) and cerelac (commercial complementary food) served as basal and control diets. Thirty weanling male albino rats aged 28-35 days weighing 33-60 g were purchased and used for the study. The rats after acclimatization were fed with gruel produced with the experimental diets and the control with water ad libitum daily for 35days. Effect of the blends on lipid profile, blood glucose, haematological (RBC, HB, PCV, MCV), liver and kidney function and weight gain of the rats were assessed. Acceptability of the gruel was conducted at the end of rat feeding on forty mothers of infants’ ≥ 6 months who gave their informed consent to participate using a 9 point hedonic scale. Data was analyzed for means and standard deviation, analysis of variance and means were separated using Duncan multiple range test and significance judged at 0.05, all using SPSS version 22.0. The results indicated that crude protein, fibre, ash and carbohydrate of the formulated diets were either comparable or higher than values in cerelac. The formulated diets (SGCP1- SGCP4) were significantly (P>0.05) higher in vitamin A and thiamin compared to cerelac. The iron content of the formulated diets SGCP1- SGCP4 (4.23-6.36 mg/100) were within the recommended iron intake of infants (0.55 mg/day). Phytate (1.56-2.55 mg/100g) and oxalate (0.23-0.35 mg/100g) contents of the formulated diets were within the permissible limits of 0-5%. In functional properties, bulk density, swelling index, % dispersibility and water absorption capacity significantly (P<0.05) increased and compared favourably with cerelac. The essential amino acids of the formulated blends were within the amino acid profile of the FAO/WHO/UNU reference protein for children 0.5 -2 years of age. Urea concentration of rats fed with SGCP1-SGCP4 (19.48 mmol/L),(23.76 mmol/L),(24.07 mmol/L),(23.65 mmol/L) respectively was significantly higher than that of rat fed cerelac (16.98 mmol/L); however, plain pap had the least value (9.15 mmol/L). Rats fed with SGCP1-SGCP4 (116 mg/dl), (119 mg/dl), (115 mg/dl), (117 mg/dl) respectively had significantly higher glucose levels those fed with cerelac (108 mg/dl). Liver function parameters (AST, ALP and ALT), lipid profile (triglyceride, HDL, LDL, VLDL) and hematological parameters of rats fed with formulated diets were within normal range. Rats fed SGCP1 gained more weight (90.45 g) than other rats fed with SGCP2-SGCP4 (71.65 g, 79.76 g, 75.68 g), TCF (20.13 g) and cerelac (59.06 g). In all the sensory attributes, the control was preferred with respect to the formulated diets. The formulated diets were generally adequate and may likely have potentials to meet nutrient requirements of infants as complementary food.

Keywords: biochemical, chemical evaluation, complementary food, quadrimix

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2380 Clinical Impact of Ultra-Deep Versus Sanger Sequencing Detection of Minority Mutations on the HIV-1 Drug Resistance Genotype Interpretations after Virological Failure

Authors: S. Mohamed, D. Gonzalez, C. Sayada, P. Halfon

Abstract:

Drug resistance mutations are routinely detected using standard Sanger sequencing, which does not detect minor variants with a frequency below 20%. The impact of detecting minor variants generated by ultra-deep sequencing (UDS) on HIV drug-resistance (DR) interpretations has not yet been studied. Fifty HIV-1 patients who experienced virological failure were included in this retrospective study. The HIV-1 UDS protocol allowed the detection and quantification of HIV-1 protease and reverse transcriptase variants related to genotypes A, B, C, E, F, and G. DeepChek®-HIV simplified DR interpretation software was used to compare Sanger sequencing and UDS. The total time required for the UDS protocol was found to be approximately three times longer than Sanger sequencing with equivalent reagent costs. UDS detected all of the mutations found by population sequencing and identified additional resistance variants in all patients. An analysis of DR revealed a total of 643 and 224 clinically relevant mutations by UDS and Sanger sequencing, respectively. Three resistance mutations with > 20% prevalence were detected solely by UDS: A98S (23%), E138A (21%) and V179I (25%). A significant difference in the DR interpretations for 19 antiretroviral drugs was observed between the UDS and Sanger sequencing methods. Y181C and T215Y were the most frequent mutations associated with interpretation differences. A combination of UDS and DeepChek® software for the interpretation of DR results would help clinicians provide suitable treatments. A cut-off of 1% allowed a better characterisation of the viral population by identifying additional resistance mutations and improving the DR interpretation.

Keywords: HIV-1, ultra-deep sequencing, Sanger sequencing, drug resistance

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2379 Valorizing Traditional Greek Wheat Varieties: Use of DNA Barcoding for Species Identification and Biochemical Analysis of Their Nutritional Value

Authors: Niki Mougiou, Spyros Didos, Ioanna Bouzouka, Athina Theodorakopoulou, Michael Kornaros, Anagnostis Argiriou

Abstract:

Grains from traditional old Greek cereal varieties were evaluated and compared to commercial cultivars, like Simeto and Mexicali 81, in an effort to valorize local products and assess the nutritional benefits of ancient grains. The samples studied in this research included common wheat, durum wheat, emmer (Triticum dicoccum) and einkorn (Triticum monococcum), as well as barley, oats and rye grains. The Internal Transcribed Spacer 2 (ITS2) nuclear region was amplified and sequenced as a barcode for species identification, allowing the verification of the label of each product. After that, the total content of bound and free polyphenols and flavonoids, as well as the antioxidant activity of bound and free compounds, was measured by classic colorimetric assays using Folin- Ciocalteu, AlCl₃ and DPPH‧ (2,2-diphenyl-1-picrylhydrazyl) reagents, respectively. Moreover, the level of variation of fatty acids was determined in all samples by gas chromatography. The results showed that local old landraces of emmer and einkorn had the highest polyphenol content, 2.4 and 3.3 times higher than the average value of 5 durum wheat samples, respectively. Regarding the total flavonoid content, einkorn had 2.6-fold and emmer 2-fold higher values than common wheat. The antioxidant activity of free or bound compounds was at the same level, at about 20-30% higher in both einkorn and emmer compared to common wheat. Five main fatty acids were detected in all samples, in order of decreasing amounts: linoleic (C18:2) > palmitic (C16:0) ≈ , oleic (C18:1) > eicosenoic (C20:1, cis-11) > stearic (C18:0). Emmer and einkorn showed a higher diversity of fatty acids and a higher content of mono-unsaturated fatty acids compared to common wheat. The results of this study demonstrate the high nutritional value of old local landraces that have been put aside by more productive, yet with lower qualitative characteristics, commercial cultivars, underlining the importance of maintaining sustainable agricultural practices to ensure their continued cultivation.

Keywords: biochemical analysis, nutritional value, plant barcoding, wheat

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2378 Optimal Wheat Straw to Bioethanol Supply Chain Models

Authors: Abdul Halim Abdul Razik, Ali Elkamel, Leonardo Simon

Abstract:

Wheat straw is one of the alternative feedstocks that may be utilized for bioethanol production especially when sustainability criteria are the major concerns. To increase market competitiveness, optimal supply chain plays an important role since wheat straw is a seasonal agricultural residue. In designing the supply chain optimization model, economic profitability of the thermochemical and biochemical conversion routes options were considered. It was found that torrefied pelletization with gasification route to be the most profitable option to produce bioethanol from the lignocellulosic source of wheat straw.

Keywords: bio-ethanol, optimization, supply chain, wheat straw

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2377 Advanced Numerical and Analytical Methods for Assessing Concrete Sewers and Their Remaining Service Life

Authors: Amir Alani, Mojtaba Mahmoodian, Anna Romanova, Asaad Faramarzi

Abstract:

Pipelines are extensively used engineering structures which convey fluid from one place to another. Most of the time, pipelines are placed underground and are encumbered by soil weight and traffic loads. Corrosion of pipe material is the most common form of pipeline deterioration and should be considered in both the strength and serviceability analysis of pipes. The study in this research focuses on concrete pipes in sewage systems (concrete sewers). This research firstly investigates how to involve the effect of corrosion as a time dependent process of deterioration in the structural and failure analysis of this type of pipe. Then three probabilistic time dependent reliability analysis methods including the first passage probability theory, the gamma distributed degradation model and the Monte Carlo simulation technique are discussed and developed. Sensitivity analysis indexes which can be used to identify the most important parameters that affect pipe failure are also discussed. The reliability analysis methods developed in this paper contribute as rational tools for decision makers with regard to the strengthening and rehabilitation of existing pipelines. The results can be used to obtain a cost-effective strategy for the management of the sewer system.

Keywords: reliability analysis, service life prediction, Monte Carlo simulation method, first passage probability theory, gamma distributed degradation model

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2376 Comparative Study on Structural Behaviour of Circular Hollow Steel Tubular, Concrete Filled Steel Tubular, and Reinforced Cement Concrete Stub Columns under Pure Axial Compression

Authors: Niladri Roy, M. Longshithung Patton

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This paper is aimed at studying the structural response of circular hollow steel tubular (HST), concrete filled steel tubular (CFST), and reinforced cement concrete (RCC) stub columns when subjected to only axial compressive forces and also examining their comparative nature using finite element (FE) models. These results are further compared with the respective experimental results. FE software package ABAQUS 6.14 has been used for further parametric studies where a total of 108 FE models were modelled. The diameters of the HST, CFST, and RCC stub columns are kept as 100, 140, 180, and 220, with length to diameter ratio fixed at 3 to avoid end effects and flexural failure. To keep the same percentage of steel (by volume), the thicknesses of steel tubes in HST and CFST columns were varied in response to the change in diameter of the main reinforcement bar in RCC columns. M25 grade of concrete was used throughout. The objective is to compare the structural behaviour of HST, CFST, and RCC stub columns on the basis of their axial compressive load carrying capacity and failure modes. The studies show that filling the circular HST columns with concrete increases the Pu of the CCFST columns by 2.97 times. It was also observed that the Pu (HST) is about 0.72 times Pu (RCC) on average, and the Pu (CFST) is about 2.08 times Pu (RCC) on average. After the analysis and comparison, it has been proved that CFST has much more load carrying capacity than HST and RCC and also provides the same strength at a very less sectional size.

Keywords: HST columns, stub columns, CFST columns, RCC columns, finite element modeling, ABAQUS

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2375 Comparative Assessment of Finite Element Methodologies for Predicting Post-Buckling Collapse in Stiffened Carbon Fiber-Reinforced Plastic (CFRP) Panels

Authors: Naresh Reddy Kolanu

Abstract:

The stability and collapse behavior of thin-walled composite structures, particularly carbon fiber-reinforced plastic (CFRP) panels, are paramount concerns for structural designers. Accurate prediction of collapse loads necessitates precise modeling of damage evolution in the post-buckling regime. This study conducts a comparative assessment of various finite element (FE) methodologies employed in predicting post-buckling collapse in stiffened CFRP panels. A systematic approach is adopted, wherein FE models with various damage capabilities are constructed and analyzed. The study investigates the influence of interacting intra- and interlaminar damage modes on the post-buckling response and failure behavior of the stiffened CFRP structure. Additionally, the capabilities of shell and brick FE-based models are evaluated and compared to determine their effectiveness in capturing the complex collapse behavior. Conclusions are drawn through quantitative comparison with experimental results, focusing on post-buckling response and collapse load. This comprehensive evaluation provides insights into the most effective FE methodologies for accurately predicting the collapse behavior of stiffened CFRP panels, thereby aiding structural designers in enhancing the stability and safety of composite structures.

Keywords: CFRP stiffened panels, delamination, Hashin’s failure, post-buckling, progressive damage model

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2374 Synthesis and Preparation of Carbon Ferromagnetic Nanocontainers for Cancer Therapy

Authors: L. Szymanski, Z. Kolacinski, Z. Kamiński, G. Raniszewski, J. Fraczyk, L. Pietrzak

Abstract:

In the article the development and demonstration of method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nano containers. Methodology of the production carbon - ferromagnetic nanocontainers includes: the synthesis of carbon nanotubes, chemical and physical characterization, increasing the content of ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. Biochemical functionalization of ferromagnetic nanocontainers is necessary in order to increase the binding selectively with receptors presented on the surface of tumour cells. Multi-step modification procedure was finally used to attach folic acid on the surface of ferromagnetic nanocontainers. Folic acid is ligand of folate receptors which is overexpresion in tumor cells. The presence of ligand should ensure the specificity of the interaction between ferromagnetic nanocontainers and tumor cells. The chemical functionalization contains several step: oxidation reaction, transformation of carboxyl groups into more reactive ester or amide groups, incorporation of spacer molecule (linker), attaching folic acid. Activation of carboxylic groups was prepared with triazine coupling reagent (preparation of superactive ester attached on the nanocontainers). The spacer molecules were designed and synthesized. In order to ensure biocompatibillity of linkers they were built from amino acids or peptides. Spacer molecules were synthesized using the SPPS method. Synthesis was performed on 2-Chlorotrityl resin. The linker important feature is its length. Due to that fact synthesis of peptide linkers containing from 2 to 4 -Ala- residues was carried out. Independent synthesis of the conjugate of foilic acid with 6-aminocaproic acid was made. Final step of synthesis was connecting conjugat with spacer molecules and attaching it on the ferromagnetic nanocontainer surface. This article contains also information about special CVD and microvave plasma system to produce nanotubes and ferromagnetic nanocontainers. The first tests in the device for hyperthermal RF generator will be presented. The frequency of RF generator was in the ranges from 10 to 14Mhz and from 265 to 621kHz.

Keywords: synthesis of carbon nanotubes, hyperthermia, ligands, carbon nanotubes

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2373 Kidney Supportive Care in Canada: A Constructivist Grounded Theory of Dialysis Nurses’ Practice Engagement

Authors: Jovina Concepcion Bachynski, Lenora Duhn, Idevania G. Costa, Pilar Camargo-Plazas

Abstract:

Kidney failure is a life-limiting condition for which treatment, such as dialysis (hemodialysis and peritoneal dialysis), can exact a tremendously high physical and psychosocial symptom burden. Kidney failure can be severe enough to require a palliative approach to care. The term supportive care can be used in lieu of palliative care to avoid the misunderstanding that palliative care is synonymous with end-of-life or hospice care. Kidney supportive care, encompassing advance care planning, is an approach to care that improves the quality of life for people receiving dialysis through early identification and treatment of symptoms throughout the disease trajectory. Advanced care planning involves ongoing conversations about the values, goals, and preferences for future care between individuals and their healthcare teams. Kidney supportive care is underutilized and often initiated late in this population. There is evidence to indicate nurses are not providing the necessary elements of supportive kidney care. Dialysis nurses’ delay or lack of engagement in supportive care until close to the end of life may result in people dying without receiving optimal palliative care services. Using Charmaz’s constructivist grounded theory, the purpose of this doctoral study is to develop a substantive theory that explains the process of engagement in supportive care by nurses working in dialysis settings in Canada. Through initial purposeful and subsequent theoretical sampling, 23 nurses with current or recent work experience in outpatient hemodialysis, home hemodialysis, and peritoneal dialysis settings drawn from across Canada were recruited to participate in two intensive interviews using the Zoom© teleconferencing platform. Concurrent data collection and data analysis, constant comparative analysis of initial and focused codes until the attainment of theoretical saturation, and memo-writing, as well as researcher reflexivity, have been undertaken to aid the emergence of concepts, categories, and, ultimately, the constructed theory. At the time of abstract submission, data analysis is currently at the second level of coding (i.e., focused coding stage) of the research study. Preliminary categories include: (a) focusing on biomedical care; (b) multi-dimensional challenges to having the conversation; (c) connecting and setting boundaries with patients; (d) difficulty articulating kidney-supportive care; and (e) unwittingly practising kidney-supportive care. For the conference, the resulting theory will be presented. Nurses working in dialysis are well-positioned to ensure the delivery of quality kidney-supportive care. This study will help to determine the process and the factors enabling and impeding nurse engagement in supportive care in dialysis to effect change for normalizing advance care planning conversations in the clinical setting. This improved practice will have substantive beneficial implications for the many individuals living with kidney failure and their supporting loved ones.

Keywords: dialysis, kidney failure, nursing, supportive care

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2372 Leukocyte Transcriptome Analysis of Patients with Obesity-Related High Output Heart Failure

Authors: Samantha A. Cintron, Janet Pierce, Mihaela E. Sardiu, Diane Mahoney, Jill Peltzer, Bhanu Gupta, Qiuhua Shen

Abstract:

High output heart failure (HOHF) is characterized a high output state resulting from an underlying disease process and is commonly caused by obesity. As obesity levels increase, more individuals will be at risk for obesity-related HOHF. However, the underlying pathophysiologic mechanisms of obesity-related HOHF are not well understood and need further research. The aim of the study was to describe the differences in leukocyte transcriptomes of morbidly obese patients with HOHF and those with non-HOHF. In this cross-sectional study, the study team collected blood samples, demographics, and clinical data of six patients with morbid obesity and HOHF and six patients with morbid obesity and non-HOHF. The study team isolated the peripheral blood leukocyte RNA and applied stranded total RNA sequencing. Differential gene expression was calculated, and Ingenuity Pathway Analysis software was used to interpret the canonical pathways, functional changes, upstream regulators, and mechanistic and causal networks that were associated with the significantly different leukocyte transcriptomes. The study team identified 116 differentially expressed genes; 114 were upregulated, and 2 were downregulated in the HOHF group (Benjamini-Hochberg adjusted p-value ≤ 0.05 and log2(fold-change) of ±1). The differentially expressed genes were involved with cell proliferation, mitochondrial function, erythropoiesis, erythrocyte stability, and apoptosis. The top upregulated canonical pathways associated with differentially expressed genes were autophagy, adenosine monophosphate-activated protein kinase signaling, and senescence pathways. Upstream regulator GATA Binding Protein 1 (GATA1) and a network associated with nuclear factor kappa-light chain-enhancer of activated B cells (NF-kB) were also identified based on the different leukocyte transcriptomes of morbidly obese patients with HOHF and non-HOHF. To the author’s best knowledge, this is the first study that reported the differential gene expression in patients with obesity-related HOHF and demonstrated the unique pathophysiologic mechanisms underlying the disease. Further research is needed to determine the role of cellular function and maintenance, inflammation, and iron homeostasis in obesity-related HOHF.

Keywords: cardiac output, heart failure, obesity, transcriptomics

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2371 Wellbore Stability Evaluation of Ratawi Shale Formation

Authors: Raed Hameed Allawi

Abstract:

Wellbore instability problems are considered the majority challenge for several wells in the Ratawi shale formation. However, it results in non-productive (NPT) time and increased well-drilling expenditures. This work aims to construct an integrated mechanical earth model (MEM) to predict the wellbore failure and design optimum mud weight to improve the drilling efficiency of future wells. The MEM was based on field data, including open-hole wireline logging and measurement data. Several failure criteria were applied in this work, including Modified Lade, Mogi-Coulomb, and Mohr-Coulomb that utilized to calculate the proper mud weight and practical drilling paths and orientations. Results showed that the leading cause of wellbore instability problems was inadequate mud weight. Moreover, some improper drilling practices and heterogeneity of Ratawi formation were additional causes of the increased risk of wellbore instability. Therefore, the suitable mud weight for safe drilling in the Ratawi shale formation should be 11.5-13.5 ppg. Furthermore, the mud weight should be increased as required depending on the trajectory of the planned well. The outcome of this study is as practical tools to reduce non-productive time and well costs and design future neighboring deviated wells to get high drilling efficiency. In addition, the current results serve as a reference for similar fields in that region because of the lacking of published studies regarding wellbore instability problems of the Ratawi Formation in southern Iraqi oilfields.

Keywords: wellbore stability, hole collapse, horizontal stress, MEM, mud window

Procedia PDF Downloads 171
2370 Numerical Modelling and Experiment of a Composite Single-Lap Joint Reinforced by Multifunctional Thermoplastic Composite Fastener

Authors: Wenhao Li, Shijun Guo

Abstract:

Carbon fibre reinforced composites are progressively replacing metal structures in modern civil aircraft. This is because composite materials have large potential of weight saving compared with metal. However, the achievement to date of weight saving in composite structure is far less than the theoretical potential due to many uncertainties in structural integrity and safety concern. Unlike the conventional metallic structure, composite components are bonded together along the joints where structural integrity is a major concern. To ensure the safety, metal fasteners are used to reinforce the composite bonded joints. One of the solutions for a significant weight saving of composite structure is to develop an effective technology of on-board Structural Health Monitoring (SHM) System. By monitoring the real-life stress status of composite structures during service, the safety margin set in the structure design can be reduced with confidence. It provides a means of safeguard to minimize the need for programmed inspections and allow for maintenance to be need-driven, rather than usage-driven. The aim of this paper is to develop smart composite joint. The key technology is a multifunctional thermoplastic composite fastener (MTCF). The MTCF will replace some of the existing metallic fasteners in the most concerned locations distributed over the aircraft composite structures to reinforce the joints and form an on-board SHM network system. Each of the MTCFs will work as a unit of the AU and AE technology. The proposed MTCF technology has been patented and developed by Prof. Guo in Cranfield University, UK in the past a few years. The manufactured MTCF has been successfully employed in the composite SLJ (Single-Lap Joint). In terms of the structure integrity, the hybrid SLJ reinforced by MTCF achieves 19.1% improvement in the ultimate failure strength in comparison to the bonded SLJ. By increasing the diameter or rearranging the lay-up sequence of MTCF, the hybrid SLJ reinforced by MTCF is able to achieve the equivalent ultimate strength as that reinforced by titanium fastener. The predicted ultimate strength in simulation is in good agreement with the test results. In terms of the structural health monitoring, a signal from the MTCF was measured well before the load of mechanical failure. This signal provides a warning of initial crack in the joint which could not be detected by the strain gauge until the final failure.

Keywords: composite single-lap joint, crack propagation, multifunctional composite fastener, structural health monitoring

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2369 Poverty Versus Interest-Based Loans in East Africa: Can Interest-Free Loans Rescue the Situation?

Authors: Maulana Ayoub Ali

Abstract:

“Both Socialist as well as the capitalist in the economic systems have proven their failure to ensure economic justice that serves to benefit all in the society, both the rich and the poor. In particular, capitalism is currently causing a terrifying scenario by making the rich richer and the poor poorer” . In this paper, the author looks at the level of exploitation which is taking place to small and middle entrepreneurs (SME’s), government and private employees as well as large investors in East African countries who depends on interest-based loans which undermines their lives every day due to heavy monthly returns. Numbers of families have been evicted from their family premises and SME’s properties have been attached in the courts due to failure to return their loans timely. In fact, there are a lot of issues which have taken place on the ground which badly affected number of families socially and most importantly economically due to engagement in interest-based loans offered by commercial banks in East Africa. This paper looks on the alternative ways of eliminating interest-based loans to better lives of devastated Africans who are almost “dying” of heavy debts generated through higher interest loans. Reaching to that particular root the author has visited various literatures in a bid to deeply investigate and find out the best alternative mode of enabling African SME’s, businessmen and employees to benefit from the interest-free loans. The question is whether interest-free loans can be a long term solution towards poverty alleviation in East Africa generally and Tanzania in particular.

Keywords: interest-free loans, SME’s, financial institutions, poverty, east Africa

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2368 Using Predictive Analytics to Identify First-Year Engineering Students at Risk of Failing

Authors: Beng Yew Low, Cher Liang Cha, Cheng Yong Teoh

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Due to a lack of continual assessment or grade related data, identifying first-year engineering students in a polytechnic education at risk of failing is challenging. Our experience over the years tells us that there is no strong correlation between having good entry grades in Mathematics and the Sciences and excelling in hardcore engineering subjects. Hence, identifying students at risk of failure cannot be on the basis of entry grades in Mathematics and the Sciences alone. These factors compound the difficulty of early identification and intervention. This paper describes the development of a predictive analytics model in the early detection of students at risk of failing and evaluates its effectiveness. Data from continual assessments conducted in term one, supplemented by data of student psychological profiles such as interests and study habits, were used. Three classification techniques, namely Logistic Regression, K Nearest Neighbour, and Random Forest, were used in our predictive model. Based on our findings, Random Forest was determined to be the strongest predictor with an Area Under the Curve (AUC) value of 0.994. Correspondingly, the Accuracy, Precision, Recall, and F-Score were also highest among these three classifiers. Using this Random Forest Classification technique, students at risk of failure could be identified at the end of term one. They could then be assigned to a Learning Support Programme at the beginning of term two. This paper gathers the results of our findings. It also proposes further improvements that can be made to the model.

Keywords: continual assessment, predictive analytics, random forest, student psychological profile

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2367 Study of Cathodic Protection for Trunk Pipeline of Al-Garraf Oil Field

Authors: Maysoon Khalil Askar

Abstract:

The delineation of possible areas of corrosion along the external face of an underground oil pipeline in Trunk line of Al- Garraf oil field was investigated using the horizontal electrical resistivity profiling technique and study the contribution of pH, Moisture Content in Soil and Presence chlorides, sulfates and total dissolve salts in soil and water. The test sites represent a physical and chemical properties of soils. The hydrogen-ion concentration of soil and groundwater range from 7.2 to 9.6, and the resistivity values of the soil along the pipeline were obtained using the YH302B model resistivity meter having values between 1588 and 720 Ohm-cm. the chloride concentration in soil and groundwater is high (more than 1000 ppm), total soulable salt is more than 5000 ppm, and sulphate range from 0.17% and 0.98% in soil and more than 600 ppm in groundwater. The soil is poor aeration, the soil texture is fine (clay and silt soil), the water content is high (the groundwater is close to surface), the chloride and sulphate is high in the soil and groundwater, the total soulable salt is high in ground water and finally the soil electric resistivity is low that the soil is very corrosive and there is the possibility of the pipeline failure. These methods applied in the study are quick, economic and efficient for detecting along buried pipelines which need to be protected. Routine electrical geophysical investigations along buried oil pipelines should be undertaken for the early detection and prevention of pipeline failure with its attendant environmental, human and economic consequences.

Keywords: soil resistivity, corrosion, cathodic protection, chloride concentration, water content

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2366 Silver-Curcumin Nanoparticle Eradicate Enterococcus faecalis in Human ex vivo Dentine Model

Authors: M. Gowri, E. K. Girija, V. Ganesh

Abstract:

Background and Significance: Among the dental infections, inflammation and infection of the root canal are common among all age groups. Currently, the management of root canal infections involves cleaning the canal with powerful irrigants followed by intracanal medicament application. Though these treatments have been in vogue for a long time, root canal failures do occur. Treatment for root canal infections is limited due to the anatomical complexity in terms of small micrometer volumes and poor penetration of drugs. Thus, infections of the root canal seem to be a challenge that demands development of new agents that can eradicate E. faecalis. Methodology: In the present study, we synthesized and screened silver-curcumin nanoparticle against E. faecalis. Morphological cell damage and antibiofilm activity of silver-curcumin nanoparticle on E. faecalis was studied using scanning electron microscopy (SEM). Biochemical evidence for membrane damage was studied using flow cytometry. Further, the antifungal activity of silver-curcumin nanoparticle was evaluated in an ex vivo dentinal tubule infection model. Results: Screening data showed that silver-curcumin nanoparticle was active against E. faecalis. silver-curcumin nanoparticle exerted time kill effect. Further, SEM images of E. faecalis showed that silver-curcumin nanoparticle caused membrane damage and inhibited biofilm formation. Biochemical evidence for membrane damage was confirmed by increased propidium iodide (PI) uptake in flow cytometry. Further, the antifungal activity of silver-curcumin nanoparticle was evaluated in an ex vivo dentinal tubule infection model, which mimics human tooth root canal infection. Confocal laser scanning microscopy studies showed eradication of E. faecalis and reduction in colony forming unit (CFU) after 24 h treatment in the infected tooth samples in this model. Further, silver-curcumin nanoparticle was found to be hemocompatible, not cytotoxic to normal mammalian NIH 3T3 cells and non-mutagenic. Conclusion: The results of this study can pave the way for developing new antibacterial agents with well deciphered mechanisms of action and can be a promising antibacterial agent or medicament against root canal infection.

Keywords: ex vivo dentine model, inhibition of biofilm formation, root canal infection, silver-curcumin nanoparticle

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2365 A Study on the Vegetative and Osmolyte Accumulation of Capsicum frutescens L. under Zinc Metal Stress

Authors: Ja’afar Umar, Adamu Aliyu Aliero

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Plant growth, biochemical parameters, zinc metal concentrations were determined for Capsicum frutescens L. in response to varied concentration of zinc metal. The plant exhibited a decline in the vegetative parameters measured. Free proline and glycine betaine content increases with increasing concentration of zinc metal and differ significantly (P<0.05). It can be concluded that the osmolyte (pro and GB) accumulations, and high length of stem and wide leaf expansion are possible indicator of tolerance to heavy metals (Zinc) in Capsicum frutescens.

Keywords: zinc metal, osmolyte, Capsicum frutescens, stress

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2364 The Genetic Architecture Underlying Dilated Cardiomyopathy in Singaporeans

Authors: Feng Ji Mervin Goh, Edmund Chee Jian Pua, Stuart Alexander Cook

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Dilated cardiomyopathy (DCM) is a common cause of heart failure. Genetic mutations account for 50% of DCM cases with TTN mutations being the most common, accounting for up to 25% of DCM cases. However, the genetic architecture underlying Asian DCM patients is unknown. We evaluated 68 patients (female= 17) with DCM who underwent follow-up at the National Heart Centre, Singapore from 2013 through 2014. Clinical data were obtained and analyzed retrospectively. Genomic DNA was subjected to next-generation targeted sequencing. Nextera Rapid Capture Enrichment was used to capture the exons of a panel of 169 cardiac genes. DNA libraries were sequenced as paired-end 150-bp reads on Illumina MiSeq. Raw sequence reads were processed and analysed using standard bioinformatics techniques. The average age of onset of DCM was 46.1±10.21 years old. The average left ventricular ejection fraction (LVEF), left ventricular diastolic internal diameter (LVIDd), left ventricular systolic internal diameter (LVIDs) were 26.1±11.2%, 6.20±0.83cm, and 5.23±0.92cm respectively. The frequencies of mutations in major DCM-associated genes were as follows TTN (5.88% vs published frequency of 20%), LMNA (4.41% vs 6%), MYH7 (5.88% vs 4%), MYH6 (5.88% vs 4%), and SCN5a (4.41% vs 3%). The average callability at 10 times coverage of each major gene were: TTN (99.7%), LMNA (87.1%), MYH7 (94.8%), MYH6 (95.5%), and SCN5a (94.3%). In conclusion, TTN mutations are not common in Singaporean DCM patients. The frequencies of other major DCM-associated genes are comparable to frequencies published in the current literature.

Keywords: heart failure, dilated cardiomyopathy, genetics, next-generation sequencing

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