Search results for: transient
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 514

Search results for: transient

124 Neuroprotective Effect of Crocus sativus against Cerebral Ischemia in Rats

Authors: Rehab F. Abdel-Rahman, Sally A. El Awdan, Rehab R. Hegazy, Dina F. Mansour, Hanan A. Ogaly, Marwan Abdelbaset

Abstract:

Disorders of the cerebral circulation are the leading cause of numerous neurological and psychiatric illnesses. The transient middle cerebral artery occlusion model (MCAO) is considered to be a reliable and reproducible rodent model of cerebral ischemia. The purpose of the current study was to examine the neuroprotective effects of Crocus sativus (saffron) in a rat model of left middle cerebral artery MCAO. Male Wistar rats were anesthetized and subjected to 1 h of MCAO followed by 48 h reperfusion or sham surgery. One group of the ischemia operated animals was kept as left brain ischemia/reperfusion (I/R). Another 2 operated groups received saffron extract (100 or 200 mg/kg, i.p) four times (60 min before the surgery, during the surgery, and on days 1 and 2 after the occlusion). During the experiment, behavioral tests were performed. After 72 h the animals were euthanized and their left brain hemispheres were used in the biochemical, histopathological, and immunohistochemical studies. Saffron administration revealed an improvement in I/R-induced alteration of locomotor balance and coordination ability of rats. Moreover, saffron decreased the brain content of malondialdehyde, nitric oxide, brain natriuretic peptide and vascular endothelial growth factor with significant increase of reduced glutathione. Immunohistochemical evaluation of caspase-3 and Bax protein expression revealed reduction in I/R-enhanced apoptosis in saffron treated rats. In conclusion, saffron treatment decreases ischemic brain injury in association with inhibition of apoptotic and oxidative cell death in a dose dependent manner.

Keywords: caspase-3, cerebral ischemia, Crocus sativus, rats, vascular endothelial growth factor

Procedia PDF Downloads 235
123 Linear and Nonlinear Resonance of Flat Bottom Hole in an Aluminum Plate

Authors: Biaou Jean-Baptiste Kouchoro, Anissa Meziane, Philippe Micheau, Mathieu Renier, Nicolas Quaegebeur

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Numerous experimental and numerical studies have shown the interest of the local defects resonance (LDR) for the Non-Destructive Testing of metallic and composite plates. Indeed, guided ultrasonic waves such as Lamb waves, which are increasingly used for the inspection of these flat structures, enable the generation of local resonance phenomena by their interaction with a damaged area, allowing the detection of defects. When subjected to a large amplitude motion, a nonlinear behavior can predominate in the damaged area. This work presents a 2D Finite Element Model of the local resonance of a 12 mm long and 5 mm deep Flat Bottom Hole (FBH) in a 6 mm thick aluminum plate under the excitation induced by an incident A0 Lamb mode. The analysis of the transient response of the FBH enables the precise determination of its resonance frequencies and the associate modal deformations. Then, a linear parametric study varying the geometrical properties of the FBH highlights the sensitivity of the resonance frequency with respect to the plate thickness. It is demonstrated that the resonance effect disappears when the ratio of thicknesses between the FBH and the plate is below 0.1. Finally, the nonlinear behavior of the FBH is considered and studied introducing geometrical (taken into account the nonlinear component of the strain tensor) nonlinearities that occur at large vibration amplitudes. Experimental analysis allows observation of the resonance effects and nonlinear response of the FBH. The differences between these experimental results and the numerical results will be commented on. The results of this study are promising and allow to consider more realistic defects such as delamination in composite materials.

Keywords: guided waves, non-destructive testing, dynamic field testing, non-linear ultrasound/vibration

Procedia PDF Downloads 103
122 Value Chain Network: A Social Network Analysis of the Value Chain Actors of Recycled Polymer Products in Lagos Metropolis, Nigeria

Authors: Olamide Shittu, Olayinka Akanle

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Value Chain Analysis is a common method of examining the stages involved in the production of a product, mostly agricultural produce, from the input to the consumption stage including the actors involved in each stage. However, the Functional Institutional Analysis is the most common method in literature employed to analyze the value chain of products. Apart from studying the relatively neglected phenomenon of recycled polymer products in Lagos Metropolis, this paper adopted the use of social network analysis to attempt a grounded theory of the nature of social network that exists among the value chain actors of the subject matter. The study adopted a grounded theory approach by conducting in-depth interviews, administering questionnaires and conducting observations among the identified value chain actors of recycled polymer products in Lagos Metropolis, Nigeria. The thematic analysis of the collected data gave the researchers the needed background to formulate a truly representative network of the social relationships among the value chain actors of recycled polymer products in Lagos Metropolis. The paper introduced concepts such as Transient and Perennial Social Ties to explain the observed social relations among the actors. Some actors have more social capital than others as a result of the structural holes that exist in their triad network. Households and resource recoverers are at disadvantaged position in the network as they have high constraints in their relationships with other actors. The study attempted to provide a new perspective in the study of the environmental value chain by analyzing the network of actors to bring about policy action points and improve recycling in Nigeria. Government and social entrepreneurs can exploit the structural holes that exist in the network for the socio-economic and sustainable development of the state.

Keywords: recycled polymer products, social network analysis, social ties, value chain analysis

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121 Microstructural Evolution of an Interface Region in a Nickel-Based Superalloy Joint Produced by Direct Energy Deposition

Authors: Matthew Ferguson, Tatyana Konkova, Ioannis Violatos

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Microstructure analysis of additively manufactured (AM) materials is an important step in understanding the interrelationship between mechanical properties and materials performance. Literature on the effect of laser-based AM process parameters on the microstructure in the substrate-deposit interface is limited. The interface region, the adjoining area of substrate and deposit, is characterized by the presence of the fusion zone (FZ) and heat-affected zone (HAZ), experiencing rapid thermal gyrations resulting in thermal-induced transformations. Inconel 718 was utilized as work material for both the substrate and deposit. Three blocks of Inconel 718 material were deposited by Direct Energy Deposition (DED) using three different laser powers, 550W, 750W and 950W, respectively. A coupled thermo-mechanical transient approach was utilized to correlate temperature history to the evolution of microstructure. The thermal history of the deposition process was monitored with the thermocouples installed inside the substrate material. The interface region of the blocks was analyzed with Optical Microscopy (OM) and Scanning Electron Microscopy (SEM), including the electron back-scattered diffraction (EBSD) technique. Laser power was found to influence the dissolution of intermetallic precipitated phases in the substrate and grain growth in the interface region. Microstructure and thermal history data were utilized to draw conclusive comparisons between the investigated process parameters.

Keywords: additive manufacturing, direct energy deposition, electron back-scattered diffraction, finite element analysis, inconel 718, microstructure, optical microscopy, scanning electron microscopy, substrate-deposit interface region

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120 Haemodynamics Study in Subject Specific Carotid Bifurcation Using FSI

Authors: S. M. Abdul Khader, Anurag Ayachit, Raghuvir Pai, K. A. Ahmed, V. R. K Rao, S. Ganesh Kamath

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The numerical simulation has made tremendous advances in investigating the blood flow phenomenon through elastic arteries. Such study can be useful in demonstrating the disease progression and haemodynamics of cardiovascular diseases such as atherosclerosis. In the present study, patient specific case diagnosed with partially stenosed complete right ICA and normal left carotid bifurcation without any atherosclerotic plaque formation is considered. 3D patient specific carotid bifurcation model is generated based on CT scan data using MIMICS-4.0 and numerical analysis is performed using FSI solver in ANSYS-14.5. The blood flow is assumed to be incompressible, homogenous and Newtonian, while the artery wall is assumed to be linearly elastic. The two-way sequentially-coupled transient FSI analysis is performed using FSI solver for three pulse cycles. The haemodynamic parameters such as flow pattern, Wall Shear Stress, pressure contours and arterial wall deformation are studied at the bifurcation and critical zones such as stenosis. The variation in flow behavior is studied throughout the pulse cycle. Also, the simulation results reveals that there is a considerable increase in the flow behavior in stenosed carotid in contrast to the normal carotid bifurcation system. The investigation also demonstrates the disturbed flow pattern especially at the bifurcation and stenosed zone elevating the haemodynamics, particularly during peak systole and later part of the pulse cycle. The results obtained agree well with the clinical observation and demonstrates the potential of patient specific numerical studies in prognosis of disease progression and plaque rupture.

Keywords: fluid-structure interaction, arterial stenosis, wall shear stress, carotid artery bifurcation

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119 Viscoelastic Properties of Sn-15%Pb Measured in an Oscillation Test

Authors: Gerardo Sanjuan Sanjuan, Ángel Enrique Chavéz Castellanos

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The knowledge of the rheological behavior of partially solidified metal alloy is an important issue when modeling and simulation of die filling in semisolid processes. Many experiments for like steady state, the step change in shear rate tests, shear stress ramps have been carried out leading that semi-solid alloys exhibit shear thinning, thixotropic behavior and yield stress. More advanced investigation gives evidence some viscoelastic features can be observed. The viscoelastic properties of materials are determinate by transient or dynamic methods; unfortunately, sparse information exists about oscillation experiments. The aim of this present work is to use small amplitude oscillatory tests for knowledge properties such as G´ and G´´. These properties allow providing information about materials structure. For this purpose, we investigated tin-lead alloy (Sn-15%Pb) which exhibits a similar microstructure to aluminum alloys and is the classic alloy for semisolid thixotropic studies. The experiments were performed with parallel plates rheometer AR-G2. Initially, the liquid alloy is cooled down to the semisolid range, a specific temperature to guarantee a constant fraction solid. Oscillation was performed within the linear viscoelastic regime with a strain sweep. So, the loss modulus G´´, the storage modulus G´ and the loss angle (δ) was monitored. In addition a frequency sweep at a strain below the critical strain for characterized its structure. This provides more information about the interactions among solid particles on a liquid matrix. After testing, the sample was removed then cooled, sectioned and examined metallographically. These experiments demonstrate that the viscoelasticity is sensitive to the solid fraction, and is strongly influenced by the shape and size of particles solid.

Keywords: rheology, semisolid alloys, thixotropic, viscoelasticity

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118 Performance Comparison of Droop Control Methods for Parallel Inverters in Microgrid

Authors: Ahmed Ismail, Mustafa Baysal

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Although the energy source in the world is mainly based on fossil fuels today, there is a need for alternative energy generation systems, which are more economic and environmentally friendly, due to continuously increasing demand of electric energy and lacking power resources and networks. Distributed Energy Resources (DERs) such as fuel cells, wind and solar power have recently become widespread as alternative generation. In order to solve several problems that might be encountered when integrating DERs to power system, the microgrid concept has been proposed. A microgrid can operate both grid connected and island mode to benefit both utility and customers. For most distributed energy resources (DER) which are connected in parallel in LV-grid like micro-turbines, wind plants, fuel cells and PV cells electrical power is generated as a direct current (DC) and converted to an alternative currents (AC) by inverters. So the inverters are assumed to be primary components in a microgrid. There are many control techniques of parallel inverters to manage active and reactive sharing of the loads. Some of them are based on droop method. In literature, the studies are usually focused on improving the transient performance of inverters. In this study, the performance of two different controllers based on droop control method is compared for the inverters operated in parallel without any communication feedback. For this aim, a microgrid in which inverters are controlled by conventional droop controller and modified droop controller is designed. Modified controller is obtained by adding PID into conventional droop control. Active and reactive power sharing performance, voltage and frequency responses of those control methods are measured in several operational cases. Study cases have been simulated by MATLAB-SIMULINK.

Keywords: active and reactive power sharing, distributed generation, droop control, microgrid

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117 Upside Down Words as Initial Clinical Presentation of an Underlying Acute Ischemic Stroke

Authors: Ramuel Spirituel Mattathiah A. San Juan, Neil Ambasing

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Background: Reversal of vision metamorphopsia is a transient form of metamorphopsia described as an upside-down alteration of the visual field in the coronal plane. Patients would describe objects, such as cups, upside down, but the tea would not spill, and people would walk on their heads. It is extremely rare as a stable finding, lasting days or weeks. We report a case wherein this type of metamorphopsia occurred only in written words and lasted for six months. Objective: To the best of our knowledge, we report the first rare occurrence of reversal of vision metamorphopsia described as inverted words as the sole initial presentation of an underlying stroke. Case Presentation: We report a 59-year-old male with poorly controlled hypertension and diabetes mellitus who presented with a 3-day history of difficulty reading, described as the words were turned upside down as if the words were inverted horizontally then with the progression of deficits such as right homonymous hemianopia and achromatopsia, prosopagnosia. Cranial magnetic resonance imaging (MRI) revealed an acute infarct on the left posterior cerebral artery territory. Follow-up after six months revealed improvement of the visual field cut but with the persistence of the higher cortical function deficits. Conclusion: We report the first rare occurrence of metamorphopsia described as purely inverted words as the sole initial presentation of an underlying stroke. The differential diagnoses of a patient presenting with text reversal metamorphopsia should include stroke in the occipitotemporal areas. It further expands the landscape of metamorphopsias due to its exclusivity to written words and prolonged duration. Knowing these clinical features will help identify the lesion locus and improve subsequent stroke care, especially in time-bound management like intravenous thrombolysis.

Keywords: rare presentation, text reversal metamorphopsia, ischemic stroke, stroke

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116 Possible Neuroprotective Mechanism of Remote Limb Ischemic Post Conditioning against Global Cerebral Ischemic Injury

Authors: Sruthi Ramagiri, Rajeev Taliyan

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Background and purpose: Recent investigations on ischemia and reperfusion injury postulate that transient ischemia of remote organs after a prolonged ischemic insult confers neuroprotection. However, the molecular mechanisms of the remote limb ischemic post-conditioning (RIPOC) are yet to be elucidated. The current study was designed to investigate the protective mechanism of RIPOC against cerebral ischemic injury using global model of stroke. Materials and methods: Global ischemic reperfusion injury (IR) was achieved by 30 minutes ischemia of cerebral artery, followed by reperfusion for 24 hours. Induction of global ischemia was followed by 4 brief episodes (30 seconds each) of ischemia and reperfusion of femoral artery to accomplish RIPOC. 5-Hydroxy Decanoic acid (5-HD), a KATP channel blocker (20 mg/kg) was administered after induction of global ischemia and RIPOC intervention. Results: IR injury ensue significant behavioural deficits as manifested by rotarod performance and spontaneous locomotor activity when compared to sham control. Furthermore, IR injury significantly increased oxidonitrative stress and infarct volume as evidenced by biochemical parameters (MDA, GSH, Nitrite, SOD) and 2,3,5-triphenyltetrazolium chloride (TTC) staining respectively. Moreover, RIPOC intervention ameliorated the behavioural performance, attenuated the oxidative stress and infarct volume when compared to IR injury group. However, administration of 5-HD increased the oxidative stress and infarct size while deteriorating the behavioural parameters when compared to RIPOC group. Conclusions: In a nutshell, cerebral IR injury has significantly induced the neuronal damage, whereas RIPOC intervention decreased the neuronal injury. Moreover, 5-HD abolished the neuroprotection offered by RIPOC indicating the putative role of KATP channel opening in RIPOC against cerebral ischemic injury.

Keywords: RIPOC, cerebral injury, KATP channel, neuroprotection

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115 A Data-Driven Agent Based Model for the Italian Economy

Authors: Michele Catalano, Jacopo Di Domenico, Luca Riccetti, Andrea Teglio

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We develop a data-driven agent based model (ABM) for the Italian economy. We calibrate the model for the initial condition and parameters. As a preliminary step, we replicate the Monte-Carlo simulation for the Austrian economy. Then, we evaluate the dynamic properties of the model: the long-run equilibrium and the allocative efficiency in terms of disequilibrium patterns arising in the search and matching process for final goods, capital, intermediate goods, and credit markets. In this perspective, we use a randomized initial condition approach. We perform a robustness analysis perturbing the system for different parameter setups. We explore the empirical properties of the model using a rolling window forecast exercise from 2010 to 2022 to observe the model’s forecasting ability in the wake of the COVID-19 pandemic. We perform an analysis of the properties of the model with a different number of agents, that is, with different scales of the model compared to the real economy. The model generally displays transient dynamics that properly fit macroeconomic data regarding forecasting ability. We stress the model with a large set of shocks, namely interest policy, fiscal policy, and exogenous factors, such as external foreign demand for export. In this way, we can explore the most exposed sectors of the economy. Finally, we modify the technology mix of the various sectors and, consequently, the underlying input-output sectoral interdependence to stress the economy and observe the long-run projections. In this way, we can include in the model the generation of endogenous crisis due to the implied structural change, technological unemployment, and potential lack of aggregate demand creating the condition for cyclical endogenous crises reproduced in this artificial economy.

Keywords: agent-based models, behavioral macro, macroeconomic forecasting, micro data

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114 Experimental Study of Complete Loss of Coolant Flow (CLOF) Test by System–Integrated Modular Advanced Reactor Integral Test Loop (SMART-ITL) with Passive Residual Heat Removal System (PRHRS)

Authors: Jin Hwa Yang, Hwang Bae, Sung Uk Ryu, Byong Guk Jeon, Sung Jae Yi, Hyun Sik Park

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Experimental studies using a large-scale thermal-hydraulic integral test facility, System–integrated Modular Advanced Reactor Integral Test Loop (SMART-ITL), have been carried out to validate the performance of the prototype, SMART. After Fukushima accident, the passive safety systems have been dealt as important designs for retaining of nuclear safety. One of the concerned scenarios for evaluating the passive safety system is a Complete Loss of Coolant Flow (CLOF). The flowrate of coolant in the primary system is maintained by Reactor Coolant Pump (RCP). When the supply of electric power of RCP is shut off, the flowrate of coolant decreases sharply, and the temperature of the coolant increases rapidly. Therefore, the reactor trip signal is activated to prevent the over-heating of the core. In this situation, Passive Residual Heat Removal System (PRHRS) plays a significant role to assure the soundness of the SMART. The PRHRS using a two-phase natural circulation is a passive safety system in the SMART to eliminate the heat of steam generator in the secondary system with heat exchanger submarined in the Emergency Cooling Tank (ECT). As the RCPs continue to coast down, inherent natural circulation in the primary system transfers heat to the secondary system. The transferred heat is removed by PRHRS in the secondary system. In this paper, the progress of the CLOF accident is described with experimental data of transient condition performed by SMART-ITL. Finally, the capability of passive safety system and inherent natural circulation will be evaluated.

Keywords: CLOF, natural circulation, PRHRS, SMART-ITL

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113 Effects of Bilateral Electroconvulsive Therapy on Autobiographical Memories in Asian Patients

Authors: Lai Gwen Chan, Yining Ong, Audrey Yoke Poh Wong

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Background. The efficacy of electroconvulsive therapy (ECT) as a form of treatment to a range of mental disorders is well-established. However, ECT is often associated with either temporary or persistent cognitive side-effects, resulting in the failure of wider prescription. Of which, retrograde amnesia is the most commonly reported cognitive side-effect. Most studies found a recalling deficit in autobiographical memories to be short-term, although a few have reported more persistent amnesic effects. Little is known about ECT-related amnesic effects in Asian population. Hence, this study aims to resolve conflicting findings, as well as to better elucidate the effects of ECT on cognitive functioning in a local sample. Method: 12 patients underwent bilateral ECT under the care of Psychological Medicine Department, Tan Tock Seng Hospital, Singapore. Participants’ cognition and level of functioning were assessed at four time-points: before ECT, between the third and fourth induced seizure, at the end of the whole course of ECT, and two months after the index course of ECT. Results: It was found that Global Assessment of Functioning scores increased significantly at the completion of ECT. Case-by-case analyses also revealed an overall improvement in Personal Semantic and Autobiographical memory two months after the index course of ECT. A transient dip in both personal semantic and autobiographical memory scores was observed in one participant between the third and fourth induced seizure, but subsequently resolved and showed better performance than at baseline. Conclusions: The findings of this study suggest that ECT is an effective form of treatment to alleviate the severity of symptoms of the diagnosis. ECT does not affect attention, language, executive functioning, personal semantic and autobiographical memory adversely. The findings suggest that Asian patients may respond to bilateral ECT differently from Western samples.

Keywords: electroconvulsive therapy (ECT), autobiographical memory, cognitive impairment, psychiatric disorder

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112 An Intelligent Controller Augmented with Variable Zero Lag Compensation for Antilock Braking System

Authors: Benjamin Chijioke Agwah, Paulinus Chinaenye Eze

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Antilock braking system (ABS) is one of the important contributions by the automobile industry, designed to ensure road safety in such way that vehicles are kept steerable and stable when during emergency braking. This paper presents a wheel slip-based intelligent controller with variable zero lag compensation for ABS. It is required to achieve a very fast perfect wheel slip tracking during hard braking condition and eliminate chattering with improved transient and steady state performance, while shortening the stopping distance using effective braking torque less than maximum allowable torque to bring a braking vehicle to a stop. The dynamic of a vehicle braking with a braking velocity of 30 ms⁻¹ on a straight line was determined and modelled in MATLAB/Simulink environment to represent a conventional ABS system without a controller. Simulation results indicated that system without a controller was not able to track desired wheel slip and the stopping distance was 135.2 m. Hence, an intelligent control based on fuzzy logic controller (FLC) was designed with a variable zero lag compensator (VZLC) added to enhance the performance of FLC control variable by eliminating steady state error, provide improve bandwidth to eliminate the effect of high frequency noise such as chattering during braking. The simulation results showed that FLC- VZLC provided fast tracking of desired wheel slip, eliminate chattering, and reduced stopping distance by 70.5% (39.92 m), 63.3% (49.59 m), 57.6% (57.35 m) and 50% (69.13 m) on dry, wet, cobblestone and snow road surface conditions respectively. Generally, the proposed system used effective braking torque that is less than the maximum allowable braking torque to achieve efficient wheel slip tracking and overall robust control performance on different road surfaces.

Keywords: ABS, fuzzy logic controller, variable zero lag compensator, wheel slip tracking

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111 Dwindling the Stability of DNA Sequence by Base Substitution at Intersection of COMT and MIR4761 Gene

Authors: Srishty Gulati, Anju Singh, Shrikant Kukreti

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The manifestation of structural polymorphism in DNA depends on the sequence and surrounding environment. Ample of folded DNA structures have been found in the cellular system out of which DNA hairpins are very common, however, are indispensable due to their role in the replication initiation sites, recombination, transcription regulation, and protein recognition. We enumerate this approach in our study, where the two base substitutions and change in temperature embark destabilization of DNA structure and misbalance the equilibrium between two structures of a sequence present at the overlapping region of the human COMT gene and MIR4761 gene. COMT and MIR4761 gene encodes for catechol-O-methyltransferase (COMT) enzyme and microRNAs (miRNAs), respectively. Environmental changes and errors during cell division lead to genetic abnormalities. The COMT gene entailed in dopamine regulation fosters neurological diseases like Parkinson's disease, schizophrenia, velocardiofacial syndrome, etc. A 19-mer deoxyoligonucleotide sequence 5'-AGGACAAGGTGTGCATGCC-3' (COMT19) is located at exon-4 on chromosome 22 and band q11.2 at the intersection of COMT and MIR4761 gene. Bioinformatics studies suggest that this sequence is conserved in humans and few other organisms and is involved in recognition of transcription factors in the vicinity of 3'-end. Non-denaturating gel electrophoresis and CD spectroscopy of COMT sequences indicate the formation of hairpin type DNA structures. Temperature-dependent CD studies revealed an unusual shift in the slipped DNA-Hairpin DNA equilibrium with the change in temperature. Also, UV-thermal melting techniques suggest that the two base substitutions on the complementary strand of COMT19 did not affect the structure but reduces the stability of duplex. This study gives insight about the possibility of existing structurally polymorphic transient states within DNA segments present at the intersection of COMT and MIR4761 gene.

Keywords: base-substitution, catechol-o-methyltransferase (COMT), hairpin-DNA, structural polymorphism

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110 Hypotonia - A Concerning Issue in Neonatal Care

Authors: Eda Jazexhiu-Postoli, Gladiola Hoxha, Ada Simeoni, Sonila Biba

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Background Neonatal hypotonia represents a commonly encountered issue in the Neonatal Intensive Care Unit and newborn nursery. The differential diagnosis is broad, encompassing chromosome abnormalities, primary muscular dystrophies, neuropathies and inborn errors of metabolism. Aim of study Our study describes some of the main clinical features of hypotonia in newborns and presents clinical cases of neonatal hypotonia we treated in our Neonatal unit in the last 3 years. Case reports Four neonates born in our hospital presented with hypotonia after birth, one preterm newborn 35-36 weeks of gestational age and three other term newborns (38-39 weeks of gestational age). Prenatal data revealed a decrease in fetal movements in both cases. Intrapartum meconium-stained amniotic fluid was found in 75% of our hypotonic newborns. Clinical features included inability to establish effective respiratory movements and need for resuscitation in the delivery room, respiratory distress syndrome, feeding difficulties and need for oro-gastric tube feeding, dysmorphic features, hoarse voice and moderate to severe muscular hypotonia. The genetic workup revealed the diagnosis of Autosomal Recessive Congenital Myasthenic Syndrome 1-B, Sotos Syndrome, Spinal Muscular Atrophy Type 1 and Transient Hypotonia of the Newborn. Two out of four hypotonic neonates were transferred to the Pediatric Intensive Care Unit and died at the age of three to five months old. Conclusion Hypotonia is a concerning finding in neonatal care and it is suggested by decreased intrauterine fetal movements, failure to establish first breaths, respiratory distress and feeding difficulties in the neonate. Prognosis is determined by its etiology and time of diagnosis and intervention.

Keywords: hypotonic neonate, respiratory distress, feeding difficulties, fetal movements

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109 Influence of Carbon Addition on the Activity of Silica Supported Copper and Cobalt Catalysts in NO Reduction with CO

Authors: N. Stoeva, I. Spassova, R. Nickolov, M. Khristova

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Exhaust gases from stationary and mobile combustion sources contain nitrogen oxides that cause a variety of environmentally harmful effects. The most common approach of their elimination is the catalytic reaction in the exhaust using various reduction agents such as NH3, CO and hydrocarbons. Transition metals (Co, Ni, Cu, etc.) are the most widely used as active components for deposition on various supports. However, since the interaction between different catalyst components have been extensively studied in different types of reaction systems, the possible cooperation between active components and the support material and the underlying mechanisms have not been thoroughly investigated. The support structure may affect how these materials maintain an active phase. The objective is to investigate the addition of carbonaceous materials with different nature and texture characteristics on the properties of the resulting silica-carbon support and how it influences of the catalytic properties of the supported copper and cobalt catalysts for reduction of NO with CO. The versatility of the physico-chemical properties of the composites and the supported copper and cobalt catalysts are discussed with an emphasis on the relationship of the properties with the catalytic performance. The catalysts were prepared by sol-gel process and were characterized by XRD, XPS, AAS and BET analysis. The catalytic experiments were carried out in catalytic flow apparatus with isothermal flow reactor in the temperature range 20–300оС. After the catalytic test temperature-programmed desorption (TPD) was carried out. The transient response method was used to study the interaction of the gas phase with the catalyst surface. The role of the interaction between the support and the active phase on the catalyst’s activity in the studied reaction was discussed. We suppose the carbon particles with small sizes to participate in the formation of the active sites for the reduction of NO with CO along with their effect on the kind of deposited metal oxide phase. The existence of micropore texture for some of composites also influences by mass-transfer limitations.

Keywords: catalysts, no reduction, composites, bet analysis

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108 Internal Stresses and Structural Evolutions in Zr Alloys during Oxidation at High Temperature and Subsequent Cooling

Authors: Raphaelle Guillou, Matthieu Le Saux, Jean-Christophe Brachet, Thomas Guilbert, Elodie Rouesne, Denis Menut, Caroline Toffolon-Masclet, Dominique Thiaudiere

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In some hypothetical accidental situations, such as during a Loss Of Coolant Accident (LOCA) in pressurized water reactors, fuel cladding tubes made of zirconium alloys can be exposed for a few minutes to steam at High Temperature (HT up to 1200°C) before being cooled and then quenched in water. Under LOCA-like conditions, the cladding undergoes a number of metallurgical changes (phase transformations, oxygen diffusion and growth of an oxide layer...) and is consequently submitted to internal stresses whose state evolves during the transient. These stresses can have an effect on the oxide structure and the oxidation kinetics of the material. They evolve during cooling, owing to differences between the thermal expansion coefficients of the various phases and phase transformations of the metal and the oxide. These stresses may result in the failure of the cladding during quenching, once the material is embrittled by oxidation. In order to progress in the evaluation of these internal stresses, X-ray diffraction experiments were performed in-situ under synchrotron radiation during HT oxidation and subsequent cooling on Zircaloy-4 sheet samples. First, structural evolutions, such as phase transformations, have been studied as a function of temperature for both the oxide layer and the metallic substrate. Then, internal stresses generated within the material oxidized at temperatures between 700 and 900°C have been evaluated thanks to the 2θ diffraction peak position shift measured during the in-situ experiments. Electron backscatter diffraction (EBSD) analysis was performed on the samples after cooling in order to characterize their crystallographic texture. Furthermore, macroscopic strains induced by oxidation in the conditions investigated during the in-situ X-ray diffraction experiments were measured in-situ in a dilatometer.

Keywords: APRP, stains measurements, synchrotron diffraction, zirconium allows

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107 Comparative Analysis of Short and Long Term Salt Stress on the Photosynthetic Apparatus and Chloroplast Ultrastructure of Thellungiella salsuginea

Authors: Rahma Goussi, Walid Derbali, Arafet Manaa, Simone Cantamessa, Graziella Berta, Chedly Abdelly, Roberto Barbato

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Salinity is one of the most important abiotic affecting plant growth and productivity worldwide. Photosynthesis, together with cell growth, is among the primary processes to be affected by salinity. Here, we report the effects of salinity stress on the primary processes of photosynthesis in a model halophyte Thellungiella Salsuginea. Plants were cultivated in hydroponic system with different NaCl concentrations (0, 100, 200 and 400 mM) during 2 weeks. The obtained results showed an obvious change in the photosynthetic efficiency of photosystem I (PSI) and phostosytem II (PSII), related to NaCl concentration supplemented to the medium and the stress duration considered. With moderate salinity (100 and 200 mM NaCl), no significant variation was observed in photosynthetic parameters of PSI and PSII and Chl fluorescence whatever the time of stress application. Also, the photosynthesis apparatus Fo, Fm and Fv fluorescence, as well as Fv/Fm were not affected by salt stress. While a significant decrease was observed on quantum yields Y(I), Y(II) and electron transport rate ETR(I), ETR(II) under high salt treatment (400 mM NaCl) with prolonged period (15 days). This reduction is quantitatively compensated by a corresponding increase of energy dissipation Y(NPQ) and a progressive decrease in Fv/Fm under salt treatment. The intensity of the OJIP fluorescence transient decreased with increase in NaCl concentration, with a major effect observed during prolonged period of salt stress. Ultrastructural analysis with Light Microscopy and Transmission Electron Microscopy of T. salsuginea chloroplasts showed some cellular changes, such as the shape of the mesophyll cells and number of chloroplast/cell only under higher NaCl concentration. Salt-stress caused the swelling of thylakoids in T. Salsuginea mesophyll with more accumulation of starch as compared to control plant.

Keywords: fluorescence, halophyte, photosynthesis, salt stress

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106 Preliminary Performance of a Liquid Oxygen-Liquid Methane Pintle Injector for Thrust Variations

Authors: Brunno Vasques

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Due to the non-toxic nature and high performance in terms of vacuum specific impulse and density specific impulse, the combination of liquid oxygen and liquid methane have been identified as a promising option for future space vehicle systems. Applications requiring throttling capability include specific missions such as rendezvous, planetary landing and de-orbit as well as weapon systems. One key challenge in throttling liquid rocket engines is maintaining an adequate pressure drop across the injection elements, which is necessary to provide good propellant atomization and mixing as well as system stability. The potential scalability of pintle injectors, their great suitability to throttling and inherent combustion stability characteristics led to investigations using a variety of propellant combinations, including liquid oxygen and hydrogen and fluorine-oxygen and methane. Presented here are the preliminary performance and heat transfer information obtained during hot-fire testing of a pintle injector running on liquid oxygen and liquid methane propellants. The specific injector design selected for this purpose is a multi-configuration building block version with replaceable injection elements, providing flexibility to accommodate hardware modifications with minimum difficulty. On the basis of single point runs and the use of a copper/nickel segmented calorimetric combustion chamber and associated transient temperature measurement, the characteristic velocity efficiency, injector footprint and heat fluxes could be established for the first proposed pintle configuration as a function of injection velocity- and momentum-ratios. A description of the test-bench is presented as well as a discussion of irregularities encountered during testing, such as excessive heat flux into the pintle tip resulting from certain operating conditions.

Keywords: green propellants, hot-fire performance, rocket engine throttling, pintle injector

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105 Polymer Mixing in the Cavity Transfer Mixer

Authors: Giovanna Grosso, Martien A. Hulsen, Arash Sarhangi Fard, Andrew Overend, Patrick. D. Anderson

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In many industrial applications and, in particular in polymer industry, the quality of mixing between different materials is fundamental to guarantee the desired properties of finished products. However, properly modelling and understanding polymer mixing often presents noticeable difficulties, because of the variety and complexity of the physical phenomena involved. This is the case of the Cavity Transfer Mixer (CTM), for which a clear understanding of mixing mechanisms is still missing, as well as clear guidelines for the system optimization. This device, invented and patented by Gale at Rapra Technology Limited, is an add-on to be mounted downstream of existing extruders, in order to improve distributive mixing. It consists of two concentric cylinders, the rotor and stator, both provided with staggered rows of hemispherical cavities. The inner cylinder (rotor) rotates, while the outer (stator) remains still. At the same time, the pressure load imposed upstream, pushes the fluid through the CTM. Mixing processes are driven by the flow field generated by the complex interaction between the moving geometry, the imposed pressure load and the rheology of the fluid. In such a context, the present work proposes a complete and accurate three dimensional modelling of the CTM and results of a broad range of simulations assessing the impact on mixing of several geometrical and functioning parameters. Among them, we find: the number of cavities per row, the number of rows, the size of the mixer, the rheology of the fluid and the ratio between the rotation speed and the fluid throughput. The model is composed of a flow part and a mixing part: a finite element solver computes the transient velocity field, which is used in the mapping method implementation in order to simulate the concentration field evolution. Results of simulations are summarized in guidelines for the device optimization.

Keywords: Mixing, non-Newtonian fluids, polymers, rheology.

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104 A Benchmark System for Testing Medium Voltage Direct Current (MVDC-CB) Robustness Utilizing Real Time Digital Simulation and Hardware-In-Loop Theory

Authors: Ali Kadivar, Kaveh Niayesh

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The integration of green energy resources is a major focus, and the role of Medium Voltage Direct Current (MVDC) systems is exponentially expanding. However, the protection of MVDC systems against DC faults is a challenge that can have consequences on reliable and safe grid operation. This challenge reveals the need for MVDC circuit breakers (MVDC CB), which are in infancies of their improvement. Therefore will be a lack of MVDC CBs standards, including thresholds for acceptable power losses and operation speed. To establish a baseline for comparison purposes, a benchmark system for testing future MVDC CBs is vital. The literatures just give the timing sequence of each switch and the emphasis is on the topology, without in-depth study on the control algorithm of DCCB, as the circuit breaker control system is not yet systematic. A digital testing benchmark is designed for the Proof-of-concept of simulation studies using software models. It can validate studies based on real-time digital simulators and Transient Network Analyzer (TNA) models. The proposed experimental setup utilizes data accusation from the accurate sensors installed on the tested MVDC CB and through general purpose input/outputs (GPIO) from the microcontroller and PC Prototype studies in the laboratory-based models utilizing Hardware-in-the-Loop (HIL) equipment connected to real-time digital simulators is achieved. The improved control algorithm of the circuit breaker can reduce the peak fault current and avoid arc resignation, helping the coordination of DCCB in relay protection. Moreover, several research gaps are identified regarding case studies and evaluation approaches.

Keywords: DC circuit breaker, hardware-in-the-loop, real time digital simulation, testing benchmark

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103 A Topology-Enabled Patient Connectivity Network to Bridge the Molecular-To-Phenotype Gap in Cholestasis

Authors: Doroteya K. Staykova, Dirk J. Lefeber, Sabine A. Fuchs, Judith J. M. Jans

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Cholestasis is characterized by the accumulation of toxic bile salts and lipids in the organism. The variety in causes (genetic, immunologic, environmental) and nature (benign, transient, chronic, progressive) combined with the need for early diagnosis and rapid clinical decisions emphasizes the need for good diagnostic strategies to improve patient outcomes. In a current diagnostic analysis of cholestasis, mass-spectrometry metabolomics is a widely adopted tool to enhance clinical decisions at point-of-care, thanks to a short turnaround in measurement times while performing comprehensive molecular profiling of patient material. However, this comes at the cost of difficult-to-identify yet actionable knowledge, often buried within large and heterogenous omics data. Here, we demonstrate how topological data analysis can overcome this challenge in large metabolomics datasets of patients with twenty categories of Metabolic Disorders and overlapping clinical manifestations. To elucidate the complexity of disease progression in three cholestasis patients, we applied topological data analysis to direct-infusion mass spectrometry data collected from 190 plasma samples, including 67 controls, at the University Medical Center in Utrecht, Netherlands. Using the Mapper algorithm and filter function defined as a two-component projection based on Principal Component Analysis, we constructed a topological graph of connected patients, termed a Patient Connectivity Network (PCN). With incorporated clinical and molecular information, PCN revealed the topological shape of causes and severity of cholestasis and transitions in patients’ conditions. In conclusion, topology based PCN provides a holistic view of cholestasis state dynamics that has the potential to support and expedite clinical decisions.

Keywords: mass spectrometry-based metabolomics, patient connectivity network, topological data analysis, unmet clinical needs in Cholestasis

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102 Psychological Stress and Accelerated Aging in SCI Patients - A Longitudinal Pilot Feasibility Study

Authors: Simona Capossela, Ramona Schaniel, Singer Franziska, Aquino Fournier Catharine, Daniel Stekhoven, Jivko Stoyanov

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A spinal cord injury (SCI) is a traumatic life event that often results in ageing associated health conditions such as muscle mass decline, adipose tissue increase, decline in immune function, frailty, systemic chronic inflammation, and psychological distress and depression. Psychological, oxidative, and metabolic stressors may facilitate accelerated ageing in the SCI population with reduced life expectancy. Research designs using biomarkers of aging and stress are needed to elucidate the role of psychological distress in accelerated aging. The aim of this project is a feasibility pilot study to observe changes in stress biomarkers and correlate them with aging markers in SCI patients during their first rehabilitation (longitudinal cohort study). Biological samples were collected in the SwiSCI (Swiss Spinal Cord Injury Cohort Study) Biobank in Nottwil at 4 weeks±12 days after the injury (T1) and at the end of the first rehabilitation (discharge, T4). The "distress thermometer" is used as a selfassessment tool for psychological distress. Stress biomarkers, as cortisol and protein carbonyl content (PCC), and markers of cellular aging, such as telomere lengths, will be measured. 2 Preliminary results showed that SCI patients (N= 129) are still generally distressed at end of rehabilitation, however we found a statistically significant (p< 0.001) median decrease in distress from 6 (T1) to 5 (T4) during the rehabilitation. In addition, an explorative transcriptomics will be conducted on N=50 SCI patients to compare groups of persons with SCI who have different trajectories of selfreported distress at the beginning and end of the first rehabilitation after the trauma. We identified 4 groups: very high chronic stress (stress thermometer values above 7 at T1 and T4; n=14); transient stress (high to low; n=14), low stress (values below 5 at T1 and T4; n=14), increasing stress (low to high; n=8). The study will attempt to identify and address issues that may occur in relation to the design and conceptualization of future study on stress and aging in the SCI population.

Keywords: stress, aging, spinal cord injury, biomarkers

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101 Mathematical Modeling of the AMCs Cross-Contamination Removal in the FOUPs: Finite Element Formulation and Application in FOUP’s Decontamination

Authors: N. Santatriniaina, J. Deseure, T. Q. Nguyen, H. Fontaine, C. Beitia, L. Rakotomanana

Abstract:

Nowadays, with the increasing of the wafer's size and the decreasing of critical size of integrated circuit manufacturing in modern high-tech, microelectronics industry needs a maximum attention to challenge the contamination control. The move to 300 mm is accompanied by the use of Front Opening Unified Pods for wafer and his storage. In these pods an airborne cross contamination may occur between wafers and the pods. A predictive approach using modeling and computational methods is very powerful method to understand and qualify the AMCs cross contamination processes. This work investigates the required numerical tools which are employed in order to study the AMCs cross-contamination transfer phenomena between wafers and FOUPs. Numerical optimization and finite element formulation in transient analysis were established. Analytical solution of one dimensional problem was developed and the calibration process of physical constants was performed. The least square distance between the model (analytical 1D solution) and the experimental data are minimized. The behavior of the AMCs intransient analysis was determined. The model framework preserves the classical forms of the diffusion and convection-diffusion equations and yields to consistent form of the Fick's law. The adsorption process and the surface roughness effect were also traduced as a boundary condition using the switch condition Dirichlet to Neumann and the interface condition. The methodology is applied, first using the optimization methods with analytical solution to define physical constants, and second using finite element method including adsorption kinetic and the switch of Dirichlet to Neumann condition.

Keywords: AMCs, FOUP, cross-contamination, adsorption, diffusion, numerical analysis, wafers, Dirichlet to Neumann, finite elements methods, Fick’s law, optimization

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100 Portuguese Guitar Strings Characterization and Comparison

Authors: P. Serrão, E. Costa, A. Ribeiro, V. Infante

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The characteristic sonority of the Portuguese guitar is in great part what makes Fado so distinguishable from other traditional song styles. The Portuguese guitar is a pear-shaped plucked chordophone with six courses of double strings. This study compares the two types of plain strings available for Portuguese guitar and used by the musicians. One is stainless steel spring wire, the other is high carbon spring steel (music wire). Some musicians mention noticeable differences in sound quality between these two string materials, such as a little more brightness and sustain in the steel strings. Experimental tests were performed to characterize string tension at pitch; mechanical strength and tuning stability using the universal testing machine; dimensional control and chemical composition analysis using the scanning electron microscope. The string dynamical behaviour characterization experiments, including frequency response, inharmonicity, transient response, damping phenomena and were made in a monochord test set-up designed and built in-house. Damping factor was determined for the fundamental frequency. As musicians are able to detect very small damping differences, an accurate a characterization of the damping phenomena for all harmonics was necessary. With that purpose, another improved monochord was set and a new system identification methodology applied. Due to the complexity of this task several adjustments were necessary until obtaining good experimental data. In a few cases, dynamical tests were repeated to detect any evolution in damping parameters after break-in period when according to players experience a new string sounds gradually less dull until reaching the typically brilliant timbre. Finally, each set of strings was played on one guitar by a distinguished player and recorded. The recordings which include individual notes, scales, chords and a study piece, will be analysed to potentially characterize timbre variations.

Keywords: damping factor, music wire, portuguese guitar, string dynamics

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99 Impact of Joule Heating on the Electrical Conduction Behavior of Carbon Composite Laminates under Simulated Lightning Strike

Authors: Hong Yu, Dirk Heider, Suresh Advani

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Increasing demands for high strength and lightweight materials in aircraft industry prompted the wide use of carbon composites in recent decades. Carbon composite laminates used on aircraft structures are subject to lightning strikes. Unlike its metal/alloy counterparts, carbon fiber reinforced composites demonstrate smaller electrical conductivity, yielding more severe damages due to Joule heating. The anisotropic nature of composite laminates makes the electrical and thermal conduction within carbon composite laminates even more complicated. Good understanding of the electrical conduction behavior of carbon composites is the key to effective lightning protection design. The goal of this study is to numerically and experimentally investigate the impact of ultra-high temperature induced by simulated lightning strike on the electrical conduction of carbon composites. A lightning simulator is designed to apply standard lightning current waveform to composite laminates. Multiple carbon composite laminates made from IM7 and AS4 carbon fiber are tested and the transient resistance data is recorded. A microstructure based resistor network model is developed to describe the electrical and thermal conduction behavior, with consideration of temperature dependent material properties. Material degradations such as thermal and electrical breakdown are also modeled to include the effect of high current and high temperature induced by lightning strikes. Good match between the simulation results and experimental data indicates that the developed model captures the major conduction mechanisms. A parametric study is then conducted using the validated model to investigate the effect of system parameters such as fiber volume fraction, inter-ply interface quality, and lightning current waveforms.

Keywords: carbon composite, joule heating, lightning strike, resistor network

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98 Robust Numerical Solution for Flow Problems

Authors: Gregor Kosec

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Simple and robust numerical approach for solving flow problems is presented, where involved physical fields are represented through the local approximation functions, i.e., the considered field is approximated over a local support domain. The approximation functions are then used to evaluate the partial differential operators. The type of approximation, the size of support domain, and the type and number of basis function can be general. The solution procedure is formulated completely through local computational operations. Besides local numerical method also the pressure velocity is performed locally with retaining the correct temporal transient. The complete locality of the introduced numerical scheme has several beneficial effects. One of the most attractive is the simplicity since it could be understood as a generalized Finite Differences Method, however, much more powerful. Presented methodology offers many possibilities for treating challenging cases, e.g. nodal adaptivity to address regions with sharp discontinuities or p-adaptivity to treat obscure anomalies in physical field. The stability versus computation complexity and accuracy can be regulated by changing number of support nodes, etc. All these features can be controlled on the fly during the simulation. The presented methodology is relatively simple to understand and implement, which makes it potentially powerful tool for engineering simulations. Besides simplicity and straightforward implementation, there are many opportunities to fully exploit modern computer architectures through different parallel computing strategies. The performance of the method is presented on the lid driven cavity problem, backward facing step problem, de Vahl Davis natural convection test, extended also to low Prandtl fluid and Darcy porous flow. Results are presented in terms of velocity profiles, convergence plots, and stability analyses. Results of all cases are also compared against published data.

Keywords: fluid flow, meshless, low Pr problem, natural convection

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97 Development and Validation of a Carbon Dioxide TDLAS Sensor for Studies on Fermented Dairy Products

Authors: Lorenzo Cocola, Massimo Fedel, Dragiša Savić, Bojana Danilović, Luca Poletto

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An instrument for the detection and evaluation of gaseous carbon dioxide in the headspace of closed containers has been developed in the context of Packsensor Italian-Serbian joint project. The device is based on Tunable Diode Laser Absorption Spectroscopy (TDLAS) with a Wavelength Modulation Spectroscopy (WMS) technique in order to accomplish a non-invasive measurement inside closed containers of fermented dairy products (yogurts and fermented cheese in cups and bottles). The purpose of this instrument is the continuous monitoring of carbon dioxide concentration during incubation and storage of products over a time span of the whole shelf life of the product, in the presence of different microorganisms. The instrument’s optical front end has been designed to be integrated in a thermally stabilized incubator. An embedded computer provides processing of spectral artifacts and storage of an arbitrary set of calibration data allowing a properly calibrated measurement on many samples (cups and bottles) of different shapes and sizes commonly found in the retail distribution. A calibration protocol has been developed in order to be able to calibrate the instrument on the field also on containers which are notoriously difficult to seal properly. This calibration protocol is described and evaluated against reference measurements obtained through an industry standard (sampling) carbon dioxide metering technique. Some sets of validation test measurements on different containers are reported. Two test recordings of carbon dioxide concentration evolution are shown as an example of instrument operation. The first demonstrates the ability to monitor a rapid yeast growth in a contaminated sample through the increase of headspace carbon dioxide. Another experiment shows the dissolution transient with a non-saturated liquid medium in presence of a carbon dioxide rich headspace atmosphere.

Keywords: TDLAS, carbon dioxide, cups, headspace, measurement

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96 Insect Diversity Potential in Olive Trees in Two Orchards Differently Managed Under an Arid Climate in the Western Steppe Land, Algeria

Authors: Samir Ali-arous, Mohamed Beddane, Khaled Djelouah

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This study investigated the insect diversity of olive (Olea europaea Linnaeus (Oleaceae)) groves grown in an arid climate in Algeria. In this context, several sampling methods were used within two orchards differently managed. Fifty arthropod species belonging to diverse orders and families were recorded. Hymenopteran species were quantitatively the most abundant, followed by species associated with Heteroptera, Aranea, Coleoptera and Homoptera orders. Regarding functional feeding groups, phytophagous species were dominant in the weeded and the unweeded orchard; however, higher abundance was recorded in the weeded site. Predators were ranked second, and pollinators were more frequent in the unweeded olive orchard. Two-factor Anova with repeated measures had revealed high significant effect of the weed management system, measures repetition and interaction with measurement repetition on arthropod’s abundances (P < 0.05). Likewise, generalized linear models showed that N/S ratio varied significantly between the two weed management approaches, in contrast, the remaining diversity indices including the Shannon index H’ had no significant correlation. Moreover, diversity parameters of arthropod’s communities in each agro-system highlighted multiples significant correlations (P <0.05). Rarefaction and extrapolation (R/E) sampling curves, evidenced that the survey and monitoring carried out in both sites had a optimum coverage of entomofauna present including scarce and transient species. Overall, calculated diversity and similarity indices were greater in the unweeded orchard than in the weeded orchard, demonstrating spontaneous flora's key role in entomofaunal diversity. Principal Component Analysis (PCA) has defined correlations between arthropod’s abundances and naturally occurring plants in olive orchards, including beneficials.

Keywords: Algeria, olive, insects, diversity, wild plants

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95 Camptothecin Promotes ROS-Mediated G2/M Phase Cell Cycle Arrest, Resulting from Autophagy-Mediated Cytoprotection

Authors: Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Yung Hyun Choi, Gi-Young Kim

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Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT.

Keywords: camptothecin, cell cycle, checkpoint kinase 2, nuclear factor-erythroid 2-related factor 2, reactive oxygen species

Procedia PDF Downloads 408