Search results for: whole genome single nucleotide polymorphisms
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4964

Search results for: whole genome single nucleotide polymorphisms

3254 Integration of EEG and Motion Tracking Sensors for Objective Measure of Attention-Deficit Hyperactivity Disorder in Pre-Schoolers

Authors: Neha Bhattacharyya, Soumendra Singh, Amrita Banerjee, Ria Ghosh, Oindrila Sinha, Nairit Das, Rajkumar Gayen, Somya Subhra Pal, Sahely Ganguly, Tanmoy Dasgupta, Tanusree Dasgupta, Pulak Mondal, Aniruddha Adhikari, Sharmila Sarkar, Debasish Bhattacharyya, Asim Kumar Mallick, Om Prakash Singh, Samir Kumar Pal

Abstract:

Background: We aim to develop an integrated device comprised of single-probe EEG and CCD-based motion sensors for a more objective measure of Attention-deficit Hyperactivity Disorder (ADHD). While the integrated device (MAHD) relies on the EEG signal (spectral density of beta wave) for the assessment of attention during a given structured task (painting three segments of a circle using three different colors, namely red, green and blue), the CCD sensor depicts movement pattern of the subjects engaged in a continuous performance task (CPT). A statistical analysis of the attention and movement patterns was performed, and the accuracy of the completed tasks was analysed using indigenously developed software. The device with the embedded software, called MAHD, is intended to improve certainty with criterion E (i.e. whether symptoms are better explained by another condition). Methods: We have used the EEG signal from a single-channel dry sensor placed on the frontal lobe of the head of the subjects (3-5 years old pre-schoolers). During the painting of three segments of a circle using three distinct colors (red, green, and blue), absolute power for delta and beta EEG waves from the subjects are found to be correlated with relaxation and attention/cognitive load conditions. While the relaxation condition of the subject hints at hyperactivity, a more direct CCD-based motion sensor is used to track the physical movement of the subject engaged in a continuous performance task (CPT) i.e., separation of the various colored balls from one table to another. We have used our indigenously developed software for the statistical analysis to derive a scale for the objective assessment of ADHD. We have also compared our scale with clinical ADHD evaluation. Results: In a limited clinical trial with preliminary statistical analysis, we have found a significant correlation between the objective assessment of the ADHD subjects with that of the clinician’s conventional evaluation. Conclusion: MAHD, the integrated device, is supposed to be an auxiliary tool to improve the accuracy of ADHD diagnosis by supporting greater criterion E certainty.

Keywords: ADHD, CPT, EEG signal, motion sensor, psychometric test

Procedia PDF Downloads 92
3253 Principal Well-Being at Hong Kong: A Quantitative Investigation

Authors: Junjun Chen, Yingxiu Li

Abstract:

The occupational well-being of school principals has played a vital role in the pursuit of individual and school wellness and success. However, principals’ well-being worldwide is under increasing threat because of the challenging and complex nature of their work and growing demands for school standardisation and accountability. Pressure is particularly acute in the post-pandemicfuture as principals attempt to deal with the impact of the pandemic on top of more regular demands. This is particularly true in Hong Kong, as school principals are increasingly wedged between unparalleled political, social, and academic responsibilities. Recognizing the semantic breadth of well-being, scholars have not determined a single, mutually agreeable definition but agreed that the concept of well-being has multiple dimensions across various disciplines. The multidimensional approach promises more precise assessments of the relationships between well-being and other concepts than the ‘affect-only’ approach or other single domains for capturing the essence of principal well-being. The multiple-dimension well-being concept is adopted in this project to understand principal well-being in this study. This study aimed to understand the situation of principal well-being and its influential drivers with a sample of 670 principals from Hong Kong and Mainland China. An online survey was sent to the participants after the breakout of COVID-19 by the researchers. All participants were well informed about the purposes and procedure of the project and the confidentiality of the data prior to filling in the questionnaire. Confirmatory factor analysis and structural equation modelling performed with Mplus were employed to deal with the dataset. The data analysis procedure involved the following three steps. First, the descriptive statistics (e.g., mean and standard deviation) were calculated. Second, confirmatory factor analysis (CFA) was used to trim principal well-being measurement performed with maximum likelihood estimation. Third, structural equation modelling (SEM) was employed to test the influential factors of principal well-being. The results of this study indicated that the overall of principal well-being were above the average mean score. The highest ranking in this study given by the principals was to their psychological and social well-being (M = 5.21). This was followed by spiritual (M = 5.14; SD = .77), cognitive (M = 5.14; SD = .77), emotional (M = 4.96; SD = .79), and physical well-being (M = 3.15; SD = .73). Participants ranked their physical well-being the lowest. Moreover, professional autonomy, supervisor and collegial support, school physical conditions, professional networking, and social media have showed a significant impact on principal well-being. The findings of this study will potentially enhance not only principal well-being, but also the functioning of an individual principal and a school without sacrificing principal well-being for quality education in the process. This will eventually move one step forward for a new future - a wellness society advocated by OECD. Importantly, well-being is an inside job that begins with choosing to have wellness, whilst supports to become a wellness principal are also imperative.

Keywords: well-being, school principals, quantitative, influential factors

Procedia PDF Downloads 78
3252 Measurement of Magnetic Properties of Grainoriented Electrical Steels at Low and High Fields Using a Novel Single

Authors: Nkwachukwu Chukwuchekwa, Joy Ulumma Chukwuchekwa

Abstract:

Magnetic characteristics of grain-oriented electrical steel (GOES) are usually measured at high flux densities suitable for its typical applications in power transformers. There are limited magnetic data at low flux densities which are relevant for the characterization of GOES for applications in metering instrument transformers and low frequency magnetic shielding in magnetic resonance imaging medical scanners. Magnetic properties such as coercivity, B-H loop, AC relative permeability and specific power loss of conventional grain oriented (CGO) and high permeability grain oriented (HGO) electrical steels were measured and compared at high and low flux densities at power magnetising frequency. 40 strips comprising 20 CGO and 20 HGO, 305 mm x 30 mm x 0.27 mm from a supplier were tested. The HGO and CGO strips had average grain sizes of 9 mm and 4 mm respectively. Each strip was singly magnetised under sinusoidal peak flux density from 8.0 mT to 1.5 T at a magnetising frequency of 50 Hz. The novel single sheet tester comprises a personal computer in which LabVIEW version 8.5 from National Instruments (NI) was installed, a NI 4461 data acquisition (DAQ) card, an impedance matching transformer, to match the 600  minimum load impedance of the DAQ card with the 5 to 20  low impedance of the magnetising circuit, and a 4.7 Ω shunt resistor. A double vertical yoke made of GOES which is 290 mm long and 32 mm wide is used. A 500-turn secondary winding, about 80 mm in length, was wound around a plastic former, 270 mm x 40 mm, housing the sample, while a 100-turn primary winding, covering the entire length of the plastic former was wound over the secondary winding. A standard Epstein strip to be tested is placed between the yokes. The magnetising voltage was generated by the LabVIEW program through a voltage output from the DAQ card. The voltage drop across the shunt resistor and the secondary voltage were acquired by the card for calculation of magnetic field strength and flux density respectively. A feedback control system implemented in LabVIEW was used to control the flux density and to make the induced secondary voltage waveforms sinusoidal to have repeatable and comparable measurements. The low noise NI4461 card with 24 bit resolution and a sampling rate of 204.8 KHz and 92 KHz bandwidth were chosen to take the measurements to minimize the influence of thermal noise. In order to reduce environmental noise, the yokes, sample and search coil carrier were placed in a noise shielding chamber. HGO was found to have better magnetic properties at both high and low magnetisation regimes. This is because of the higher grain size of HGO and higher grain-grain misorientation of CGO. HGO is better CGO in both low and high magnetic field applications.

Keywords: flux density, electrical steel, LabVIEW, magnetization

Procedia PDF Downloads 288
3251 Dual-Layer Microporous Layer of Gas Diffusion Layer for Proton Exchange Membrane Fuel Cells under Various RH Conditions

Authors: Grigoria Athanasaki, Veerarajan Vimala, A. M. Kannan, Louis Cindrella

Abstract:

Energy usage has been increased throughout the years, leading to severe environmental impacts. Since the majority of the energy is currently produced from fossil fuels, there is a global need for clean energy solutions. Proton Exchange Membrane Fuel Cells (PEMFCs) offer a very promising solution for transportation applications because of their solid configuration and low temperature operations, which allows them to start quickly. One of the main components of PEMFCs is the Gas Diffusion Layer (GDL), which manages water and gas transport and shows direct influence on the fuel cell performance. In this work, a novel dual-layer GDL with gradient porosity was prepared, using polyethylene glycol (PEG) as pore former, to improve the gas diffusion and water management in the system. The microporous layer (MPL) of the fabricated GDL consists of carbon powder PUREBLACK, sodium dodecyl sulfate as a surfactant, 34% wt. PTFE and the gradient porosity was created by applying one layer using 30% wt. PEG on the carbon substrate, followed by a second layer without using any pore former. The total carbon loading of the microporous layer is ~ 3 mg.cm-2. For the assembly of the catalyst layer, Nafion membrane (Ion Power, Nafion Membrane NR211) and Pt/C electrocatalyst (46.1% wt.) were used. The catalyst ink was deposited on the membrane via microspraying technique. The Pt loading is ~ 0.4 mg.cm-2, and the active area is 5 cm2. The sample was ex-situ characterized via wetting angle measurement, Scanning Electron Microscopy (SEM), and Pore Size Distribution (PSD) to evaluate its characteristics. Furthermore, for the performance evaluation in-situ characterization via Fuel Cell Testing using H2/O2 and H2/air as reactants, under 50, 60, 80, and 100% relative humidity (RH), took place. The results were compared to a single layer GDL, fabricated with the same carbon powder and loading as the dual layer GDL, and a commercially available GDL with MPL (AvCarb2120). The findings reveal high hydrophobic properties of the microporous layer of the GDL for both PUREBLACK based samples, while the commercial GDL demonstrates hydrophilic behavior. The dual layer GDL shows high and stable fuel cell performance under all the RH conditions, whereas the single layer manifests a drop in performance at high RH in both oxygen and air, caused by catalyst flooding. The commercial GDL shows very low and unstable performance, possibly because of its hydrophilic character and thinner microporous layer. In conclusion, the dual layer GDL with PEG appears to have improved gas diffusion and water management in the fuel cell system. Due to its increasing porosity from the catalyst layer to the carbon substrate, it allows easier access of the reactant gases from the flow channels to the catalyst layer, and more efficient water removal from the catalyst layer, leading to higher performance and stability.

Keywords: gas diffusion layer, microporous layer, proton exchange membrane fuel cells, relative humidity

Procedia PDF Downloads 117
3250 Performance of Hybrid Image Fusion: Implementation of Dual-Tree Complex Wavelet Transform Technique

Authors: Manoj Gupta, Nirmendra Singh Bhadauria

Abstract:

Most of the applications in image processing require high spatial and high spectral resolution in a single image. For example satellite image system, the traffic monitoring system, and long range sensor fusion system all use image processing. However, most of the available equipment is not capable of providing this type of data. The sensor in the surveillance system can only cover the view of a small area for a particular focus, yet the demanding application of this system requires a view with a high coverage of the field. Image fusion provides the possibility of combining different sources of information. In this paper, we have decomposed the image using DTCWT and then fused using average and hybrid of (maxima and average) pixel level techniques and then compared quality of both the images using PSNR.

Keywords: image fusion, DWT, DT-CWT, PSNR, average image fusion, hybrid image fusion

Procedia PDF Downloads 596
3249 Raman Spectroscopy Analysis of MnTiO₃-TiO₂ Eutectic

Authors: Adrian Niewiadomski, Barbara Surma, Katarzyna Kolodziejak, Dorota A. Pawlak

Abstract:

Oxide-oxide eutectic is attracting increasing interest of scientific community because of their unique properties and numerous potential applications. Some of the most interesting examples of applications are metamaterials, glucose sensors, photoactive materials, thermoelectric materials, and photocatalysts. Their unique properties result from the fact that composite materials consist of two or more phases. As a result, these materials have additive and product properties. Additive properties originate from particular phases while product properties originate from the interaction between phases. MnTiO3-TiO2 eutectic is one of such materials. TiO2 is a well-known semiconductor, and it is used as a photocatalyst. Moreover, it may be used to produce solar cells, in a gas sensing devices and in electrochemistry. MnTiO3 is a semiconductor and antiferromagnetic. Therefore it has potential application in integrated circuits devices, and as a gas and humidity sensor, in non-linear optics and as a visible-light activated photocatalyst. The above facts indicate that eutectic MnTiO3-TiO2 constitutes an extremely promising material that should be studied. Despite that Raman spectroscopy is a powerful method to characterize materials, to our knowledge Raman studies of eutectics are very limited, and there are no studies of the MnTiO3-TiO2 eutectic. While to our knowledge the papers regarding this material are scarce. The MnTiO3-TiO2 eutectic, as well as TiO2 and MnTiO3 single crystals, were grown by the micro-pulling-down method at the Institute of Electronic Materials Technology in Warsaw, Poland. A nitrogen atmosphere was maintained during whole crystal growth process. The as-grown samples of MnTiO3-TiO2 eutectic, as well as TiO2 and MnTiO3 single crystals, are black and opaque. Samples were cut perpendicular to the growth direction. Cross sections were examined with scanning electron microscopy (SEM) and with Raman spectroscopy. The present studies showed that maintaining nitrogen atmosphere during crystal growth process may result in obtaining black TiO2 crystals. SEM and Raman experiments showed that studied eutectic consists of three distinct regions. Furthermore, two of these regions correspond with MnTiO3, while the third region corresponds with the TiO2-xNx phase. Raman studies pointed out that TiO2-xNx phase crystallizes in rutile structure. The studies show that Raman experiments may be successfully used to characterize eutectic materials. The MnTiO3-TiO2 eutectic was grown by the micro-pulling-down method. SEM and micro-Raman experiments were used to establish phase composition of studied eutectic. The studies revealed that the TiO2 phase had been doped with nitrogen. Therefore the TiO2 phase is, in fact, a solid solution with TiO2-xNx composition. The remaining two phases exhibit Raman lines of both rutile TiO2 and MnTiO3. This points out to some kind of coexistence of these phases in studied eutectic.

Keywords: compound materials, eutectic growth and characterization, Raman spectroscopy, rutile TiO₂

Procedia PDF Downloads 189
3248 A Study of the Prevalence of Trichinellosis in Domestic and Wild Animals for the Region of Sofia, Bulgaria

Authors: Valeria Dilcheva, Svetlozara Petkova, Ivelin Vladov

Abstract:

Nemathodes of the genus Trichinella are zoonotic parasites with a cosmopolitan distribution. More than 100 species of mammals, birds and reptiles are involved in the natural cycle of this nematode. At present, T. spiralis, T. pseudospiralis, and T. britovi have been found in Bulgaria. The existence of natural wildlife and domestic reservoirs of Trichinella spp. can be a serious threat to human health. Three trichinella isolates caused human trichinella infection outbreaks from three regions of Sofia City Province were used for the research: sample No. 1 - Ratus norvegicus, sample No. 2 – domestic pig (Sus scrofa domestica), sample No. 3 - domestic pig (Sus scrofa domestica). Trichinella larvae of the studied species were isolated via digestive method (pepsin, hydrochloric acid, water) at 37ºC by standard procedure and were determined by gender (male and female) based on their morphological characteristics. As a reference trichinella species were used: T. spiralis, T. pseudospiralis, T. nativa and T. britovi. Single male and female larvae of the three isolates were crossed with single male and female larvae of the reference trichinella species as well as reciprocally. As a result of cross-breeding, offspring of muscular larvae with T. spiralis and T. britovi were obtained, while in experiments with T. pseudospiralis and T. nativa, trichinella larvae were not found in the laboratory mice. The results obtained in the control groups indicate that the trichinella larvae used from the isolates and the four trichinella species are infective. Also, the infective ability of the F1 offspring from the successful cross-breeding between isolates and reference species was investigated. Through the data obtained in the experiment was found that isolates No. 1 and No. 2 belong to the species T. spiralis, and isolate No. 3 belongs to the species T. britovi. The results were confirmed by PCR and real-time PCR analysis. Thus the presence and circulation of the species T. spiralis and T. britovi in Bulgaria was confirmed. Probably the rodents (rats) are involved in the distribution of T. spiralis in urban environment. The species T. britovi found in a domestic pig speaks of some contact with wild animals for which T. britovi is characteristic. The probable reason is that a large number of farmers in Bulgaria practice the free-range breeding of domestic pigs. Part of the farmers also used as food for domestic pigs waste products from the game (foxes, jackals, bears, wolves) and probably thus the infection was obtained. The distribution range of trichinella species in Bulgaria is not strictly outlined. It is believed that T. spiralis is most common in domestic animals and T. britovi and T. pseudospiralis are characteristic of wildlife. To answer the question whether wild and synanthropic animals are infected with the same or different trichinella species, which species predominate in nature and what their distribution among different hosts is, further research is required.

Keywords: cross-breeding, Sofia, trichinellosis, Trichinella britovi, Trichinella spiralis

Procedia PDF Downloads 180
3247 Thermosalient Effect of an Organic Aminonitrile and its Derivatives

Authors: Lukman O. Alimi, Vincent J. Smith, Leonard J. Barbour

Abstract:

The thermosalient effect is an extremely rare propensity of certain crystalline solids for self-actuation by elastic deformation or a ballistic event1. Thermosalient compounds, colloquially known as ‘jumping crystals’ are promising materials for fabrication of actuators that are also being considered as materials for clean energy conversion because of their capabilities to convert thermal energy into mechanical motion directly. Herein, an organic aminonitrile and its derivatives have been probed by a combination of structural, microscopic and thermoanalytical techniques. Crystals of these compounds were analysed by means of single crystal XRD and hotstage microscopy in the temperature range of 100 to 298 K and found to exhibit the thermosalient effect. We also carried out differential scanning calorimetric analysis at the temperature corresponding to that at which the crystal jumps as observed under a hotstage microscope.

Keywords: aminonitrile, jumping crystal, self actuation, thermosalient effect

Procedia PDF Downloads 428
3246 Molecular Dynamics Analysis onI mpact Behaviour of Carbon Nanotubes and Graphene Sheets

Authors: Sajjad Seifoori

Abstract:

Impact behavior of striker on graphene sheet and carbon nanotube is investigated based on molecular dynamics (MD) simulations. A MD simulation is conducted to obtain the maximum dynamic deflections of a square and rectangular single-layered graphene sheets (SLGSs) with various values of side-length and striker parameter. Effect of (i) chirality, (ii) graphene side-length and nanotube length, (iii) striker mass on the maximum dynamic deflections of graphene and nanotube are investigated. The effect of different types of boundary condition on the maximum dynamic deflections is studied for zigzag and armchair SWCNTs with various aspect ratios (Length/Diameter).

Keywords: impact, molecular dynamic, graphene, spring mass

Procedia PDF Downloads 323
3245 Pulmonary Valve Papillary Fibroelastoma: A Case Report of a Fibroelastoma Presenting as a Pulmonary Embolism

Authors: Frazer Kirk, Matthew Yong, Peter Williams, Andrie Strobel

Abstract:

Pulmonary valve papillary fibroelastoma is an exceedingly rare pathology. The experience and literature regarding them are largely anecdotal and based on sporadic, single case reports. Throughout their known history, two features remain salient that they are classically asymptomatic and found incidentally. The demographic profile of those affected is unclear, as reports regarding those affected are mixed, and there is no clear gender or age predominance, although there is some suggestion of a predisposition to affect females. Nor has there been a well-structured epidemiological study of the entity. Interestingly they are becoming more common on peri-mortum examination. Here-after we describe our experience with a symptomatic presentation of pulmonary papillary fibroelastoma masquerading as a pulmonary embolism and its subsequent assessment and management, with intraoperative photography and echocardiography for reference.

Keywords: cardiac tumor, pulmonary valve, fibroelastoma, cardiac surgery

Procedia PDF Downloads 209
3244 Social Ties and the Prevalence of Single Chronic Morbidity and Multimorbidity among the Elderly Population in Selected States of India

Authors: Sree Sanyal

Abstract:

Research in ageing often highlights the age-related health dimension more than the psycho-social characteristics of the elderly, which also influences and challenges the health outcomes. Multimorbidity is defined as the person having more than one chronic non-communicable diseases and their prevalence increases with ageing. The study aims to evaluate the influence of social ties on self-reported prevalence of multimorbidity (selected chronic non-communicable diseases) among the selected states of elderly population in India. The data is accessed from Building Knowledge Base on Population Ageing in India (BKPAI), collected in 2011 covering the self-reported chronic non-communicable diseases like arthritis, heart disease, diabetes, lung disease with asthma, hypertension, cataract, depression, dementia, Alzheimer’s disease, and cancer. The data of the above diseases were taken together and categorized as: ‘no disease’, ‘one disease’ and ‘multimorbidity’. The predicted variables were demographic, socio-economic, residential types, and the variable of social ties includes social support, social engagement, perceived support, connectedness, and importance of the elderly. Predicted probability for multiple logistic regression was used to determine the background characteristics of the old in association with chronic morbidities showing multimorbidity. The finding suggests that 24.35% of the elderly are suffering from multimorbidity. Research shows that with reference to ‘no disease’, according to the socio-economic characteristics of the old, the female oldest old (80+) from others in caste and religion, widowed, never had any formal education, ever worked in their life, coming from the second wealth quintile standard, from rural Maharashtra are more prone with ‘one disease’. From the social ties background, the elderly who perceives they are important to the family, after getting older their decision-making status has been changed, prefer to stay with son and spouse only, satisfied with the communication from their children are more likely to have less single morbidity and the results are significant. Again, with respect to ‘no disease’, the female oldest old (80+), who are others in caste, Christian in religion, widowed, having less than 5 years of education completed, ever worked, from highest wealth quintile, residing in urban Kerala are more associated with multimorbidity. The elderly population who are more socially connected through family visits, public gatherings, gets support in decision making, who prefers to spend their later years with son and spouse only but stays alone shows lesser prevalence of multimorbidity. In conclusion, received and perceived social integration and support from associated neighborhood in the older days, knowing about their own needs in life facilitates better health and wellbeing of the elderly population in selected states of India.

Keywords: morbidity, multi-morbidity, prevalence, social ties

Procedia PDF Downloads 113
3243 Author Name Disambiguation for Biomedical Literature

Authors: Parthiban Srinivasan

Abstract:

PubMed provides online access to the National Library of Medicine database (MEDLINE) and other publications, which contain close to 25 million scientific citations from 1865 to the present. There are close to 80 million author name instances in those close to 25 million citations. For any work of literature, a fundamental issue is to identify the individual(s) who wrote it, and conversely, to identify all of the works that belong to a given individual. Due to the lack of universal standards for name information, there are two aspects of name ambiguity: name synonymy (a single author with multiple name representations), and name homonymy (multiple authors sharing the same name representation). In this talk, we present some results from our extensive work in author name disambiguation for PubMed citations. Information will be presented on the effectiveness and shortcomings of different aspects of successful name disambiguation such as parsing, validation, standardization and normalization.

Keywords: disambiguation, normalization, parsing, PubMed

Procedia PDF Downloads 290
3242 Challenges to Change and Innovation in Educational System

Authors: Felicia Kikelomo Oluwalola

Abstract:

The study was designed to identify the challenges to change and innovation in educational system in Nigeria. Educational institutions, like all other organizations, require constant monitoring, to identify areas for potential improvement. However, educational reforms are often not well-implemented. This results in massive wastage of finances, human resources, and lost potential. Educational institutions are organised on many levels, from the individual classroom under the management of a single teacher, to groups of classrooms supervised by a Head Teacher or Executive Teacher, to a whole-school structure, under the guidance of the principal. Therefore, there is need for changes and innovation in our educational system since we are in the era of computer age. In doing so, this paper examined the psychology of change, concept of change and innovation with suggested view points. Educational administrators and individuals should be ready to have the challenge of monitoring changes in technologies. Educational planners/policy makers should be encouraged to involve in change process.

Keywords: challenges, change, education, innovation

Procedia PDF Downloads 604
3241 Numerical Modeling the Cavitating Flow in Injection Nozzle Holes

Authors: Ridha Zgolli, Hatem Kanfoudi

Abstract:

Cavitating flows inside a diesel injection nozzle hole were simulated using a mixture model. A 2D numerical model is proposed in this paper to simulate steady cavitating flows. The Reynolds-averaged Navier-Stokes equations are solved for the liquid and vapor mixture, which is considered as a single fluid with variable density which is expressed as function of the vapor volume fraction. The closure of this variable is provided by the transport equation with a source term TEM. The processes of evaporation and condensation are governed by changes in pressure within the flow. The source term is implanted in the CFD code ANSYS CFX. The influence of numerical and physical parameters is presented in details. The numerical simulations are in good agreement with the experimental data for steady flow.

Keywords: cavitation, injection nozzle, numerical simulation, k–ω

Procedia PDF Downloads 391
3240 Evaluation of Cooperative Hand Movement Capacity in Stroke Patients Using the Cooperative Activity Stroke Assessment

Authors: F. A. Thomas, M. Schrafl-Altermatt, R. Treier, S. Kaufmann

Abstract:

Stroke is the main cause of adult disability. Especially upper limb function is affected in most patients. Recently, cooperative hand movements have been shown to be a promising type of upper limb training in stroke rehabilitation. In these movements, which are frequently found in activities of daily living (e.g. opening a bottle, winding up a blind), the force of one upper limb has to be equally counteracted by the other limb to successfully accomplish a task. The use of standardized and reliable clinical assessments is essential to evaluate the efficacy of therapy and the functional outcome of a patient. Many assessments for upper limb function or impairment are available. However, the evaluation of cooperative hand movement tasks are rarely included in those. Thus, the aim of this study was (i) to develop a novel clinical assessment (CASA - Cooperative Activity Stroke Assessment) for the evaluation of patients’ capacity to perform cooperative hand movements and (ii) to test its inter- and interrater reliability. Furthermore, CASA scores were compared to current gold standard assessments for upper extremity in stroke patients (i.e. Fugl-Meyer Assessment, Box & Blocks Test). The CASA consists of five cooperative activities of daily living including (1) opening a jar, (2) opening a bottle, (3) open and closing of a zip, (4) unscrew a nut and (5) opening a clipbox. Here, the goal is to accomplish the tasks as fast as possible. In addition to the quantitative rating (i.e. time) which is converted to a 7-point scale, also the quality of the movement is rated in a 4-point scale. To test the reliability of CASA, fifteen stroke subjects were tested within a week twice by the same two raters. Intra-and interrater reliability was calculated using the intraclass correlation coefficient (ICC) for total CASA score and single items. Furthermore, Pearson-correlation was used to compare the CASA scores to the scores of Fugl-Meyer upper limb assessment and the box and blocks test, which were assessed in every patient additionally to the CASA. ICC scores of the total CASA score indicated an excellent- and single items established a good to excellent inter- and interrater reliability. Furthermore, the CASA score was significantly correlated to the Fugl-Meyer and Box & Blocks score. The CASA provides a reliable assessment for cooperative hand movements which are crucial for many activities of daily living. Due to its non-costly setup, easy and fast implementation, we suggest it to be well suitable for clinical application. In conclusion, the CASA is a useful tool in assessing the functional status and therapy related recovery in cooperative hand movement capacity in stroke patients.

Keywords: activitites of daily living, clinical assessment, cooperative hand movements, reliability, stroke

Procedia PDF Downloads 316
3239 Experimental and Computational Fluid Dynamic Modeling of a Progressing Cavity Pump Handling Newtonian Fluids

Authors: Deisy Becerra, Edwar Perez, Nicolas Rios, Miguel Asuaje

Abstract:

Progressing Cavity Pump (PCP) is a type of positive displacement pump that is being awarded greater importance as capable artificial lift equipment in the heavy oil field. The most commonly PCP used is driven single lobe pump that consists of a single external helical rotor turning eccentrically inside a double internal helical stator. This type of pump was analyzed by the experimental and Computational Fluid Dynamic (CFD) approach from the DCAB031 model located in a closed-loop arrangement. Experimental measurements were taken to determine the pressure rise and flow rate with a flow control valve installed at the outlet of the pump. The flowrate handled was measured by a FLOMEC-OM025 oval gear flowmeter. For each flowrate considered, the pump’s rotational speed and power input were controlled using an Invertek Optidrive E3 frequency driver. Once a steady-state operation was attained, pressure rise measurements were taken with a Sper Scientific wide range digital pressure meter. In this study, water and three Newtonian oils of different viscosities were tested at different rotational speeds. The CFD model implementation was developed on Star- CCM+ using an Overset Mesh that includes the relative motion between rotor and stator, which is one of the main contributions of the present work. The simulations are capable of providing detailed information about the pressure and velocity fields inside the device in laminar and unsteady regimens. The simulations have a good agreement with the experimental data due to Mean Squared Error (MSE) in under 21%, and the Grid Convergence Index (GCI) was calculated for the validation of the mesh, obtaining a value of 2.5%. In this case, three different rotational speeds were evaluated (200, 300, 400 rpm), and it is possible to show a directly proportional relationship between the rotational speed of the rotor and the flow rate calculated. The maximum production rates for the different speeds for water were 3.8 GPM, 4.3 GPM, and 6.1 GPM; also, for the oil tested were 1.8 GPM, 2.5 GPM, 3.8 GPM, respectively. Likewise, an inversely proportional relationship between the viscosity of the fluid and pump performance was observed, since the viscous oils showed the lowest pressure increase and the lowest volumetric flow pumped, with a degradation around of 30% of the pressure rise, between performance curves. Finally, the Productivity Index (PI) remained approximately constant for the different speeds evaluated; however, between fluids exist a diminution due to the viscosity.

Keywords: computational fluid dynamic, CFD, Newtonian fluids, overset mesh, PCP pressure rise

Procedia PDF Downloads 121
3238 Comparison of Methodologies to Compute the Probabilistic Seismic Hazard Involving Faults and Associated Uncertainties

Authors: Aude Gounelle, Gloria Senfaute, Ludivine Saint-Mard, Thomas Chartier

Abstract:

The long-term deformation rates of faults are not fully captured by Probabilistic Seismic Hazard Assessment (PSHA). PSHA that use catalogues to develop area or smoothed-seismicity sources is limited by the data available to constraint future earthquakes activity rates. The integration of faults in PSHA can at least partially address the long-term deformation. However, careful treatment of fault sources is required, particularly, in low strain rate regions, where estimated seismic hazard levels are highly sensitive to assumptions concerning fault geometry, segmentation and slip rate. When integrating faults in PSHA various constraints on earthquake rates from geologic and seismologic data have to be satisfied. For low strain rate regions where such data is scarce it would be especially challenging. Faults in PSHA requires conversion of the geologic and seismologic data into fault geometries, slip rates and then into earthquake activity rates. Several approaches exist for translating slip rates into earthquake activity rates. In the most frequently used approach, the background earthquakes are handled using a truncated approach, in which earthquakes with a magnitude lower or equal to a threshold magnitude (Mw) occur in the background zone, with a rate defined by the rate in the earthquake catalogue. Although magnitudes higher than the threshold are located on the fault with a rate defined using the average slip rate of the fault. As high-lighted by several research, seismic events with magnitudes stronger than the selected magnitude threshold may potentially occur in the background and not only at the fault, especially in regions of slow tectonic deformation. It also has been known that several sections of a fault or several faults could rupture during a single fault-to-fault rupture. It is then essential to apply a consistent modelling procedure to allow for a large set of possible fault-to-fault ruptures to occur aleatory in the hazard model while reflecting the individual slip rate of each section of the fault. In 2019, a tool named SHERIFS (Seismic Hazard and Earthquake Rates in Fault Systems) was published. The tool is using a methodology to calculate the earthquake rates in a fault system where the slip-rate budget of each fault is conversed into rupture rates for all possible single faults and faultto-fault ruptures. The objective of this paper is to compare the SHERIFS method with one other frequently used model to analyse the impact on the seismic hazard and through sensibility studies better understand the influence of key parameters and assumptions. For this application, a simplified but realistic case study was selected, which is in an area of moderate to hight seismicity (South Est of France) and where the fault is supposed to have a low strain.

Keywords: deformation rates, faults, probabilistic seismic hazard, PSHA

Procedia PDF Downloads 54
3237 A New Approach to the Digital Implementation of Analog Controllers for a Power System Control

Authors: G. Shabib, Esam H. Abd-Elhameed, G. Magdy

Abstract:

In this paper, a comparison of discrete time PID, PSS controllers is presented through small signal stability of power system comprising of one machine connected to infinite bus system. This comparison achieved by using a new approach of discretization which converts the S-domain model of analog controllers to a Z-domain model to enhance the damping of a single machine power system. The new method utilizes the Plant Input Mapping (PIM) algorithm. The proposed algorithm is stable for any sampling rate, as well as it takes the closed loop characteristic into consideration. On the other hand, the traditional discretization methods such as Tustin’s method is produce satisfactory results only; when the sampling period is sufficiently low.

Keywords: PSS, power system stabilizer PID, proportional-integral-derivative PIM, plant input mapping

Procedia PDF Downloads 500
3236 A Numerical Simulation of Arterial Mass Transport in Presence of Magnetic Field-Links to Atherosclerosis

Authors: H. Aminfar, M. Mohammadpourfard, K. Khajeh

Abstract:

This paper has focused on the most important parameters in the LSC uptake; inlet Re number and Sc number in the presence of non-uniform magnetic field. The magnetic field is arising from the thin wire with electric current placed vertically to the arterial blood vessel. According to the results of this study, applying magnetic field can be a treatment for atherosclerosis by reducing LSC along the vessel wall. Homogeneous porous layer as a arterial wall has been regarded. Blood flow has been considered laminar and incompressible containing Ferro fluid (blood and 4 % vol. Fe₃O₄) under steady state conditions. Numerical solution of governing equations was obtained by using the single-phase model and control volume technique for flow field.

Keywords: LDL surface concentration (LSC), magnetic field, computational fluid dynamics, porous wall

Procedia PDF Downloads 400
3235 Effect of Synthesis Method on Structural, Morphological Properties of Zr0.8Y0.2-xLax Oxides (x=0, 0.1, 0.2)

Authors: Abdelaziz Ghrib, Samir Hattali, Mouloud Ghrib, Mohamed Lamine Aouissia, David Ruch

Abstract:

In the present study, the solid solutions with a chemical composition of Zr0.8Y0.2-xLaxO2 (x=0, 0.1, 0.2) were synthesized via two routes, by hydrothermal method using NaOH as precipitating agent at 230°C for 15h and by the sol–gel process using citric acid as complexing agent. Compounds have been characterized by powder X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Thermo gravimetric Analysis (TGA) and Differential Thermal Analysis (DTA) techniques for appropriate characterization of the distinct thermal events occurring during synthesis. All the compounds crystallize in cubic fluorite structure, as indicated by X-ray diffraction studie. The microstructure of oxides synthesized by sol-gel showed porosity that increased with the lanthanum La3+ contents compared to hydrothermal method which gives a single crystal oxide.

Keywords: oxide, hydrothermal, rare earth, solubility, sol-gel, ternary mixture

Procedia PDF Downloads 626
3234 Membrane Spanning DNA Origami Nanopores for Protein Translocation

Authors: Genevieve Pugh, Johnathan Burns, Stefan Howorka

Abstract:

Single-molecule sensing via protein nanopores has achieved a step-change in portable and label-free DNA sequencing. However, protein pores of both natural or engineered origin are not able to produce the tunable diameters needed for effective protein sensing. Here, we describe a generic strategy to build synthetic DNA nanopores that are wide enough to accommodate folded protein. The pores are composed of interlinked DNA duplexes and carry lipid anchors to achieve the required membrane insertion. Our demonstrator pore has a contiguous cross-sectional channel area of 50 nm2 which is 6-times larger than the largest protein pore. Consequently, transport of folded protein across bilayers is possible. The modular design is amenable for different pore dimensions and can be adapted for protein sensing or to create molecular gates in synthetic biology.

Keywords: biosensing, DNA nanotechnology, DNA origami, nanopore sensing

Procedia PDF Downloads 318
3233 Electro-Winning of Dilute Solution of Copper Metal from Sepon Mine, Lao PDR

Authors: S. Vasailor, C. Rattanakawin

Abstract:

Electro-winning of copper metal from dilute sulfate solution (13.7 g/L) was performed in a lab electrolytic cell with stainless-steel cathode and lead-alloy anode. The effects of various parameters including cell voltage, electro-winning temperature and time were studied in order to acquire an appropriate current efficiency of copper deposition. The highest efficiency is about 95% obtaining from electro-winning condition of 3V, 55°C and 3,600 s correspondingly. The cathode copper with 95.5% Cu analyzed using atomic absorption spectrometry can be obtained from this single-winning condition. In order to increase the copper grade, solvent extraction should be used to increase the sulfate concentration, say 50 g/L, prior to winning the cathode copper effectively.

Keywords: copper metal, current efficiency, dilute sulfate solution, electro-winning

Procedia PDF Downloads 132
3232 Differential Expression Analysis of Busseola fusca Larval Transcriptome in Response to Cry1Ab Toxin Challenge

Authors: Bianca Peterson, Tomasz J. Sańko, Carlos C. Bezuidenhout, Johnnie Van Den Berg

Abstract:

Busseola fusca (Fuller) (Lepidoptera: Noctuidae), the maize stem borer, is a major pest in sub-Saharan Africa. It causes economic damage to maize and sorghum crops and has evolved non-recessive resistance to genetically modified (GM) maize expressing the Cry1Ab insecticidal toxin. Since B. fusca is a non-model organism, very little genomic information is publicly available, and is limited to some cytochrome c oxidase I, cytochrome b, and microsatellite data. The biology of B. fusca is well-described, but still poorly understood. This, in combination with its larval-specific behavior, may pose problems for limiting the spread of current resistant B. fusca populations or preventing resistance evolution in other susceptible populations. As part of on-going research into resistance evolution, B. fusca larvae were collected from Bt and non-Bt maize in South Africa, followed by RNA isolation (15 specimens) and sequencing on the Illumina HiSeq 2500 platform. Quality of reads was assessed with FastQC, after which Trimmomatic was used to trim adapters and remove low quality, short reads. Trinity was used for the de novo assembly, whereas TransRate was used for assembly quality assessment. Transcript identification employed BLAST (BLASTn, BLASTp, and tBLASTx comparisons), for which two libraries (nucleotide and protein) were created from 3.27 million lepidopteran sequences. Several transcripts that have previously been implicated in Cry toxin resistance was identified for B. fusca. These included aminopeptidase N, cadherin, alkaline phosphatase, ATP-binding cassette transporter proteins, and mitogen-activated protein kinase. MEGA7 was used to align these transcripts to reference sequences from Lepidoptera to detect mutations that might potentially be contributing to Cry toxin resistance in this pest. RSEM and Bioconductor were used to perform differential gene expression analysis on groups of B. fusca larvae challenged and unchallenged with the Cry1Ab toxin. Pairwise expression comparisons of transcripts that were at least 16-fold expressed at a false-discovery corrected statistical significance (p) ≤ 0.001 were extracted and visualized in a hierarchically clustered heatmap using R. A total of 329,194 transcripts with an N50 of 1,019 bp were generated from the over 167.5 million high-quality paired-end reads. Furthermore, 110 transcripts were over 10 kbp long, of which the largest one was 29,395 bp. BLAST comparisons resulted in identification of 157,099 (47.72%) transcripts, among which only 3,718 (2.37%) were identified as Cry toxin receptors from lepidopteran insects. According to transcript expression profiles, transcripts were grouped into three subclusters according to the similarity of their expression patterns. Several immune-related transcripts (pathogen recognition receptors, antimicrobial peptides, and inhibitors) were up-regulated in the larvae feeding on Bt maize, indicating an enhanced immune status in response to toxin exposure. Above all, extremely up-regulated arylphorin genes suggest that enhanced epithelial healing is one of the resistance mechanisms employed by B. fusca larvae against the Cry1Ab toxin. This study is the first to provide a resource base and some insights into a potential mechanism of Cry1Ab toxin resistance in B. fusca. Transcriptomic data generated in this study allows identification of genes that can be targeted by biotechnological improvements of GM crops.

Keywords: epithelial healing, Lepidoptera, resistance, transcriptome

Procedia PDF Downloads 197
3231 A Pull-Out Fiber/Matrix Interface Characterization of Vegetal Fibers Reinforced Thermoplastic Polymer Composites, the Influence of the Processing Temperature

Authors: Duy Cuong Nguyen, Ali Makke, Guillaume Montay

Abstract:

This work presents an improved single fiber pull-out test for fiber/matrix interface characterization. This test has been used to study the Inter-Facial Shear Strength ‘IFSS’ of hemp fibers reinforced polypropylene (PP). For this aim, the fiber diameter has been carefully measured using a tomography inspired method. The fiber section contour can then be approximated by a circle or a polygon. The results show that the IFSS is overestimated if the circular approximation is used. The Influence of the molding temperature on the IFSS has also been studied. We find a molding temperature of 183°C leads to better interface properties. Above or below this temperature the interface strength is reduced.

Keywords: composite, hemp, interface, pull-out, processing, polypropylene, temperature

Procedia PDF Downloads 385
3230 Glass-Ceramics for Emission in the IR Region

Authors: V. Nikolov, I. Koseva, R. Sole, F. Diaz

Abstract:

Cr4+ doped oxide compounds are particularly preferred active media for solid-state lasers with a wide emission region from 1.1 to 1.6 µm. However, obtaining of single crystals of these compounds is often problematic. An alternative solution of this problem is replacing the single crystals with a transparent glassceramics containing the desired crystalline phase. Germanate compounds, especially Li2MgGeO4, Li2ZnGeO4 and Li2CaGeO4, are suitable for Cr4+ doped glass-ceramics because of their relatively low melting temperature and tetrahedral coordination of all ions. The latter ensures the presence of chromium in the 4+ valence. Cr doped Li2CaGeO4 g lass-ceramic was synthesized by thermal treating using glasses from the Li2O-CaO-GeO2-B2O3 system. Special investigations were carried out for optimizing the initial glasscomposition, as well as the thermal treated conditions. The synthesis of the glass ceramics was accompanied by appropriate characterization methods such as: XRD, TEM, EPR, UVVIS-NIR, emission spectra and time decay as main characteristic for the laser emission. From the systematic studies carried out in the four-component system Li2O-CaO-GeO2-B2O3 for establishing the Li2CaGeO4 crystallization area and suitable thermal treatment conditions, several main conclusions can be drawn: 1. The crystallization region of Li2CaGeO4 is relatively narrow, localized around the stoichiometric composition of the Li2CaGeO4 compound. 2. The presence of the glass former B2O3 strongly supports the obtaining of homogeneous glasses at relatively low temperatures, but it is also the reason for the crystallization of borate phases. 3. The crystallization of glasses during thermal treatment is related to the production of more than one phase and it is correct to speak for crystallization of a main phase and accompanying crystallization of other phases. The crystallization of a given phase is related to changing the composition of the residual glass and creating conditions for the crystallization of other phases. 4. The separate studies show that glass-ceramics with different crystallized phases in different quantitative ratios can be obtained from the same composition of glass playing by the thermal treatment conditions. In other words, the choice of temperature and time of thermal treatment of the glass is an extremely important condition, along with the optimization of the starting glass composition. As a result of the conducted research, an optimal composition of the starting glass and an optimal mode of thermal treatment were selected. Glass-ceramic with a main phase Li2CaGeO4 doped by Cr4+ was obtained. The obtained glass-ceramic possess very good properties containing up to 60 mass% of Li2CaGeO4, with an average size of nanoparticles of 20 nm and with transparency about 70 % relative to the transparency of the parent glass. The emission of the obtained glass-ceramics is in a wide range between 1050 and 1500 nm. The obtained results are the basis for further optimization of the glass-ceramic characteristics to obtain an effective laser-active medium with radiation in the 1.1-1.6 nm range.

Keywords: glass, glass-ceramics, multicomponent systems, NIR emission

Procedia PDF Downloads 4
3229 A Secure Survey against Black Hole Attack in MANET

Authors: G. Usha, S. Kannimuthu, K. Mahalakshmi

Abstract:

Mobile Adhoc Network (MANET) is one of the most promising technologies that have applications ranging from various portable devices to military networks. MANET has no fixed infrastructure and the security of such network is a big concern. Therefore, in order to operate MANET’s securely, the misbehavior and intrusions should be detected before the attackers affect the network communication. In this article, we make a comprehensive survey against black hole attack that is a serious threat against MANET that exploits the routing behavior of the MANET. We have given broad survey solutions that detect black hole attacks in MANET. This is achieved by analyzing the techniques involved in detecting the attacks in each scheme. Furthermore, we examine about the challenges to the researchers for constructing an in-depth solution against black hole attack.

Keywords: AODV, cross layer security, mobile Adhoc network (MANET), packet delivery ratio, single layer security

Procedia PDF Downloads 403
3228 Bonding Characteristics Between FRP and Concrete Substrates

Authors: Houssam A. Toutanji, Meng Han

Abstract:

This study focuses on the development of a fracture mechanics based-model that predicts the debonding behavior of FRP strengthened RC beams. In this study, a database includes 351 concrete prisms bonded with FRP plates tested in single and double shear were prepared. The existing fracture-mechanics-based models are applied to this database. Unfortunately the properties of adhesive layer, especially a soft adhesive layer, used on the specimens in the existing studies were not always able to found. Thus, the new model’s proposal was based on fifteen newly conducted pullout tests and twenty four data selected from two independent existing studies with the application of a soft adhesive layers and the availability of adhesive properties.

Keywords: carbon fiber composite materials, interface response, fracture characteristics, maximum shear stress, ultimate transferable load

Procedia PDF Downloads 256
3227 Valorization of Underutilized Fish Species Through a Multidisciplinary Approach

Authors: Tiziana Pepe, Gerardo Manfreda, Adriana Ianieri, Aniello Anastasio

Abstract:

The sustainable exploitation of marine biological resources is among the most important objectives of the EU's Common Fisheries Policy (CFP). Currently, Europe imports about 65% of its fish products, indicating that domestic production does not meet consumer demand. Despite the availability of numerous commercially significant fish species, European consumption is concentrated on a limited number of products (e.g., sea bass, sea bream, shrimp). Many native species, present in large quantities in the Mediterranean Sea, are little known to consumers and are therefore considered ‘fishing by-products’. All the data presented so far indicate a significant waste of local resources and the overexploitation of a few fish stocks. It is therefore necessary to develop strategies that guide the market towards sustainable conversion. The objective of this work was to valorize underutilized fish species of the Mediterranean Sea through a multidisciplinary approach. To this end, three fish species were sampled: Atlantic Horse Mackerel (Trachurus trachurus), Bogue (Boops boops), and Common Dolphinfish (Coryphaena hippurus). Nutritional properties (water %, fats, proteins, ashes, salts), physical/chemical properties (TVB-N, histamine, pH), and rheological properties (color, texture, viscosity) were analyzed. The analyses were conducted on both fillets and processing by-products. Additionally, mitochondrial DNA (mtDNA) was extracted from the muscle of each species. The mtDNA was then sequenced using the Illumina NGS technique. The analysis of nutritional properties classified the fillets of the sampled species as lean or semi-fat, as they had a fat content of less than 3%, while the by-products showed a higher lipid content (2.7-5%). The protein percentage for all fillets was 22-23%, while for processing by-products, the protein concentration was 18-19% for all species. Rheological analyses showed an increase in viscosity in saline solution in all species, indicating their potential suitability for industrial processing. High-quality and quantity complete mtDNA was extracted from all analyzed species. The complete mitochondrial genome sequences were successfully obtained and annotated. The results of this study suggest that all analyzed species are suitable for both human consumption and feed production. The sequencing of the complete mtDNA and its availability in international databases will be useful for accurate phylogenetic analysis and proper species identification, even in prepared and processed products. Underutilized fish species represent an important economic resource. Encouraging their consumption could limit the phenomenon of overfishing, protecting marine biodiversity. Furthermore, the valorization of these species will increase national fish production, supporting the local economy, cultural, and gastronomic tradition, and optimizing the exploitation of Mediterranean resources in accordance with the CFP.

Keywords: mtDNA, nutritional analysis, sustainable fisheries, underutilized fish species

Procedia PDF Downloads 19
3226 Growth and Yield Response of Solanum retroflexum to Different Level of Salinity

Authors: Fhatuwani Herman Nndwambi, P. W. Mashela

Abstract:

Salinity is a major constraint limiting crop productivity. It has been predicted that by the year 2050, more than 50% of the arable land will be affected by salinity. Two similar salinity experiments were conducted in two seasons under greenhouse condition. Six levels of salinity plus control (viz; control, 2, 4, 8, 16, 32 and 64 % NaCl and CaCl2 at 3:1 ratio) were applied in a form of irrigation water in a single factor experiment arranged in a complete block design with 20 replications. Plant growth and yield were negatively affected by salinity treatments especially at the high levels of salinity. For example, our results suggest that the 32 and 64% of NaCl and CaCl2 treatment were too much for the plant to withstand as determined by reduced dry shoot mass, stem diameter and plant height in both seasons. On the other hand, stomatal conductance and chlorophyll content increased with an increased level of salinity.

Keywords: growth, salinity, season, yield

Procedia PDF Downloads 156
3225 Combination Therapies Targeting Apoptosis Pathways in Pediatric Acute Myeloid Leukemia (AML)

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

Abstract:

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

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

Procedia PDF Downloads 197