Search results for: target specificity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3157

Search results for: target specificity

877 Jail Reentry in Rural America: A Quasi-Experimental Examination of a Rural Behavioral Health Reentry Program

Authors: Debra L. Stanley, Gabriela Wasileski

Abstract:

Offenders face many challenges as they transition from being incarcerated to the community, ranging from housing and employment needs to long standing problems with addictions and mental health issues. A lack of appropriate behavioral health services in the more remote parts of the United States has led to a significant illegal substance abuse problem, housing instability, and unaddressed mental health and trauma issues. High rates of poverty and unemployment exacerbate the growing behavioral health issues, drug overdoses, co-occurring disorders, and crime that are so prevalent across rural communities. This study examines the challenges of rural jail reentry faced by offenders in a treatment capacity. The client-centered evidence-based program is uniquely designed to provide continuity of care that focuses on issues which affect rural communities. Prior to release from jail, individuals go through comprehensive assessment screenings to measure mental health and substance use disorder as well as trauma and prior crime victimization histories; the assessments help to target client-specific services. The quasi-experimental research design tracks clients throughout their recovery and reintegration into the community. Individuals in a rural program often do not have the benefit of easy access or peer mentoring that is so often found in urban recovery programs. Therefore, much of the support is provided through telehealth and e-services. The goal of this study is to explore the nature of rural reentry programs and measures of recidivism, drug overdoses, and other behavioral health needs and successful reentry to include stable housing and employment.

Keywords: jail reentry, rehabilitation, behavioral health, drug abuse, recidivism

Procedia PDF Downloads 73
876 Sexual Health in the Over Forty-Fives: A Cross-Europe Project

Authors: Tess Hartland, Moitree Banerjee, Sue Churchill, Antonina Pereira, Ian Tyndall, Ruth Lowry

Abstract:

Background: Sexual health services and policies for middle-aged and older adults are underdeveloped, while global sexually transmitted infections in this age group are on the rise. The Interreg cross-Europe Sexual Health In Over 45s (SHIFT) project aims to increase participation in sexual health services and improve sexual health and wellbeing in people aged over 45, with an additional focus on disadvantaged groups. Methods: A two-pronged mixed-methodology is being used to develop a model for good service provision in sexual health for over 45s. (1) Following PRISMA-ScR guidelines, a scoping review is being conducted, using the databases PsychINFO, Web of Science, ERIC and PubMed. A key search strategy using terms around sexual health, good practice, over 45s and disadvantaged groups. The initial search for literature yielded 7914 results. (2) Surveys (n=1000) based on the Theory of Planned Behaviour are being administered across the UK, Belgium and Netherlands to explore current sexual health knowledge, awareness and attitudes. Expected results: It is expected that sexual health needs and potential gaps in service provision will be identified in order to inform good practice for sexual health services for the target population. Results of the scoping review are being analysed, while focus group and survey data is being gathered. Preliminary analysis of the survey data highlights barriers to access such as limited risk awareness and stigma. All data analysis will be completed by the time of the conference. Discussion: Findings will inform the development of a model to improve sexual health and wellbeing for among over 45s, a population which is often missed in sexual health policy improvement.

Keywords: adult health, disease prevention, health promotion, over 45s, sexual health

Procedia PDF Downloads 113
875 Sensing of Cancer DNA Using Resonance Frequency

Authors: Sungsoo Na, Chanho Park

Abstract:

Lung cancer is one of the most common severe diseases driving to the death of a human. Lung cancer can be divided into two cases of small-cell lung cancer (SCLC) and non-SCLC (NSCLC), and about 80% of lung cancers belong to the case of NSCLC. From several studies, the correlation between epidermal growth factor receptor (EGFR) and NSCLCs has been investigated. Therefore, EGFR inhibitor drugs such as gefitinib and erlotinib have been used as lung cancer treatments. However, the treatments result showed low response (10~20%) in clinical trials due to EGFR mutations that cause the drug resistance. Patients with resistance to EGFR inhibitor drugs usually are positive to KRAS mutation. Therefore, assessment of EGFR and KRAS mutation is essential for target therapies of NSCLC patient. In order to overcome the limitation of conventional therapies, overall EGFR and KRAS mutations have to be monitored. In this work, the only detection of EGFR will be presented. A variety of techniques has been presented for the detection of EGFR mutations. The standard detection method of EGFR mutation in ctDNA relies on real-time polymerase chain reaction (PCR). Real-time PCR method provides high sensitive detection performance. However, as the amplification step increases cost effect and complexity increase as well. Other types of technology such as BEAMing, next generation sequencing (NGS), an electrochemical sensor and silicon nanowire field-effect transistor have been presented. However, those technologies have limitations of low sensitivity, high cost and complexity of data analyzation. In this report, we propose a label-free and high-sensitive detection method of lung cancer using quartz crystal microbalance based platform. The proposed platform is able to sense lung cancer mutant DNA with a limit of detection of 1nM.

Keywords: cancer DNA, resonance frequency, quartz crystal microbalance, lung cancer

Procedia PDF Downloads 213
874 Evaluating the Dosimetric Performance for 3D Treatment Planning System for Wedged and Off-Axis Fields

Authors: Nashaat A. Deiab, Aida Radwan, Mohamed S. Yahiya, Mohamed Elnagdy, Rasha Moustafa

Abstract:

This study is to evaluate the dosimetric performance of our institution's 3D treatment planning system for wedged and off-axis 6MV photon beams, guided by the recommended QA tests documented in the AAPM TG53; NCS report 15 test packages, IAEA TRS 430 and ESTRO booklet no.7. The study was performed for Elekta Precise linear accelerator designed for clinical range of 4, 6 and 15 MV photon beams with asymmetric jaws and fully integrated multileaf collimator that enables high conformance to target with sharp field edges. Ten tests were applied on solid water equivalent phantom along with 2D array dose detection system. The calculated doses using 3D treatment planning system PrecisePLAN were compared with measured doses to make sure that the dose calculations are accurate for simple situations such as square and elongated fields, different SSD, beam modifiers e.g. wedges, blocks, MLC-shaped fields and asymmetric collimator settings. The QA results showed dosimetric accuracy of the TPS within the specified tolerance limits. Except for large elongated wedged field, the central axis and outside central axis have errors of 0.2% and 0.5%, respectively, and off- planned and off-axis elongated fields the region outside the central axis of the beam errors are 0.2% and 1.1%, respectively. The dosimetric investigated results yielded differences within the accepted tolerance level as recommended. Differences between dose values predicted by the TPS and measured values at the same point are the result from limitations of the dose calculation, uncertainties in the measurement procedure, or fluctuations in the output of the accelerator.

Keywords: quality assurance, dose calculation, wedged fields, off-axis fields, 3D treatment planning system, photon beam

Procedia PDF Downloads 419
873 Development the Potential of Parking Tax and Parking Retribution Revenues: Case Study in Bekasi City

Authors: Ivan Yudianto

Abstract:

The research objectives are to analyze the factors that impede the Parking Tax and Parking Retribution collection in Bekasi City Government, analyzing the factors that can increase local own revenue from the tax sector of parking tax and parking retribution, analyze monitoring the parking retribution collection by the Bekasi City Government, analyze strategies Bekasi City Government through the preparation of a roadmap and action plan to increase parking tax and parking retribution revenues. The approach used in this research is a qualitative approach. Qualitative research is used because the problem is not yet clear and the object to be studied will be holistic, complex, and dynamic, and the relationship will be interactive symptoms. Methods of data collection and technical analysis of the data was in-depth interviews, participant observation, documentary materials, literature, and triangulation, as well as new methods such as the methods of visual materials and internet browsing. The results showed that there are several factors that become an obstacle such as the parking taxpayer does not disclose the actual parking revenue, the parking taxpayer are late or do not pay Parking Tax, many parking locations controlled by illegal organizations, shortage of human resources in charge levy and supervise the parking tax and parking retribution collection in the Bekasi City Government, surveillance parking tax and parking retribution are not scheduled on a regular basis. Several strategic priorities in order to develop the potential of the Parking Tax and Parking Retribution in the Bekasi City Government, namely through increased controling and monitoring of the Parking Taxpayer, forming a team of auditors to audit the Parking Taxpayer, seek law enforcement persuasive and educative to reduce Parking Taxpayer wayward, providing strict sanctions against the Parking Taxpayer disobedient, revised regulations mayors about locations of parking in Bekasi City, rationalize revenues target of Parking Retribution, conducting takeover attempts parking location on the roadside of the individual or specific group, and drafting regional regulations on parking subscribe.

Keywords: local own revenue, parking retribution, parking tax, parking taxpayer

Procedia PDF Downloads 307
872 Multivariate Analysis on Water Quality Attributes Using Master-Slave Neural Network Model

Authors: A. Clementking, C. Jothi Venkateswaran

Abstract:

Mathematical and computational functionalities such as descriptive mining, optimization, and predictions are espoused to resolve natural resource planning. The water quality prediction and its attributes influence determinations are adopted optimization techniques. The water properties are tainted while merging water resource one with another. This work aimed to predict influencing water resource distribution connectivity in accordance to water quality and sediment using an innovative proposed master-slave neural network back-propagation model. The experiment results are arrived through collecting water quality attributes, computation of water quality index, design and development of neural network model to determine water quality and sediment, master–slave back propagation neural network back-propagation model to determine variations on water quality and sediment attributes between the water resources and the recommendation for connectivity. The homogeneous and parallel biochemical reactions are influences water quality and sediment while distributing water from one location to another. Therefore, an innovative master-slave neural network model [M (9:9:2)::S(9:9:2)] designed and developed to predict the attribute variations. The result of training dataset given as an input to master model and its maximum weights are assigned as an input to the slave model to predict the water quality. The developed master-slave model is predicted physicochemical attributes weight variations for 85 % to 90% of water quality as a target values.The sediment level variations also predicated from 0.01 to 0.05% of each water quality percentage. The model produced the significant variations on physiochemical attribute weights. According to the predicated experimental weight variation on training data set, effective recommendations are made to connect different resources.

Keywords: master-slave back propagation neural network model(MSBPNNM), water quality analysis, multivariate analysis, environmental mining

Procedia PDF Downloads 455
871 Cognitive Behaviour Drama: A Research-Based Intervention Model to Improve Social Thinking in High-Functioning Children with Autism

Authors: Haris Karnezi, Kevin Tierney

Abstract:

Cognitive Behaviour Drama is a research-based intervention model that brought together the science of psychology with the art form of drama to create an unobtrusive and exciting approach that would provide children on the higher end of the autism spectrum the motivation to explore the rules of social interaction and develop competencies associated with communicative success. The method involves engaging the participants in exciting fictional scenarios and encouraging them to seek various solutions on a number of problems that will lead them to an understanding of causal relationships and how a different course of action may lead to a different outcome. The sessions are structured to offer opportunities to the participants to practice target behaviours and understand the functions they serve. The study involved six separate interventions and employed both single case and group designs. Overall 8 children aged between 6 to 13 years, diagnosed with ASD participated in the study. Outcomes were measured using theory of mind tests, executive functioning tests, behavioural observations, pre and post intervention standardised social competence questionnaires for parents and teachers. Collectively, the results indicated positive changes in the self esteem and behaviour of all eight participants. In particular, improvements in the ability to solve theory of mind tasks were noted in the younger group; and qualitative improvements in social communication, in terms of verbal (content) and non verbal expression (body posture, vocal expression, fluency, eye contact, reduction of ritualistic mannerisms) were noted in the older group. The need for reliable impact measures to assess the effectiveness of the model in generating global changes in the participants’ behaviour outside the therapeutic context was identified.

Keywords: autism, drama, intervention, social skills

Procedia PDF Downloads 139
870 Liminal Disabled Tweens’ Identification with Disney Animations in Algeria

Authors: Selma Aitsaid

Abstract:

Disney canon texts, mainly animations, are believed to have authority over children’s identities. However, most research on Disney tends to focus either on textual analysis, or Western and non-western adult audiences. In fact, there is a lack of scholarship on Disney child audiences from non-western countries though children are believed to be Disney‘s main target audience, and Disney is a global corporation that appeals to audiences from all over the world as well. Therefore, qualitative research was conducted by interviewing around twenty five Algerian disabled tweens between the age 11 to 14 on their familiarity and identification with Disney animations. The reason behind choosing disabled children is because minority groups have not been interviewed on their possible interpretations of Disney animations despite the fact that these texts have been interpreted by some scholars as being inclusive of minority groups such as queer and disabled people. To that end, this project aims to decolonize disability and Global Southern Academia by three ways. The first way is to uncover inequalities of the metropolitan thought enshrined in the global power of the metropole vis a vis the subaltern. This approach was called postcolonialism. The second way is to value non-western academic and non-academic resources. This is the project of ‘indigenous knowledge. The third way is to analyse the forms of knowledge that were produced by intellectuals in colonized countries as a response to Western Academic hegemony. Consequently, this research endeavored to unravel the inequality, the dynamics of neocolonialism and subordination to colonial discourses within the Algerian discourse on disability and other knowledge such as tweenhood, childhood and non-western viewership, which are mainly defined through Western lenses. Algerian resources were included with the aim of enhancing an academic collaboration between the North and South as well. The findings showed that the postcolonial context had an impact on how children perceive Disney animations. They also demonstrated that children are able to negotiate the meaning of Disney texts within their own context.

Keywords: child audiences, Algeria, childhood, disability, Disney animations, global South, postcolonialism, tweens, Western hegemony

Procedia PDF Downloads 92
869 Chronolgy and Developments in Inventory Control Best Practices for FMCG Sector

Authors: Roopa Singh, Anurag Singh, Ajay

Abstract:

Agriculture contributes a major share in the national economy of India. A major portion of Indian economy (about 70%) depends upon agriculture as it forms the main source of income. About 43% of India’s geographical area is used for agricultural activity which involves 65-75% of total population of India. The given work deals with the Fast moving Consumer Goods (FMCG) industries and their inventories which use agricultural produce as their raw material or input for their final product. Since the beginning of inventory practices, many developments took place which can be categorised into three phases, based on the review of various works. The first phase is related with development and utilization of Economic Order Quantity (EOQ) model and methods for optimizing costs and profits. Second phase deals with inventory optimization method, with the purpose of balancing capital investment constraints and service level goals. The third and recent phase has merged inventory control with electrical control theory. Maintenance of inventory is considered negative, as a large amount of capital is blocked especially in mechanical and electrical industries. But the case is different in food processing and agro-based industries and their inventories due to cyclic variation in the cost of raw materials of such industries which is the reason for selection of these industries in the mentioned work. The application of electrical control theory in inventory control makes the decision-making highly instantaneous for FMCG industries without loss in their proposed profits, which happened earlier during first and second phases, mainly due to late implementation of decision. The work also replaces various inventories and work-in-progress (WIP) related errors with their monetary values, so that the decision-making is fully target-oriented.

Keywords: control theory, inventory control, manufacturing sector, EOQ, feedback, FMCG sector

Procedia PDF Downloads 340
868 Characterization of the GntR Family Transcriptional Regulator Rv0792c: A Potential Drug Target for Mycobacterium tuberculosis

Authors: Thanusha D. Abeywickrama, Inoka C. Perera, Genji Kurisu

Abstract:

Tuberculosis, considered being as the ninth leading cause of death worldwide, cause from a single infectious agent M. tuberculosis and the drug resistance nature of this bacterium is a continuing threat to the world. Therefore TB preventing treatment is expanding, where this study designed to analyze the regulatory mechanism of GntR transcriptional regulator gene Rv0792c, which lie between several genes codes for some hypothetical proteins, a monooxygenase and an oxidoreductase. The gene encoding Rv0792c was cloned into pET28a and expressed protein was purified to near homogeneity by Nickel affinity chromatography. It was previously reported that the protein binds within the intergenic region (BS region) between Rv0792c gene and monooxygenase (Rv0793). This resulted in binding of three protein molecules with the BS region suggesting tight control of monooxygenase as well as its own gene. Since monooxygenase plays a key role in metabolism, this gene may have a global regulatory role. The natural ligand for this regulator is still under investigation. In relation to the Rv0792 protein structure, a Circular Dichroism (CD) spectrum was carried out to determine its secondary structure elements. Percentage-wise, 17.4% Helix, 21.8% Antiparallel, 5.1% Parallel, 12.3% turn and 43.5% other were revealed from CD spectrum data under room temperature. Differential Scanning Calorimetry (DSC) was conducted to assess the thermal stability of Rv0792, which the melting temperature of protein is 57.2 ± 0.6 °C. The graph of heat capacity (Cp) versus temperature for the best fit was obtained for non-two-state model, which concludes the folding of Rv0792 protein occurs through stable intermediates. Peak area (∆HCal ) and Peak shape (∆HVant ) was calculated from the graph and ∆HCal / ∆HVant was close to 0.5, suggesting dimeric nature of the protein.

Keywords: CD spectrum, DSC analysis, GntR transcriptional regulator, protein structure

Procedia PDF Downloads 206
867 Free Radical Scavenging Activity and Total Phenolic Assessment of Drug Repurposed Medicinal Plant Metabolites: Promising Tools against Post COVID-19 Syndromes and Non-Communicable Diseases in Botswana

Authors: D. Motlhanka, M. Mine, T. Bagaketse, T. Ngakane

Abstract:

There is a plethora of evidence from numerous sources that highlights the triumph of naturally derived medicinal plant metabolites with antioxidant capability for repurposed therapeutics. As post-COVID-19 syndromes and non-communicable diseases are on the rise, there is an urgent need to come up with new therapeutic strategies to address the problem. Non-communicable diseases and Post COVID-19 syndromes are classified as socio-economic diseases and are ranked high among threats to health security due to the economic burden they pose to any government budget commitment. Research has shown a strong link between accumulation of free radicals and oxidative stress critical for pathogenesis of non-communicable diseases and COVID-19 syndromes. Botswana has embarked on a robust programme derived from ethno-pharmacognosy and drug repurposing to address these threats to health security. In the current approach, a number of medicinally active plant-derived polyphenolics are repurposed and combined into new medicinal tools to target diabetes, Hypertension, Prostate Cancer and oxidative stress induced Post COVID 19 syndromes such as “brain fog”. All four formulants demonstrated Free Radical scavenging capacities above 95% at 200µg/ml using the diphenylpicryalhydrazyl free radical scavenging assay and the total phenolic contents between 6899-15000GAE(g/L) using the folin-ciocalteau assay respectively. These repurposed medicinal tools offer new hope and potential in the fight against emerging health threats driven by hyper-inflammation and free radical-induced oxidative stress.

Keywords: drug repurposed plant polyphenolics, free radical damage, non-communicable diseases, post COVID 19 syndromes

Procedia PDF Downloads 102
866 The Utilization of Healthcare by African Migrants: The Lived Experiences of Unaccompanied Adolescent Migrants in South Africa

Authors: Kwanele Shishane

Abstract:

Numerous countries are faced with challenges such as disease, poverty and other social ills and inadequate government support to meet the needs of the entire population. In developing countries, the concept of child-headed households has become a ubiquitous phenomenon and lived experience. As such, migration of children is common in these countries. This study aims to explore the lived experiences of unaccompanied adolescent migrant, with regards to the utilization of health care in South Africa. The objectives of the study are to examine the lived experiences of health care utilization by unaccompanied adolescent migrants; examine the predisposing, enabling and need factors influencing utilization of health care among unaccompanied adolescent migrants; examine the social and cultural influences on health care utilization among unaccompanied adolescent migrants; and identify the health system barriers to utilization of health care by unaccompanied adolescent migrants. Andersen and Newman’s Model of Health Care Utilization (1995) which explains factors determining the utilization of healthcare will provide the theoretical framework for the empirical investigation of this study. The target population for this study is unaccompanied adolescent migrants, seeking to access services from migrant service organizations in four provinces in South Africa (Limpopo, KwaZulu-Natal, Free State, and Gauteng). Participants will be selected using a purposive sampling procedure. A qualitative research approach utilizing a descriptive phenomenological epistemology will be utilized in this study. Data will be collected through conducting in-depth interviews and focus group discussions with unaccompanied migrant adolescents, to explore their lived experiences related to access and utilization of health care, as an unaccompanied migrant in SA. The qualitative data will be analysed using Tech’s (1990) thematic analytical approach.

Keywords: health care utilisation, unaccompanied migrant youth, South Africa, lived experiences

Procedia PDF Downloads 155
865 Molecular Design and Synthesis of Heterocycles Based Anticancer Agents

Authors: Amna J. Ghith, Khaled Abu Zid, Khairia Youssef, Nasser Saad

Abstract:

Backgrounds: The multikinase and vascular endothelial growth factor (VEGF) receptor inhibitors interrupt the pathway by which angiogenesis becomes established and promulgated, resulting in the inadequate nourishment of metastatic disease. VEGFR-2 has been the principal target of anti-angiogenic therapies. We disclose the new thieno pyrimidines as inhibitors of VEGFR-2 designed by a molecular modeling approach with increased synergistic activity and decreased side effects. Purpose: 2-substituted thieno pyrimidines are designed and synthesized with anticipated anticancer activity based on its in silico molecular docking study that supports the initial pharmacophoric hypothesis with a same binding mode of interaction at the ATP-binding site of VEGFR-2 (PDB 2QU5) with high docking score. Methods: A series of compounds were designed using discovery studio 4.1/CDOCKER with a rational that mimic the pharmacophoric features present in the reported active compounds that targeted VEGFR-2. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. Results: The Compounds to be synthesized showed interaction energy comparable to or within the range of the benzimidazole inhibitor ligand when docked with VEGFR-2. ADMET study showed comparable results most of the compounds showed absorption within (95-99) zone varying according to different substitutions attached to thieno pyrimidine ring system. Conclusions: A series of 2-subsituted thienopyrimidines are to be synthesized with anticipated anticancer activity and according to docking study structure requirement for the design of VEGFR-2 inhibitors which can act as powerful anticancer agents.

Keywords: docking, discovery studio 4.1/CDOCKER, heterocycles based anticancer agents, 2-subsituted thienopyrimidines

Procedia PDF Downloads 225
864 A Novel Epitope Prediction for Vaccine Designing against Ebola Viral Envelope Proteins

Authors: Manju Kanu, Subrata Sinha, Surabhi Johari

Abstract:

Viral proteins of Ebola viruses belong to one of the best studied viruses; however no effective prevention against EBOV has been developed. Epitope-based vaccines provide a new strategy for prophylactic and therapeutic application of pathogen-specific immunity. A critical requirement of this strategy is the identification and selection of T-cell epitopes that act as vaccine targets. This study describes current methodologies for the selection process, with Ebola virus as a model system. Hence great challenge in the field of ebola virus research is to design universal vaccine. A combination of publicly available bioinformatics algorithms and computational tools are used to screen and select antigen sequences as potential T-cell epitopes of supertypes Human Leukocyte Antigen (HLA) alleles. MUSCLE and MOTIF tools were used to find out most conserved peptide sequences of viral proteins. Immunoinformatics tools were used for prediction of immunogenic peptides of viral proteins in zaire strains of Ebola virus. Putative epitopes for viral proteins (VP) were predicted from conserved peptide sequences of VP. Three tools NetCTL 1.2, BIMAS and Syfpeithi were used to predict the Class I putative epitopes while three tools, ProPred, IEDB-SMM-align and NetMHCII 2.2 were used to predict the Class II putative epitopes. B cell epitopes were predicted by BCPREDS 1.0. Immunogenic peptides were identified and selected manually by putative epitopes predicted from online tools individually for both MHC classes. Finally sequences of predicted peptides for both MHC classes were looked for common region which was selected as common immunogenic peptide. The immunogenic peptides were found for viral proteins of Ebola virus: epitopes FLESGAVKY, SSLAKHGEY. These predicted peptides could be promising candidates to be used as target for vaccine design.

Keywords: epitope, b cell, immunogenicity, ebola

Procedia PDF Downloads 294
863 Performance Evaluation of a Very High-Resolution Satellite Telescope

Authors: Walid A. Attia, Taher M. Bazan, Fawzy Eltohamy, Mahmoud Fathy

Abstract:

System performance evaluation is an essential stage in the design of high-resolution satellite telescopes prior to the development process. In this paper, a system performance evaluation of a very high-resolution satellite telescope is investigated. The evaluated system has a Korsch optical scheme design. This design has been discussed in another paper with respect to three-mirror anastigmat (TMA) scheme design and the former configuration showed better results. The investigated system is based on the Korsch optical design integrated with a time-delay and integration charge coupled device (TDI-CCD) sensor to achieve a ground sampling distance (GSD) of 25 cm. The key performance metrics considered are the spatial resolution, the signal to noise ratio (SNR) and the total modulation transfer function (MTF) of the system. In addition, the national image interpretability rating scale (NIIRS) metric is assessed to predict the image quality according to the modified general image quality equation (GIQE). Based on the orbital, optical and detector parameters, the estimated GSD is found to be 25 cm. The SNR has been analyzed at different illumination conditions of target albedos, sun and sensor angles. The system MTF has been computed including diffraction, aberration, optical manufacturing, smear and detector sampling as the main contributors for evaluation the MTF. Finally, the system performance evaluation results show that the computed MTF value is found to be around 0.08 at the Nyquist frequency, the SNR value was found to be 130 at albedo 0.2 with a nadir viewing angles and the predicted NIIRS is in the order of 6.5 which implies a very good system image quality.

Keywords: modulation transfer function, national image interpretability rating scale, signal to noise ratio, satellite telescope performance evaluation

Procedia PDF Downloads 370
862 Using the Textbook to Promote Thinking Skills in Intermediate School EFL Classrooms in Saudi Arabia: An Analysis of the Tasks and an Exploration of Teachers' and Perceptions

Authors: Nurah Saleh Alfares

Abstract:

An aim of TS in EFL is to help learners to understand how they learn, which could help them in using the target language with other learners in language classrooms, and in their social life. The early researchers have criticised the system of teaching methods in EFL applied in Saudi schools, as they claim that it does not produce students who are highly proficient in English. Some of them suggested that enhancing learners’ TS would help to improve the learners’ proficiency of using the EFL. The textbook in Saudi schools is the central material for teachers to follow in the EFL classroom. Thus, this study is investigating the main issues that could promote TS in Saudi EFL: the textbook and the teachers. The purposes of the study are: to find out the extent to which the tasks in the textbook have the potential to support teachers in promoting TS; to discover insights into the nature of classroom activities that teachers use to encourage TS from the textbook and to explore the teachers’ views on the role of the textbook in promoting TS in the English language. These aims will improve understanding of the connection between the potential of the textbook content and the participants’ theoretical knowledge and their teaching practice. The investigation employed research techniques including the following: (1) analysis of the textbook; (2) questionnaire for EFL teachers; (3) observation for EFL classroom; (4) interviews with EFL teachers. Analysis of the third intermediate grade textbook has been undertaken, and six EFL teachers from five intermediate schools were involved in the study. Data analysis revealed that 36.71 % of the tasks in the textbook could have the potential to promote TS, and 63.29 % of the tasks in the textbook could not have the potential to promote TS. Therefore, the result of the textbook analysis showed that the majority of the tasks do not have the potential to help teachers to promote TS. Although not all teachers of the observed lessons displayed behaviour helpful to promote TS, teachers, who presented potential TS tasks in their lesson encouraged learners’ interaction and students’ engagement more than teachers who presented tasks that did not have the potential to promote TS. Therefore, the result of the teachers’ data showed that having a textbook that has the potential to promote TS is not enough to develop teaching TS in Saudi EFL since teachers’ behaviour could make the task more or less productive.

Keywords: English as a Foreign Language, metacognitive skills, textbook, thinking skills

Procedia PDF Downloads 111
861 Managing and Marketing a Modern Art Museum in a Small Town: A Case Study on Odunpazarı Modern Museum

Authors: Mehmet Sinan Erguven

Abstract:

Modern art is relatively new but a popular area in Turkish art society. Modern art museums are mainly located in big cities like Istanbul and Ankara where cultural life is more dynamic. Odunpazarı Modern Museum (OMM) will open its doors on September 2019 and be the only modern art museum located in a small town in Turkey. OMM executives declare the mission of the museum as; art must go beyond the metropolises of the world, give a new lease of life to cities that make a difference with their cultural texture, and reach a greater audience through that expansion. So OMM will not only serve as a museum but a landmark for regenerating the city brand of Eskişehir like the Guggenheim in Bilbao. OMM is located in the Odunpazarı area, the heart of Eskişehir. Named after the historical timber market it once hosted, Odunpazarı is a nominated site for the UNESCO Intangible Cultural Heritage List, and is Eskişehir’s first area of settlement. This study focuses on the complex nature of opening a modern art museum in a small town. The management and marketing dynamics of OMM are discussed in the study. Content analysis technique is used on local and national news to display the perception differences before and after the opening of OMM. In depth interviews with the executives of the museum are conducted in order to enlighten the insights of opening a modern art museum in a small town. Early findings of the content analysis point out that, the comments on the national press are mostly positive. On the other hand, different views occur on the local press. The location OMM is constructed and grandness of the museum building are criticized by some of the local newspapers. OMM’s potential as a tourist attraction is agreed by most of the media. OMM executives stated the most challenging task as reaching the different target audiences on international, national and local levels. These early findings will be improved and compared shortly before and after the opening of the museum.

Keywords: management, marketing, Odunpazarı modern museum, small town

Procedia PDF Downloads 208
860 The Challenges of Intercultural Transfer: The Italian Reception of Aotearoa/New Zealand Films

Authors: Martina Depentor

Abstract:

While the cinematic medium contributes to bringing images of a culture to foreign audiences, Audiovisual Translation contributes to deciphering those cultural representations to those same audiences. Through Audiovisual Translation, in fact, elements permeate the reception system and contribute to forging a cultural image of the original/source system in the target/reception system. By analyzing a number of Italian critical reviews, blogs and forum posts, this paper examines the impact and reception in Italy of five of the most successful and influential New Zealand films of the last two decades - An Angel at my Table (1990), The Piano (1993), Heavenly Creatures (1994), Once Were Warriors (1994), Whale Rider (2002) - with the aim of exploring how the adaptation of New Zealand films might condition the representation of New Zealand in the Italian imaginary. The analysis seeks to identify whether a certain degree of cultural loss results from the 'translation' of these films. The films selected share common ground in that they all reveal cultural, social and historical characteristics of New Zealand, from aspects that are unique to this country and that on the surface may render it difficult to penetrate (unfamiliar landscapes, aspects of indigenous culture) to more universal themes (intimate family stories, dysfunctional relationship). They contributed to situating New Zealand on an international stage and to bringing images of the country to many audiences, the Italian one included, with little previous cultural knowledge of the social and political history of New Zealand. Differences in film types pose clearly different levels of interpretative challenges to non-New Zealander audiences, and examples from the films will show how these challenges are or are not overcome if the adaptations display misinterpretations or rendition gaps, and how the process of intercultural transfer further 'domesticates' or 'exoticises' the source culture.

Keywords: audiovisual translation, cultural representation, intercultural transfer, New Zealand Films

Procedia PDF Downloads 283
859 Nanowire Sensor Based on Novel Impedance Spectroscopy Approach

Authors: Valeriy M. Kondratev, Ekaterina A. Vyacheslavova, Talgat Shugabaev, Alexander S. Gudovskikh, Alexey D. Bolshakov

Abstract:

Modern sensorics imposes strict requirements on the biosensors characteristics, especially technological feasibility, and selectivity. There is a growing interest in the analysis of human health biological markers, which indirectly testifying the pathological processes in the body. Such markers are acids and alkalis produced by the human, in particular - ammonia and hydrochloric acid, which are found in human sweat, blood, and urine, as well as in gastric juice. Biosensors based on modern nanomaterials, especially low dimensional, can be used for this markers detection. Most classical adsorption sensors based on metal and silicon oxides are considered non-selective, because they identically change their electrical resistance (or impedance) under the action of adsorption of different target analytes. This work demonstrates a feasible frequency-resistive method of electrical impedance spectroscopy data analysis. The approach allows to obtain of selectivity in adsorption sensors of a resistive type. The method potential is demonstrated with analyzis of impedance spectra of silicon nanowires in the presence of NH3 and HCl vapors with concentrations of about 125 mmol/L (2 ppm) and water vapor. We demonstrate the possibility of unambiguous distinction of the sensory signal from NH3 and HCl adsorption. Moreover, the method is found applicable for analysis of the composition of ammonia and hydrochloric acid vapors mixture without water cross-sensitivity. Presented silicon sensor can be used to find diseases of the gastrointestinal tract by the qualitative and quantitative detection of ammonia and hydrochloric acid content in biological samples. The method of data analysis can be directly translated to other nanomaterials to analyze their applicability in the field of biosensory.

Keywords: electrical impedance spectroscopy, spectroscopy data analysis, selective adsorption sensor, nanotechnology

Procedia PDF Downloads 96
858 Free Energy Computation of A G-Quadruplex-Ligand Structure: A Classical Molecular Dynamics and Metadynamics Simulation Study

Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria

Abstract:

The DNA G-quadruplex is a four-stranded DNA structure formed by stacked planes of four base paired guanines (G-quartet). Guanine rich DNA sequences appear in many sites of genomic DNA and can potential form G-quadruplexes, such as those occurring at 3'-terminus of the human telomeric DNA. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to down regulate oncogene expression making G-quadruplex an attractive target for anticancer therapy. Many G-quadruplex ligands have been proposed with a planar core to facilitate the pi–pi stacking and electrostatic interactions with the G-quartets. However, many drug candidates are impossibilitated to discriminate a G-quadruplex from a double helix DNA structure. In this context, it is important to investigate the site topology for the interaction of a G-quadruplex with a ligand. In this work, we determine the free energy surface of a G-quadruplex-ligand to study the binding modes of the G-quadruplex (TG4T) with the daunomycin (DM) drug. The complex TG4T-DM is studied using classical molecular dynamics in combination with metadynamics simulations. The metadynamics simulations permit an enhanced sampling of the conformational space with a modest computational cost and obtain free energy surfaces in terms of the collective variables (CV). The free energy surfaces of TG4T-DM exhibit other local minima, indicating the presence of additional binding modes of daunomycin that are not observed in short MD simulations without the metadynamics approach. The results are compared with similar calculations on a different structure (the mutated mu-G4T-DM where the 5' thymines on TG4T-DM have been deleted). The results should be of help to design new G-quadruplex drugs, and understand the differences in the recognition topology sites of the duplex and quadruplex DNA structures in their interaction with ligands.

Keywords: g-quadruplex, cancer, molecular dynamics, metadynamics

Procedia PDF Downloads 440
857 Digital Portfolio as Mediation to Enhance Willingness to Communicate in English

Authors: Saeko Toyoshima

Abstract:

This research will discuss if performance tasks with technology would enhance students' willingness to communicate. The present study investigated how Japanese learners of English would change their attitude to communication in their target language by experiencing a performance task, called 'digital portfolio', in the classroom, applying the concepts of action research. The study adapted questionnaires including four-Likert and open-end questions as mixed-methods research. There were 28 students in the class. Many of Japanese university students with low proficiency (A1 in Common European Framework of References in Language Learning and Teaching) have difficulty in communicating in English due to the low proficiency and the lack of practice in and outside of the classroom at secondary education. They should need to mediate between themselves in the world of L1 and L2 with completing a performance task for communication. This paper will introduce the practice of CALL class where A1 level students have made their 'digital portfolio' related to the topics of TED® (Technology, Entertainment, Design) Talk materials. The students had 'Portfolio Session' twice in one term, once in the middle, and once at the end of the course, where they introduced their portfolio to their classmates and international students in English. The present study asked the students to answer a questionnaire about willingness to communicate twice, once at the end of the first term and once at the end of the second term. The four-Likert questions were statistically analyzed with a t-test, and the answers to open-end questions were analyzed to clarify the difference between them. They showed that the students had a more positive attitude to communication in English and enhanced their willingness to communicate through the experiences of the task. It will be the implication of this paper that making and presenting portfolio as a performance task would lead them to construct themselves in English and enable them to communicate with the others enjoyably and autonomously.

Keywords: action research, digital portfoliio, computer-assisted language learning, ELT with CALL system, mixed methods research, Japanese English learners, willingness to communicate

Procedia PDF Downloads 104
856 Enabling Translanguaging in the EFL Classroom, Affordances of Learning and Reflections

Authors: Nada Alghali

Abstract:

Translanguaging pedagogy suggests a new perspective in language education relating to multilingualism; multilingual learners have one linguistic repertoire and not two or more separate language systems (García and Wei, 2014). When learners translanguage, they are able to draw on all their language features in a flexible and integrated way (Otheguy, García, & Reid, 2015). In the Foreign Language Classroom, however, the tendency to use the target language only is still advocated as a pedagogy. This study attempts to enable learners in the English as a foreign language classroom to draw on their full linguistic repertoire through collaborative reading lessons. In observations prior to this study, in a classroom where English only policy prevails, learners still used their first language in group discussions yet were constrained at times by the teacher’s language policies. Through strategically enabling translanguaging in reading lessons (Celic and Seltzer, 2011), this study has revealed that learners showed creative ways of language use for learning and reflected positively on thisexperience. This case study enabled two groups in two different proficiency level classrooms who are learning English as a foreign language in their first year at University in Saudi Arabia. Learners in the two groups wereobserved over six weeks and wereasked to reflect their learning every week. The same learners were also interviewed at the end of translanguaging weeks after completing a modified model of the learning reflection (Ash and Clayton, 2009). This study positions translanguaging as collaborative and agentive within a sociocultural framework of learning, positioning translanguaging as a resource for learning as well as a process of learning. Translanguaging learning episodes are elicited from classroom observations, artefacts, interviews, reflections, and focus groups, where they are analysed qualitatively following the sociocultural discourse analysis (Fairclough &Wodak, 1997; Mercer, 2004). Initial outcomes suggest functions of translanguaging in collaborative reading tasks and recommendations for a collaborative translanguaging pedagogy approach in the EFL classroom.

Keywords: translanguaging, EFL, sociocultural theory, discourse analysis

Procedia PDF Downloads 156
855 Establishing Combustion Behaviour for Refuse Derived Fuel Firing at Kiln Inlet through Computational Fluid Dynamics at a Cement Plant in India

Authors: Prateek Sharma, Venkata Ramachandrarao Maddali, Kapil Kukreja, B. N. Mohapatra

Abstract:

Waste management is one of the pressing issues of India. Several initiatives by the Indian Government, including the recent one “Swachhata hi Seva” campaign launched by Prime Minister on 15th August 2018, can be one of the game changers to waste disposal. Under this initiative, the government, cement industry and other stakeholders are working hand in hand to dispose of single-use plastics in cement plants in rotary kilns. This is an exemplary effort and a move that establishes the Indian Cement industry as one of the key players in a circular economy. One of the cement plants in Southern India has been mandated by the state government to co-process shredded plastic and refuse-derived fuel (RDF) available in nearby regions as an alternative fuel in their cement plant. The plant has set a target of 25 % thermal substitution rate (TSR) by RDF in the next five years. Most of the cement plants in India and abroad have achieved high TSR through pre calciner firing. But the cement plant doesn’t have the precalciner and has to achieve this daunting task of 25 % TSR by firing through the main kiln burner. Since RDF is a heterogeneous waste with the change in fuel quality, it is difficult to achieve this task; hence plant has to resort to firing some portion of RDF/plastics at kiln inlet. But kiln inlet has reducing conditions as observed during measurements) under baseline condition. The combustion behavior of RDF of different sizes at different firing locations in riser was studied with the help of a computational fluid dynamics tool. It has been concluded that RDF above 50 mm size results in incomplete combustion leading to CO formation. Moreover, best firing location appears to be in the bottom portion of the kiln riser.

Keywords: kiln inlet, plastics, refuse derived fuel, thermal substitution rate

Procedia PDF Downloads 107
854 The Design of an Afghan Refugee Camp in Kerman City through Ecotech Architecture

Authors: Kourosh Ghaffari, Baghaei Azhang

Abstract:

This study aims to address two main questions whether a camp designed for refugees will affect their quality of life and how to effectively incorporate ecotech architecture into the architectural design of a refugee camp. The current study planned to ensure that the final design reflects the principles of ecotech architecture in most refugee camps. The design process has taken into account various factors, including flexibility, diversity in the camp space according to the ecotech approach, expandability in the building, spatial hierarchy in the design of camp spaces, and the assignment of territories and space sanctuaries to refugees. It should be noted that this study is not a research-oriented type of study and is only limited to collecting information and making hypotheses and questions related to the plan. The researchers attempted to provide a general summary of similar domestic and foreign examples and examine them in similar conditions using the ecotech architecture. The research method utilized in this study was qualitative. Afterwards, the climate studies of the target area, citing and paying attention to the criteria and points extracted from the theoretical framework, reaching the desired conclusion and examining similar examples were followed. Additionally, placement on the site, compliance with relevant standards and regulations, attention to the content and physical program, and addressing the idea and its evolution in all the details of the plan were presented. The data collection procedure included observation and library studies, and the design method was to determine and recognize the subject and examine similar samples. In conclusion, the principles of theoretical foundations, the design protocols in ecotech architecture and the scope of the study are dealt. Furthermore, the site analysis, the design process and the final plan are presented.

Keywords: ecotech architecture, livable city, shelter, refugee camp

Procedia PDF Downloads 58
853 Multi-source Question Answering Framework Using Transformers for Attribute Extraction

Authors: Prashanth Pillai, Purnaprajna Mangsuli

Abstract:

Oil exploration and production companies invest considerable time and efforts to extract essential well attributes (like well status, surface, and target coordinates, wellbore depths, event timelines, etc.) from unstructured data sources like technical reports, which are often non-standardized, multimodal, and highly domain-specific by nature. It is also important to consider the context when extracting attribute values from reports that contain information on multiple wells/wellbores. Moreover, semantically similar information may often be depicted in different data syntax representations across multiple pages and document sources. We propose a hierarchical multi-source fact extraction workflow based on a deep learning framework to extract essential well attributes at scale. An information retrieval module based on the transformer architecture was used to rank relevant pages in a document source utilizing the page image embeddings and semantic text embeddings. A question answering framework utilizingLayoutLM transformer was used to extract attribute-value pairs incorporating the text semantics and layout information from top relevant pages in a document. To better handle context while dealing with multi-well reports, we incorporate a dynamic query generation module to resolve ambiguities. The extracted attribute information from various pages and documents are standardized to a common representation using a parser module to facilitate information comparison and aggregation. Finally, we use a probabilistic approach to fuse information extracted from multiple sources into a coherent well record. The applicability of the proposed approach and related performance was studied on several real-life well technical reports.

Keywords: natural language processing, deep learning, transformers, information retrieval

Procedia PDF Downloads 178
852 The Role of Metaphor in Communication

Authors: Fleura Shkëmbi, Valbona Treska

Abstract:

In elementary school, we discover that a metaphor is a decorative linguistic device just for poets. But now that we know, it's also a crucial tactic that individuals employ to understand the universe, from fundamental ideas like time and causation to the most pressing societal challenges today. Metaphor is the use of language to refer to something other than what it was originally intended for or what it "literally" means in order to suggest a similarity or establish a connection between the two. People do not identify metaphors as relevant in their decisions, according to a study on metaphor and its effect on decision-making; instead, they refer to more "substantive" (typically numerical) facts as the basis for their problem-solving decision. Every day, metaphors saturate our lives via language, cognition, and action. They argue that our conceptions shape our views and interactions with others and that concepts define our reality. Metaphor is thus a highly helpful tool for both describing our experiences to others and forming notions for ourselves. In therapeutic contexts, their shared goal appears to be twofold. The cognitivist approach to metaphor regards it as one of the fundamental foundations of human communication. The benefits and disadvantages of utilizing the metaphor differ depending on the target domain that the metaphor portrays. The challenge of creating messages and surroundings that affect customers' notions of abstract ideas in a variety of industries, including health, hospitality, romance, and money, has been studied for decades in marketing and consumer psychology. The aim of this study is to examine, through a systematic literature review, the role of the metaphor in communication and in advertising. This study offers a selected analysis of this literature, concentrating on research on customer attitudes and product appraisal. The analysis of the data identifies potential research questions. With theoretical and applied implications for marketing, design, and persuasion, this study sheds light on how, when, and for whom metaphoric communications are powerful.

Keywords: metaphor, communication, advertising, cognition, action

Procedia PDF Downloads 76
851 Conceptualizing Clashing Values in the Field of Media Ethics

Authors: Saadia Izzeldin Malik

Abstract:

Lack of ethics is the crisis of the 21-century. Today’s global world is filled with economic, political, environmental, media/communication, and social crises that all generated by the eroding fabric of ethics and moral values that guide human’s decisions in all aspects of live. Our global world is guided by liberal western democratic principles and liberal capitalist economic principles that define and reinforce each other. In economic terms, capitalism has turned world economic systems into one market place of ideas and products controlled by big multinational corporations that not only determine the conditions and terms of commodity production and commodity exchange between countries, but also transform the political economy of media systems around the globe. The citizen (read the consumer) today is the target of persuasion by all types of media at a time when her/his interests should be, ethically and in principle, the basic significant factor in the selection of media content. It is very important in this juncture of clashing media values –professional and commercial- and wide spread ethical lapses of media organizations and media professionals to think of a perspective to theorize these conflicting values within a broader framework of media ethics. Thus, the aim of this paper is to, epistemologically, bring to the center a perspective on media ethics as a basis for reconciliation of clashing values of the media. The paper focuses on conflicting ethical values in current media debate; namely ownership of media vs. press freedom, individual right for privacy vs. public right to know, and global western consumerism values vs. media values. The paper concludes that a framework to reconcile conflicting values of media ethics should focus on the “individual” journalist and his/her moral development as well as focus on maintaining ethical principles of the media as an institution with a primary social responsibility for the “public” it serves.

Keywords: ethics, media, journalism, social responsibility, conflicting values, global

Procedia PDF Downloads 461
850 In vitro and vivo Studies for Assessing the Anti-Proliferative, Anti-Migration and Apoptotic Activity of A. squamosa L. Leaves Extract

Authors: Rawan Al-Nemari, Abdulrahman Al-Senaidy, Abdelhabib Semlali

Abstract:

Background and objectives: The most common cause of death in women worldwide is breast cancer. Regarding all chemotherapy disadvantages and side effects, it’s becoming necessary to identify natural products that target cancer cells with lesser harmful side effects on non-targeted cells and biological environment. Different parts of A. squamosa L., commonly known as custard apple, show varied therapeutic effects. The objective of this study is to investigate in vitro and in vivo, the anti-cancer activity of A. squamosa leaves extract. Methods: The physiological responses using MTT, nucleus staining, and LDH assays were used to evaluate cell survival and proliferation in both ER+ and ER- cells when they were exposed to extract. Monolayer wound repair assay was used to investigate the effect of extracts on cell migration. Apoptotic gene’s expression was investigated by real-time polymerase chain reaction. To study the effect of the extract on the size of tumor, breast cancer induced rats were used. Results: A. squamosa leaves extract showed high anti-proliferative and cytotoxicity effects against different breast cancer cell lines with high concentration, 100 ug/ml. The extracts have reduced the cells wound closure. Polymerase chain reaction revealed downregulation of Bcl-2 and upregulation of Bax. In breast cancer model animal developed in our laboratory, after 4 weeks treatment, treated groups have shown smaller tumor size in comparison with control group (n=4). Conclusion: These results suggest that A. squamosa leaves extract has anti-cancer activity against breast cancer in both in vitro and in vivo, and it may be developed as a potential novel agent to treat breast cancer.

Keywords: apoptosis, breast cancer, migration, proliferation

Procedia PDF Downloads 128
849 Dermoscopy Compliance: Improving Melanoma Detection Pathways Through Quality Improvement

Authors: Max Butler

Abstract:

Melanoma accounts for 80% of skin cancer-related deaths globally. The poor prognosis and increasing incidence of melanoma impose a significant burden on global healthcare systems. Early detection, precise diagnosis, and preventative strategies are critical to improving patient outcomes. Dermoscopy is the gold standard for specialist assessments of pigmented skin lesions, as it can differentiate between benign and malignant growths with greater accuracy than visual inspection. In the United Kingdom, guidelines from the National Institute of Clinical Excellence (NICE) state dermoscopy should be used in all specialist assessments of pigmented skin lesions. Compliance with this guideline is low, resulting in missed and delayed melanoma diagnoses. To address this problem, a quality improvement project was initiated at Buckinghamshire Healthcare Trust (BHT) within the plastic surgery department. The target group was a trainee and consultant plastic surgeons conducting outpatient skin cancer clinics. Analysis of clinic documentation over a one-month period found that only 62% (38/61) of patients referred with pigmented skin lesions were examined using dermoscopy. To increase dermoscopy rates, teaching was delivered to the department highlighting national guidelines and the evidence base for dermoscopic examination. In addition, clinic paperwork was redesigned to include a text box for dermoscopic examination. Reauditing after the intervention found a significant increase in dermoscopy rates (52/61, p = 0.014). In conclusion, implementing a quality improvement project with targeted teaching and documentation template templates successfully increased dermoscopy rates. This is a promising step toward improving early melanoma detection and patient outcomes.

Keywords: melanoma, dermoscopy, plastic surgery, quality improvement

Procedia PDF Downloads 53
848 Mechanism of Modeling the Level of Bcr-Abl Oncoprotein by Ubiquitin-Proteasome System in Chronic Myeloid Leukemia

Authors: Svitlana Antonenko, Gennady Telegeev

Abstract:

Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.

Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell

Procedia PDF Downloads 47