Search results for: core protein
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4208

Search results for: core protein

2018 A Crystal Plasticity Approach to Model Dynamic Strain Aging

Authors: Burak Bal, Demircan Canadinc

Abstract:

Dynamic strain aging (DSA), resulting from the reorientation of C-Mn clusters in the core of dislocations, can provide a strain hardening mechanism. In addition, in Hadfield steel, negative strain rate sensitivity is observed due to the DSA. In our study, we incorporated dynamic strain aging onto crystal plasticity computations to predict the local instabilities and corresponding negative strain rate sensitivity. Specifically, the material response of Hadfield steel was obtained from monotonic and strain-rate jump experiments under tensile loading. The strain rate range was adjusted from 10⁻⁴ to 10⁻¹s ⁻¹. The crystal plasticity modeling of the material response was carried out based on Voce-type hardening law and corresponding Voce hardening parameters were determined. The solute pinning effect of carbon atom was incorporated to crystal plasticity simulations at microscale level by computing the shear stress contribution imposed on an arrested dislocation by carbon atom. After crystal plasticity simulations with modifying hardening rule, which takes into account the contribution of DSA, it was seen that the model successfully predicts both the role of DSA and corresponding strain rate sensitivity.

Keywords: crystal plasticity, dynamic strain aging, Hadfield steel, negative strain rate sensitivity

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2017 The Stem Cell Transcription Co-factor Znf521 Sustains Mll-af9 Fusion Protein In Acute Myeloid Leukemias By Altering The Gene Expression Landscape

Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

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ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

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2016 Each One, Reach One: Peer Mentoring Support for Faculty Women of Color

Authors: Teresa Leary Handy

Abstract:

As awareness of the importance of diversity has increased in society, higher education has also begun to recognize the importance of supporting faculty of color. In the university setting, faculty women of color specifically encounter barriers that impact their level of job satisfaction, retention rates, and pedagogical practices. These barriers and challenges not only undermine faculty diversity efforts but also hinder the ability of colleges and universities to provide a supportive environment that fosters students' academic success and sense of belonging. Faculty who are marginalized and on the periphery in higher education institutions need support so that they can feel confident in building a student’s sense of belonging which can impact a student’s academic success and goal of earning a college degree. This study examined and sought to understand the importance of supporting faculty of color, specifically women faculty of color, and how this type of faculty support can impact student academic success and a student’s sense of belonging. The study furthered original research on strategies to move an institution forward on the equity spectrum to support belonging and inclusions as core culture elements.

Keywords: equity, inclusion, belonging, women, faculty support

Procedia PDF Downloads 64
2015 Proximate, Functional and Sensory Evaluation of Some Brands of Instant Noodles in Nigeria

Authors: Olakunle Moses Makanjuola, Adebola Ajayi

Abstract:

Noodles are made from unleavened dough, rolled flat and cut into shapes. The instant noodle market is growing fast in Asian countries and is gaining popularity in the western market. This project reports on the proximate functional and sensory evaluation of different brands of instant noodles in Nigeria. The comparisons were based on proximate functional and sensory evaluation of the product. The result obtained from the proximate analysis showed that sample QHR has the highest moisture content, sample BMG has the highest protein content, sample CPO has the highest fat content, sample. The obtained result from the functional properties showed that sample BMG (Dangote noodles) had the highest volume increase after cooking due to its high swelling capacity, high water absorption capacity and high hydration capacity. Sample sensory analysis of the noodles showed that all the samples are of significant difference (at P < 0.05) in terms of colour, texture, and aroma but there is no significant difference in terms of taste and overall acceptability. Sample QHR (Indomie noodles) is the most preferred by the panelists.

Keywords: proximate, functional, sensory evaluation, noodles

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2014 DEM Simulation of the Formation of Seed Granules in Twin-Screw Granulation Process

Authors: Tony Bediako Arthur, Nejat Rahmanian, Nana Gyan Sekyi

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The possibility of producing seeded granules from fine and course powders is a major challenge as the control parameters that affect its producibility is still under investigation. The seeded granulation is a novel form of producing granules where the granule is made up of larger particles at the core, which are surrounded by fine particles. The possibility of managing granulation through course particle feed rate control makes seeded granulation in continuous granulation useful in terms of process control. Twin screw granulation is now a major process of choice for the wet continuous granulation process in the industry. It is, therefore, imperative to investigate the process control parameters that influence the formation of seeded granules in twin screw granulation. In this paper, the effect of the twin screws rotating speed on the production of seeded granules has been examined. Pictorial and quantitative analysis indicates a high number of seeded granules forming at low screw rotating speeds. It is also instructive to say that higher tensile stress occurs at the kneading section of the screws; thus, higher rotating speed courses the fines for breaking off from the seed particle.

Keywords: DEM, twin-screw, Seeded granules, Simulation

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2013 Immunization-Data-Quality in Public Health Facilities in the Pastoralist Communities: A Comparative Study Evidence from Afar and Somali Regional States, Ethiopia

Authors: Melaku Tsehay

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The Consortium of Christian Relief and Development Associations (CCRDA), and the CORE Group Polio Partners (CGPP) Secretariat have been working with Global Alliance for Vac-cines and Immunization (GAVI) to improve the immunization data quality in Afar and Somali Regional States. The main aim of this study was to compare the quality of immunization data before and after the above interventions in health facilities in the pastoralist communities in Ethiopia. To this end, a comparative-cross-sectional study was conducted on 51 health facilities. The baseline data was collected in May 2019, while the end line data in August 2021. The WHO data quality self-assessment tool (DQS) was used to collect data. A significant improvment was seen in the accuracy of the pentavalent vaccine (PT)1 (p = 0.012) data at the health posts (HP), while PT3 (p = 0.010), and Measles (p = 0.020) at the health centers (HC). Besides, a highly sig-nificant improvment was observed in the accuracy of tetanus toxoid (TT)2 data at HP (p < 0.001). The level of over- or under-reporting was found to be < 8%, at the HP, and < 10% at the HC for PT3. The data completeness was also increased from 72.09% to 88.89% at the HC. Nearly 74% of the health facilities timely reported their respective immunization data, which is much better than the baseline (7.1%) (p < 0.001). These findings may provide some hints for the policies and pro-grams targetting on improving immunization data qaulity in the pastoralist communities.

Keywords: data quality, immunization, verification factor, pastoralist region

Procedia PDF Downloads 110
2012 New Vision of 'Social Europe': Renationalising the Integration Process in the Internal Market of the European Union

Authors: Robert Grzeszczak, Magdalena Gniadzik

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The article deals with one of the most significant issues concerning the functioning of the internal market of the European Union – the free movement of workers and free movement of persons. The purpose is to identify the political and legal effects of the “renationalisation process” on the EU and its Member States. The concept of renationalisation is expressed through Member States’ aim to verify the relationship with the EU. The tendency is more visible in the public opinion of several MS’s of the ‘EU core’ and may be confirmed by the changes applied by the regulatory body. The thesis for the article is the return of renationalisation tendencies in the area of the Single Market, which is supported by, among others, an open criticism of the foundations of EU integration or considerations on withdrawal from the EU by some MS. This analysis will focus primarily on the effects that renationalisation may have on the free movement of persons. The free movement of persons is one of the key issues for the development of the European integration. It is still subject to theoretical reflections, new doubts and practical issues. The latest developments in politics, law and jurisprudence demonstrate the need to reflect on the attempts to redefine certain principles regarding migrant EU workers and their protection against nationality-based discrimination.

Keywords: European Union, Singel Market, free movement of persons, posting of workers

Procedia PDF Downloads 228
2011 Older Consumer’s Willingness to Trust Social Media Advertising: A Case of Australian Social Media Users

Authors: Simon J. Wilde, David M. Herold, Michael J. Bryant

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Social media networks have become the hotbed for advertising activities due mainly to their increasing consumer/user base and, secondly, owing to the ability of marketers to accurately measure ad exposure and consumer-based insights on such networks. More than half of the world’s population (4.8 billion) now uses social media (60%), with 150 million new users having come online within the last 12 months (to June 2022). As the use of social media networks by users grows, key business strategies used for interacting with these potential customers have matured, especially social media advertising. Unlike other traditional media outlets, social media advertising is highly interactive and digital channel specific. Social media advertisements are clearly targetable, providing marketers with an extremely powerful marketing tool. Yet despite the measurable benefits afforded to businesses engaged in social media advertising, recent controversies (such as the relationship between Facebook and Cambridge Analytica in 2018) have only heightened the role trust and privacy play within these social media networks. Using a web-based quantitative survey instrument, survey participants were recruited via a reputable online panel survey site. Respondents to the survey represented social media users from all states and territories within Australia. Completed responses were received from a total of 258 social media users. Survey respondents represented all core age demographic groupings, including Gen Z/Millennials (18-45 years = 60.5% of respondents) and Gen X/Boomers (46-66+ years = 39.5% of respondents). An adapted ADTRUST scale, using a 20 item 7-point Likert scale, measured trust in social media advertising. The ADTRUST scale has been shown to be a valid measure of trust in advertising within traditional media, such as broadcast media and print media, and, more recently, the Internet (as a broader platform). The adapted scale was validated through exploratory factor analysis (EFA), resulting in a three-factor solution. These three factors were named reliability, usefulness and affect, and the willingness to rely on. Factor scores (weighted measures) were then calculated for these factors. Factor scores are estimates of the scores survey participants would have received on each of the factors had they been measured directly, with the following results recorded (Reliability = 4.68/7; Usefulness and Affect = 4.53/7; and Willingness to Rely On = 3.94/7). Further statistical analysis (independent samples t-test) determined the difference in factor scores between the factors when age (Gen Z/Millennials vs. Gen X/Boomers) was utilized as the independent, categorical variable. The results showed the difference in mean scores across all three factors to be statistically significant (p<0.05) for these two core age groupings: (1) Gen Z/Millennials Reliability = 4.90/7 vs. Gen X/Boomers Reliability = 4.34/7; (2) Gen Z/Millennials Usefulness and Affect = 4.85/7 vs Gen X/Boomers Usefulness and Affect = 4.05/7; and (3) Gen Z/Millennials Willingness to Rely On = 4.53/7 vs Gen X/Boomers Willingness to Rely On = 3.03/7. The results clearly indicate that older social media users lack trust in the quality of information conveyed in social media ads when compared to younger, more social media-savvy consumers. This is especially evident with respect to Factor 3 (Willingness to Rely On), whose underlying variables reflect one’s behavioral intent to act based on the information conveyed in advertising. These findings can be useful to marketers, advertisers, and brand managers in that the results highlight a critical need to design ‘authentic’ advertisements on social media sites to better connect with these older users in an attempt to foster positive behavioral responses from within this large demographic group – whose engagement with social media sites continues to increase year on year.

Keywords: social media advertising, trust, older consumers, internet studies

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2010 Molecular Docking of Marrubiin in Candida Rugosa Lipase

Authors: Benarous Khedidja, Yousfi Mohamed

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Infections caused by Candida species manifest in a number of diseases, including candidemia, vulvovaginal candidiasis, endocarditis, and peritonitis. These Candida species have been reported to have lipolytic activity by secretion of lipolytic enzymes such as esterases, lipases and phospholipases. These Extracellular hydrolytic enzymes seem to play an important role in Candida overgrowth. Candidiasis is commonly treated with antimycotics such as clotrimazole and nystatin, which bind to a major component of the fungal cell membrane (ergosterol). This binding forms pores in the membrane that lead to death of the fungus. Due to their secondary effects, scientists have thought of another treatment basing on lipase inhibition but we haven’t found any lipase inhibitors used as candidiasis treatment. In this work, we are interested to lipases inhibitors such as alkaloids as another candidiasis treatment. In the first part, we have proceeded to optimize the alkaloid structures and protein 3D structure using Hyperchem software. Secondly, we have docked inhibitors using Genetic algorithm with GOLD software. The results have shown ten possibilities of binding inhibitor to Candida rugosa lipase (CRL) but only one possibility has been accepted depending on the weakest binding energy.

Keywords: marrubiin, candida rugosa lipase, docking, gold

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2009 An Analytical Study of FRP-Concrete Bridge Superstructures

Authors: Wael I. Alnahhal

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It is a major challenge to build a bridge superstructure that has long-term durability and low maintenance requirements. A solution to this challenge may be to use new materials or to implement new structural systems. Fiber reinforced polymer (FRP) composites have continued to play an important role in solving some of persistent problems in infrastructure applications because of its high specific strength, light weight, and durability. In this study, the concept of the hybrid FRP-concrete structural systems is applied to a bridge superstructure. The hybrid FRP-concrete bridge superstructure is intended to have durable, structurally sound, and cost effective hybrid system that will take full advantage of the inherent properties of both FRP materials and concrete. In this study, two hybrid FRP-concrete bridge systems were investigated. The first system consists of trapezoidal cell units forming a bridge superstructure. The second one is formed by arch cells. The two systems rely on using cellular components to form the core of the bridge superstructure, and an outer shell to warp around those cells to form the integral unit of the bridge. Both systems were investigated analytically by using finite element (FE) analysis. From the rigorous FE studies, it was concluded that first system is more efficient than the second.

Keywords: bridge superstructure, hybrid system, fiber reinforced polymer, finite element analysis

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2008 Enhancing the Effectiveness of Air Defense Systems through Simulation Analysis

Authors: F. Felipe

Abstract:

Air Defense Systems contain high-value assets that are expected to fulfill their mission for several years - in many cases, even decades - while operating in a fast-changing, technology-driven environment. Thus, it is paramount that decision-makers can assess how effective an Air Defense System is in the face of new developing threats, as well as to identify the bottlenecks that could jeopardize the security of the airspace of a country. Given the broad extent of activities and the great variety of assets necessary to achieve the strategic objectives, a systems approach was taken in order to delineate the core requirements and the physical architecture of an Air Defense System. Then, value-focused thinking helped in the definition of the measures of effectiveness. Furthermore, analytical methods were applied to create a formal structure that preliminarily assesses such measures. To validate the proposed methodology, a powerful simulation was also used to determine the measures of effectiveness, now in more complex environments that incorporate both uncertainty and multiple interactions of the entities. The results regarding the validity of this methodology suggest that the approach can support decisions aimed at enhancing the capabilities of Air Defense Systems. In conclusion, this paper sheds some light on how consolidated approaches of Systems Engineering and Operations Research can be used as valid techniques for solving problems regarding a complex and yet vital matter.

Keywords: air defense, effectiveness, system, simulation, decision-support

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2007 Numerical Simulation of Supersonic Gas Jet Flows and Acoustics Fields

Authors: Lei Zhang, Wen-jun Ruan, Hao Wang, Peng-Xin Wang

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The source of the jet noise is generated by rocket exhaust plume during rocket engine testing. A domain decomposition approach is applied to the jet noise prediction in this paper. The aerodynamic noise coupling is based on the splitting into acoustic sources generation and sound propagation in separate physical domains. Large Eddy Simulation (LES) is used to simulate the supersonic jet flow. Based on the simulation results of the flow-fields, the jet noise distribution of the sound pressure level is obtained by applying the Ffowcs Williams-Hawkings (FW-H) acoustics equation and Fourier transform. The calculation results show that the complex structures of expansion waves, compression waves and the turbulent boundary layer could occur due to the strong interaction between the gas jet and the ambient air. In addition, the jet core region, the shock cell and the sound pressure level of the gas jet increase with the nozzle size increasing. Importantly, the numerical simulation results of the far-field sound are in good agreement with the experimental measurements in directivity.

Keywords: supersonic gas jet, Large Eddy Simulation(LES), acoustic noise, Ffowcs Williams-Hawkings(FW-H) equations, nozzle size

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2006 Development and Usability Assessment of a Connected Resistance Exercise Band Application for Strength-Monitoring

Authors: J. A. Batsis, G. G. Boateng, L. M. Seo, C. L. Petersen, K. L. Fortuna, E. V. Wechsler, R. J. Peterson, S. B. Cook, D. Pidgeon, R. S. Dokko, R. J. Halter, D. F. Kotz

Abstract:

Resistance exercise bands are a core component of any physical activity strengthening program. Strength training can mitigate the development of sarcopenia, the loss of muscle mass or strength and function with aging. Yet, the adherence of such behavioral exercise strategies in a home-based setting are fraught with issues of monitoring and compliance. Our group developed a Bluetooth-enabled resistance exercise band capable of transmitting data to an open-source platform. In this work, we developed an application to capture this information in real-time, and conducted three usability studies in two mixed-aged groups of participants (n=6 each) and a group of older adults with obesity participating in a weight-loss intervention (n=20). The system was favorable, acceptable and provided iterative information that could assist in future deployment on ubiquitous platforms. Our formative work provides the foundation to deliver home-based monitoring interventions in a high-risk, older adult population.

Keywords: application, mHealth, older adult, resistance exercise band, sarcopenia

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2005 Extracellular Protein Secreted by Bacillus subtilis ATCC21332 in the Presence of Streptomycin Sulfate

Authors: M. N. Hanina, M. Hairul Shahril, I. Ismatul Nurul Asyikin, A. K. Abdul Jalil, M. R. Salina, M. R. Maryam, M. Rosfarizan

Abstract:

The extracellular proteins secreted by bacteria may be increased in stressful surroundings, such as in the presence of antibiotics. It appears that many antibiotics, when used at low concentrations, have in common the ability to activate or repress gene transcription, which is distinct from their inhibitory effect. There have been comparatively few studies on the potential of antibiotics as a specific chemical signal that can trigger a variety of biological functions. Therefore, this study was carried out to determine the effect of Streptomycin Sulfate in regulating extracellular proteins secreted by Bacillus subtilis ATCC21332. Results of Microdilution assay showed that the Minimum Inhibition Concentration (MIC) of Streptomycin Sulfate on B. subtilis ATCC21332 was 2.5 mg/ml. The bacteria cells were then exposed to Streptomycin Sulfate at concentration of 0.01 MIC before being further incubated for 48h to 72 h. The extracellular proteins secreted were then isolated and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Proteins profile revealed that three additional bands with approximate sizes of 30 kDa, 22 kDa and 23 kDa were appeared for the treated bacteria with Streptomycin Sulfate. Thus, B. subtilis ATCC21332 in stressful condition with the presence of Streptomycin Sulfate at low concentration could induce the extracellular proteins secretion.

Keywords: Bacillus subtilis ATCC21332, streptomycin sulfate, extracellular proteins, antibiotics

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2004 Grape Seed Extract and Zinc Containing Multivitamin-Mineral Nutritional Food Supplement Protects Heart against Myocardial Ischemic-Reperfusion Injury in Wistar Rats

Authors: S. M. Satyam, K. L. Bairy, R. Pirasanthan, R. L. Vaishnav

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Zincovit tablets have been used as nutritional food supplement over a prolonged period of time. The aim of the present study was to investigate the cardio-protective effect of combined formulation of grape seed extract and Zincovit tablets (40, 80 and 160 mg/kg) using a Langendorff model of ischemia-reperfusion in Wistar rats. Following 21 days of pre-treatment, combined formulation of grape seed extract and Zincovit tablets significantly attenuated ischemia-reperfusion induced cardiac injury in terms of increased coronary flow rate (p < 0.01), decreased creatine kinase activity in coronary effluent (p < 0.05), decreased MDA (p < 0.001), 4-HNE (p < 0.001) and increased protein thiol content (p < 0.01) in comparison with the untreated (control) group. This study opens an avenue to clinical studies to demonstrate the validity of this paradigm as a nutritional food supplement, which could improve the clinical outcome of patients subjected to percutaneous angioplasty.

Keywords: grape seed extract, myocardial ischemia-reperfusion injury, oxidative stress, Zincovit tablets

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2003 An Intelligent Nondestructive Testing System of Ultrasonic Infrared Thermal Imaging Based on Embedded Linux

Authors: Hao Mi, Ming Yang, Tian-yue Yang

Abstract:

Ultrasonic infrared nondestructive testing is a kind of testing method with high speed, accuracy and localization. However, there are still some problems, such as the detection requires manual real-time field judgment, the methods of result storage and viewing are still primitive. An intelligent non-destructive detection system based on embedded linux is put forward in this paper. The hardware part of the detection system is based on the ARM (Advanced Reduced Instruction Set Computer Machine) core and an embedded linux system is built to realize image processing and defect detection of thermal images. The CLAHE algorithm and the Butterworth filter are used to process the thermal image, and then the boa server and CGI (Common Gateway Interface) technology are used to transmit the test results to the display terminal through the network for real-time monitoring and remote monitoring. The system also liberates labor and eliminates the obstacle of manual judgment. According to the experiment result, the system provides a convenient and quick solution for industrial non-destructive testing.

Keywords: remote monitoring, non-destructive testing, embedded Linux system, image processing

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2002 Gene Expression Meta-Analysis of Potential Shared and Unique Pathways Between Autoimmune Diseases Under anti-TNFα Therapy

Authors: Charalabos Antonatos, Mariza Panoutsopoulou, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos

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The extended tissue damage and severe clinical outcomes of autoimmune diseases, accompanied by the high annual costs to the overall health care system, highlight the need for an efficient therapy. Increasing knowledge over the pathophysiology of specific chronic inflammatory diseases, namely Psoriasis (PsO), Inflammatory Bowel Diseases (IBD) consisting of Crohn’s disease (CD) and Ulcerative colitis (UC), and Rheumatoid Arthritis (RA), has provided insights into the underlying mechanisms that lead to the maintenance of the inflammation, such as Tumor Necrosis Factor alpha (TNF-α). Hence, the anti-TNFα biological agents pose as an ideal therapeutic approach. Despite the efficacy of anti-TNFα agents, several clinical trials have shown that 20-40% of patients do not respond to treatment. Nowadays, high-throughput technologies have been recruited in order to elucidate the complex interactions in multifactorial phenotypes, with the most ubiquitous ones referring to transcriptome quantification analyses. In this context, a random effects meta-analysis of available gene expression cDNA microarray datasets was performed between responders and non-responders to anti-TNFα therapy in patients with IBD, PsO, and RA. Publicly available datasets were systematically searched from inception to 10th of November 2020 and selected for further analysis if they assessed the response to anti-TNFα therapy with clinical score indexes from inflamed biopsies. Specifically, 4 IBD (79 responders/72 non-responders), 3 PsO (40 responders/11 non-responders) and 2 RA (16 responders/6 non-responders) datasetswere selected. After the separate pre-processing of each dataset, 4 separate meta-analyses were conducted; three disease-specific and a single combined meta-analysis on the disease-specific results. The MetaVolcano R package (v.1.8.0) was utilized for a random-effects meta-analysis through theRestricted Maximum Likelihood (RELM) method. The top 1% of the most consistently perturbed genes in the included datasets was highlighted through the TopConfects approach while maintaining a 5% False Discovery Rate (FDR). Genes were considered as Differentialy Expressed (DEGs) as those with P ≤ 0.05, |log2(FC)| ≥ log2(1.25) and perturbed in at least 75% of the included datasets. Over-representation analysis was performed using Gene Ontology and Reactome Pathways for both up- and down-regulated genes in all 4 performed meta-analyses. Protein-Protein interaction networks were also incorporated in the subsequentanalyses with STRING v11.5 and Cytoscape v3.9. Disease-specific meta-analyses detected multiple distinct pro-inflammatory and immune-related down-regulated genes for each disease, such asNFKBIA, IL36, and IRAK1, respectively. Pathway analyses revealed unique and shared pathways between each disease, such as Neutrophil Degranulation and Signaling by Interleukins. The combined meta-analysis unveiled 436 DEGs, 86 out of which were up- and 350 down-regulated, confirming the aforementioned shared pathways and genes, as well as uncovering genes that participate in anti-inflammatory pathways, namely IL-10 signaling. The identification of key biological pathways and regulatory elements is imperative for the accurate prediction of the patient’s response to biological drugs. Meta-analysis of such gene expression data could aid the challenging approach to unravel the complex interactions implicated in the response to anti-TNFα therapy in patients with PsO, IBD, and RA, as well as distinguish gene clusters and pathways that are altered through this heterogeneous phenotype.

Keywords: anti-TNFα, autoimmune, meta-analysis, microarrays

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2001 Characterization of the Queuine Salvage Pathway From Bacteria in the Human Parasite Entamoeba Histolytica

Authors: Lotem Sarid, Meirav Trebicz-Geffen, Serge Ankri

Abstract:

Queuosine (Q) is a naturally occurring modified nucleoside that occurs in the first position of transfer RNA anticodons such as Asp, Asn, His, and Tyr. As eukaryotes lack pathways to synthesize queuine, the nucleobase of queuosine, they must obtain it from their diet or gut microbiota. Our previous work investigated the effects of queuine on the physiology of the eukaryotic parasite Entamoeba histolytica and defined the enzyme EhTGT responsible for its incorporation into tRNA. To our best knowledge, it is unknown how E. histolytica salvages Q from gut bacteria. We used N-acryloyl-3-aminophenylboronic acid (APB) PAGE analysis to demonstrate that E. histolytica trophozoites can salvage queuine from Q or E. coli K12 but not from the modified E. coli QueC strain, which cannot produce queuine. Next, we examined the role of EhDUF2419, a protein with homology to DNA glycosylase, as a queuine salvage enzyme in E. histolytica. When EhDUF2419 expression is silenced, it inhibits Q's conversion to queuine, resulting in a decrease in Q-tRNA levels. We also observed that Q protects control trophozoites from oxidative stress (OS), but not siEhDUF2419 trophozoites. Overall, our data reveal that EhDUF2419 is central for the salvaging of queuine from bacteria and for the resistance of the parasite to OS.

Keywords: entamoeba histolytica, epitranscriptomics, gut microbiota, queuine, queuosine, response to oxidative stress, tRNA modification.

Procedia PDF Downloads 118
2000 The Principles of Democracy and Development: The Political and Philosophical Foundations of Development-Democracy in Africa

Authors: Fadeke Olu-Owolabi, Fayomi Oluyemi

Abstract:

The political and societal orders face the awesome task of overcoming the difficulties which lead to growing tensions and conflicts in Africa. At the core of analysis is the question, how stable and adaptable are established democracies, new democracies, and political and societal actors? The idea of development-democracy as implying the strong linkage between economic development and political democracy appropriately describes the distinguishing characteristic of this new demand for democracy in Africa. The theoretical study examines the political and philosophical foundation of the idea of development-democracy and the arguments presented to support the need for its adoption in Africa today. This paper critically examines the polemic between the advocates of developmental dictatorship and developmental-democracy and argues for the adoption of the latter in Africa. The paper sets out to expose for the political and philosophical foundation of developmental democracy maintaining that only democracy can facilitate development. This argument is supported further by the claim that both democracy and development are two sides of the same coin in the sense that the two are both ethical concepts. The paper also maintained that the only way by which democracy is worthwhile is when it is developmental. Finally, the paper affirms that since the two concepts of democracy and development are like the Siamese twins then the way out of Africa’s present crisis of development is to wholeheartedly embrace democracy. It posits that when genuine democracy is adopted, genuine and sustainable development can then be attained.

Keywords: democracy, development, polemic, principles

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1999 Multilocus Phylogenetic Approach Reveals Informative DNA Barcodes for Studying Evolution and Taxonomy of Fusarium Fungi

Authors: Alexander A. Stakheev, Larisa V. Samokhvalova, Sergey K. Zavriev

Abstract:

Fusarium fungi are among the most devastating plant pathogens distributed all over the world. Significant reduction of grain yield and quality caused by Fusarium leads to multi-billion dollar annual losses to the world agricultural production. These organisms can also cause infections in immunocompromised persons and produce the wide range of mycotoxins, such as trichothecenes, fumonisins, and zearalenone, which are hazardous to human and animal health. Identification of Fusarium fungi based on the morphology of spores and spore-forming structures, colony color and appearance on specific culture media is often very complicated due to the high similarity of these features for closely related species. Modern Fusarium taxonomy increasingly uses data of crossing experiments (biological species concept) and genetic polymorphism analysis (phylogenetic species concept). A number of novel Fusarium sibling species has been established using DNA barcoding techniques. Species recognition is best made with the combined phylogeny of intron-rich protein coding genes and ribosomal DNA sequences. However, the internal transcribed spacer of (ITS), which is considered to be universal DNA barcode for Fungi, is not suitable for genus Fusarium, because of its insufficient variability between closely related species and the presence of non-orthologous copies in the genome. Nowadays, the translation elongation factor 1 alpha (TEF1α) gene is the “gold standard” of Fusarium taxonomy, but the search for novel informative markers is still needed. In this study, we used two novel DNA markers, frataxin (FXN) and heat shock protein 90 (HSP90) to discover phylogenetic relationships between Fusarium species. Multilocus phylogenetic analysis based on partial sequences of TEF1α, FXN, HSP90, as well as intergenic spacer of ribosomal DNA (IGS), beta-tubulin (β-TUB) and phosphate permease (PHO) genes has been conducted for 120 isolates of 19 Fusarium species from different climatic zones of Russia and neighboring countries using maximum likelihood (ML) and maximum parsimony (MP) algorithms. Our analyses revealed that FXN and HSP90 genes could be considered as informative phylogenetic markers, suitable for evolutionary and taxonomic studies of Fusarium genus. It has been shown that PHO gene possesses more variable (22 %) and parsimony informative (19 %) characters than other markers, including TEF1α (12 % and 9 %, correspondingly) when used for elucidating phylogenetic relationships between F. avenaceum and its closest relatives – F. tricinctum, F. acuminatum, F. torulosum. Application of novel DNA barcodes confirmed the fact that F. arthrosporioides do not represent a separate species but only a subspecies of F. avenaceum. Phylogeny based on partial PHO and FXN sequences revealed the presence of separate cluster of four F. avenaceum strains which were closer to F. torulosum than to major F. avenaceum clade. The strain F-846 from Moldova, morphologically identified as F. poae, formed a separate lineage in all the constructed dendrograms, and could potentially be considered as a separate species, but more information is needed to confirm this conclusion. Variable sites in PHO sequences were used for the first-time development of specific qPCR-based diagnostic assays for F. acuminatum and F. torulosum. This work was supported by Russian Foundation for Basic Research (grant № 15-29-02527).

Keywords: DNA barcode, fusarium, identification, phylogenetics, taxonomy

Procedia PDF Downloads 321
1998 The Principles of Democracy and Development: The Political and Philosophical Foundations of Development-Development in Africa

Authors: Fadeke E. Olu-Owolabi, Fayomi Oluyemi

Abstract:

The political and societal orders face the awesome task of overcoming the difficulties which lead to growing tensions and conflicts in Africa. At the core of analysis is the question, how stable and adaptable are established democracies, new democracies, and political and societal actors? The idea of development-democracy as implying the strong linkage between economic development and political democracy appropriately describes the distinguishing characteristic of this new demand for democracy in Africa. The theoretical study examines the political and philosophical foundation of the idea of development-democracy and the arguments presented to support the need for its adoption in Africa today. This paper critically examines the polemic between the advocates of developmental dictatorship and developmental-democracy and argues for the adoption of the latter in Africa. The paper sets out to expose for the political and philosophical foundation of developmental democracy maintaining that only democracy can facilitate development. This argument is supported further by the claim that both democracy and development are two sides of the same coin in the sense that the two are both ethical concepts. The paper also maintained that the only way by which democracy is worthwhile is when it is developmental. Finally the paper affirms that since the two concepts of democracy and development are like the Siamese twins then the way out of Africa’s present crisis of development is to wholeheartedly embrace democracy. It posits that when genuine democracy is adopted, genuine and sustainable development can then be attained.

Keywords: democracy, development, polemic, principles

Procedia PDF Downloads 428
1997 Factors Affecting Consumers’ Online Shopping Behavior in Vietnam during the COVID-19 Pandemic: A Case Study of Tiki

Authors: Thi Hai Anh Nguyen, Pantea Aria

Abstract:

Tiki is one of the leading e-commerce companies in Viet Nam. Since the beginning of 2020, COVID-19 has been spreading around the world. Thanks to this pandemic, the Tiki platform has many strengths and has faced many threats. Customer behaviour was forecasted to change during the COVID-19 pandemic. The aim of the investigation is (1) Identifying factors affecting online consumer behaviour of Tiki in Ho Chi Minh City, Vietnam, (2) Measuring the level of impact of these factors, and (3) Recommendations for Tiki to improve its business strategy for the next stage. This research studies eight factors and collected 378 online surveys for analysis. Using SPSS software identified five factors (product, price, reliability, and web design) positively influencing customer behaviour. COVID-19 factor does not impact significantly Tiki’s customer behaviour. This research conducted some qualitative interviews to understand shopping experiences and customers’ expectations. One of these interviews’ main points is that Tiki’s customers have high trust in the Tiki brand and its high-quality products. Based on the results, the Tiki corporation should secure its core value. Tiki’s employees and logistics systems should be well-trained and optimized to improve customer experiences.

Keywords: COVID-19, e-commerce, impact, pandemic, Vietnam

Procedia PDF Downloads 158
1996 Masked Candlestick Model: A Pre-Trained Model for Trading Prediction

Authors: Ling Qi, Matloob Khushi, Josiah Poon

Abstract:

This paper introduces a pre-trained Masked Candlestick Model (MCM) for trading time-series data. The pre-trained model is based on three core designs. First, we convert trading price data at each data point as a set of normalized elements and produce embeddings of each element. Second, we generate a masked sequence of such embedded elements as inputs for self-supervised learning. Third, we use the encoder mechanism from the transformer to train the inputs. The masked model learns the contextual relations among the sequence of embedded elements, which can aid downstream classification tasks. To evaluate the performance of the pre-trained model, we fine-tune MCM for three different downstream classification tasks to predict future price trends. The fine-tuned models achieved better accuracy rates for all three tasks than the baseline models. To better analyze the effectiveness of MCM, we test the same architecture for three currency pairs, namely EUR/GBP, AUD/USD, and EUR/JPY. The experimentation results demonstrate MCM’s effectiveness on all three currency pairs and indicate the MCM’s capability for signal extraction from trading data.

Keywords: masked language model, transformer, time series prediction, trading prediction, embedding, transfer learning, self-supervised learning

Procedia PDF Downloads 120
1995 Influence of Shield Positions on Thermo/Fluid Performance of Pin Fin Heat Sink

Authors: Ramy H. Mohammed

Abstract:

In heat sinks, the flow within the core exhibits separation and hence does not lend itself to simple analytical boundary layer or duct flow analysis of the wall friction. In this paper, I present some findings from an experimental and numerical study aimed to obtain physical insight into the influence of the presence of the shield and its position on the hydraulic and thermal performance of square pin fin heat sink without top by-pass. The variations of the Nusselt number and friction factor are obtained under varied parameters, such as the Reynolds number and the shield position. The numerical code is validated by comparing the numerical results with the available experimental data. It is shown that, there is a good agreement between the temperature predictions based on the model and the experimental data. Results show that, as the presence of the shield, the heat transfer of fin array is enhanced and the flow resistance increased. The surface temperature distribution of the heat sink base is more uniform when the dimensionless shield position equals to 1/3 or 2/3. The comprehensive performance evaluation approach based on identical pumping power criteria is adopted and shows that the optimum shield position is at x/l=0.43 where energy is saved.

Keywords: shield, fin array, performance evaluation, heat transfer, energy

Procedia PDF Downloads 304
1994 Near Infrared Spectrometry to Determine the Quality of Milk, Experimental Design Setup and Chemometrics: Review

Authors: Meghana Shankara, Priyadarshini Natarajan

Abstract:

Infrared (IR) spectroscopy has revolutionized the way we look at materials around us. Unraveling the pattern in the molecular spectra of materials to analyze the composition and properties of it has been one of the most interesting challenges in modern science. Applications of the IR spectrometry are numerous in the field’s pharmaceuticals, health, food and nutrition, oils, agriculture, construction, polymers, beverage, fabrics and much more limited only by the curiosity of the people. Near Infrared (NIR) spectrometry is applied robustly in analyzing the solids and liquid substances because of its non-destructive analysis method. In this paper, we have reviewed the application of NIR spectrometry in milk quality analysis and have presented the modes of measurement applied in NIRS measurement setup, Design of Experiment (DoE), classification/quantification algorithms used in the case of milk composition prediction like Fat%, Protein%, Lactose%, Solids Not Fat (SNF%) along with different approaches for adulterant identification. We have also discussed the important NIR ranges for the chosen milk parameters. The performance metrics used in the comparison of the various Chemometric approaches include Root Mean Square Error (RMSE), R^2, slope, offset, sensitivity, specificity and accuracy

Keywords: chemometrics, design of experiment, milk quality analysis, NIRS measurement modes

Procedia PDF Downloads 265
1993 Haematological and Internal Organs Characteristics of Rabbit Bucks Feed Boiled Pigeon Pea (Cajanus Cajan) Seed Meal

Authors: N. S. Okoro

Abstract:

An experiment was conducted to determine the growth performance, blood parameters and reproductive characteristics of 8-week old male weaner rabbits fed 2% boiled pigeon pea seed meal. The study lasted for 16 weeks. Results showed that hematological parameters of the two groups of rabbit bucks were not significantly affected (p > 0.05) by the treatment, meaning that the PPSM was adequate for maintaining the blood parameters at the normal levels. The 20% boiled PPSM significantly affected (P < 0.05) serum Alanine Aminotransferase (ALT) (67.72±2.5 I.U/I) more than the ALT (57.50±2.02 I.U/I) of the control, which is an indication of liver problem. The globulin level (3.00 ± 0.23g/dl) of the 20% boiled PPSM group was significantly higher than that of the control (2.60±0.06 g/dl), indicating that the test diet did not alter protein metabolism in the rabbits. Boiled pigeon pea seed meal supported organ weight and testicular development in rabbit bucks, suggesting that boiling reduced the level of the anti-nutritional factors in pigeon pea seed meal. Thus, 20% boiled pigeon pea can be included in diets of rabbits without adverse effect on blood parameters and internal organs characteristics.

Keywords: hematology, internal organs, Pigeon pea, rabbits, serum biochemistry

Procedia PDF Downloads 390
1992 Confinement and Storage of Cyanate in the Nano Scale via Nanolayered Structures

Authors: Osama Saber

Abstract:

Cyanate is one such anion which is produced during protein poisoning in the body and has been studied extensively in the field of biochemistry because of its toxicity. The present work aims at confinement and storage of cyanate in the nano scale. It was achieved through the intercalation of cyanate anions into nanolayerd structures of Ni-Al LDH. In addition, the effect of aging time on the intercalation of cyanate was clarified using X-ray diffraction and scanning electron microscopy. Furthermore, the effect of cations on the affinity towards the intercalation of cyanate anions inside LDH structure was studied by replacement of tetra-valent cations Ti4+ instead of the tri-vallent cations Al3+ during the preparation of LDH structure. X-ray diffraction patterns of the Ni-Ti LDH showed that the interlayer spacing was 0.73 nm. This spacing was smaller than that of Ni-Al LDH suggesting that the interlayered anions into Ni-Ti LDH are different from those into Ni-Al LDH. Thermal analyses (TG, DTG, and DTA) and Infra-red spectra revealed the presence of only cyanate anions into Ni-Ti LDH while, in the case of Ni-Al LDH, both cyanate and carbonate anions were observed. SEM images showed plate-like morphology for both Ni-Ti and Ni-Al LDHs although the shapes of their plates are not similar. Our results suggested that the LDH structures containing titanium cations have higher affinity for cyanate anions than those containing aluminum cations. Therefore, this choice for cyanate in the interlayered spacing widens the applicability to study the effect of the confinement on the toxicity of cyanate by bio researchers.

Keywords: nanolayered structures, Ni-Al LDH, Ni-Ti LDH, intercalation of cyanate anions, urea hydrolysis

Procedia PDF Downloads 513
1991 Membrane Permeability of Middle Molecules: A Computational Chemistry Approach

Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

Abstract:

Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

Procedia PDF Downloads 182
1990 Modeling of the Mechanism of Ion Channel Opening of the Visual Receptor's Rod on the Light and Allosteric Effect of Rhodopsin in the Phosphorylation Process

Authors: N. S. Vassilieva-Vashakmadze, R. A. Gakhokidze, I. M. Khachatryan

Abstract:

In the first part of the paper it is shown that both the depolarization of the cytoplasmic membrane of rods observed in invertebrates and hyperpolarization characteristic of vertebrates on the light may activate the functioning of ion (Na+) channels of cytoplasmic membrane of rods and thus provide the emergence of nerve impulse and its transfer to the neighboring neuron etc. In the second part, using the quantum mechanical program for modeling of the molecular processes, we got a clear picture demonstrating the effect of charged phosphate groups on the protein components of α-helical subunits of the visual rhodopsin receptor. The analysis shows that the phosphorylation of terminal amino acid of seventh α-helical subunits of the visual rhodopsin causes a redistribution of electron density on the atoms, i.e. polarization of subunits, also the changing the configuration of the nuclear subsystem, which corresponds to the deformation process in the molecule. Based on the use of models it can be concluded that this system has an internal relationship between polarization and deformation processes that indicates on the allosteric effect. The allosteric effect is based on quantum-mechanical principle of the self-consistency of the molecules.

Keywords: membrane potential, ion channels, visual rhodopsin, allosteric effect

Procedia PDF Downloads 268
1989 A Dynamic Model for Assessing the Advanced Glycation End Product Formation in Diabetes

Authors: Victor Arokia Doss, Kuberapandian Dharaniyambigai, K. Julia Rose Mary

Abstract:

Advanced Glycation End (AGE) products are the end products due to the reaction between excess reducing sugar present in diabetes and free amino group in protein lipids and nucleic acids. Thus, non-enzymic glycation of molecules such as hemoglobin, collagen, and other structurally and functionally important proteins add to the pathogenic complications such as diabetic retinopathy, neuropathy, nephropathy, vascular changes, atherosclerosis, Alzheimer's disease, rheumatoid arthritis, and chronic heart failure. The most common non-cross linking AGE, carboxymethyl lysine (CML) is formed by the oxidative breakdown of fructosyllysine, which is a product of glucose and lysine. CML is formed in a wide variety of tissues and is an index to assess the extent of glycoxidative damage. Thus we have constructed a mathematical and computational model that predicts the effect of temperature differences in vivo, on the formation of CML, which is now being considered as an important intracellular milieu. This hybrid model that had been tested for its parameter fitting and its sensitivity with available experimental data paves the way for designing novel laboratory experiments that would throw more light on the pathological formation of AGE adducts and in the pathophysiology of diabetic complications.

Keywords: advanced glycation end-products, CML, mathematical model, computational model

Procedia PDF Downloads 128