Search results for: Biomarker Discovery
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 859

Search results for: Biomarker Discovery

409 Nanomaterials Based Biosensing Chip for Non-Invasive Detection of Oral Cancer

Authors: Suveen Kumar

Abstract:

Oral cancer (OC) is the sixth most death causing cancer in world which includes tumour of lips, floor of the mouth, tongue, palate, cheeks, sinuses, throat, etc. Conventionally, the techniques used for OC detection are toluidine blue staining, biopsy, liquid-based cytology, visual attachments, etc., however these are limited by their highly invasive nature, low sensitivity, time consumption, sophisticated instrument handling, sample processing and high cost. Therefore, we developed biosensing chips for non-invasive detection of OC via CYFRA-21-1 biomarker. CYFRA-21-1 (molecular weight: 40 kDa) is secreted in saliva of OC patients which is a non-invasive biological fluid with a cut-off value of 3.8 ng mL-1, above which the subjects will be suffering from oral cancer. Therefore, in first work, 3-aminopropyl triethoxy silane (APTES) functionalized zirconia (ZrO2) nanoparticles (APTES/nZrO2) were used to successfully detect CYFRA-21-1 in a linear detection range (LDR) of 2-16 ng mL-1 with sensitivity of 2.2 µA mL ng-1. Successively, APTES/nZrO2-RGO was employed to prevent agglomeration of ZrO2 by providing high surface area reduced graphene oxide (RGO) support and much wider LDR (2-22 ng mL-1) was obtained with remarkable limit of detection (LOD) as 0.12 ng mL-1. Further, APTES/nY2O3/ITO platform was used for oral cancer bioseneor development. The developed biosensor (BSA/anti-CYFRA-21-1/APTES/nY2O3/ITO) have wider LDR (0.01-50 ng mL-1) with remarkable limit of detection (LOD) as 0.01 ng mL-1. To improve the sensitivity of the biosensing platform, nanocomposite of yattria stabilized nanostructured zirconia-reduced graphene oxide (nYZR) based biosensor has been developed. The developed biosensing chip having ability to detect CYFRA-21-1 biomolecules in the range of 0.01-50 ng mL-1, LOD of 7.2 pg mL-1 with sensitivity of 200 µA mL ng-1. Further, the applicability of the fabricated biosensing chips were also checked through real sample (saliva) analysis of OC patients and the obtained results showed good correlation with the standard protein detection enzyme linked immunosorbent assay (ELISA) technique.

Keywords: non-invasive, oral cancer, nanomaterials, biosensor, biochip

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408 Treatment of Non-Small Cell Lung Cancer (NSCLC) With Activating Mutations Considering ctDNA Fluctuations

Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

Abstract:

Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

Procedia PDF Downloads 55
407 Osteoprotegerin and Osteoprotegerin/TRAIL Ratio are Associated with Cardiovascular Dysfunction and Mortality among Patients with Renal Failure

Authors: Marek Kuźniewski, Magdalena B. Kaziuk , Danuta Fedak, Paulina Dumnicka, Ewa Stępień, Beata Kuśnierz-Cabala, Władysław Sułowicz

Abstract:

Background: The high prevalence of cardiovascular morbidity and mortality among patients with chronic kidney disease (CKD) is observed especially in those undergoing dialysis. Osteoprotegerin (OPG) and its ligands, receptor activator of nuclear factor kappa-B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been associated with cardiovascular complications. Our aim was to study their role as cardiovascular risk factors in stage 5 CKD patients. Methods: OPG, RANKL and TRAIL concentrations were measured in 69 hemodialyzed CKD patients and 35 healthy volunteers. In CKD patients, cardiovascular dysfunction was assessed with aortic pulse wave velocity (AoPWV), carotid artery intima-media thickness (CCA-IMT), coronary artery calcium score (CaSc) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentration. Cardiovascular and overall mortality data were collected during a 7-years follow-up. Results: OPG plasma concentrations were higher in CKD patients comparing to controls. Total soluble RANKL was lower and OPG/RANKL ratio higher in patients. Soluble TRAIL concentrations did not differ between the groups and OPG/TRAIL ratio was higher in CKD patients. OPG and OPG/TRAIL positively predicted long-term mortality (all-cause and cardiovascular) in CKD patients. OPG positively correlated with AoPWV, CCA-IMT and NT-proBNP whereas OPG/TRAIL with AoPWV and NT-proBNP. Described relationships were independent of classical and non-classical cardiovascular risk factors, with exception of age. Conclusions: Our study confirmed the role of OPG as a biomarker of cardiovascular dysfunction and a predictor of mortality in stage 5 CKD. OPG/TRAIL ratio can be proposed as a predictor of cardiovascular dysfunction and mortality.

Keywords: osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, receptor activator of nuclear factor kappa-B ligand, hemodialysis, chronic kidney disease, cardiovascular disease

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406 Bibliometric Analysis of Global Research Trends on Organization Culture, Strategic Leadership and Performance Using Scopus Database

Authors: Anyia Nduka, Aslan Bin Amad Senin

Abstract:

Taking a behavioral perspective of Organization Culture, Strategic Leadership, and performance (OC, SLP). We examine the role of Strategic Leadership as key vicious mechanism linking OC,SLP to the organizational capacities. Given the increasing degree of dependence of modern businesses on the use and scientific discovery of relevant data, research efforts around the entire globe have been accelerated. In today's corporate world, Strategic Leadership is still the most sustainable option of performance and competitive advantage. This is why it is critical to gain a deep understanding of research area and to strengthen new collaborative networks in efforts to support research transition towards these integrative efforts. This bibliometric analysis is aimed to examine global trends in OC,SLP research based on publication output, author co-authorships, and co-occurrences of author keywords among authors and affiliated countries. 2829 journal articles were retrieved from the Scopus database Between 1974 and 2021. From the research findings, there is a significant increase in number of publications with strong global collaboration (e.g., USA & UK). We also discovered that while most countries/territories without affiliations were centered in developing countries, the outstanding performance of Asian countries and the volume of their collaborations should be emulated.

Keywords: organizational culture, strategic leadership, organizational resilience, performance

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405 CompPSA: A Component-Based Pairwise RNA Secondary Structure Alignment Algorithm

Authors: Ghada Badr, Arwa Alturki

Abstract:

The biological function of an RNA molecule depends on its structure. The objective of the alignment is finding the homology between two or more RNA secondary structures. Knowing the common functionalities between two RNA structures allows a better understanding and a discovery of other relationships between them. Besides, identifying non-coding RNAs -that is not translated into a protein- is a popular application in which RNA structural alignment is the first step A few methods for RNA structure-to-structure alignment have been developed. Most of these methods are partial structure-to-structure, sequence-to-structure, or structure-to-sequence alignment. Less attention is given in the literature to the use of efficient RNA structure representation and the structure-to-structure alignment methods are lacking. In this paper, we introduce an O(N2) Component-based Pairwise RNA Structure Alignment (CompPSA) algorithm, where structures are given as a component-based representation and where N is the maximum number of components in the two structures. The proposed algorithm compares the two RNA secondary structures based on their weighted component features rather than on their base-pair details. Extensive experiments are conducted illustrating the efficiency of the CompPSA algorithm when compared to other approaches and on different real and simulated datasets. The CompPSA algorithm shows an accurate similarity measure between components. The algorithm gives the flexibility for the user to align the two RNA structures based on their weighted features (position, full length, and/or stem length). Moreover, the algorithm proves scalability and efficiency in time and memory performance.

Keywords: alignment, RNA secondary structure, pairwise, component-based, data mining

Procedia PDF Downloads 458
404 Effect of Social Media on Online Buyer Behavior

Authors: Zebider Asire Munyelet, Yibeltal Chanie Manie

Abstract:

In the modern digital landscape, the increase of social media platforms has become identical to the evolution of online consumer behavior. This study investigates the complicated relationship between social media and the purchasing decisions of online buyers. Through an extensive review of existing literature and empirical research, the aim is to comprehensively analyze the multidimensional impact that social media exerts on the various stages of the online buyer's journey. The investigation encompasses the exploration of how social media platforms serve as influential channels for information dissemination, product discovery, and consumer engagement. Additionally, the study investigates the psychological aspects underlying the role of social media in shaping buyer preferences, perceptions, and trust in online transactions. The methodologies employed include both quantitative and qualitative analyses, incorporating surveys, interviews, and data analytics to derive meaningful insights. Statistical models are applied to distinguish patterns in online buyer behavior concerning product awareness, brand loyalty, and decision-making processes. The expected outcomes of this research contribute not only to the academic understanding of the dynamic interplay between social media and online buyer behavior but also offer practical implications for marketers, e-commerce platforms, and policymakers.

Keywords: social platforms, buyer behavior, consumer behavior, digital era

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403 Orbiting Intelligence: A Comprehensive Survey of AI Applications and Advancements in Space Exploration

Authors: Somoshree Datta, Chithra A. V., Sandeep Nithyanandan, Smitha K. K.

Abstract:

Space exploration has always been at the forefront of technological innovation, pushing the boundaries of human knowledge and capabilities. In recent years, the integration of Artificial Intelligence (AI) has revolutionized the field, offering unprecedented opportunities to enhance the efficiency, autonomy and intelligence of space missions. This survey paper aims to provide a comprehensive overview of the multifaceted applications of AI in space exploration, exploring the evolution of this synergy and its impact on mission success, scientific discovery, and the future of space endeavors. Indian Space Research Organization (ISRO) has achieved great feats in the recent moon mission (Chandrayaan-3) and sun mission (Aditya L1) by using artificial intelligence to enhance moon navigation as well as help young scientists to study the Sun even before the launch by creating AI-generated image visualizations. Throughout this survey, we will review key advancements, challenges and prospects in the intersection of AI and space exploration. As humanity continues its quest to explore the cosmos, the integration of AI promises to unlock new frontiers, reshape mission architectures, and redefine our understanding of the universe. This survey aims to serve as a comprehensive resource for researchers, engineers and enthusiasts interested in the dynamic and evolving landscape of AI applications in space exploration.

Keywords: artificial intelligence, space exploration, space missions, deep learning

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402 Electrochemical Bioassay for Haptoglobin Quantification: Application in Bovine Mastitis Diagnosis

Authors: Soledad Carinelli, Iñigo Fernández, José Luis González-Mora, Pedro A. Salazar-Carballo

Abstract:

Mastitis is the most relevant inflammatory disease in cattle, affecting the animal health and causing important economic losses on dairy farms. This disease takes place in the mammary gland or udder when some opportunistic microorganisms, such as Staphylococcus aureus, Streptococcus agalactiae, Corynebacterium bovis, etc., invade the teat canal. According to the severity of the inflammation, mastitis can be classified as sub-clinical, clinical and chronic. Standard methods for mastitis detection include counts of somatic cells, cell culture, electrical conductivity of the milk, and California test (evaluation of “gel-like” matrix consistency after cell lysed with detergents). However, these assays present some limitations for accurate detection of subclinical mastitis. Currently, haptoglobin, an acute phase protein, has been proposed as novel and effective biomarker for mastitis detection. In this work, an electrochemical biosensor based on polydopamine-modified magnetic nanoparticles (MNPs@pDA) for haptoglobin detection is reported. Thus, MNPs@pDA has been synthesized by our group and functionalized with hemoglobin due to its high affinity to haptoglobin protein. The protein was labeled with specific antibodies modified with alkaline phosphatase enzyme for its electrochemical detection using an electroactive substrate (1-naphthyl phosphate) by differential pulse voltammetry. After the optimization of assay parameters, the haptoglobin determination was evaluated in milk. The strategy presented in this work shows a wide range of detection, achieving a limit of detection of 43 ng/mL. The accuracy of the strategy was determined by recovery assays, being of 84 and 94.5% for two Hp levels around the cut off value. Milk real samples were tested and the prediction capacity of the electrochemical biosensor was compared with a Haptoglobin commercial ELISA kit. The performance of the assay has demonstrated this strategy is an excellent and real alternative as screen method for sub-clinical bovine mastitis detection.

Keywords: bovine mastitis, haptoglobin, electrochemistry, magnetic nanoparticles, polydopamine

Procedia PDF Downloads 173
401 Emotion Mining and Attribute Selection for Actionable Recommendations to Improve Customer Satisfaction

Authors: Jaishree Ranganathan, Poonam Rajurkar, Angelina A. Tzacheva, Zbigniew W. Ras

Abstract:

In today’s world, business often depends on the customer feedback and reviews. Sentiment analysis helps identify and extract information about the sentiment or emotion of the of the topic or document. Attribute selection is a challenging problem, especially with large datasets in actionable pattern mining algorithms. Action Rule Mining is one of the methods to discover actionable patterns from data. Action Rules are rules that help describe specific actions to be made in the form of conditions that help achieve the desired outcome. The rules help to change from any undesirable or negative state to a more desirable or positive state. In this paper, we present a Lexicon based weighted scheme approach to identify emotions from customer feedback data in the area of manufacturing business. Also, we use Rough sets and explore the attribute selection method for large scale datasets. Then we apply Actionable pattern mining to extract possible emotion change recommendations. This kind of recommendations help business analyst to improve their customer service which leads to customer satisfaction and increase sales revenue.

Keywords: actionable pattern discovery, attribute selection, business data, data mining, emotion

Procedia PDF Downloads 199
400 Factors of Social Media Platforms on Consumer Behavior

Authors: Zebider Asire Munyelet, Yibeltal Chanie Manie

Abstract:

In the modern digital landscape, the increase of social media platforms has become identical to the evolution of online consumer behavior. This study investigates the complicated relationship between social media and the purchasing decisions of online buyers. Through an extensive review of existing literature and empirical research, the aim is to comprehensively analyze the multidimensional impact that social media exerts on the various stages of the online buyer's journey. The investigation encompasses the exploration of how social media platforms serve as influential channels for information dissemination, product discovery, and consumer engagement. Additionally, the study investigates into the psychological aspects underlying the role of social media in shaping buyer preferences, perceptions, and trust in online transactions. The methodologies employed include both quantitative and qualitative analyses, incorporating surveys, interviews, and data analytics to derive meaningful insights. Statistical models are applied to distinguish patterns in online buyer behavior concerning product awareness, brand loyalty, and decision-making processes. The expected outcomes of this research contribute not only to the academic understanding of the dynamic interplay between social media and online buyer behavior but also offer practical implications for marketers, e-commerce platforms, and policymakers.

Keywords: consumer Behavior, social media, online purchasing, online transaction

Procedia PDF Downloads 77
399 Application of Human Biomonitoring and Physiologically-Based Pharmacokinetic Modelling to Quantify Exposure to Selected Toxic Elements in Soil

Authors: Eric Dede, Marcus Tindall, John W. Cherrie, Steve Hankin, Christopher Collins

Abstract:

Current exposure models used in contaminated land risk assessment are highly conservative. Use of these models may lead to over-estimation of actual exposures, possibly resulting in negative financial implications due to un-necessary remediation. Thus, we are carrying out a study seeking to improve our understanding of human exposure to selected toxic elements in soil: arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), and lead (Pb) resulting from allotment land-use. The study employs biomonitoring and physiologically-based pharmacokinetic (PBPK) modelling to quantify human exposure to these elements. We recruited 37 allotment users (adults > 18 years old) in Scotland, UK, to participate in the study. Concentrations of the elements (and their bioaccessibility) were measured in allotment samples (soil and allotment produce). Amount of produce consumed by the participants and participants’ biological samples (urine and blood) were collected for up to 12 consecutive months. Ethical approval was granted by the University of Reading Research Ethics Committee. PBPK models (coded in MATLAB) were used to estimate the distribution and accumulation of the elements in key body compartments, thus indicating the internal body burden. Simulating low element intake (based on estimated ‘doses’ from produce consumption records), predictive models suggested that detection of these elements in urine and blood was possible within a given period of time following exposure. This information was used in planning biomonitoring, and is currently being used in the interpretation of test results from biological samples. Evaluation of the models is being carried out using biomonitoring data, by comparing model predicted concentrations and measured biomarker concentrations. The PBPK models will be used to generate bioavailability values, which could be incorporated in contaminated land exposure models. Thus, the findings from this study will promote a more sustainable approach to contaminated land management.

Keywords: biomonitoring, exposure, PBPK modelling, toxic elements

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398 Frequency Analysis Using Multiple Parameter Probability Distributions for Rainfall to Determine Suitable Probability Distribution in Pakistan

Authors: Tasir Khan, Yejuan Wang

Abstract:

The study of extreme rainfall events is very important for flood management in river basins and the design of water conservancy infrastructure. Evaluation of quantiles of annual maximum rainfall (AMRF) is required in different environmental fields, agriculture operations, renewable energy sources, climatology, and the design of different structures. Therefore, the annual maximum rainfall (AMRF) was performed at different stations in Pakistan. Multiple probability distributions, log normal (LN), generalized extreme value (GEV), Gumbel (max), and Pearson type3 (P3) were used to find out the most appropriate distributions in different stations. The L moments method was used to evaluate the distribution parameters. Anderson darling test, Kolmogorov- Smirnov test, and chi-square test showed that two distributions, namely GUM (max) and LN, were the best appropriate distributions. The quantile estimate of a multi-parameter PD offers extreme rainfall through a specific location and is therefore important for decision-makers and planners who design and construct different structures. This result provides an indication of these multi-parameter distribution consequences for the study of sites and peak flow prediction and the design of hydrological maps. Therefore, this discovery can support hydraulic structure and flood management.

Keywords: RAMSE, multiple frequency analysis, annual maximum rainfall, L-moments

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397 Surface Segregation-Inspired Design for Bimetallic Nanoparticle Catalysts

Authors: Yaxin Tang, Mingao Hou, Qian He, Guangfu Luo

Abstract:

Bimetallic nanoparticles serve as a promising class of catalysts with tunable properties suitable for diverse catalytic reactions, yet a comprehensive understanding of their actual structures under operating conditions and the optimal design principles remains largely elusive. In this study, we unveil a prevalent surface segregation phenomenon in nearly 100 platinum-group-element-based bimetallic nanoparticles through first principles-based molecular dynamics simulations. Our findings highlight that two components in a nanoparticle with relatively lower surface energy tend to segregate to the surface. Motivated by this discovery, we propose a deliberate exploitation of surface segregation in designing bimetallic nanoparticle catalysts, aiming for heightened stability and reduced consumption of precious metals. To validate this strategy, we further investigate 36 platinum-based bimetallic nanoparticles for propane dehydrogenation catalysis. Through a systematic examination of catalytic sites on nanoparticles, we identify several systems as top candidates with Pt-enriched surfaces, remarkable thermal stability, and superior catalytic activity for propane dehydrogenation. The insights gained garnered from this study are anticipated to provide a valuable framework for the optimal design of other bimetallic nanoparticles.

Keywords: bimetallic nanoparticles, platinum-group element, catalysis, surface segregation, first-principles calculations

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396 Electrochemical Biosensor Based on Chitosan-Gold Nanoparticles, Carbon Nanotubes for Detection of Ovarian Cancer Biomarker

Authors: Parvin Samadi Pakchin, Reza Saber, Hossein Ghanbari, Yadollah Omidi

Abstract:

Ovarian cancer is one of the leading cause of mortality among the gynecological malignancies, and it remains the one of the most prevalent cancer in females worldwide. Tumor markers are biochemical molecules in blood or tissues which can indicates cancers occurrence in the human body. So, the sensitive and specific detection of cancer markers typically recruited for diagnosing and evaluating cancers. Recently extensive research efforts are underway to achieve a simple, inexpensive and accurate device for detection of cancer biomarkers. Compared with conventional immunoassay techniques, electrochemical immunosensors are of great interest, because they are specific, simple, inexpensive, easy to handling and miniaturization. Moreover, in the past decade nanotechnology has played a crucial role in the development of biosensors. In this study, a signal-off electrochemical immunosensor for the detection of CA125 antigen has been developed using chitosan-gold nanoparticles (CS-AuNP) and multi-wall carbon nanotubes (MWCNT) composites. Toluidine blue (TB) is used as redox probe which is immobilized on the electrode surface. CS-AuNP is synthesized by a simple one step method that HAuCl4 is reduced by NH2 groups of chitosan. The CS-AuNP-MWCNT modified electrode has shown excellent electrochemical performance compared with bare Au electrode. MWCNTs and AuNPs increased electrochemical conductivity and accelerate electrons transfer between solution and electrode surface while excessive amine groups on chitosan lead to the effective loading of the biological material (CA125 antibody) and TB on the electrode surface. The electrochemical, immobilization and sensing properties CS-AuNP-MWCNT-TB modified electrodes are characterized by cyclic voltammetry, electrochemical impedance spectroscopy, differential pulse voltammetry and square wave voltammetry with Fe(CN)63−/4−as an electrochemical redox indicator.

Keywords: signal-off electrochemical biosensor, CA125, ovarian cancer, chitosan-gold nanoparticles

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395 Regulation of SHP-2 Activity by Small Molecules for the Treatment of T Cell-Mediated Diseases

Authors: Qiang Xu, Xingxin Wu, Wenjie Guo, Xingqi Wang, Yang Sun, Renxiang Tan

Abstract:

The phosphatase SHP-2 is known to exert regulatory activities on cytokine receptor signaling and the dysregulation of SHP-2 has been implicated in the pathogenesis of a variety of diseases. Here we report several small molecule regulators of SHP-2 for the treatment of T cell-mediated diseases. The new cyclodepsipeptide trichomides A, isolated from the fermentation products of Trichothecium roseum, increased the phosphorylation of SHP-2 in activated T cells, and ameliorated contact dermatitis in mice. The trichomides A’s effects were significantly reversed by using the SHP-2-specific inhibitor PHPS1 or T cell-conditional SHP-2 knockout mice. Another compound is a cerebroside Fusaruside isolated from the endophytic fungus Fusarium sp. IFB-121. Fusaruside also triggered the tyrosine phosphorylation of SHP-2, which provided a possible mean of selectively targeting STAT1 for the treatment of Th1 cell-mediated inflammation and led to the discovery of the non-phosphatase-like function of SHP-2. Namely, the Fusaruside-activated pY-SHP-2 selectively sequestrated the cytosolic STAT1 to prevent its recruitment to IFN-R, which contributed to the improvement of experimental colitis in mice. Blocking the pY-SHP-2-STAT1 interaction, with SHP-2 inhibitor NSC-87877 or using T cells from conditional SHP-2 knockout mice, reversed the effects of fusaruside. Furthermore, the fusaruside’s effect is independent of the phosphatase activity of SHP-2, demonstrating a novel role for SHP-2 in regulating STAT1 signaling and Th1-type immune responses.

Keywords: SHP-2, small molecules, T cell, T cell-mediated diseases

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394 The Physicochemical Properties of Two Rivers in Eastern Cape South Africa as Relates to Vibrio Spp Density

Authors: Oluwatayo Abioye, Anthony Okoh

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In the past view decades; human has experienced outbreaks of infections caused by pathogenic Vibrio spp which are commonly found in aquatic milieu. Asides the well-known Vibrio cholerae, discovery of other pathogens in this genus has been on the increase. While the dynamics of occurrence and distribution of Vibrio spp have been linked to some physicochemical parameters in salt water, data in relation to fresh water is limited. Hence, two rivers of importance in the Eastern Cape, South Africa were selected for this study. In all, eleven sampling sites were systematically identified and relevant physicochemical parameters, as well as Vibrio spp density, were determined for the period of six months using standard instruments and methods. Results were statistically analysed to determined key physicochemical parameters that determine the density of Vibrio spp in the selected rivers. Results: The density of Vibrio spp in all the sampling points ranges between < 1 CFU/mL to 174 x 10-2 CFU/mL. The physicochemical parameters of some of the sampling points were above the recommended standards. The regression analysis showed that Vibrio density in the selected rivers depends on a complex relationship between various physicochemical parameters. Conclusion: This study suggests that Vibrio spp density in fresh water does not depend on only temperature and salinity as suggested by earlier studies on salt water but rather on a complex relationship between several physicochemical parameters.

Keywords: vibrio density, physicochemical properties, pathogen, aquatic milieu

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393 The Biology of Persister Cells and Antibiotic Resistance

Authors: Zikora K. G. Anyaegbunam, Annabel A. Nnawuihe, Ngozi J. Anyaegbunam, Emmanuel A. Eze

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The discovery and production of new antibiotics is unavoidable in the fight against drug-resistant bacteria. However, this is only part of the problem; we have never really had medications that could completely eradicate an infection. All pathogens create a limited number of dormant persister cells that are resistant to antibiotic treatment. When the concentration of antibiotics decreases, surviving persisters repopulate the population, resulting in a recurrent chronic infection. Bacterial populations have an alternative survival strategy to withstand harsh conditions or antibiotic exposure, in addition to the well-known methods of antibiotic resistance and biofilm formation. Persister cells are a limited subset of transiently antibiotic-tolerant phenotypic variations capable of surviving high-dose antibiotic therapy. Persisters that flip back to a normal phenotype can restart growth when antibiotic pressure drops, assuring the bacterial population's survival. Persister cells have been found in every major pathogen, and they play a role in antibiotic tolerance in biofilms as well as the recalcitrance of chronic infections. Persister cells has been implicated to play a role in the establishment of antibiotic resistance, according to growing research. Thusthe need to basically elucidate the biology of persisters and how they are linked to antibiotic resistance, and as well it's link to diseases.

Keywords: persister cells, phenotypic variations, repopulation, mobile genetic transfers, antibiotic resistance

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392 Characterising Rates of Renal Dysfunction and Sarcoidosis in Patients with Elevated Serum Angiotensin-Converting Enzyme

Authors: Fergal Fouhy, Alan O’Keeffe, Sean Costelloe, Michael Clarkson

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Background: Sarcoidosis is a systemic, non-infectious disease of unknown aetiology, characterized by non-caseating granulomatous inflammation. The lung is most often affected (90%); however, the condition can affect all organs, including the kidneys. There is limited evidence describing the incidence and characteristics of renal involvement in sarcoidosis. Serum angiotensin-converting enzyme (ACE) is a recognised biomarker used in the diagnosis and monitoring of sarcoidosis. Methods: A single-centre, retrospective cohort study of patients presenting to Cork University Hospital (CUH) in 2015 with first-time elevations of serum ACE was performed. This included an initial database review of ACE and other biochemistry results, followed by a medical chart review to confirm the presence or absence of sarcoidosis and management thereof. Acute kidney injury (AKI) was staged using the AKIN criteria, and chronic kidney disease (CKD) was staged using the KDIGO criteria. Follow-up was assessed over five years tracking serum creatinine, serum calcium, and estimated glomerular filtration rates (eGFR). Results: 119 patients were identified as having a first raised serum ACE in 2015. Seventy-nine male patients and forty female patients were identified. The mean age of patients identified was 47 years old. 11% had CKD at baseline. 18% developed an AKI at least once within the next five years. A further 6% developed CKD during this time period. 13% developed hypercalcemia. The patients within the lowest quartile of serums ACE had an incidence of sarcoidosis of 5%. None of this group developed hypercalcemia, 23% developed AKI, and 7% developed CKD. Of the patients with a serum ACE in the highest quartile, almost all had documented diagnoses of sarcoidosis with an incidence of 96%. 3% of this group developed hypercalcemia, 13% AKI and 3% developed CKD. Conclusions: There was an unexpectedly high incidence of AKI in patients who had a raised serum ACE. Not all patients with a raised serum ACE had a confirmed diagnosis of sarcoidosis. There does not appear to be a relationship between increased serum ACE levels and increased incidence of hypercalcaemia, AKI, and CKD. Ideally, all patients should have biopsy-proven sarcoidosis. This is an initial study that should be replicated with larger numbers and including multiple centres.

Keywords: sarcoidosis, acute kidney injury, chronic kidney disease, hypercalcemia

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391 Rational Design of Potent Compounds for Inhibiting Ca2+ -Dependent Calmodulin Kinase IIa, a Target of Alzheimer’s Disease

Authors: Son Nguyen, Thanh Van, Ly Le

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Ca2+ - dependent calmodulin kinase IIa (CaMKIIa) has recently been found to associate with protein tau missorting and polymerization in Alzheimer’s Disease (AD). However, there has yet inhibitors targeting CaMKIIa to investigate the correlation between CaMKIIa activity and protein tau polymer formation. Combining virtual screening and our statistics in binding contribution scoring function (BCSF), we rationally identified potential compounds that bind to specific CaMKIIa active site and specificity-affinity distribution of the ligand within the active site. Using molecular dynamics simulation, we identified structural stability of CaMKIIa and potent inhibitors, and site-directed bonding, separating non-specific and specific molecular interaction features. Despite of variation in confirmation of simulation time, interactions of the potent inhibitors were found to be strongly associated with the unique chemical features extracted from molecular binding poses. In addition, competitive inhibitors within CaMKIIa showed an important molecular recognition pattern toward specific ligand features. Our approach combining virtual screening with BCSF may provide an universally applicable method for precise identification in the discovery of compounds.

Keywords: Alzheimer’s disease, Ca 2+ -dependent calmodulin kinase IIa, protein tau, molecular docking

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390 Early Childhood Teacher Turnover in an Early Head Start Setting: A Qualitative Examination

Authors: Jennifer Sturgeon

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Stable relationships provide a predictable and trusting environment and are essential for early development, but high teacher turnover rates in childcare settings make it challenging for infants and toddlers to form stable relationships with their teachers. This can have an adverse effect on development and learning. The qualitative study discussed in this article draws from the experiences of early Head Start teachers and administrators to describe both the impact of teacher turnover and the motivational factors that contribute to teacher retention. A case study approach was used and included classroom observations, a review of exit interviews, and perceptions from focus groups of early Head Start staff in an urban early Head Start childcare center. Emerging from the case study was the discovery that teacher turnover has an impact on the social-emotional development of toddlers, particularly in self-regulation. Additional key findings that emerged include teacher turnover leading to negative effects on learning, a decrease in preschool preparation, and increased chaos in the classroom and center. Motivational factors that contributed to teacher retention included positive leadership, the mission to make a difference, and fair compensation.

Keywords: early childhood, teacher turnover, continuity of care, early head start

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389 Correlation between Calpain 1 Expression and Proliferating/Apoptotic Index and Prognostic Factors in Triple Negative Breast Cancer

Authors: Shadia Al-Bahlani, Ruqaya Al-Rashdi, Shadia Al-Sinawi, Maya Al-Bahri

Abstract:

Background: Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer, which is defined by the absence of Estrogen (ER), Progesterone (PR) and Human epidermal growth factor (Her-2) receptors. The calpain system plays an important role in many cellular processes including apoptosis, necrosis, cell signaling and proliferation. The role of clapins in pathogenesis and tumor progression has been studied in certain cancer types; however, its definite role is not yet established in breast cancer especially in the TNBC subtype. Objectives: This study aims to measure calpain-1 expression and correlate this measurement with the proliferating/apoptotic index as well with the prognostic factors in TNBC patients’ tissue. Materials and Methods: Thirty nine paraffin blocks from patients diagnosed with TNBC were used to measure the expression of calpain-1 and Ki-67 (proliferating marker) proteins using immunohistochemistry. Apoptosis was assessed morphological and biochemically using conventional Haematoxylin and Eosin (H&E) staining method and terminal deoxynucleotidyl transferase-mediate dUTP nick and labeling (TUNEL) assay respectively. Data was statistically analyzed using Pearson X2 test of association. Results: Calpain-1 content was visualized in the nucleus of the TNBC cells and its expression varied from low to high among the patients tissue. Calpain expression showed no significant correlation with the proliferating/apoptotic index as well with the clinicopathological variables. Apoptotic counts quantified by H&E staining showed significant association with the apoptotic TUNEL assay, validating both approaches. Conclusion: Although calpain-1 expression showed no significant association with the clinical outcome, its variable level of expression might indicate a hidden role in breast cancer tissue. Larger number of samples and different mode of assessments are needed to fully investigate such role. Exploring the involvement of calpain-1 in cancer progression might help in considering it as a biomarker of breast cancer.

Keywords: breast cancer, calpain, apoptosis, prognosis

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388 Whole Coding Genome Inter-Clade Comparisons to Predict Global Cancer-Protecting Variants

Authors: Lamis Naddaf, Yuval Tabach

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We identified missense genetic variants with the potential to enhance resistance against cancer. Such a field has not been widely explored as researchers tend to investigate the mutations that cause diseases, in response to the suffering of patients, rather than those mutations that protect from them. In conjunction with the genomic revolution and the advances in genetic engineering and synthetic biology, identifying the protective variants will increase the power of genotype-phenotype predictions and have significant implications for improved risk estimation, diagnostics, prognosis, and even personalized therapy and drug discovery. To approach our goal, we systematically investigated the sites of the coding genomes and selected the alleles that showed a correlation with the species’ cancer resistance. Interestingly, we found several amino acids that are more generally preferred (like the Proline) or avoided (like the Cysteine) by the resistant species. Furthermore, Cancer resistance in mammals and reptiles is significantly predicted by the number of the predicted protecting variants (PVs) a species has. Moreover, PVs-enriched-genes are enriched in pathways relevant to tumor suppression. For example, they are enriched in the Hedgehog signaling and silencing pathways, which its improper activation is associated with the most common form of cancer malignancy. We also showed that the PVs are mostly more abundant in healthy people compared to cancer patients within different human races.

Keywords: cancer resistance, protecting variant, naked mole rat, comparative genomics

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387 Intelligent Building as a Pragmatic Approach towards Achieving a Sustainable Environment

Authors: Zahra Hamedani

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Many wonderful technological developments in recent years has opened up the possibility of using intelligent buildings for a number of important applications, ranging from minimizing resource usage as well as increasing building efficiency to maximizing comfort, adaption to inhabitants and responsiveness to environmental changes. The concept of an intelligent building refers to the highly embedded, interactive environment within which by exploiting the use of artificial intelligence provides the ability to know its configuration, anticipate the optimum dynamic response to prevailing environmental stimuli, and actuate the appropriate physical reaction to provide comfort and efficiency. This paper contains a general identification of the intelligence paradigm and its impacts on the architecture arena, that with examining the performance of artificial intelligence, a mechanism to analyze and finally for decision-making to control the environment will be described. This mechanism would be a hierarchy of the rational agents which includes decision-making, information, communication and physical layers. This multi-agent system relies upon machine learning techniques for automated discovery, prediction and decision-making. Then, the application of this mechanism regarding adaptation and responsiveness of intelligent building will be provided in two scales of environmental and user. Finally, we review the identifications of sustainability and evaluate the potentials of intelligent building systems in the creation of sustainable architecture and environment.

Keywords: artificial intelligence, intelligent building, responsiveness, adaption, sustainability

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386 Characterization of Penicillin V Acid and Its Related Compounds by HPLC

Authors: Bahdja Guerfi, N. Hadhoum, I. Azouz, M. Bendoumia, S. Bouafia, F. Z. Hadjadj Aoul

Abstract:

Background: 'Penicillin V' is a narrow, bactericidal antibiotic of the beta-lactam family of the naturally occurring penicillin group. It is limited to infections due to the germs defined as sensitive. The objective of this work was to identify and to characterize Penicillin V acid and its related compounds by High-performance liquid chromatography (HPLC). Methods: Firstly phenoxymethylpenicillin was identified by an infrared absorption. The organoleptic characteristics, pH, and determination of water content were also studied. The dosage of Penicillin V acid active substance and the determination of its related compounds were carried on waters HPLC, equipped with a UV detector at 254 nm and Discovery HS C18 column (250 mm X 4.6 mm X 5 µm) which is maintained at room temperature. The flow rate was about 1 ml per min. A mixture of water, acetonitrile and acetic acid (65:35:01) was used as mobile phase for phenoxyacetic acid ‘impurity B' and a mixture of water, acetonitrile and acetic acid (650:150:5.75) for the assay and 4-hydroxypenicillin V 'impurity D'. Results: The identification of Penicillin V acid active substance and the evaluation of its chemical quality showed conformity with USP 35th edition. The Penicillin V acid content in the raw material is equal to 1692.22 UI/mg. The percentage content of phenoxyacetic acid and 4-hydroxypenicillin V was respectively: 0.035% and 0.323%. Conclusion: Through these results, we can conclude that the Penicillin V acid active substance tested is of good physicochemical quality.

Keywords: characterization, HPLC, Penicillin V acid, related substances

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385 Performance Comparison of Outlier Detection Techniques Based Classification in Wireless Sensor Networks

Authors: Ayadi Aya, Ghorbel Oussama, M. Obeid Abdulfattah, Abid Mohamed

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Nowadays, many wireless sensor networks have been distributed in the real world to collect valuable raw sensed data. The challenge is to extract high-level knowledge from this huge amount of data. However, the identification of outliers can lead to the discovery of useful and meaningful knowledge. In the field of wireless sensor networks, an outlier is defined as a measurement that deviates from the normal behavior of sensed data. Many detection techniques of outliers in WSNs have been extensively studied in the past decade and have focused on classic based algorithms. These techniques identify outlier in the real transaction dataset. This survey aims at providing a structured and comprehensive overview of the existing researches on classification based outlier detection techniques as applicable to WSNs. Thus, we have identified key hypotheses, which are used by these approaches to differentiate between normal and outlier behavior. In addition, this paper tries to provide an easier and a succinct understanding of the classification based techniques. Furthermore, we identified the advantages and disadvantages of different classification based techniques and we presented a comparative guide with useful paradigms for promoting outliers detection research in various WSN applications and suggested further opportunities for future research.

Keywords: bayesian networks, classification-based approaches, KPCA, neural networks, one-class SVM, outlier detection, wireless sensor networks

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384 The Droplet Generation and Flow in the T-Shape Microchannel with the Side Wall Fluctuation

Authors: Yan Pang, Xiang Wang, Zhaomiao Liu

Abstract:

Droplet microfluidics, in which nanoliter to picoliter droplets acted as individual compartments, are common to a diverse array of applications such as analytical chemistry, tissue engineering, microbiology and drug discovery. The droplet generation in a simplified two dimension T-shape microchannel with the main channel width of 50 μm and the side channel width of 25 μm, is simulated to investigate effects of the forced fluctuation of the side wall on the droplet generation and flow. The periodic fluctuations are applied on a length of the side wall in the main channel of the T-junction with the deformation shape of the double-clamped beam acted by the uniform force, which varies with the flow time and fluctuation periods, forms and positions. The fluctuations under most of the conditions expand the distribution range of the droplet size but have a little effect on the average size, while the shape of the fixed side wall changes the average droplet size chiefly. Droplet sizes show a periodic pattern along the relative time when the fluctuation is forced on the side wall near the T-junction. The droplet emerging frequency is not varied by the fluctuation of the side wall under the same flow rate and geometry conditions. When the fluctuation period is similar with the droplet emerging period, the droplet size shows a nice stability as the no fluctuation case.

Keywords: droplet generation, droplet size, flow flied, forced fluctuation

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383 Role of von Willebrand Factor Antigen as Non-Invasive Biomarker for the Prediction of Portal Hypertensive Gastropathy in Patients with Liver Cirrhosis

Authors: Mohamed El Horri, Amine Mouden, Reda Messaoudi, Mohamed Chekkal, Driss Benlaldj, Malika Baghdadi, Lahcene Benmahdi, Fatima Seghier

Abstract:

Background/aim: Recently, the Von Willebrand factor antigen (vWF-Ag)has been identified as a new marker of portal hypertension (PH) and its complications. Few studies talked about its role in the prediction of esophageal varices. VWF-Ag is considered a non-invasive approach, In order to avoid the endoscopic burden, cost, drawbacks, unpleasant and repeated examinations to the patients. In our study, we aimed to evaluate the ability of this marker in the prediction of another complication of portal hypertension, which is portal hypertensive gastropathy (PHG), the one that is diagnosed also by endoscopic tools. Patients and methods: It is about a prospective study, which include 124 cirrhotic patients with no history of bleeding who underwent screening endoscopy for PH-related complications like esophageal varices (EVs) and PHG. Routine biological tests were performed as well as the VWF-Ag testing by both ELFA and Immunoturbidimetric techniques. The diagnostic performance of our marker was assessed using sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and receiver operating characteristic curves. Results: 124 patients were enrolled in this study, with a mean age of 58 years [CI: 55 – 60 years] and a sex ratio of 1.17. Viral etiologies were found in 50% of patients. Screening endoscopy revealed the presence of PHG in 20.2% of cases, while for EVsthey were found in 83.1% of cases. VWF-Ag levels, were significantly increased in patients with PHG compared to those who have not: 441% [CI: 375 – 506], versus 279% [CI: 253 – 304], respectively (p <0.0001). Using the area under the receiver operating characteristic curve (AUC), vWF-Ag was a good predictor for the presence of PHG. With a value higher than 320% and an AUC of 0.824, VWF-Ag had an 84% sensitivity, 74% specificity, 44.7% positive predictive value, 94.8% negative predictive value, and 75.8% diagnostic accuracy. Conclusion: VWF-Ag is a good non-invasive low coast marker for excluding the presence of PHG in patients with liver cirrhosis. Using this marker as part of a selective screening strategy might reduce the need for endoscopic screening and the coast of the management of these kinds of patients.

Keywords: von willebrand factor, portal hypertensive gastropathy, prediction, liver cirrhosis

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382 Downregulation of Epidermal Growth Factor Receptor in Advanced Stage Laryngeal Squamous Cell Carcinoma

Authors: Sarocha Vivatvakin, Thanaporn Ratchataswan, Thiratest Leesutipornchai, Komkrit Ruangritchankul, Somboon Keelawat, Virachai Kerekhanjanarong, Patnarin Mahattanasakul, Saknan Bongsebandhu-Phubhakdi

Abstract:

In this globalization era, much attention has been drawn to various molecular biomarkers, which may have the potential to predict the progression of cancer. Epidermal growth factor receptor (EGFR) is the classic member of the ErbB family of membrane-associated intrinsic tyrosine kinase receptors. EGFR expression was found in several organs throughout the body as its roles involve in the regulation of cell proliferation, survival, and differentiation in normal physiologic conditions. However, anomalous expression, whether over- or under-expression is believed to be the underlying mechanism of pathologic conditions, including carcinogenesis. Even though numerous discussions regarding the EGFR as a prognostic tool in head and neck cancer have been established, the consensus has not yet been met. The aims of the present study are to assess the correlation between the level of EGFR expression and demographic data as well as clinicopathological features and to evaluate the ability of EGFR as a reliable prognostic marker. Furthermore, another aim of this study is to investigate the probable pathophysiology that explains the finding results. This retrospective study included 30 squamous cell laryngeal carcinoma patients treated at King Chulalongkorn Memorial Hospital from January 1, 2000, to December 31, 2004. EGFR expression level was observed to be significantly downregulated with the progression of the laryngeal cancer stage. (one way ANOVA, p = 0.001) A statistically significant lower EGFR expression in the late stage of the disease compared to the early stage was recorded. (unpaired t-test, p = 0.041) EGFR overexpression also showed the tendency to increase recurrence of cancer (unpaired t-test, p = 0.128). A significant downregulation of EGFR expression was documented in advanced stage laryngeal cancer. The results indicated that EGFR level correlates to prognosis in term of stage progression. Thus, EGFR expression might be used as a prevailing biomarker for laryngeal squamous cell carcinoma prognostic prediction.

Keywords: downregulation, epidermal growth factor receptor, immunohistochemistry, laryngeal squamous cell carcinoma

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381 A Next Generation Multi-Scale Modeling Theatre for in silico Oncology

Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

Abstract:

Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

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380 Development of Open Source Geospatial Certification Model Based on Geospatial Technology Competency Model

Authors: Tanzeel Ur Rehman Khan, Franz Josef Behr, Phillip Davis

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Open source geospatial certifications are needed in geospatial technology education and industry sector. In parallel with proprietary software, free and open source software solutions become important in geospatial technology research and play an important role for the growth of the geospatial industry. ESRI, GISCI (GIS Certification Institute), ASPRS (American Society of Photogrammetry and remote sensing), and Meta spatial are offering certifications on proprietary and open source software. These are portfolio and competency based certifications depending on GIS Body of Knowledge (Bok). The analysis of these certification approaches might lead to the discovery of some gaps in them and will open a new way to develop certifications related to the geospatial open source (OS). This new certification will investigate the different geospatial competencies according to open source tools that help to identify geospatial professionals and strengthen the geospatial academic content. The goal of this research is to introduce a geospatial certification model based on geospatial technology competency model (GTCM).The developed certification will not only incorporate the importance of geospatial education and production of the geospatial competency-based workforce in universities and companies (private or public) as well as describe open source solutions with tools and technology. Job analysis, market analysis, survey analysis of this certification opens a new horizon for business as well.

Keywords: geospatial certification, open source, geospatial technology competency model, geoscience

Procedia PDF Downloads 566