Search results for: myogenic differentiation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 489

Search results for: myogenic differentiation

189 Rival Conceptions of Sovereignty in Modern South Asian Political Thought: An Analysis Through the Writings of Maulana Syed Abul Ala Maududi and Maulana Hifzurrahman Seoharvi

Authors: Mohammad Saif

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In the post-Westphalianworld order, the concept of sovereignty has been a fundamental area of inquiry in Political Science, International Relations, and International Law. Modern Islamic political thought has also dedicated a fair share of debate on the subject. The debate fundamentally revolves around the ‘ontological differentiation’ between western and Islamic political thought. While the centrality of the individual in western political thought regards the individual as the center of universe, Islamic Political thought provides that space to God. The modern liberal democratic principles suggest sovereignty as one of the major attributes of modern nation state; Islamists regard sovereignty as an attribute of God. However, the position regarding God’ssovereignty in Islamic political thought is not coherent in conception. Some scholars regard such a position as ‘the political interpretation of Islam’. This paper is an attempt to first analyze the fundamental discord between two rival political ideologies (western and Islamic), and then forward a debate on the subject of sovereignty in South Asian Islamic Political thought, particularly between Syed Abul Ala Maududi (ideological father of modern islamist movements) andHifzurrahmanSeoharvi (lesser known in Academia but highly influential in shaping Deobandi position of principles related to political nature of Islamic theology). Maududi regardssovereignty as an attribute of God and the rulers as subservient to Gods will, Seoharvi suggests that God's sovereignty does not entail that the caliph or amir cannot be a ruler or hakim, nor can his command or hukum be an order. Certain references have also been made to contemporary scholars like Sayidd Qutub, Rashid al Ghanouchi, who in one way or the other have contributed to the debate on ‘sovereignty in Islamic thought’.

Keywords: nation state, sovereigty, sovereignty of God (Hakimmiyah), deoband

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188 Marketing of Non Timber Forest Products and Forest Management in Kaffa Biosphere Reserve, Ethiopia

Authors: Amleset Haile

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Non-timber forest products (NTFPs) are harvested for both subsistence and commercial use and play a key role in the livelihoods of millions of rural people. Non-timber forest products (NTFPs) are important in rural southwest Ethiopia, Kaffa as a source of household income. market players at various levels in marketing chains are interviewed to getther information on elements of marketing system–products, product differentiation, value addition, pricing, promotion, distribution, and marketing chains. The study, therefore, was conducted in Kaffa Biosphere reserve of southwest Ethiopia with the main objective of assessing and analyzing the contribution of NTFPs to rural livelihood and to the conservation of the biosphere reserve and to identify factors influencing in the marketing of the NTFP. Five villages were selected based on their proximity gradient from Bonga town and availability of NTFP. Formal survey was carried out on rural households selected using stratified random sampling. The results indicate that Local people practice diverse livelihood activities mainly crops cultivation (cereals and cash crops) and livestock husbandry, gather forest products and off-farm/off-forest activities for surviva. NTFP trade is not a common phenomenon in southwest Ethiopia. The greatest opportunity exists for local level marketing of spices and other non timber forest products. Very little local value addition takes place within the region,and as a result local market players have little control. Policy interventions arc required to enhance the returns to local collectors, which will also contribute to sustainable management of forest resources in Kaffa biosphere reserve.

Keywords: forest management, biosphere reserve, marketing, local people

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187 Skills and Abilities Expected from Professionals Conducting Serious Crimes Investigations: A Descriptive Study from Turkey

Authors: Burak M. Gonultas

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Criminal investigation provides a practical contribution to this process while criminology provides a theoretical background in the apprehension of criminals arrest and clarification of crimes. However, studies on criminal investigation, which is a practical aspect of this process, are not sufficient. Every crime involves different dynamics in terms of investigation. But investigations of serious crimes are versatile and contains complex processes because of cases they are conducted. Therefore, professionals who conduct serious crime investigations differ in some aspects from others in the field. The most fundamental element of this differentiation is skills and abilities of these professionals. According to Eurostat data, Turkey is in an important position in terms of homicide rates. Therefore, in Turkey practice of serious crime investigation is specialized. The present study aims to research the skills and abilities expected from professionals in conducting an effective serious criminal investigation in Turkey and so aims to offer a number of suggestions. 25 emerged ability and skills collected from literature were asked to professionals (n=289) with semi-structured form according to 5 provinces with the highest and 2 provinces with the lowest number of serious crime cases. Three data categories were collected during experience: 1- Five most important skills and abilities, 2- The most important skills for knowledge and inquiry management and 3- Ability and skills that stand out for five stages of serious criminal investigation. The most rated skills and abilities are investigative skill (13%, n=134), planning/designing (9,2%, n=95) and interpersonal relations/communication (8,8%, n=91) in 1010 skills and abilities. While the 1st and 2nd suggest elections of these professionals, the 3rd also suggests how and what type of training will be given to these professionals. This practice differs from other studies in the area in terms of separately addressing the skills and abilities expected in stages of investigation and in terms of selected methodology.

Keywords: ability, criminal investigation, criminology, homicide, serious crimes, skill, Turkey

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186 The Effect of Simultaneous Doping of Silicate Bioglass with Alkaline and Alkaline-Earth Elements on Biological Behavior

Authors: Tannaz Alimardani, Amirhossein Moghanian, Morteza Elsa

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Bioactive glasses (BGs) are a group of surface-reactive biomaterials used in clinical applications as implants or filler materials in the human body to repair and replace diseased or damaged bone. Sol-gel technique was employed to prepare a SiO₂-CaO-P₂O₅ glass with a nominal composition of 58S BG with the addition of Sr and Li modifiers which imparts special properties to the BG. The effect of simultaneous addition of Sr and Li on bioactivity and biocompatibility, proliferation, alkaline phosphatase (ALP) activity of osteoblast cell line MC3T3-E1 and antibacterial property against methicillin-resistant Staphylococcus aureus (MRSA) bacteria were examined. BGs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy before and after soaking the samples in the simulated body fluid (SBF) for different time intervals to characterize the formation of hydroxyapatite (HA) formed on the surface of BGs. Structural characterization indicated that the simultaneous presence of 5% Sr and 5% Li in 58S-BG composition not only did not retard HA formation because of the opposite effect of Sr and Li of the dissolution of BG in the SBF, but also stimulated the differentiation and proliferation of MC3T3-E1s. Moreover, the presence of Sr and Li on the dissolution of the ions resulted in an increase in the mean number of DAPI-labeled nuclei which was in good agreement with the live/dead assay. The result of antibacterial tests revealed that Sr and Li-substituted 58S bioactive glass exhibited a potential antibacterial effect against MRSA bacteria. Because of optimal proliferation and ALP activity of MC3T3-E1cells, proper bioactivity and high antibacterial potential against MRSA, BG-5/5 is suggested as a multifunctional candidate for bone tissue engineering.

Keywords: alkaline, alkaline earth, bioglass, co-doping, ion release

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185 System for Mechanical Stimulation of the Mesenchymal Stem Cells Supporting Differentiation into Osteogenic Cells

Authors: Jana Stepanovska, Roman Matejka, Jozef Rosina, Marta Vandrovcova, Lucie Bacakova

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The aim of this study was to develop a system for mechanical and also electrical stimulation controlling in vitro osteogenesis under conditions more similar to the in vivo bone microenvironment than traditional static cultivation, which would achieve good adhesion, growth and other specific behaviors of osteogenic cells in cultures. An engineered culture system for mechanical stimulation of the mesenchymal stem cells on the charged surface was designed. The bioreactor allows efficient mechanical loading inducing an electrical response and perfusion of the culture chamber with seeded cells. The mesenchymal stem cells were seeded to specific charged materials, like polarized hydroxyapatite (Hap) or other materials with piezoelectric and ferroelectric features, to create electrical potentials for stimulating of the cells. The material of the matrix was TiNb alloy designed for these purposes, and it was covered by BaTiO3 film, like a kind of piezoelectric material. The process of mechanical stimulation inducing electrical response is controlled by measuring electrical potential in the chamber. It was performed a series of experiments, where the cells were seeded, perfused and stimulated up to 48 hours under different conditions, especially pressure and perfusion. The analysis of the proteins expression was done, which demonstrated the effective mechanical and electrical stimulation. The experiments demonstrated effective stimulation of the cells in comparison with the static culture. This work was supported by the Ministry of Health, grant No. 15-29153A and the Grant Agency of the Czech Republic grant No. GA15-01558S.

Keywords: charged surface, dynamic cultivation, electrical stimulation, ferroelectric layers, mechanical stimulation, piezoelectric layers

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184 Classification of Small Towns: Three Methodological Approaches and Their Results

Authors: Jerzy Banski

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Small towns represent a key element of settlement structure and serve a number of important functions associated with the servicing of rural areas that surround them. It is in light of this that scientific studies have paid considerable attention to the functional structure of centers of this kind, as well as the relationships with both surrounding rural areas and other urban centers. But a preliminary to such research has typically involved attempts at classifying the urban centers themselves, with this also assisting with the planning and shaping of development policy on different spatial scales. The purpose of the work is to test out the methods underpinning three different classifications of small urban centers, as well as to offer a preliminary interpretation of the outcomes obtained. Research took in 722 settlement units in Poland, granted town rights and populated by fewer than 20,000 inhabitants. A morphologically-based classification making reference to the database of topographic objects as regards land cover within the administrative boundaries of towns and cities was carried out, and it proved possible to distinguish the categories of “housing-estate”, industrial and R&R towns, as well as towns characterized by dichotomy. Equally, a functional/morphological approach taken with the same database allowed for the identification – via an alternative method – of three main categories of small towns (i.e., the monofunctional, multifunctional or oligo functional), which could then be described in far greater detail. A third, multi-criterion classification made simultaneous reference to the conditioning of a structural, a location-related, and an administrative hierarchy-related nature, allowing for distinctions to be drawn between small towns in 9 different categories. The results obtained allow for multifaceted analysis and interpretation of the geographical differentiation characterizing the distribution of Poland’s urban centers across space in the country.

Keywords: small towns, classification, local planning, Poland

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183 Development of 3D Printed, Conductive, Biodegradable Nerve Conduits for Neural Regeneration

Authors: Wei-Chia Huang, Jane Wang

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Damage to nerves is considered one of the most irreversible injuries. The regeneration of nerves has always been an important topic in regenerative medicine. In general, damage to human tissue will naturally repair overtime. However, when the nerves are damaged, healed flesh wound cannot guarantee full restoration to its original function, as truncated nerves are often irreversible. Therefore, the development of treatment methods to successfully guide and accelerate the regeneration of nerves has been highly sought after. In order to induce nerve tissue growth, nerve conduits are commonly used to help reconnect broken nerve bundles to provide protection to the location of the fracture while guiding the growth of the nerve bundles. To prevent the protected tissue from becoming necrotic and to ensure the growth rate, the conduits used are often modified with microstructures or blended with neuron growth factors that may facilitate nerve regeneration. Electrical stimulation is another attempted treatment for medical rehabilitation. With appropriate range of voltages and stimulation frequencies, it has been demonstrated to promote cell proliferation and migration. Biodegradability are critical for medical devices like nerve conduits, while conductive polymers pose great potential toward the differentiation and growth of nerve cells. In this work, biodegradability and conductivity were combined into a novel biodegradable, photocurable, conductive polymer composite materials by embedding conductive nanoparticles in poly(glycerol sebacate) acrylate (PGSA) and 3D-printed into nerve conduits. Rat pheochromocytoma cells and rat neuronal Schwann cells were chosen for the in vitro tests of the conduits and had demonstrate selective growth upon culture in the conductive conduits with built-in microchannels and electrical stimulation.

Keywords: biodegradable polymer, 3d printing, neural regeneration, electrical stimulation

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182 Structural Characterization of TIR Domains Interaction

Authors: Sara Przetocka, Krzysztof Żak, Grzegorz Dubin, Tadeusz Holak

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Toll-like receptors (TLRs) play central role in the innate immune response and inflammation by recognizing pathogen-associated molecular patterns (PAMPs). A fundamental basis of TLR signalling is dependent upon the recruitment and association of adaptor molecules that contain the structurally conserved Toll/interleukin-1 receptor (TIR) domain. MyD88 (myeloid differentiation primary response gene 88) is the universal adaptor for TLRs and cooperates with Mal (MyD88 adapter-like protein, also known as TIRAP) in TLR4 response which is predominantly used in inflammation, host defence and carcinogenesis. Up to date two possible models of MyD88, Mal and TLR4 interactions have been proposed. The aim of our studies is to confirm or abolish presented models and accomplish the full structural characterisation of TIR domains interaction. Using molecular cloning methods we obtained several construct of MyD88 and Mal TIR domain with GST or 6xHis tag. Gel filtration method as well as pull-down analysis confirmed that recombinant TIR domains from MyD88 and Mal are binding in complexes. To examine whether obtained complexes are homo- or heterodimers we carried out cross-linking reaction of TIR domains with BS3 compound combined with mass spectrometry. To investigate which amino acid residues are involved in this interaction the NMR titration experiments were performed. 15N MyD88-TIR solution was complemented with non-labelled Mal-TIR. The results undoubtedly indicate that MyD88-TIR interact with Mal-TIR. Moreover 2D spectra demonstrated that simultaneously Mal-TIR self-dimerization occurs which is necessary to create proper scaffold for Mal-TIR and MyD88-TIR interaction. Final step of this study will be crystallization of MyD88 and Mal TIR domains complex. This crystal structure and characterisation of its interface will have an impact in understanding the TLR signalling pathway and possibly will be used in development of new anti-cancer treatment.

Keywords: cancer, MyD88, TIR domains, Toll-like receptors

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181 Method Development for the Determination of Gamma-Aminobutyric Acid in Rice Products by Lc-Ms-Ms

Authors: Cher Rong Matthew Kong, Edmund Tian, Seng Poon Ong, Chee Sian Gan

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Gamma-aminobutyric acid (GABA) is a non-protein amino acid that is a functional constituent of certain rice varieties. When consumed, it decreases blood pressure and reduces the risk of hypertension-related diseases. This has led to more research dedicated towards the development of functional food products (e.g. germinated brown rice) with enhanced GABA content, and the development of these functional food products has led to increased demand for instrument-based methods that can efficiently and effectively determine GABA content. Current analytical methods require analyte derivatisation, and have significant disadvantages such as being labour intensive and time-consuming, and being subject to analyte loss due to the increased complexity of the sample preparation process. To address this, an LC-MS-MS method for the determination of GABA in rice products has been developed and validated. This developed method involves a relatively simple sample preparation process before analysis using HILIC LC-MS-MS. This method eliminates the need for derivatisation, thereby significantly reducing the labour and time associated with such an analysis. Using LC-MS-MS also allows for better differentiation of GABA from any potential co-eluting compounds in the sample matrix. Results obtained from the developed method demonstrated high linearity, accuracy, and precision for the determination of GABA (1ng/L to 8ng/L) in a variety of brown rice products. The method can significantly simplify sample preparation steps, improve the accuracy of quantitation, and increase the throughput of analyses, thereby providing a quick but effective alternative to established instrumental analysis methods for GABA in rice.

Keywords: functional food, gamma-aminobutyric acid, germinated brown rice, method development

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180 Assessment of Genetic Diversity and Population Structure of Goldstripe Sardinella, Sardinella gibbosa in the Transboundary Area of Kenya and Tanzania Using mtDNA and msDNA Markers

Authors: Sammy Kibor, Filip Huyghe, Marc Kochzius, James Kairo

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Goldstripe Sardinella, Sardinella gibbosa, (Bleeker, 1849) is a commercially and ecologically important small pelagic fish common in the Western Indian Ocean region. The present study aimed to assess genetic diversity and population structure of the species in the Kenya-Tanzania transboundary area using mtDNA and msDNA markers. Some 630 bp sequence in the mitochondrial DNA (mtDNA) Cytochrome C Oxidase I (COI) and five polymorphic microsatellite DNA loci were analyzed. Fin clips of 309 individuals from eight locations within the transboundary area were collected between July and December 2018. The S. gibbosa individuals from the different locations were distinguishable from one another based on the mtDNA variation, as demonstrated with a neighbor-joining tree and minimum spanning network analysis. None of the identified 22 haplotypes were shared between Kenya and Tanzania. Gene diversity per locus was relatively high (0.271-0.751), highest Fis was 0.391. The structure analysis, discriminant analysis of Principal component (DAPC) and the pair-wise (FST = 0.136 P < 0.001) values after Bonferroni correction using five microsatellite loci provided clear inference on genetic differentiation and thus evidence of population structure of S. gibbosa along the Kenya-Tanzania coast. This study shows a high level of genetic diversity and the presence of population structure (Φst =0.078 P < 0.001) resulting to the existence of four populations giving a clear indication of minimum gene flow among the population. This information has application in the designing of marine protected areas, an important tool for marine conservation.

Keywords: marine connectivity, microsatellites, population genetics, transboundary

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179 Plasma Engineered Nanorough Substrates for Stem Cells in vitro Culture

Authors: Melanie Macgregor-Ramiasa, Isabel Hopp, Patricia Murray, Krasimir Vasilev

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Stem cells based therapies are one of the greatest promises of new-age medicine due to their potential to help curing most dreaded conditions such as cancer, diabetes and even auto-immune disease. However, establishing suitable in vitro culture materials allowing to control the fate of stem cells remain a challenge. Amongst the factor influencing stem cell behavior, substrate chemistry and nanotopogaphy are particularly critical. In this work, we used plasma assisted surface modification methods to produce model substrates with tailored nanotopography and controlled chemistry. Three different sizes of gold nanoparticles were bound to amine rich plasma polymer layers to produce homogeneous and gradient surface nanotopographies. The outer chemistry of the substrate was kept constant for all substrates by depositing a thin layer of our patented biocompatible polyoxazoline plasma polymer on top of the nanofeatures. For the first time, protein adsorption and stem cell behaviour (mouse kidney stem cells and mesenchymal stem cells) were evaluated on nanorough plasma deposited polyoxazoline thin films. Compared to other nitrogen rich coatings, polyoxazoline plasma polymer supports the covalent binding of proteins. Moderate surface nanoroughness, in both size and density, triggers cell proliferation. In association with polyoxazoline coating, cell proliferation is further enhanced on nanorough substrates. Results are discussed in term of substrates wetting properties. These findings provide valuable insights on the mechanisms governing the interactions between stem cells and their growth support.

Keywords: nanotopography, stem cells, differentiation, plasma polymer, oxazoline, gold nanoparticles

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178 Brain Derived Neurotrophic Factor (BDNF) Down Regulation in Peritoneal Carcinomatosis Patients

Authors: Awan A. Zaima, Tanvieer Ayesha, Mirshahi Shahsoltan, Pocard Marc, Mirshahi Massoud

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Brain-derived neurotrophic factor (BDNF) is described as a factor helping to support the survival of existing neurons by involving the growth and differentiation of new neurons and synapses. Cancer diagnosis impacts the mental health, and in consequences, depression arise eventually hinders recovery and disrupts the quality of life and surviving chances of patients. The focus of this study is to hint upon a prospective biomarker as a promising diagnostic tool for an early indicator/predictor of depression prevalence in cancer patients for better care and treatment options. The study aims to analyze peripheral biomarkers from neuro immune axis (BDNF, IL21 as a NK cell activator) using co-relation approach. Samples were obtained from random non cancer candidates and advanced peritoneum carcinomatosis patients with 25% pseudomyxoma, 21% Colon cancer,19% stomach cancer, 10% ovarian cancer, 8% appendices cancer, and 10% other area of peritoneum cancer patients. Both groups of the study were categorized by gender and age, with a range of 18 to 86 years old. Biomarkers were analyzed in collected plasma by performing multiplex sandwich ELISA system. Data were subjected to statistical analysis for the assessment of the correlation. Our results demonstrate that BNDF and IL 21 down regulated significantly in patient groupas compared to non-cancer candidates (ratio of patients/normalis 2.57 for BNDF and 1.32 for IL21). This preliminary investigation suggested that the neuro immune biomarkers are down regulated in carcinomatosis patients and can be associated with cancer expansion and cancer genesis. Further studies on larger cohort are necessary to validate this hypothesis.

Keywords: biomarkers, depression, peritoneum carcinoma, BNDF, IL21

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177 Analysis, Evaluation and Optimization of Food Management: Minimization of Food Losses and Food Wastage along the Food Value Chain

Authors: G. Hafner

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A method developed at the University of Stuttgart will be presented: ‘Analysis, Evaluation and Optimization of Food Management’. A major focus is represented by quantification of food losses and food waste as well as their classification and evaluation regarding a system optimization through waste prevention. For quantification and accounting of food, food losses and food waste along the food chain, a clear definition of core terms is required at the beginning. This includes their methodological classification and demarcation within sectors of the food value chain. The food chain is divided into agriculture, industry and crafts, trade and consumption (at home and out of home). For adjustment of core terms, the authors have cooperated with relevant stakeholders in Germany for achieving the goal of holistic and agreed definitions for the whole food chain. This includes modeling of sub systems within the food value chain, definition of terms, differentiation between food losses and food wastage as well as methodological approaches. ‘Food Losses’ and ‘Food Wastes’ are assigned to individual sectors of the food chain including a description of the respective methods. The method for analyzing, evaluation and optimization of food management systems consist of the following parts: Part I: Terms and Definitions. Part II: System Modeling. Part III: Procedure for Data Collection and Accounting Part. IV: Methodological Approaches for Classification and Evaluation of Results. Part V: Evaluation Parameters and Benchmarks. Part VI: Measures for Optimization. Part VII: Monitoring of Success The method will be demonstrated at the example of an invesigation of food losses and food wastage in the Federal State of Bavaria including an extrapolation of respective results to quantify food wastage in Germany.

Keywords: food losses, food waste, resource management, waste management, system analysis, waste minimization, resource efficiency

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176 Use of Dual-Energy CT Post Endovascular Treatment of Cerebral Aneurysm

Authors: Mitchell Stanton

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Background: Endovascular management is well established as a mainstay treatment option for cerebral aneurysms. It is also well established that immediate post procedural imaging can be difficult to interpret due to the presence of contrast material. However, through the use of Dual-Energy computed tomography, it has become possible to differentiate contrast extravasation and intracranial haemorrhage. This case illustrates the importance of this technology following endovascular treatment of an unruptured cerebral aneurysm. Case Presentation: A 79-year-old female was found to have an unruptured large intracavernous ICA fusiform aneurysm on CT Brain Angiogram after presenting with acute ophthalmoplegia. This ophthalmoplegia was caused by mass effect from the aneurysm and subsequently the aneurysm was treated with an endovascular flow diverting stent. CT brain was performed post operatively due to a reduced level of consciousness and this showed diffuse subarachnoid hyperdensity of the left hemisphere. The use of Dual-Energy CT allowed accurate differentiation and illustrated diffuse contrast material extravasation, allowing patient to continue on dual-antiplatelets and therapeutic anticoagulation to reduce the risk of ischaemic injury post endovascular stent. Conclusion: Endovascular treatment options for management of intracranial aneurysms are constantly evolving. The use of Dual-Energy CT therefore has an integral role in accurately diagnosing any post-operative complications. Specifically, differentiating between subarachnoid haemorrhage and contrast extravasation is vital in these patients due to the significant consequences to their ongoing management in regards to continuation or cessation of antiplatelets or anticoagulation. With increasing access to this technology, its use should become standard practice in the post-operative investigation of these patients undergoing endovascular treatment.

Keywords: aneurysm, computed tomography, contrast extravasation, dual-energy CT, endovascular, subarachnoid haemorrhage

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175 The Effect of Vitamin D Supplementation on Prostate Cancer: A Systematic Review and Meta-Analysis of Clinical Trials

Authors: Simin Shahvazi, Sepideh Soltani, Seyed Mehdi Ahmadi, Russell J. De Souza, Amin Salehi-Abargouei

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Background and Objectives: Vitamin D has received attention for its potential to disrupt cancer processes such as attenuating cell proliferation and exacerbating differentiation and apoptosis. However, whether there exists a role for vitamin D in the treatment of prostate cancer specifically remains controversial. We systematically review the literature to assess whether supplementation with vitamin D influences PSA response and overall survival in patients with prostate cancer. Methods: We searched PubMed, Scopus, ISI Web of Science and Google scholar from inception through up to 10 September 2017 for both before-and-after and randomized trials that evaluated the effect of vitamin D supplementation on the prostate specific antigen (PSA) response rate in participants with prostate cancer. The DerSimonian and Laird, inverse-weighted random-effects model was used to pool effect estimates from the studies. Heterogeneity and potential publication bias were evaluated. Subgroup analyses were also performed. Results: Twenty-two studies (16 before-after and 6 randomized controlled trials) were found and included in meta-analysis. The analysis on controlled clinical trials revealed that PSA change from baseline [weighted mean difference (WMD) = -1.66 ng/ml, 95%CI: -0.69, 0.36, P= 0.543)], PSA response (RR=1.18, 95%CI: 0.97, 1.45, P=0.104) and mortality rate (risk ratio (RR) = 1.05, 95% CI: 0.81-1.36; P=0.713) was not significantly different between vitamin D supplementation and placebo groups. Single arm trials revealed that vitamin D supplementation had had a modest effect on PSA response rate: 19% of those enrolled had at least a 50% reduction in PSA by the end of treatment (95% CI: 7% to 31%; p=0.002). Conclusion: We found that vitamin D modestly increases the PSA response rate in single arm studies. No effect on serum PSA levels, PSA response and mortality was seen in randomized controlled clinical trials. It does not seem patients with prostate cancer benefit from vitamin D supplementation.

Keywords: mortality, prostatic neoplasms, PSA response, vitamin D

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174 Parameters Identification and Sensitivity Study for Abrasive WaterJet Milling Model

Authors: Didier Auroux, Vladimir Groza

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This work is part of STEEP Marie-Curie ITN project, and it focuses on the identification of unknown parameters of the proposed generic Abrasive WaterJet Milling (AWJM) PDE model, that appears as an ill-posed inverse problem. The necessity of studying this problem comes from the industrial milling applications where the possibility to predict and model the final surface with high accuracy is one of the primary tasks in the absence of any knowledge of the model parameters that should be used. In this framework, we propose the identification of model parameters by minimizing a cost function, measuring the difference between experimental and numerical solutions. The adjoint approach based on corresponding Lagrangian gives the opportunity to find out the unknowns of the AWJM model and their optimal values that could be used to reproduce the required trench profile. Due to the complexity of the nonlinear problem and a large number of model parameters, we use an automatic differentiation software tool (TAPENADE) for the adjoint computations. By adding noise to the artificial data, we show that in fact the parameter identification problem is highly unstable and strictly depends on input measurements. Regularization terms could be effectively used to deal with the presence of data noise and to improve the identification correctness. Based on this approach we present results in 2D and 3D of the identification of the model parameters and of the surface prediction both with self-generated data and measurements obtained from the real production. Considering different types of model and measurement errors allows us to obtain acceptable results for manufacturing and to expect the proper identification of unknowns. This approach also gives us the ability to distribute the research on more complex cases and consider different types of model and measurement errors as well as 3D time-dependent model with variations of the jet feed speed.

Keywords: Abrasive Waterjet Milling, inverse problem, model parameters identification, regularization

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173 The Differentiation of Performances among Immigrant Entrepreneurs: A Biographical Approach

Authors: Daniela Gnarini

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This paper aims to contribute to the field of immigrants' entrepreneurial performance. The debate on immigrant entrepreneurship has been dominated by cultural explanations, which argue that immigrants’ entrepreneurial results are linked to groups’ characteristics. However, this approach does not consider important dimensions that influence entrepreneurial performances. Furthermore, cultural theories do not take into account the huge differences in performances also within the same ethnic group. For these reason, this study adopts a biographical approach, both at theoretical and at methodological level, which can allow to understand the main aspects that make the difference in immigrants' entrepreneurial performances, by exploring the narratives of immigrant entrepreneurs, who operate in the restaurant sector in two different Italian metropolitan areas: Milan and Rome. Through the qualitative method of biographical interviews, this study analyses four main dimensions and their combinations: a) individuals' entrepreneurial and migratory path: this aspect is particularly relevant to understand the biographical resources of immigrant entrepreneurs and their change and evolution during time; b) entrepreneurs' social capital, with a particular focus on their networks, through the adoption of a transnational perspective, that takes into account both the local level and the transnational connections. This study highlights that, though entrepreneurs’ connections are significant, especially as far as those with family members are concerned, often their entrepreneurial path assumes an individualised trajectory. c) Entrepreneurs' human capital, including both formal education and skills acquired through informal channels. The latter are particularly relevant since in the interviews and data collected the role of informal transmission emerges. d) Embeddedness within the social, political and economic context, to understand the main constraints and opportunities both at local and national level. The comparison between two different metropolitan areas within the same country helps to understand this dimension.

Keywords: biographies, immigrant entrepreneurs, life stories, performance

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172 The Happiness Pulse: A Measure of Individual Wellbeing at a City Scale, Development and Validation

Authors: Rosemary Hiscock, Clive Sabel, David Manley, Sam Wren-Lewis

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As part of the Happy City Index Project, Happy City have developed a survey instrument to measure experienced wellbeing: how people are feeling and functioning in their everyday lives. The survey instrument, called the Happiness Pulse, was developed in partnership with the New Economics Foundation (NEF) with the dual aim of collecting citywide wellbeing data and engaging individuals and communities in the measurement and promotion of their own wellbeing. The survey domains and items were selected through a review of the academic literature and a stakeholder engagement process, including local policymakers, community organisations and individuals. The Happiness Pulse was included in the Bristol pilot of the Happy City Index (n=722). The experienced wellbeing items were subjected to factor analysis. A reduced number of items to be included in a revised scale for future data collection were again entered into a factor analysis. These revised factors were tested for reliability and validity. Among items to be included in a revised scale for future data collection three factors emerged: Be, Do and Connect. The Be factor had good reliability, convergent and criterion validity. The Do factor had good discriminant validity. The Connect factor had adequate reliability and good discriminant and criterion validity. Some age, gender and socioeconomic differentiation was found. The properties of a new scale to measure experienced wellbeing, intended for use by municipal authorities, are described. Happiness Pulse data can be combined with local data on wellbeing conditions to determine what matters for peoples wellbeing across a city and why.

Keywords: city wellbeing , community wellbeing, engaging individuals and communities, measuring wellbeing and happiness

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171 CSR and Employer Attractiveness: The Relationship of Value Orientation of High-Potential Applicants and Their Decision for an Employer

Authors: Silke Bustamante, Andrea Pelzeter, Andreas Deckmann, Rudi Ehlscheidt, Franziska Freudenberger

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Against the background of demographic changes and the need for motivated and talented employees, companies have a growing interest in being perceived as an attractive employer and gain a competitive edge in the market for talents. Research indicates that corporate social responsibility plays an important role employer choice. This is assumed to be particularly true for the cohorts of the so-called generations y younger applicants born later. Several studies identified cultural, educational and generational differences in CSR preferences. However, until now literature that links preferences for employers’ responsibility with the individual value orientation of the job applicant is scarce. This paper seeks to close this gap and analyzes the preference structure of 500 German university graduates for CSR-related and non-CSR-related employer attributes contingent on their value orientation. In a first step, we identified 17 CSR related attributes in five CSR dimensions (ecology, community, workplace, governance, and market) as well as 11 traditional attributes such as salary, reputation, personal development etc. based on literature review and focus groups. We then used an adapted Conjoint Analysis framework in order to understand the relative preference of each attribute for each participant. Additionally, we surveyed the value orientation of participants based on the European Social Survey (ESS) 21-item human values scale that allow a differentiation of participants into clusters of value orientation. The results allow us not only to operationalize preferences for CSR and other important employer attributes, but – more importantly – to answer the question how different values structures play together with CSR preferences of potential employees. They hereby allow companies to customize employee directed messages to their respective target group and design their employer brand accordingly.

Keywords: corporate social responsibility, employer attractiveness, employer brand, recruiting, values

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170 A Rare Case of Metastatic Basal Cell Carcinoma

Authors: Nitesh Kumar, Eoin Twohig, jasparl cheema, Sadiq mawji, Yousif al najjar

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Basal cell carcinoma (BCC) is the commonest cutaneous malignancy affecting humans. Despite this, distant spread is exceptionally rare. Metastatic BCC (mBCC) is estimated to occur in 0.0028 - 0.5%. it aim to illustrate with the aid of histological slides, a case of mBCC occurring in a fit and well 67-year-old. Initial diagnosis of desmoplastic BCC was made in 2006 from a scalp biopsy with the lesion then being excised. Re-excision of local recurrence was undertaken the following year. In 2014 the patient presented with an ipsilateral level 2a mass. Fine Needle Aspiration raised the suspicion of metastatic carcinoma. The patient had excision of two nodes from the left neck alongside pharyngeal tonsillectomy and tongue base biopsies. Histologically, the nodes closely resembled the immunophenotype of the initial scalp lesion. The patient subsequently had a modified radical neck dissection, and residual mBCC was excised from the left Sternocleidomastoid muscle. In 2023 the patient developed haematuria. On further investigation bilateral lung lesions on CT were noted with subsequent biopsy confirming mBCC. Spinal and renal lesions have also been found. Histopathology showed clear resemblance of the lung metastases to both those in the neck and the primary (scalp BCC) – with no squamous differentiation seen. The time span from primary to occurrence of lung metastasis (18 years) affirms the indolent and slow growing nature of BCC.  This case fulfils Lattes and Kessler diagnostic criteria. High risk cases are described as those with advanced local presentation, primary tumour on the Head and Neck and locally recurrent lesions.

Keywords: BCC, metastasis, rare, skin cancer

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169 Increased Cytolytic Activity of Effector T-Cells against Cholangiocarcinoma Cells by Self-Differentiated Dendritic Cells with Down-Regulation of Interleukin-10 and Transforming Growth Factor-β Receptors

Authors: Chutamas Thepmalee, Aussara Panya, Mutita Junking, Jatuporn Sujjitjoon, Nunghathai Sawasdee, Pa-Thai Yenchitsomanus

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Cholangiocarcinoma (CCA) is an aggressive malignancy of bile duct epithelial cells in which the standard treatments, including surgery, radiotherapy, chemotherapy, and targeted therapy are partially effective. Many solid tumors including CCA escape host immune responses by creating tumor microenvironment and generating immunosuppressive cytokines such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). These cytokines can inhibit dendritic cell (DC) differentiation and function, leading to decreased activation and response of effector CD4+ and CD8+ T cells for cancer cell elimination. To overcome the effects of these immunosuppressive cytokines and to increase ability of DC to activate effector CD4+ and CD8+ T cells, we generated self-differentiated DCs (SD-DCs) with down-regulation of IL-10 and TGF-β receptors for activation of effector CD4+ and CD8+ T cells. Human peripheral blood monocytes were initially transduced with lentiviral particles containing the genes encoding GM-CSF and IL-4 and then secondly transduced with lentiviral particles containing short-hairpin RNAs (shRNAs) to knock-down mRNAs of IL-10 and TGF-β receptors. The generated SD-DCs showed up-regulation of MHC class II (HLA-DR) and co-stimulatory molecules (CD40 and CD86), comparable to those of DCs generated by convention method. Suppression of IL-10 and TGF-β receptors on SD-DCs by specific shRNAs significantly increased levels of IFN-γ and also increased cytolytic activity of DC-activated effector T cells against CCA cell lines (KKU-213 and KKU-100), but it had little effect to immortalized cholangiocytes (MMNK-1). Thus, SD-DCs with down-regulation of IL-10 and TGF-β receptors increased activation of effector T cells, which is a recommended method to improve DC function for the preparation of DC-activated effector T cells for adoptive T-cell therapy.

Keywords: cholangiocarcinoma, IL-10 receptor, self-differentiated dendritic cells, TGF-β receptor

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168 Egg Yolk Peptide Stimulated Osteogenic Gene Expression

Authors: Hye Kyung Kim, Myung-Gyou Kim, Kang-Hyun Leem

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Postmenopausal osteoporosis is characterized by low bone density which leads to increased bone fragility and greater susceptibility to fracture. Current treatments for osteoporosis are dominated by drugs that inhibit bone resorption although they also suppress bone formation that may contribute to pathogenesis of osteonecrosis. To restore the extensive bone loss, there is a great need for anabolic treatments that induce osteoblasts to build new bone. Pre-osteoblastic cells produce proteins of the extra-cellular matrix, including type I collagen at first, and then to successively produce alkaline phosphatase (ALP) and osteocalcin during differentiation to osteoblasts. Finally, osteoblasts deposit calcium. Present study investigated the effects of egg yolk peptide (EYP) on osteogenic activities and bone matrix gene expressions in human osteoblastic MG-63 cells. The effects of EYP on cell proliferation, alkaline phosphatase (ALP) activity, collagen synthesis, and mineralization were measured. The expression of osteogenic genes including COL1A1 (collagen, type I, alpha 1), ALP, BGLAP (osteocalcin), and SPP1 (secreted phosphoprotein 1, osteopontin) were measured by quantitative realtime PCR. EYP dose-dependently increased MG-63 cell proliferation, ALP activity, collagen synthesis, and calcium deposition. Furthermore, COL1A1, ALP, and SPP1 gene expressions were increased by EYP treatment. Present study suggested that EYP treatment enhanced osteogenic activities and increased bone matrix osteogenicgenes. These results could provide a mechanistic explanation for the bone-strengthening effects of EYP.

Keywords: egg yolk peptide, osteoblastic MG-63 cells, alkaline phosphatase, collagen synthesis, osteogenic genes, COL1A1, osteocalcin, osteopontin

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167 Second Language Development with an Intercultural Approach: A Pilot Program Applied to Higher Education Students from a Escuela Normal in Atequiza, Mexico

Authors: Frida C. Jaime Franco, C. Paulina Navarro Núñez, R. Jacob Sánchez Nájera

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The importance of developing multi-language abilities in our global society is noteworthy. However, the necessity, interest, and consciousness of the significance that the development of another language represents, apart from the mother tongue, is not always the same in all contexts as it is in multicultural communities, especially in rural higher education institutions immersed in small communities. Leading opportunities for digital interaction among learners from Mexico and abroad partners represents scaffolding towards, not only language skills development but also intercultural communicative competences (ICC). This study leads us to consider what should be the best approach to work while applying a program of ICC integrated into the practice of EFL. While analyzing the roots of the language, it is possible to obtain the main objective of learning another language, to communicate with a functional purpose, as well as attaching social practices to the learning process, giving a result of functionality and significance to the target language. Hence, the collateral impact that collaborative learning leads to, aims to contribute to a better global understanding as well as a means of self and other cultural awareness through intercultural communication. While communicating through the target language by online collaboration among students in platforms of long-distance communication, language is used as a tool of interaction to broaden students’ perspectives reaching a substantial improvement with the help of their differences. This process should consider the application of the target language in the inquiry of sociocultural information, expecting the learners to integrate communicative skills to handle cultural differentiation at the same time they apply the knowledge of their target language in a real scenario of communication, despite being through virtual resources.

Keywords: collaborative learning, communicative approach, culture, interaction, interculturalism, target language, virtual partnership

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166 Family Models in Contemporary Multicultural Society: Exploratory Study Applied to Immigrants of Second and Third Generations

Authors: Danièle Peto

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A qualitative research based on twenty-eight semi-structured interviews of students in Social Work, in Brussels (Belgium), showed specific results for the Arab and Muslim students: second and third generations immigrants build their identity on the basis of a mix of differentiation with and recognition of their parents' culture of origin. Building a bridge between Modernity and Tradition, they claim active citizenship; at the same time they show and live by values and religious believes which reinforce the link to their parents’ origins. But they present those values and believes as their own rational choices among other choices, all available and rich for our multicultural society. The way they speak of themselves is highly modern. But, they still have to build a third way to find a place for themselves in society: one allowing them to live their religion as a partially public matter (when the Occidental society leaves no such place for religion) while ensuring, at the same time, the development of independent critical thought. On this basis, other semi-structured interviews are being laid with Social workers working with families from diverse ethnic backgrounds. They will verify the reality of those identity and cultural bricolages when those young adults of second and third generations build their own family. In between the theoretical models of traditional family and modern family, shall we find a new model, hybrid and more or less stable, combining some aspects of the former and the latter? The exploratory research phase focuses on three aspects of building a family life in this context : the way those generations play, discursively or not, in between their parents and the society in which they grew up; the importance of intercultural dialogue in this process of building; and testing the hypothesis that some families, in our society, show a special way of courting Modernity.

Keywords: family models, identity bricolages, intercultural, modernity and tradition

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165 Rights, Differences and Inclusion: The Role of Transdisciplinary Approach in the Education for Diversity

Authors: Ana Campina, Maria Manuela Magalhaes, Eusebio André Machado, Cristina Costa-Lobo

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Inclusive school advocates respect for differences, for equal opportunities and for a quality education for all, including for students with special educational needs. In the pursuit of educational equity, guaranteeing equality in access and results, it becomes the responsibility of the school to recognize students' needs, adapting to the various styles and rhythms of learning, ensuring the adequacy of curricula, strategies and resources, materials and humans. This paper presents a set of theoretical reflections in the disciplinary interface between legal and education sciences, school administration and management, with the aim of understand the real inclusion characteristics in a balance with the inclusion policies and the need(s) of an education for Human Rights, especially for diversity. Considering the actual social complexity but the important education instruments and strategies, mostly patented in the policies, this paper aims expose the existing contexts opposed to the laws, policies and inclusion educational needs. More than a single study, this research aims to develop a map of the reality and the guidelines to implement the action. The results point to the usefulness and pertinence of a school in which educational managers, teachers, parents, and students, are involved in the creation, implementation and monitoring of flexible curricula and adapted to the educational needs of students, promoting a collaborative work among teachers. We are then faced with a scenario that points to the need to reflect on the legislation and curricular management of inclusive classes and to operationalize the processes of elaboration of curricular adaptations and differentiation in the classroom. The transdisciplinary is a pedagogic and social education perfect approach using the Human Rights binomio – teaching and learning – supported by the inclusion laws according to the realistic needs for an effective successful society construction.

Keywords: rights, transdisciplinary, inclusion policies, education for diversity

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164 Exploring the Growth Path under Coupling Relationship between Space and Economy of Mountain Village and Townlets: Case Study of Southwest China

Authors: Runlin Liu, Shilong Li

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China is a mountainous country, with two-thirds of its territory covered by plateaus, hills, and mountains, and nearly half of the cities and towns are distributed in mountainous areas. Compared with the environmental constraints in the development path of cities and towns in the plains, there are heterogeneities in aspects such as spatial characteristics, growth mode, and ecological protection and so on for mountain village and townlets, and the development path of mountain village and townlets has a bidirectional relationship between mountain space and economic growth. Based on classical growth theory, this article explores the two-dimensional coupling relation between space and economy in mountain village and townlets under background of rural rejuvenation. GIS technology is adopted in the study to analyze spatial trends and patterns, economical spatial differentiation characteristics of village and townlets. This powerful tool can also help differentiate and analyze limiting factors and assessment systems in the economic growth of village and townlets under spatial dimension of mountainous space. To make the research more specific, this article selects mountain village and townlets in Southwest China as the object of study; this provides good cases for analyzing parallel coupling mechanism of the duality structure system between economic growth and spatial expansion and discussing the path selection of spatial economic growth of mountain village and towns with multiple constraints. The research results can provide quantitative references for the spatial and economic development paths of mountain villages and towns, which is helpful in realizing efficient and high-quality development mode with equal emphasis on spatial and economic benefits for these type of towns.

Keywords: coupling mechanism, geographic information technology, mountainous town, synergetic development, spatial economy

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163 Incorporation of Growth Factors onto Hydrogels via Peptide Mediated Binding for Development of Vascular Networks

Authors: Katie Kilgour, Brendan Turner, Carly Catella, Michael Daniele, Stefano Menegatti

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In vivo, the extracellular matrix (ECM) provides biochemical and mechanical properties that are instructional to resident cells to form complex tissues with characteristics to develop and support vascular networks. In vitro, the development of vascular networks can be guided by biochemical patterning of substrates via spatial distribution and display of peptides and growth factors to prompt cell adhesion, differentiation, and proliferation. We have developed a technique utilizing peptide ligands that specifically bind vascular endothelial growth factor (VEGF), erythropoietin (EPO), or angiopoietin-1 (ANG1) to spatiotemporally distribute growth factors to cells. This allows for the controlled release of each growth factor, ultimately enhancing the formation of a vascular network. Our engineered tissue constructs (ETCs) are fabricated out of gelatin methacryloyl (GelMA), which is an ideal substrate for tailored stiffness and bio-functionality, and covalently patterned with growth factor specific peptides. These peptides mimic growth factor receptors, facilitating the non-covalent binding of the growth factors to the ETC, allowing for facile uptake by the cells. We have demonstrated in the absence of cells the binding affinity of VEGF, EPO, and ANG1 to their respective peptides and the ability for each to be patterned onto a GelMA substrate. The ability to organize growth factors on an ETC provides different functionality to develop organized vascular networks. Our results demonstrated a method to incorporate biochemical cues into ETCs that enable spatial and temporal control of growth factors. Future efforts will investigate the cellular response by evaluating gene expression, quantifying angiogenic activity, and measuring the speed of growth factor consumption.

Keywords: growth factor, hydrogel, peptide, angiogenesis, vascular, patterning

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162 NLRP3-Inflammassome Participates in the Inflammatory Response Induced by Paracoccidioides brasiliensis

Authors: Eduardo Kanagushiku Pereira, Frank Gregory Cavalcante da Silva, Barbara Soares Gonçalves, Ana Lúcia Bergamasco Galastri, Ronei Luciano Mamoni

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The inflammatory response initiates after the recognition of pathogens by receptors expressed by innate immune cells. Among these receptors, the NLRP3 was associated with the recognition of pathogenic fungi in experimental models. NLRP3 operates forming a multiproteic complex called inflammasome, which actives caspase-1, responsible for the production of the inflammatory cytokines IL-1beta and IL-18. In this study, we aimed to investigate the involvement of NLRP3 in the inflammatory response elicited in macrophages against Paracoccidioides brasiliensis (Pb), the etiologic agent of PCM. Macrophages were differentiated from THP-1 cells by treatment with phorbol-myristate-acetate. Following differentiation, macrophages were stimulated by Pb yeast cells for 24 hours, after previous treatment with specific NLRP3 (3,4-methylenedioxy-beta-nitrostyrene) and/or caspase-1 (VX-765) inhibitors, or specific inhibitors of pathways involved in NLRP3 activation such as: Reactive Oxigen Species (ROS) production (N-Acetyl-L-cysteine), K+ efflux (Glibenclamide) or phagossome acidification (Bafilomycin). Quantification of IL-1beta and IL-18 in supernatants was performed by ELISA. Our results showed that the production of IL-1beta and IL-18 by THP-1-derived-macrophages stimulated with Pb yeast cells was dependent on NLRP3 and caspase-1 activation, once the presence of their specific inhibitors diminished the production of these cytokines. Furthermore, we found that the major pathways involved in NLRP3 activation, after Pb recognition, were dependent on ROS production and K+ efflux. In conclusion, our results showed that NLRP3 participates in the recognition of Pb yeast cells by macrophages, leading to the activation of the NLRP3-inflammasome and production of IL-1beta and IL-18. Together, these cytokines can induce an inflammatory response against P. brasiliensis, essential for the establishment of the initial inflammatory response and for the development of the subsequent acquired immune response.

Keywords: inflammation, IL-1beta, IL-18, NLRP3, Paracoccidioidomycosis

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161 The Utility of Sonographic Features of Lymph Nodes during EBUS-TBNA for Predicting Malignancy

Authors: Atefeh Abedini, Fatemeh Razavi, Mihan Pourabdollah Toutkaboni, Hossein Mehravaran, Arda Kiani

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In countries with the highest prevalence of tuberculosis, such as Iran, the differentiation of malignant tumors from non-malignant is very important. In this study, which was conducted for the first time among the Iranian population, the utility of the ultrasonographic morphological characteristics in patients undergoing EBUS was used to distinguish the non-malignant versus malignant lymph nodes. The morphological characteristics of lymph nodes, which consist of size, shape, vascular pattern, echogenicity, margin, coagulation necrosis sign, calcification, and central hilar structure, were obtained during Endobronchial Ultrasound-Guided Trans-Bronchial Needle Aspiration and were compared with the final pathology results. During this study period, a total of 253 lymph nodes were evaluated in 93 cases. Round shape, non-hilar vascular pattern, heterogeneous echogenicity, hyperechogenicity, distinct margin, and the presence of necrosis sign were significantly higher in malignant nodes. On the other hand, the presence of calcification and also central hilar structure were significantly higher in the benign nodes (p-value ˂ 0.05). Multivariate logistic regression showed that size>1 cm, heterogeneous echogenicity, hyperechogenicity, the presence of necrosis signs and, the absence of central hilar structure are independent predictive factors for malignancy. The accuracy of each of the aforementioned factors is 42.29 %, 71.54 %, 71.90 %, 73.51 %, and 65.61 %, respectively. Of 74 malignant lymph nodes, 100% had at least one of these independent factors. According to our results, the morphological characteristics of lymph nodes based on Endobronchial Ultrasound-Guided Trans-Bronchial Needle Aspiration can play a role in the prediction of malignancy.

Keywords: EBUS-TBNA, malignancy, nodal characteristics, pathology

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160 Aberrant Genome‐Wide DNA Methylation Profiles of Peripheral Blood Mononuclear Cells from Patients Hospitalized with COVID-19

Authors: Inam Ridha, Christine L. Kuryla, Madhuranga Thilakasiri Madugoda Ralalage Don, Norman J. Kleiman, Yunro Chung, Jin Park, Vel Murugan, Joshua LaBaer

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To date, more than 275 million people worldwide have been diagnosed with COVID-19 and the rapid spread of the omicron variant suggests many millions more will soon become infected. Many infections are asymptomatic, while others result in mild to moderate illness. Unfortunately, some infected individuals exhibit more serious symptoms including respiratory distress, thrombosis, cardiovascular disease, multi-organ failure, cognitive difficulties, and, in roughly 2% of cases, death. Studies indicate other coronaviruses can alter the host cell's epigenetic profile and lead to alterations in the immune response. To better understand the mechanism(s) by which SARS-CoV-2 infection causes serious illness, DNA methylation profiles in peripheral blood mononuclear cells (PBMCs) from 90 hospitalized severely ill COVID-19 patients were compared to profiles from uninfected control subjects. Exploratory epigenome-wide DNA methylation analyses were performed using multiplexed methylated DNA immunoprecipitation (MeDIP) followed by pathway enrichment analysis. The findings demonstrated significant DNA methylation changes in infected individuals as compared to uninfected controls. Pathway analysis indicated that apoptosis, cell cycle control, Toll-like receptors (TLR), cytokine interactions, and T cell differentiation were among the most affected metabolic processes. In addition, changes in specific gene methylation were compared to SARS-CoV-2 induced changes in RNA expression using published RNA-seq data from 3 patients with severe COVID-19. These findings demonstrate significant correlations between differentially methylated and differentially expressed genes in a number of critical pathways.

Keywords: COVID19, epigenetics, DNA mathylation, viral infection

Procedia PDF Downloads 148