Search results for: proliferating cell nuclear antigen
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4461

Search results for: proliferating cell nuclear antigen

4341 Process Safety Evaluation of a Nuclear Power Plant through Virtual Process Hazard Analysis Using Hazard and Operability Technique

Authors: Elysa V. Largo, Lormaine Anne A. Branzuela, Julie Marisol D. Pagalilauan, Neil C. Concibido, Monet Concepcion M. Detras

Abstract:

The energy demand in the country is increasing; thus, nuclear energy is recently mandated to add to the energy mix. The Philippines has the Bataan Nuclear Power Plant (BNPP), which can be a source of nuclear energy; however, it has not been operated since the completion of its construction. Thus, evaluating the safety of BNPP is vital. This study explored the possible deviations that may occur in the operation of a nuclear power plant with a pressurized water reactor, which is similar to BNPP, through a virtual process hazard analysis (PHA) using the hazard and operability (HAZOP) technique. Temperature, pressure, and flow were used as parameters. A total of 86 causes of various deviations were identified, wherein the primary system and line from reactor coolant pump to reactor vessel are the most critical system and node, respectively. A total of 348 scenarios were determined. The critical events are radioactive leaks due to nuclear meltdown and sump overflow that could lead to multiple worker fatalities, one or more public fatalities, and environmental remediation. There were existing safeguards identified; however, further recommendations were provided to have additional and supplemental barriers to reduce the risk.

Keywords: PSM, PHA, HAZOP, nuclear power plant

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4340 Structural Evaluation of Cell-Filled Pavement

Authors: Subrat Roy

Abstract:

This paper describes the findings of a study carried out for evaluating the performance of cell-filled pavement for low volume roads. Details of laboratory investigations and the methodology adopted for construction of cell-filled pavement are presented. The aim of this study is to evaluate the structural behaviour of cement concrete filled cell pavement laid over three different types of subbases (water bound macadam, soil-cement and moorum). A formwork of cells of a thin plastic sheet was used to construct the cell-filled pavements to form flexible, interlocked block pavements. Surface deflections were measured using falling weight deflectometer and benkelman beam methods. Resilient moduli of pavement layers were estimated from the measured deflections. A comparison of deflections obtained from both the methodology is also presented.

Keywords: cell-filled pavement, WBM, FWD, Moorum

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4339 Parental Monitoring of Learners’ Cell Phone Use in the Eastern Cape, South Africa

Authors: Melikhaya Skhephe, Robert Mawuli Kwasi Boadzo, Zanoxolo Berington Gobingca

Abstract:

This research study sought to examine parental monitoring of learners’ cell phone use in the Eastern Cape, South Africa. To this end, the researchers employed a quantitative approach. Data were obtained through questionnaires, with a sample of 15 parents having been purposively selected. The findings revealed that parents are unaware that they have to monitor the learner’s cell phone. Another finding was that parents in the 21-century did not support the use of mobile phones in education. The researchers recommend that parent’s discussion forums be created to educate parents on how a cell phone can be used in education. Cellphone companies need to be encouraged to educate parents on how they monitor cell phones used by learners. Another recommendation was that network providers need to restrict access to searching on the internet according to age.

Keywords: parental monitoring, app blocking services, learner’s cell phone use, cell phone

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4338 The Effect of Different Levels of Seed and Extract of Harmal (Peganum harmala L.) on Immune Responses of Broiler Chicks

Authors: M. Toghyani, A. Ghasemi, S. A. Tabeidian

Abstract:

The present study was carried out to evaluate the effect of different levels of dietary seed and extract of Harmal (Peganum harmala L.) on immunity of broiler chicks. A total of 350 one-day old broiler chicks (Ross 308) were randomly allocated to five dietary treatments with four replicates pen of 14 birds each. Dietary treatments consisted of control, 1 and 2 g/kg Harmal seed in diet, 100 and 200 mg/L Harmal seed extract in water. Broilers received dietary treatments from 1 to 42 d. Two birds from each pen were randomly weighed and sacrificed at 42 d of age, the relative weight of lymphoid organs (bursa of Fabercius and spleen) to live weight were calculated. Antibody titers against Newcastle and influenza viruses and sheep red blood cell were measured at 30 d of age. Results showed that the relative weights of lymphoid organs were not affected by dietary treatments. Furthermore, antibody titer against Newcastle and influenza viruses as well as sheep red blood cell antigen were significantly (P<0.05) enhanced by feeding Harmal seed and extract. In conclusion, the results indicated that dietary inclusion of Harmal seed and extract enhanced immunological responses in broiler chicks.

Keywords: broiler chicks, Harmal, immunity, Peganum harmala

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4337 Heavy Liquid Metal Coolant – the Key Safety Element in the Complex of New Nuclear Energy Technologies

Authors: A. Orlov, V. Rachkov

Abstract:

The future of Nuclear Energetics is seen in fast reactors with inherent safety working in the closed nuclear fuel cycle. The concept of inherent safety, which lies in deterministic elimination of the most severe accidents due to inherent properties of the reactor rather than through building up engineered barriers, is a cornerstone of success in ensuring safety and economic efficiency of future Nuclear Energetics. The focus of this paper is one of the key elements of inherent safety - the lead coolant of a nuclear reactor. Advantages of lead coolant for reactor application, influence on safety are reviewed. BREST-OD-300 fast reactor, currently being developed in Russia withing the “Proryv” Project utilizes lead coolant and a special set of measures and devices, called technology of lead coolant that ensures safe operation in a wide range of temperatures. Here these technological elements are reviewed, and current progress in their development is discussed.

Keywords: BREST-OD-300. , fast reactor, inherent safety, lead coolant

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4336 Antigen Stasis can Predispose Primary Ciliary Dyskinesia (PCD) Patients to Asthma

Authors: Nadzeya Marozkina, Joe Zein, Benjamin Gaston

Abstract:

Introduction: We have observed that many patients with Primary Ciliary Dyskinesia (PCD) benefit from asthma medications. In healthy airways, the ciliary function is normal. Antigens and irritants are rapidly cleared, and NO enters the gas phase normally to be exhaled. In the PCD airways, however, antigens, such as Dermatophagoides, are not as well cleared. This defect leads to oxidative stress, marked by increased DUOX1 expression and decreased superoxide dismutase [SOD] activity (manuscript under revision). H₂O₂, in high concentrations in the PCD airway, injures the airway. NO is oxidized rather than being exhaled, forming cytotoxic peroxynitrous acid. Thus, antigen stasis on PCD airway epithelium leads to airway injury and may predispose PCD patients to asthma. Indeed, recent population genetics suggest that PCD genes may be associated with asthma. We therefore hypothesized that PCD patients would be predisposed to having asthma. Methods. We analyzed our database of 18 million individual electronic medical records (EMRs) in the Indiana Network for Patient Care research database (INPCR). There is not an ICD10 code for PCD itself; code Q34.8 is most commonly used clinically. To validate analysis of this code, we queried patients who had an ICD10 code for both bronchiectasis and situs inversus totalis in INPCR. We also studied a validation cohort using the IBM Explorys® database (over 80 million individuals). Analyses were adjusted for age, sex and race using a 1 PCD: 3 controls matching method in INPCR and multivariable logistic regression in the IBM Explorys® database. Results. The prevalence of asthma ICD10 codes in subjects with a code Q34.8 was 67% vs 19% in controls (P < 0.0001) (Regenstrief Institute). Similarly, in IBM*Explorys, the OR [95% CI] for having asthma if a patient also had ICD10 code 34.8, relative to controls, was =4.04 [3.99; 4.09]. For situs inversus alone the OR [95% CI] was 4.42 [4.14; 4.71]; and bronchiectasis alone the OR [95% CI] =10.68 (10.56; 10.79). For both bronchiectasis and situs inversus together, the OR [95% CI] =28.80 (23.17; 35.81). Conclusions: PCD causes antigen stasis in the human airway (under review), likely predisposing to asthma in addition to oxidative and nitrosative stress and to airway injury. Here, we show that, by several different population-based metrics, and using two large databases, patients with PCD appear to have between a three- and 28-fold increased risk of having asthma. These data suggest that additional studies should be undertaken to understand the role of ciliary dysfunction in the pathogenesis and genetics of asthma. Decreased antigen clearance caused by ciliary dysfunction may be a risk factor for asthma development.

Keywords: antigen, PCD, asthma, nitric oxide

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4335 Mathematical Modeling of Cell Volume Alterations under Different Osmotic Conditions

Authors: Juliana A. Knocikova, Yann Bouret, Médéric Argentina, Laurent Counillon

Abstract:

Cell volume, together with membrane potential and intracellular hydrogen ion concentration, is an essential biophysical parameter for normal cellular activity. Cell volumes can be altered by osmotically active compounds and extracellular tonicity. In this study, a simple mathematical model of osmotically induced cell swelling and shrinking is presented. Emphasis is given to water diffusion across the membrane. The mathematical description of the cellular behavior consists in a system of coupled ordinary differential equations. We compare experimental data of cell volume alterations driven by differences in osmotic pressure with mathematical simulations under hypotonic and hypertonic conditions. Implications for a future model are also discussed.

Keywords: eukaryotic cell, mathematical modeling, osmosis, volume alterations

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4334 An Institutional Mapping and Stakeholder Analysis of ASEAN’s Preparedness for Nuclear Power Disaster

Authors: Nur Azha Putra Abdul Azim, Denise Cheong, S. Nivedita

Abstract:

Currently, there are no nuclear power reactors among the Association of Southeast Asian Nations (ASEAN) member states (AMS) but there are seven operational nuclear research reactors, and Indonesia is about to construct the region’s first experimental power reactor by the end of the decade. If successful, the experimental power reactor will lay the foundation for the country’s and region’s first nuclear power plant. Despite projecting confidence during the period of nuclear power renaissance in the region in the last decade, none of the AMS has committed to a political decision on the use of nuclear energy and this is largely due to the Fukushima nuclear power accident in 2011. Of the ten AMS, Vietnam, Indonesia and Malaysia have demonstrated the most progress in developing nuclear energy based on the nuclear power infrastructure development assessments made by the International Atomic Energy Agency. Of these three states, Vietnam came closest to building its first nuclear power plant but decided to delay construction further due to safety and security concerns. Meanwhile, Vietnam along with Indonesia and Malaysia continue with their nuclear power infrastructure development and the remaining SEA states, with the exception of Brunei and Singapore, continue to build their expertise and capacity for nuclear power energy. At the current rate of progress, Indonesia is expected to make a national decision on the use of nuclear power by 2023 while Malaysia, the Philippines, and Thailand have included the use of nuclear power in their mid to long-term power development plans. Vietnam remains open to nuclear power but has not placed a timeline. The medium to short-term power development projection in the region suggests that the use of nuclear energy in the region is a matter of 'when' rather than 'if'. In lieu of the prospects for nuclear energy in Southeast Asia (SEA), this presentation will review the literature on ASEAN radiological emergency and preparedness response (EPR) plans and examine ASEAN’s disaster management and emergency framework. Through a combination of institutional mapping and stakeholder analysis methods, which we examine in the context of the international EPR, and nuclear safety and security regimes, we will identify the issues and challenges in developing a regional radiological EPR framework in the SEA. We will conclude with the observation that ASEAN faces serious structural, institutional and governance challenges due to the AMS inherent political structures and history of interstate conflicts, and propose that ASEAN should either enlarge the existing scope of its disaster management and response framework or that its radiological EPR framework should exist as a separate entity.

Keywords: nuclear power, nuclear accident, ASEAN, Southeast Asia

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4333 Mycophenolate Mofetil Increases Mucin Expression in Primary Cultures of Oral Mucosal Epithelial Cells for Application in Limbal Stem Cell Deficiency

Authors: Sandeep Kumar Agrawal, Aditi Bhattacharya, Janvie Manhas, Krushna Bhatt, Yatin Kholakiya, Nupur Khera, Ajoy Roychoudhury, Sudip Sen

Abstract:

Autologous cultured explants of human oral mucosal epithelial cells (OMEC) are a potential therapeutic modality for limbal stem cell deficiency (LSCD). Injury or inflammation of the ocular surface in the form of burns, chemicals, Stevens Johnson syndrome, ocular cicatricial pemphigoid etc. can lead to destruction and deficiency of limbal stem cells. LSCD manifests in the form of severe ocular surface diseases (OSD) characterized by persistent and recurrent epithelial defects, conjuntivalisation and neovascularisation of the corneal surface, scarring and ultimately opacity and blindness. Most of the cases of OSD are associated with severe dry eye pertaining to diminished mucin and aqueous secretion. Mycophenolate mofetil (MMF) has been shown to upregulate the mucin expression in conjunctival goblet cells in vitro. The aim of this study was to evaluate the effects of MMF on mucin expression in primary cultures of oral mucosal epithelial cells. With institutional ethics committee approval and written informed consent, thirty oral mucosal epithelial tissue samples were obtained from patients undergoing oral surgery for non-malignant conditions. OMEC were grown on human amniotic membrane (HAM, obtained from expecting mothers undergoing elective caesarean section) scaffold for 2 weeks in growth media containing DMEM & Ham’s F12 (1:1) with 10% FBS and growth factors. In vitro dosage of MMF was standardised by MTT assay. Analysis of stem cell markers was done using RT-PCR while mucin mRNA expression was quantified using RT-PCR and q-PCR before and after treating cultured OMEC with graded concentrations of MMF for 24 hours. Protein expression was validated using immunocytochemistry. Morphological studies revealed a confluent sheet of proliferating, stratified oral mucosal epithelial cells growing over the surface of HAM scaffold. The presence of progenitor stem cell markers (p63, p75, β1-Integrin and ABCG2) and cell surface associated mucins (MUC1, MUC15 and MUC16) were elucidated by RT-PCR. The mucin mRNA expression was found to be upregulated in MMF treated primary cultures of OMEC, compared to untreated controls as quantified by q-PCR with β-actin as internal reference gene. Increased MUC1 protein expression was validated by immunocytochemistry on representative samples. Our findings conclude that OMEC have the ability to form a multi-layered confluent sheet on the surface of HAM similar to a cornea, which is important for the reconstruction of the damaged ocular surface. Cultured OMEC has stem cell properties as demonstrated by stem cell markers. MMF can be a novel enhancer of mucin production in OMEC. It has the potential to improve dry eye in patients undergoing OMEC transplantation for bilateral OSD. Further clinical trials are required to establish the role of MMF in patients undergoing OMEC transplantation.

Keywords: limbal stem cell deficiency, mycophenolate mofetil, mucin, ocular surface disease

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4332 Dynamic Thermal Modelling of a PEMFC-Type Fuel Cell

Authors: Marco Avila Lopez, Hasnae Ait-Douchi, Silvia De Los Santos, Badr Eddine Lebrouhi, Pamela Ramírez Vidal

Abstract:

In the context of the energy transition, fuel cell technology has emerged as a solution for harnessing hydrogen energy and mitigating greenhouse gas emissions. An in-depth study was conducted on a PEMFC-type fuel cell, with an initiation of an analysis of its operational principles and constituent components. Subsequently, the modelling of the fuel cell was undertaken using the Python programming language, encompassing both steady-state and transient regimes. In the case of the steady-state regime, the physical and electrochemical phenomena occurring within the fuel cell were modelled, with the assumption of uniform temperature throughout all cell compartments. Parametric identification was carried out, resulting in a remarkable mean error of only 1.62% when the model results were compared to experimental data documented in the literature. The dynamic model that was developed enabled the scrutiny of the fuel cell's response in terms of temperature and voltage under varying current conditions.

Keywords: fuel cell, modelling, dynamic, thermal model, PEMFC

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4331 ‘Saying’ the Nuclear Power in France: Evolution of the Images and Perceptions of a Sensitive Theme

Authors: Jandot Aurélia

Abstract:

As the nuclear power is a sensitive field leading to controversy, the quality of the communication about it is important. Between 1965 and 1981, in France, this one had gradually changed. This change is studied here in the main French news magazine L’Express, in connection with several parameters. As this represents a huge number of copies and occurrences, thus a considerable amount of information; this paper is focused on the main articles as well as the main “mental images”. These ones are important, as their aim is to direct the thought of the readers, and as they have led the public awareness to evolve. Over this 17 years, two trends are in confrontation: The first one is promoting the perception of the nuclear power, while the second one is discrediting it. These trends are organized in two axes: the evolution of engineering, and the risks. In both cases, the changes in the language allow discerning the deepest intentions of the magazine editing, over a period when the nuclear technology, to there a laboratory object accompanied with mystery and secret, has become a social issue seemingly open to all.

Keywords: French news magazine, mental images, nuclear power, public awareness

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4330 Introduction of PMMA-Tag to VHH for Improving Recovery and Immobilization Rate of VHHS

Authors: Bongmun Kang, Kagnari Yamakawa, Yoshihisa Hagihara, Yuji Ito, Michimasa Kishimoto, Yoichi Kumada

Abstract:

The PMMA-tag was genetically fused with the C-terminal region of VHH molecules. This antibody, VHH, is known as a single-chain domain, which is devoid of light chains. The PMMA-tag, which could affect the isoelectric point (pI) changeable with a charge of amino acid in VHHs were closely related to the solubility of VHH molecules during refolding. The genetic fusion of PMMA-tag to C-terminal region of VHHs significantly affects the recovery of their soluble protein during refolding by 50 mM TAPS at pH 8.5. It could be refolded with a recovery of more than 95% by dialysis at pH 8.5. A marked difference in the antigen-binding activities in the adsorption state was significantly high in VHH-PM compared to the wild type of VHH. There are approximately 8-fold differences in the antigen-binding activities in the adsorption state between VHH-PM and VHH.

Keywords: VHH, PMMA-tag, isoelectric point, pH, Solubility, refolding, immobilization, ELISA

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4329 Human Leukocyte Antigen Class 1 Phenotype Distribution and Analysis in Persons from Central Uganda with Active Tuberculosis and Latent Mycobacterium tuberculosis Infection

Authors: Helen K. Buteme, Rebecca Axelsson-Robertson, Moses L. Joloba, Henry W. Boom, Gunilla Kallenius, Markus Maeurer

Abstract:

Background: The Ugandan population is heavily affected by infectious diseases and Human leukocyte antigen (HLA) diversity plays a crucial role in the host-pathogen interaction and affects the rates of disease acquisition and outcome. The identification of HLA class 1 alleles and determining which alleles are associated with tuberculosis (TB) outcomes would help in screening individuals in TB endemic areas for susceptibility to TB and to predict resistance or progression to TB which would inevitably lead to better clinical management of TB. Aims: To be able to determine the HLA class 1 phenotype distribution in a Ugandan TB cohort and to establish the relationship between these phenotypes and active and latent TB. Methods: Blood samples were drawn from 32 HIV negative individuals with active TB and 45 HIV negative individuals with latent MTB infection. DNA was extracted from the blood samples and the DNA samples HLA typed by the polymerase chain reaction-sequence specific primer method. The allelic frequencies were determined by direct count. Results: HLA-A*02, A*01, A*74, A*30, B*15, B*58, C*07, C*03 and C*04 were the dominant phenotypes in this Ugandan cohort. There were differences in the distribution of HLA types between the individuals with active TB and the individuals with LTBI with only HLA-A*03 allele showing a statistically significant difference (p=0.0136). However, after FDR computation the corresponding q-value is above the expected proportion of false discoveries (q-value 0.2176). Key findings: We identified a number of HLA class I alleles in a population from Central Uganda which will enable us to carry out a functional characterization of CD8+ T-cell mediated immune responses to MTB. Our results also suggest that there may be a positive association between the HLA-A*03 allele and TB implying that individuals with the HLA-A*03 allele are at a higher risk of developing active TB.

Keywords: HLA, phenotype, tuberculosis, Uganda

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4328 Giant Cancer Cell Formation: A Link between Cell Survival and Morphological Changes in Cancer Cells

Authors: Rostyslav Horbay, Nick Korolis, Vahid Anvari, Rostyslav Stoika

Abstract:

Introduction: Giant cancer cells (GCC) are common in all types of cancer, especially after poor therapy. Some specific features of such cells include ~10-fold enlargement, drug resistance, and the ability to propagate similar daughter cells. We used murine NK/Ly lymphoma, an aggressive and fast growing lymphoma model that has already shown drastic changes in GCC comparing to parental cells (chromatin condensation, nuclear fragmentation, tighter OXPHOS/cellular respiration coupling, multidrug resistance). Materials and methods: In this study, we compared morpho-functional changes of GCC that predominantly show either a cytostatic or a cytotoxic effect after treatment with drugs. We studied the effect of a combined cytostatic/cytotoxic drug treatment to determine the correlation of drug efficiency and GCC formation. Doses of G1/S-specific drug paclitaxel/PTX (G2/M-specific, 50 mg/mouse), vinblastine/VBL (50 mg/mouse), and DNA-targeting agents doxorubicin/DOX (125 ng/mouse) and cisplatin/CP (225 ng/mouse) on C57 black mice. Several tests were chosen to estimate morphological and physiological state (propidium iodide, Rhodamine-123, DAPI, JC-1, Janus Green, Giemsa staining and other), which included cell integrity, nuclear fragmentation and chromatin condensation, mitochondrial activity, and others. A single and double factor ANOVA analysis were performed to determine correlation between the criteria of applied drugs and cytomorphological changes. Results: In all cases of treatment, several morphological changes were observed (intracellular vacuolization, membrane blebbing, and interconnected mitochondrial network). A lower gain in ascites (49.97% comparing to control group) and longest lifespan (22+9 days) after tumor injection was obtained with single VBL and single DOX injections. Such ascites contained the highest number of GCC (83.7%+9.2%), lowest cell count number (72.7+31.0 mln/ml), and a strong correlation coefficient between increased mitochondrial activity and percentage of giant NK/Ly cells. A high number of viable GCC (82.1+9.2%) was observed compared to the parental forms (15.4+11.9%) indicating that GCC are more drug resistant than the parental cells. All this indicates that the giant cell formation and its ability to obtain drug resistance is an expanding field in cancer research.

Keywords: ANOVA, cisplatin, doxorubicin, drug resistance, giant cancer cells, NK/Ly lymphoma, paclitaxel, vinblastine

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4327 Directional Search for Dark Matter Using Nuclear Emulsion

Authors: Ali Murat Guler

Abstract:

A variety of experiments have been developed over the past decades, aiming at the detection of Weakly Interactive Massive Particles (WIMPs) via their scattering in an instrumented medium. The sensitivity of these experiments has improved with a tremendous speed, thanks to a constant development of detectors and analysis methods. Detectors capable of reconstructing the direction of the nuclear recoil induced by the WIMP scattering are opening a new frontier to possibly extend Dark Matter searches beyond the neutrino background. Measurement of WIMP’s direction will allow us to detect the galactic origin of dark matter and, therefore to have a clear signal-background separation. The NEWSdm experiment, based on nuclear emulsions, is intended to measure the direction of WIMP-induced nuclear coils with a solid-state detector, thus with high sensitivity. We discuss the discovery potential of a directional experiment based on the use of a solid target made of newly developed nuclear emulsions and novel read-out systems achieving nanometric resolution. We also report results of a technical test conducted in Gran Sasso.

Keywords: dark matter, direct detection, nuclear emulsion, WIMPS

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4326 Online Measurement of Fuel Stack Elongation

Authors: Sung Ho Ahn, Jintae Hong, Chang Young Joung, Tae Ho Yang, Sung Ho Heo, Seo Yun Jang

Abstract:

The performances of nuclear fuels and materials are qualified at an irradiation system in research reactors operating under the commercial nuclear power plant conditions. Fuel centerline temperature, coolant temperature, neutron flux, deformations of fuel stack and swelling are important parameters needed to analyze the nuclear fuel performances. The dimensional stability of nuclear fuels is a key parameter measuring the fuel densification and swelling. In this study, the fuel stack elongation is measured using a LVDT. A mockup LVDT instrumented fuel rod is developed. The performances of mockup LVDT instrumented fuel rod is evaluated by experiments.

Keywords: axial deformation, elongation measurement, in-pile instrumentation, LVDT

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4325 A Comprehensive Analysis of LACK (Leishmania Homologue of Receptors for Activated C Kinase) in the Context of Visceral Leishmaniasis

Authors: Sukrat Sinha, Abhay Kumar, Shanthy Sundaram

Abstract:

The Leishmania homologue of activated C kinase (LACK) is known T cell epitope from soluble Leishmania antigens (SLA) that confers protection against Leishmania challenge. This antigen has been found to be highly conserved among Leishmania strains. LACK has been shown to be protective against L. donovani challenge. A comprehensive analysis of several LACK sequences was completed. The analysis shows a high level of conservation, lower variability and higher antigenicity in specific portions of the LACK protein. This information provides insights for the potential consideration of LACK as a putative candidate in the context of visceral Leishmaniasis vaccine target.

Keywords: bioinformatics, genome assembly, leishmania activated protein kinase c (lack), next-generation sequencing

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4324 Characterization of Dota-Girentuximab Conjugates for Radioimmunotherapy

Authors: Tais Basaco, Stefanie Pektor, Josue A. Moreno, Matthias Miederer, Andreas Türler

Abstract:

Radiopharmaceuticals based in monoclonal anti-body (mAb) via chemical linkers have become a potential tool in nuclear medicine because of their specificity and the large variability and availability of therapeutic radiometals. It is important to identify the conjugation sites and number of attached chelator to mAb to obtain radioimmunoconjugates with required immunoreactivity and radiostability. Girentuximab antibody (G250) is a potential candidate for radioimmunotherapy of clear cell carcinomas (RCCs) because it is reactive with CAIX antigen, a transmembrane glycoprotein overexpressed on the cell surface of most ( > 90%) (RCCs). G250 was conjugated with the bifunctional chelating agent DOTA (1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid) via a benzyl-thiocyano group as a linker (p-SCN-Bn-DOTA). DOTA-G250 conjugates were analyzed by size exclusion chromatography (SE-HPLC) and by electrophoresis (SDS-PAGE). The potential site-specific conjugation was identified by liquid chromatography–mass spectrometry (LC/MS-MS) and the number of linkers per molecule of mAb was calculated using the molecular weight (MW) measured by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The average number obtained in the conjugates in non-reduced conditions was between 8-10 molecules of DOTA per molecule of mAb. The average number obtained in the conjugates in reduced conditions was between 1-2 and 3-4 molecules of DOTA per molecule of mAb in the light chain (LC) and heavy chain (HC) respectively. Potential DOTA modification sites of the chelator were identified in lysine residues. The biological activity of the conjugates was evaluated by flow cytometry (FACS) using CAIX negative (SKRC-18) and CAIX positive (SKRC-52). The DOTA-G250 conjugates were labelled with 177Lu with a radiochemical yield > 95% reaching specific activities of 12 MBq/µg. The stability in vitro of different types of radioconstructs was analyzed in human serum albumin (HSA). The radiostability of 177Lu-DOTA-G250 at high specific activity was increased by addition of sodium ascorbate after the labelling. The immunoreactivity was evaluated in vitro and in vivo. Binding to CAIX positive cells (SK-RC-52) at different specific activities was higher for conjugates with less DOTA content. Protein dose was optimized in mice with subcutaneously growing SK-RC-52 tumors using different amounts of 177Lu- DOTA-G250.

Keywords: mass spectrometry, monoclonal antibody, radiopharmaceuticals, radioimmunotheray, renal cancer

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4323 Regulatory Measures on Effective Nuclear Security and Safeguards System in Nigeria

Authors: Nnodi Chinweikpe Akelachi, Adebayo Oladini Kachollom Ifeoma

Abstract:

Insecurity and the possession of nuclear weapons for non-peaceful purposes constitute a major threat to global peace and security, and this undermines the capacity for sustainable development. In Nigeria, the threat of terrorism is a challenge to national stability. For over a decade, Nigeria has been faced with insecurity ranging from Boko-Haram terrorist groups, kidnapping and banditry. The threat exhibited by this non-state actor poses a huge challenge to nuclear and radiological high risks facilities in Nigeria. This challenge has resulted in the regulatory authority and International stakeholders formulating policies for a good mitigation strategy. This strategy is enshrined in formulated laws, regulations and guides like the repealed Nuclear Safety and Radiation Protection Act 19 of 1995 (Nuclear safety, Physical Security and Safeguards Bill), the Nigerian Physical Protection of Nuclear Material and Nuclear Facilities, and Nigerian Nuclear Safeguards Regulations of 2021. All this will help Nigeria’s effort to meet its national nuclear security and safeguards obligations. To further enhance the implementation of nuclear security and safeguards system, Nigeria has signed the Non-Proliferation Treaty (NPT) in 1970, the Comprehensive Safeguards Agreement (INFCIRC/358) in 1988, Additional Protocol in 2007 as well as the Convention on Physical Protection of Nuclear Material and its amendment in 2005. In view of the evolving threats by non-state actors in Nigeria, physical protection security upgrades are being implemented in nuclear and all high-risk radiological facilities through the support of the United States Department of Energy (US-DOE). Also, the IAEA has helped strengthen nuclear security and safeguard systems through the provision of technical assistance and capacity development. Efforts are being made to address some of the challenges identified in the cause of implementing the measures for effective nuclear security and safeguards systems in Nigeria. However, there are eminent challenges in the implementation of the measures within the security and systems in Nigeria. These challenges need to be addressed for an effective security and safeguard regime in Nigeria. This paper seeks to address the challenges encountered in implementing the regulatory and stakeholder measures for effective security and safeguards regime in Nigeria, amongst others.

Keywords: nuclear regulatory body, nuclear facilities and activities, international stakeholders, security and safeguards measures

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4322 The Nuclear Power Plant Environment Monitoring System through Mobile Units

Authors: P. Tanuska, A. Elias, P. Vazan, B. Zahradnikova

Abstract:

This article describes the information system for measuring and evaluating the dose rate in the environment of nuclear power plants Mochovce and Bohunice in Slovakia. The article presents the results achieved in the implementation of the EU project–Research of monitoring and evaluation of non-standard conditions in the area of nuclear power plants. The objectives included improving the system of acquisition, measuring and evaluating data with mobile and autonomous units applying new knowledge from research. The article provides basic and specific features of the system and compared to the previous version of the system, also new functions.

Keywords: information system, dose rate, mobile devices, nuclear power plant

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4321 Comparison of Several Diagnostic Methods for Detecting Bovine Viral Diarrhea Virus Infection in Cattle

Authors: Azizollah Khodakaram- Tafti, Ali Mohammadi, Ghasem Farjanikish

Abstract:

Bovine viral diarrhea virus (BVDV) is one of the most important viral pathogens of cattle worldwide caused by Pestivirus genus, Flaviviridae family.The aim of the present study was to comparison several diagnostic methods and determine the prevalence of BVDV infection for the first time in dairy herds of Fars province, Iran. For initial screening, a total of 400 blood samples were randomly collected from 12 industrial dairy herds and analyzed using reverse transcription (RT)-PCR on the buffy coat. In the second step, blood samples and also ear notch biopsies were collected from 100 cattle of infected farms and tested by antigen capture ELISA (ACE), RT-PCR and immunohistochemistry (IHC). The results of nested RT-PCR (outer primers 0I100/1400R and inner primers BD1/BD2) was successful in 16 out of 400 buffy coat samples (4%) as acute infection in initial screening. Also, 8 out of 100 samples (2%) were positive as persistent infection (PI) by all of the diagnostic tests similarly including RT-PCR, ACE and IHC on buffy coat, serum and skin samples, respectively. Immunoreactivity for bovine BVDV antigen as brown, coarsely to finely granular was observed within the cytoplasm of epithelial cells of epidermis and hair follicles and also subcutaneous stromal cells. These findings confirm the importance of monitoring BVDV infection in cattle of this region and suggest detection and elimination of PI calves for controlling and eradication of this disease.

Keywords: antigen capture ELISA, bovine viral diarrhea virus, immunohistochemistry, RT-PCR, cattle

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4320 Influence of Preheating Self-Adhesive Cements on the Degree of Conversion, Cell Migration and Cell Viability in NIH/3T3

Authors: Celso Afonso Klein Jr., Henrique Cantarelli, Fernando Portella, Keiichi Hosaka, Eduardo Reston, Fabricio Collares, Roberto Zimmer

Abstract:

TTo evaluate the influence of preheating self-adhesive cement at 39ºC on cell migration, cytotoxicity and degree of conversion. RelyX U200, Set PP and MaxCem Elite were subjected to a degree of conversion analysis (FTIR-ATR). For the cytotoxicity analysis, extracts (24 h and 7 days) were placed in contact with NIH/3T3 cells. For cell migration, images were captured of each sample until the possible closure of the cleft occurred. In the results of the degree of conversion, preheating did not improve the conversion of cement. For the MTT, preheating did not improve the results within 24 hours. However, it generated positive results within 7 days for the Set PP resin cement. For cell migration, high rates of cell death were found in all groups. It is concluded that preheating at 39ºC caused a positive effect only in increasing the cell viability of the Set PP resin cement and that both materials analyzed are highly cytotoxic.

Keywords: dental cements, resin cements, degree of conversion, cytotoxicity, cell migration assays

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4319 Rauvolfine B Isolated from the Bark of Rauvolfia reflexa (Apocynaceae) Induces Apoptosis through Activation of Caspase-9 Coupled with S Phase Cell Cycle Arrest

Authors: Mehran Fadaeinasab, Hamed Karimian, Najihah Mohd Hashim, Hapipah Mohd Ali

Abstract:

In this study, three indole alkaloids namely; rauvolfine B, macusine B, and isoreserpiline have been isolated from the dichloromethane crude extract of Rauvolfia reflexa bark (Apocynaceae). The structural elucidation of the isolated compounds has been performed using spectral methods such as UV, IR, MS, 1D, and 2D NMR. Rauvolfine B showed anti proliferation activity on HCT-116 cancer cell line, its cytotoxicity induction was observed using MTT assay in eight different cell lines. Annexin-V is serving as a marker for apoptotic cells and the Annexin-V-FITC assay was carried out to observe the detection of cell-surface Phosphatidylserine (PS). Apoptosis was confirmed by using caspase-8 and -9 assays. Cell cycle arrest was also investigated using flowcytometric analysis. rauvolfine B had exhibited significantly higher cytotoxicity against HCT-116 cell line. The treatment significantly arrested HCT-116 cells in the S phase. Together, the results presented in this study demonstrated that rauvolfine B inhibited the proliferation of HCT-116 cells and programmed cell death followed by cell cycle arrest.

Keywords: apocynacea, indole alkaloid, apoptosis, cell cycle arrest

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4318 High Rate of Dual Carriage of Hepatitis B Surface and Envelope Antigen in Gombe in Infants and Young Children, North-East Nigeria: 2000-2015

Authors: E. Isaac, I. Jalo, Y. Alkali, A. Ajani, A. Rasaki, Y. Jibrin, K. Mustapha, S. Charanchi, A. Kudi, H. Danlami

Abstract:

Introduction: Hepatitis B infection is endemic in sub-Saharan Africa, where transmission predominantly occurs in infants and children by perinatal and horizontal routes. The risk of chronic infection peaks when infection is acquired early. Materials and Methods: Records of Hepatitis B surface and envelope antigen results in Federal Teaching Hospital, Gombe between May 2000 and May 2015 were retrieved and analyzed. Results: Paediatric outpatient visits and in-patient admissions were 64,193 accounting for 13% of total. Individuals tested for Hepatitis B surface antigenaemia were 23,866. Children aged 0-18 years constituted 11% (2,626). Among children tested, males accounted for 52.8% (1386/2626) and females 47.2% (1240/2626). Infants contributed 65 (2.3%); 1-4 year old children 309 (11.7%); 5-9 year old children 564 (21.4%) and adolescents 1717 (65.1%). HbSAg sero-positivity was 18% (496/2626) among children tested. The highest number of children tested per year was in 2009 (518) and 2014 (569) and the lowest, in the first study year (62). The highest sero-positivity rate was in 2010; 21.7% (54/255). Children aged 0-18years accounted for 10.5% (496/4720) of individuals with Hepatitis B surface antigenaemia. Sero-positivity was 3.1% (2/65); 12.9% (40/309); 18.1% (102/564); and 20.5% (352/1717) in infants, children ages 1-4years, 5-9years and adolescents respectively. 2.5% (1/40) and 4% (1/25) of male and female infants respectively had HbSAg. Among children aged 1-4years, 15.1% (30/198) of males and 9.0% (10/111) of females were seropositive; 14.8% (52/350) and 22% (50/224) of male and female 5-9year old children respectively has HbSAg. 14.3% (138/943) of adolescent females had Hepatitis B surface antigenaemia. Adolescent males demonstrated the highest sero-positivity rate 27.6% (214/774). 97.3% (483/496) of children who demonstrated Hepatitis B surface antigenaemia were tested for dual carriage with the e antigen. Males accounted for 296/483 (63.1%) and females 187/483 (36.9%). Infants constituted 0.97% (4/482); children aged 1-4years, 5-9years and adolescents were 6.8% (33/483); 20.9% (100/483) and 71.3% (342/483) respectively. 17.6% (85/483) of children tested had HBe antigenaemia. Of these, males accounted for 69.4% (59/85). 1.2% (1/85) were infants; 9.4% (8/85%) 1-4years; 22.3% (19/85) 5-9years and 68.2% (58/85) adolescents. 25% (1/4) infants; 24% (8/33) children aged 1-4 years; 19% (19/100) 5-9 year old children and 16.9% (58/342) adolescents had dual carriage. Infants and young children demonstrated the highest rate of dual carriage but were less likely to be tested for dual carriage 37/42 (88%) than their 5-9 year old 98% (100/102) and adolescent 342/352 (97%) counterparts. HB e antigen positivity rate was 45.4% (59/130) males and 36.0% (27/75) in females. Conclusion: Hepatitis B surface antigenaemia is high among adolescent males. Infants and young children who had HBSAg had the highest rate of envelope antigen carriage. Testing in pregnancy, vaccination programmes and prophylaxis need to be strengthened.

Keywords: children, dual carriage, Gombe, hepatitis B

Procedia PDF Downloads 276
4317 Magnetic Bio-Nano-Fluids for Hyperthermia

Authors: Z. Kolacinski, L. Szymanski. G. Raniszewski, D. Koza, L. Pietrzak

Abstract:

Magnetic Bio-Nano-Fluid (BNF) can be composed of a buffer fluid such as plasma and magnetic nanoparticles such as iron, nickel, cobalt and their oxides. However iron is one of the best elements for magnetization by electromagnetic radiation. It can be used as a tool for medical diagnosis and treatment. Radio frequency (RF) radiation is able to heat iron nanoparticles due to magnetic hysteresis. Electromagnetic heating of iron nanoparticles and ferro-fluids BNF can be successfully used for non-invasive thermal ablation of cancer cells. Moreover iron atoms can be carried by carbon nanotubes (CNTs) if iron is used as catalyst for CNTs synthesis. Then CNTs became the iron containers and they screen the iron content against oxidation. We will present a method of CNTs addressing to the required cells. For thermal ablation of cancer cells we use radio frequencies for which the interaction with human body should be limited to minimum. Generally, the application of RF energy fields for medical treatment is justified by deep tissue penetration. The highly iron doped CNTs as the carriers creating magnetic fluid will be presented. An excessive catalyst injection method using electrical furnace and microwave plasma reactor will be presented. This way it is possible to grow the Fe filled CNTs on a moving surface in continuous synthesis process. This also allows producing uniform carpet of the Fe filled CNTs carriers. For the experimental work targeted to cell ablation we used RF generator to measure the increase in temperature for some samples like: solution of Fe2O3 in BNF which can be plasma-like buffer, solutions of pure iron of different concentrations in plasma-like buffer and in buffer used for a cell culture, solutions of carbon nanotubes (MWCNTs) of different concentrations in plasma-like buffer and in buffer used for a cell culture. Then the targeted therapies which can be effective if the carriers are able to distinguish the difference between cancerous and healthy cell’s physiology are considered. We have developed an approach based on ligand-receptor or antibody-antigen interactions for the case of colon cancer.

Keywords: cancer treatment, carbon nano tubes, drag delivery, hyperthermia, iron

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4316 In Silico Study of Cell Surface Structures of Parabacteroides distasonis Involved in Its Maintain Within the Gut Microbiota and Its Potential Pathogenicity

Authors: Jordan Chamarande, Lisiane Cunat, Corentine Alauzet, Catherine Cailliez-Grimal

Abstract:

Gut microbiota (GM) is now considered a new organ mainly due to the microorganism’s specific biochemical interaction with its host. Although mechanisms underlying host-microbiota interactions are not fully described, it is now well-defined that cell surface molecules and structures of the GM play a key role in such relation. The study of surface structures of GM members is also fundamental for their role in the establishment of species in the versatile and competitive environment of the digestive tract and as a potential virulence factor. Among these structures are capsular polysaccharides (CPS), fimbriae, pili and lipopolysaccharides (LPS), all well-described for their central role in microorganism colonization and communication with host epithelium. The health-promoting Parabacteroides distasonis, which is part of the core microbiome, has recently received a lot of attention, showing beneficial properties for its host and as a new potential biotherapeutic product. However, to the best of the authors’ knowledge, the cell surface molecules and structures of P. distasonis that allow its maintain within the GM are not identified. Moreover, although P. distasonis is strongly recognized as intestinal commensal species with benefits for its host, it has also been recognized as an opportunistic pathogen. In this study, we reported gene clusters potentially involved in the synthesis of the capsule, fimbriae-like and pili-like cell surface structures in 26 P. distasonis genomes and applied the new RfbA-Typing classification in order to better understand and characterize the beneficial/pathogenic behaviour related to P. distasonis strains. In context, 2 different types of fimbriae, 3 of pilus and up to 14 capsular polysaccharide loci, have been identified over the 26 genomes studied. Moreover, the addition of data to the rfbA-Type classification modified the outcome by rearranging rfbA genes and adding a fifth group to the classification. In conclusion, the strain variability in terms of external proteinaceous structure could explain the inter-strain differences previously observed in P. distasonis adhesion capacities and its potential pathogenicity.

Keywords: gut microbiota, Parabacteroides distasonis, capsular polysaccharide, fimbriae, pilus, O-antigen, pathogenicity, probiotic, comparative genomics

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4315 The Politics of Renewable Energy Generation and Its Challenges: A Case Study of Iran

Authors: Naresh Kumar Verma

Abstract:

Nuclear energy being adapted as a renewable energy source and its production by developing countries has turned into a major strategic concern and politics by the developed world. The West seem to be the sole proprietor of such energy source and any country opting for such energy production either face significant hurdles or geopolitical challenges in developing such energy source. History of West Asia is full of interference by external powers which has been integral in the incessant conflict in the region. Whether it was the creation of Israel, the Gulf war of 1991, or the invasion of Iraq in 2003, and more recently the Iranian nuclear conundrum, the soil of West Asia has always been a witness to the play of extra regional powers game. Iran, being a theocratic state has been facing such threats and challenges, regarding its intentions and its capability in such energy production. The paper will try to assess the following issues: -Politics of Renewable Energy Generation. -Geographical and strategic significance of Iran’s nuclear programme. -Challenges in the path of Iran developing nuclear energy as a RE source. -The interests of the regional and extra-regional actors in challenging Iranian Nuclear Programme.

Keywords: developing countries, geopolitics, Iran, nuclear energy, renewable energy

Procedia PDF Downloads 602
4314 Determination of Biomolecular Interactions Using Microscale Thermophoresis

Authors: Lynn Lehmann, Dinorah Leyva, Ana Lazic, Stefan Duhr, Philipp Baaske

Abstract:

Characterization of biomolecular interactions, such as protein-protein, protein-nucleic acid or protein-small molecule, provides critical insights into cellular processes and is essential for the development of drug diagnostics and therapeutics. Here we present a novel, label-free, and tether-free technology to analyze picomolar to millimolar affinities of biomolecular interactions by Microscale Thermophoresis (MST). The entropy of the hydration shell surrounding molecules determines thermophoretic movement. MST exploits this principle by measuring interactions using optically generated temperature gradients. MST detects changes in the size, charge and hydration shell of molecules and measures biomolecule interactions under close-to-native conditions: immobilization-free and in bioliquids of choice, including cell lysates and blood serum. Thus, MST measures interactions under close-to-native conditions, and without laborious sample purification. We demonstrate how MST determines the picomolar affinities of antibody::antigen interactions, and protein::protein interactions measured from directly from cell lysates. MST assays are highly adaptable to fit to the diverse requirements of different and complex biomolecules. NanoTemper´s unique technology is ideal for studies requiring flexibility and sensitivity at the experimental scale, making MST suitable for basic research investigations and pharmaceutical applications.

Keywords: biochemistry, biophysics, molecular interactions, quantitative techniques

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4313 Designing of Multi-Epitope Peptide Vaccines for Fasciolosis (Fasciola gigantica) using Immune Epitope and Analysis Resource (IEDB) Server

Authors: Supanan Chansap, Werachon Cheukamud, Pornanan Kueakhai, Narin Changklungmoa

Abstract:

Fasciola species (Fasciola spp.) is caused fasciolosis in ruminants such as cattle, sheep, and buffalo. Fasciola gigantica (F.gigantica) commonly infects tropical regions. Fasciola hepatica (F.hepatica) in temperate regions. Liver fluke infection affects livestock economically, for example, reduced milk and meat production, weight loss, sterile animals. Currently, Triclabendazole is used to treat liver flukes. However, liver flukes have also been found to be resistant to drugs in countries. Therefore, vaccination is an attractive alternative to prevent liver fluke infection. Peptide vaccines are new vaccine technologies that mimic epitope antigens that trigger an immune response. An interesting antigen used in vaccine production is catepsin L, a family of proteins that play an important role in the life of the parasite in the host. This study aims to identify immunogenic regions of protein and construct a multi-epidetope vaccine using an immunoinformatic tool. Fasciola gigantica Cathepsin L1 (FgCatL1), Fasciola gigantica Cathepsin L1G (FgCatL1G), and Fasciola gigantica Cathepsin L1H (FgCatL1H) were predicted B-cell and Helper T lymphocytes (HTL) by Immune Epitope and Analysis Resource (IEDB) servers. Both B-cell and HTL epitopes aligned with cathepsin L of the host and Fasciola hepatica (F. hepatica). Epitope groups were selected from non-conserved regions and overlapping sequences with F. hepatica. All overlapping epitopes were linked with the GPGPG and KK linker. GPGPG linker was linked between B-cell epitope. KK linker was linked between HTL epitope and B-cell and HTL epitope. The antigenic scores of multi-epitope peptide vaccine was 0.7824. multi-epitope peptide vaccine was non-allergen, non-toxic, and good soluble. Multi-epitope peptide vaccine was predicted tertiary structure and refinement model by I-Tasser and GalaxyRefine server, respectively. The result of refine structure model was good quality that was generated by Ramachandran plot analysis. Discontinuous and linear B-cell epitopes were predicted by ElliPro server. Multi-epitope peptide vaccine model was two and seven of discontinuous and linear B-cell epitopes, respectively. Furthermore, multi-epitope peptide vaccine was docked with Toll-like receptor 2 (TLR-2). The lowest energy ranged from -901.3 kJ/mol. In summary, multi-epitope peptide vaccine was antigenicity and probably immune response. Therefore, multi-epitope peptide vaccine could be used to prevent F. gigantica infections in the future.

Keywords: fasciola gigantica, Immunoinformatic tools, multi-epitope, Vaccine

Procedia PDF Downloads 42
4312 On the Thermodynamics of Biological Cell Adhesion

Authors: Ben Nadler

Abstract:

Cell adhesion plays a vital role in many cell activities. The motivation to model cell adhesion is to study important biological processes, such as cell spreading, cell aggregation, tissue formation, and cell adhesion, which are very challenging to study by experimental methods alone. This study provides important insight into cell adhesion, which can lead to improve regenerative medicine and tissue formation techniques. In this presentation the biological cells adhesion is mediated by receptors–ligands binding and the diffusivity of the receptor on the cell membrane surface. The ability of receptors to diffuse on the cell membrane surface yields a very unique and complicated adhesion mechanism, which is exclusive to cells. The phospholipid bilayer, which is the main component in the cell membrane, shows fluid-like behavior associated with the molecules’ diffusivity. The biological cell is modeled as a fluid-like membrane with negligible bending stiffness enclosing the cytoplasm fluid. The in-plane mechanical behavior of the cell membrane is assumed to depend only on the area change, which is motivated by the fluidity of the phospholipid bilayer. In addition, the presence of receptors influences on the local mechanical properties of the cell membrane is accounted for by including stress-free area change, which depends on the receptor density. Based on the physical properties of the receptors and ligands the attraction between the receptors and ligands is modeled as a charged-nonpolar which is a noncovalent interaction. Such interaction is a short-range type, which decays fast with distance. The mobility of the receptor on the cell membrane is modeled using the diffusion equation and Fick’s law is used to model the receptor–receptor interactions. The resultant interaction force, which includes receptor–ligand and receptor–receptor interaction, is decomposed into tangential part, which governs the receptor diffusion, and normal part, which governs the cell deformation and adhesion. The formulation of the governing equations and numerical simulations will be presented. Analysis of the adhesion characteristic and properties are discussed. The roles of various thermomechanical properties of the cell, receptors and ligands on the cell adhesion are investigated.

Keywords: cell adhesion, cell membrane, receptor-ligand interaction, receptor diffusion

Procedia PDF Downloads 310