Search results for: proliferating cell nuclear antigen
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4578

Search results for: proliferating cell nuclear antigen

4488 TNF Modulation of Cancer Stem Cells in Renal Clear Cell Carcinoma

Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

Abstract:

Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

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4487 Transcriptomine: The Nuclear Receptor Signaling Transcriptome Database

Authors: Scott A. Ochsner, Christopher M. Watkins, Apollo McOwiti, David L. Steffen Lauren B. Becnel, Neil J. McKenna

Abstract:

Understanding signaling by nuclear receptors (NRs) requires an appreciation of their cognate ligand- and tissue-specific transcriptomes. While target gene regulation data are abundant in this field, they reside in hundreds of discrete publications in formats refractory to routine query and analysis and, accordingly, their full value to the NR signaling community has not been realized. One of the mandates of the Nuclear Receptor Signaling Atlas (NURSA) is to facilitate access of the community to existing public datasets. Pursuant to this mandate we are developing a freely-accessible community web resource, Transcriptomine, to bring together the sum total of available expression array and RNA-Seq data points generated by the field in a single location. Transcriptomine currently contains over 25,000,000 gene fold change datapoints from over 1200 contrasts relevant to over 100 NRs, ligands and coregulators in over 200 tissues and cell lines. Transcriptomine is designed to accommodate a spectrum of end users ranging from the bench researcher to those with advanced bioinformatic training. Visualization tools allow users to build custom charts to compare and contrast patterns of gene regulation across different tissues and in response to different ligands. Our resource affords an entirely new paradigm for leveraging gene expression data in the NR signaling field, empowering users to query gene fold changes across diverse regulatory molecules, tissues and cell lines, target genes, biological functions and disease associations, and that would otherwise be prohibitive in terms of time and effort. Transcriptomine will be regularly updated with gene lists from future genome-wide expression array and expression-sequencing datasets in the NR signaling field.

Keywords: target gene database, informatics, gene expression, transcriptomics

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4486 Antigenic Diversity of Theileria parva Isolates from Cattle and Buffalo at the Wildlife-Livestock Interface in Southern and Eastern Africa

Authors: Mukolwe D. Lubembe, Odongo O. David, Githaka Naftali, Kanduma Esther, Marinda Oosthuizen, Kgomotso P. Sibeko

Abstract:

Theileriosis is a tick-borne disease of cattle caused by an apicomplexan protozoan parasite of the genus Theileria. In eastern and southern Africa, Theileria infections in cattle are caused by the species Theileria parva whose natural reservoir is the African buffalo (Syncerus caffer). Currently, East Coast Fever (ECF) caused by the cattle-derived Theileria parva is still a major problem in eastern Africa and some parts of southern Africa but not in South Africa following its eradication in the 1950s. However, Corridor disease (CD) caused by the buffalo-derived Theileria parva still remains a concern in South Africa. The diversity of Theileria parva in South Africa in comparison to other affected countries is poorly defined yet its known to be the survival strategy of this parasite. We assessed the antigenic diversity of Theileria parva isolates from Buffalo and cattle at the wildlife-livestock interface comparing samples from South Africa, Zimbabwe, Kenya, Tanzania, and Uganda. Antigenic epitopes of eight schizont antigen genes (Tp1, Tp3, Tp4, Tp5, Tp6, Tp7, Tp8 and Tp10) were amplified by PCR from genomic DNA extracted from blood samples collected from cattle and buffalo at the wildlife-livestock interface. Amplicons were purified and then sequenced on NGS platform. Full length open reading frames (ORFs) of two schizont antigen genes (Tp2 and Tp9) and one sporozoite antigen gene, p67 were also amplified from genomic DNA. Amplicons were then purified and cloned for sequencing. Analysis was based on sequence differences in the genes. Preliminary results show an extensively diverse population of Theileria parva circulating in buffalo and cattle populations at the wildlife-livestock interface. Diversity of the antigen genes contributes to the evasion of the immune system of the host by Theileria parva. This possess a concern in that, some of the Theileria parva populations may re-assort and become adapted to cattle to cause a form of theileriosis that is as fatal as ECF in areas where ECF was eradicated or is absent

Keywords: Theileria parva, east coast fever, corridor diseases, antigen genes, diversity

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4485 Comparative Analysis of Local Acceptance of Renewable Energy Facilities and Spent Nuclear Fuel Repositories

Authors: Taehyun Kim, Hyunjoo Park, Taehyun Kim

Abstract:

Public deliberation committee on Shin-Gori Nuclear Reactors No. 5 & 6 in South Korea recently suggested policy recommendation in July 2017 including complementary measures for resumption of construction: 1) nuclear power generation reduction, 2) expansion of investment to increase proportion of renewable energy, 3) repositories of spent nuclear fuel. Even when constructing eco-friendly renewable energy facilities such as solar and wind power plants, local residents are opposed to construction of these facilities due to environmental pollution and health impacts. In order to transform eco-friendly energy, it is necessary to convert nuclear energy into renewable energy and to take measures to increase the acceptance of residents through the participation of citizens. Therefore, this study aims to compare the factors of local acceptance of renewable energy facilities and spent nuclear fuel repositories through literature review and in-depth interview. The results show that environmental and economic concerns, risk perceptions, sociality, demographic characteristics and subjective recognition types affect the local acceptance for spent nuclear fuel repository. The factors of local acceptance for renewable energy facilities are partially coincide with those for spent nuclear fuel repository. The results of this study will contribute to improving residents' acceptance and reducing conflicts when determining the location of facilities in the future.

Keywords: local acceptance, renewable energy facility, spent nuclear fuel repository, interview

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4484 Application of the Mesoporous Silica Oxidants on Immunochromatography Detections

Authors: Chang, Ya-Ju, Hsieh, Pei-Hsin, Wu, Jui-Chuang, Chen-Yang, Yui Whei

Abstract:

A mesoporous silica material was prepared to apply to the lateral-flow immunochromatography for detecting a model biosample. The probe antibody is immobilized on the silica surface as the test line to capture its affinity antigen, which laterally flows through the chromatography strips. The antigen is labeled with nano-gold particles, such that the detection can be visually read out from the test line without instrument aids. The result reveals that the mesoporous material provides a vast area for immobilizing the detection probes. Biosening surfaces corresponding with a positive proportion of detection signals is obtained with the biosample loading.

Keywords: mesoporous silica, immunochromatography, lateral-flow strips, biosensors, nano-gold particles

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4483 Sloshing-Induced Overflow Assessment of the Seismically-Isolated Nuclear Tanks

Authors: Kihyon Kwon, Hyun T. Park, Gil Y. Chung, Sang-Hoon Lee

Abstract:

This paper focuses on assessing sloshing-induced overflow of the seismically-isolated nuclear tanks based on Fluid-Structure Interaction (FSI) analysis. Typically, fluid motion in the seismically-isolated nuclear tank systems may be rather amplified and even overflowed under earthquake. Sloshing-induced overflow in those structures has to be reliably assessed and predicted since it can often cause critical damages to humans and environments. FSI analysis is herein performed to compute the total cumulative overflowed water volume more accurately, by coupling ANSYS with CFX for structural and fluid analyses, respectively. The approach is illustrated on a nuclear liquid storage tank, Spent Fuel Pool (SFP), forgiven conditions under consideration: different liquid levels, Peak Ground Accelerations (PGAs), and post earthquakes.

Keywords: FSI analysis, seismically-isolated nuclear tank system, sloshing-induced overflow

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4482 Synergistic Effect of Curcumin and Insulin on GLUT4 Translocation in C2C12 Cell

Authors: Javad Mohiti-Ardekani, Shabodin Asadii, Ali Moradi

Abstract:

Introduction: Curcumin, the yellow pigment in turmeric, has been shown as an anti-diabetic agent for centuries but only in recent few years, its mechanism of action has been under investigation. Some studies showed that curcumin might exert its anti-diabetic effect via increasing glucose transporter isotype-4 (GLUT4) gene and glycoprotein contents in cells. To investigate this possibility, we investigate the effects of extract and commercial curcumin with and without insulin on GLUT4 translocation from intracellular compartments of nuclear or endoplasmic reticulum membranes (N/ER) into the cytoplasmic membrane (CM). Methods and Material: C2C12 myoblastic cell line were seeded in DMEM plus 20 % FBS and differentiated to myotubes using 2 % horse serum. After myotubes formation, 40 µmolar Extract and Commercial curcumin, with or without insulin as intervention, and as control 1 % DMSO were added for 3 h. Cells were washed and homogenized followed by ultracentrifuge fractionation, protein separation by SDS-PAGE and GLUT4 detection using semi-quantitative Western blotting. Data analysis was done by two independent samples t-test for comparison of mean ± SD of GLUT4 percent in categories. GLUT4 contents were higher in CM groups curcumin and curcumin with insulin in comparison to 1 % DMSO-treated myotubes control group. Results: As our results have shown extract and commercial curcumin induces GLUT4 translocation from intra-cell into cell surface. The results have also shown synergic effect of curcumin on translocation of GLUT4 from intra-cell into cell surface in the presence of 100 nm insulin. Discussion: We conclude that curcumin may be a choice of type-2 diabetes mellitus treatment because its extract and commercial enhances GLUT4 contents in CM where it facilitates glucose entrance into the cell. However, it is necessary to trace the signaling pathways which are activated by curcumin.

Keywords: Curcumin, insulin, Diabetes type-2, GLUT4

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4481 Preparation of Gramine Nanosuspension and Protective Effect of Gramine on Human Oral Cell Lines by Induction of Apoptosis

Authors: K. Suresh, R. Arunkumar

Abstract:

The objective of this study is to investigate the preparation of gramine nano suspension and protective effect of Gramine on the apoptosis of laryngeal cancer cells cell line (HEp-2 and KB). The growth inhibition rate of Hep-2 and KB cells in vitro were measured by MTT assay and apoptosis by, levels of reactive oxygen species, mitochondrial membrane potential, morphological changes and flowcytometry. Based on the results, we determined the effective doses of gramine as 127.23µm/ml for 24 hr and 119.81 µm/ml for 48hr in hep-2 cell line and 147.58 µm ml for 24 hr and 123.74µm µm/ml for 48hr in KB cell line. cytotoxicity effects of gramine were confirmed by treatment of HEp-2 cell and KB cell with IC50 concentration of gramine resulted in sequences of events marked by the enhance the apoptosis accompanied by loss of cell viability, modulation of reactive oxygen species and cell cycle arrest through the induction of G0/G1 phase arrest on HEp-2 cells. Our study suggests that the nanosuspension of gramine possesses the more cytotoxic effect of cancer cells and a novel candidate for cancer chemoprevention.

Keywords: apoptosis, HEp-2 cell line, KB cell line mitochondria, gramine, nanosuspension

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4480 Pion/Muon Identification in a Nuclear Emulsion Cloud Chamber Using Neural Networks

Authors: Kais Manai

Abstract:

The main part of this work focuses on the study of pion/muon separation at low energy using a nuclear Emulsion Cloud Chamber (ECC) made of lead and nuclear emulsion films. The work consists of two parts: particle reconstruction algorithm and a Neural Network that assigns to each reconstructed particle the probability to be a muon or a pion. The pion/muon separation algorithm has been optimized by using a detailed Monte Carlo simulation of the ECC and tested on real data. The algorithm allows to achieve a 60% muon identification efficiency with a pion misidentification smaller than 3%.

Keywords: nuclear emulsion, particle identification, tracking, neural network

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4479 Diagnostics via Biophysical Resistotrons

Authors: Matt Vellkorn, Mara Sarinski

Abstract:

The field of advanced diagnostics is a very rapidly changing one. A new technology that has not been fully used yet are resistotrons. A resistotron is a physical device thatis used to detect the presence of low energy alpha particles. It has been used for many years in nuclear physics as an alpha particle detector. Since they are used in nuclear physics, they have to be accurate. They have to be able to differentiate between alpha particles and other types of radiation. The resistotrons are primarily used for safety. They are used in areas where people or animals can get exposed to radiation. A typical example is in the treatment of nuclear waste. As it is with any nuclear physics instrument, a resistotron has to be very accurate and reliable. In the past, the instrument was very expensive because they were made out of copper. Today, they are made out of brass. The main difference is that brass is much less expensive than copper.

Keywords: biosensors, resistotrons, biophysics, diagnostics

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4478 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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4477 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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4476 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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4475 Combining in vitro Protein Expression with AlphaLISA Technology to Study Protein-Protein Interaction

Authors: Shayli Varasteh Moradi, Wayne A. Johnston, Dejan Gagoski, Kirill Alexandrov

Abstract:

The demand for a rapid and more efficient technique to identify protein-protein interaction particularly in the areas of therapeutics and diagnostics development is growing. The method described here is a rapid in vitro protein-protein interaction analysis approach based on AlphaLISA technology combined with Leishmania tarentolae cell-free protein production (LTE) system. Cell-free protein synthesis allows the rapid production of recombinant proteins in a multiplexed format. Among available in vitro expression systems, LTE offers several advantages over other eukaryotic cell-free systems. It is based on a fast growing fermentable organism that is inexpensive in cultivation and lysate production. High integrity of proteins produced in this system and the ability to co-express multiple proteins makes it a desirable method for screening protein interactions. Following the translation of protein pairs in LTE system, the physical interaction between proteins of interests is analysed by AlphaLISA assay. The assay is performed using unpurified in vitro translation reaction and therefore can be readily multiplexed. This approach can be used in various research applications such as epitope mapping, antigen-antibody analysis and protein interaction network mapping. The intra-viral protein interaction network of Zika virus was studied using the developed technique. The viral proteins were co-expressed pair-wise in LTE and all possible interactions among viral proteins were tested using AlphaLISA. The assay resulted to the identification of 54 intra-viral protein-protein interactions from which 19 binary interactions were found to be novel. The presented technique provides a powerful tool for rapid analysis of protein-protein interaction with high sensitivity and throughput.

Keywords: AlphaLISA technology, cell-free protein expression, epitope mapping, Leishmania tarentolae, protein-protein interaction

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4474 ‘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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4473 Study of Magnetic Nanoparticles’ Endocytosis in a Single Cell Level

Authors: Jefunnie Matahum, Yu-Chi Kuo, Chao-Ming Su, Tzong-Rong Ger

Abstract:

Magnetic cell labeling is of great importance in various applications in biomedical fields such as cell separation and cell sorting. Since analytical methods for quantification of cell uptake of magnetic nanoparticles (MNPs) are already well established, image analysis on single cell level still needs more characterization. This study reports an alternative non-destructive quantification methods of single-cell uptake of positively charged MNPs. Magnetophoresis experiments were performed to calculate the number of MNPs in a single cell. Mobility of magnetic cells and the area of intracellular MNP stained by Prussian blue were quantified by image processing software. ICP-MS experiments were also performed to confirm the internalization of MNPs to cells. Initial results showed that the magnetic cells incubated at 100 µg and 50 µg MNPs/mL concentration move at 18.3 and 16.7 µm/sec, respectively. There is also an increasing trend in the number and area of intracellular MNP with increasing concentration. These results could be useful in assessing the nanoparticle uptake in a single cell level.

Keywords: magnetic nanoparticles, single cell, magnetophoresis, image analysis

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4472 Expression of Ki-67 in Multiple Myeloma: A Clinicopathological Study

Authors: Kangana Sengar, Sanjay Deb, Ramesh Dawar

Abstract:

Introduction: Ki-67 can be a useful marker in determining proliferative activity in patients with multiple myeloma (MM). However, using Ki-67 alone results in the erroneous inclusion of non-myeloma cells leading to false high counts. We have used Dual IHC (immunohistochemistry) staining with Ki-67 and CD138 to enhance specificity in assessing proliferative activity of bone marrow plasma cells. Aims and objectives: To estimate the proportion of proliferating (Ki-67 expressing) plasma cells in patients with MM and correlation of Ki-67 with other known prognostic parameters. Materials and Methods: Fifty FFPE (formalin fixed paraffin embedded) blocks of trephine biopsies of cases diagnosed as MM from 2010 to 2015 are subjected to H & E staining and Dual IHC staining for CD 138 and Ki-67. H & E staining is done to evaluate various histological parameters like percentage of plasma cells, pattern of infiltration (nodular, interstitial, mixed and diffuse), routine parameters of marrow cellularity and hematopoiesis. Clinical data is collected from patient records from Medical Record Department. Each of CD138 expressing cells (cytoplasmic, red) are scored as proliferating plasma cells (containing a brown Ki¬67 nucleus) or non¬proliferating plasma cells (containing a blue, counter-stained, Ki-¬67 negative nucleus). Ki-67 is measured as percentage positivity with a maximum score of hundred percent and lowest of zero percent. The intensity of staining is not relevant. Results: Statistically significant correlation of Ki-67 in D-S Stage (Durie & Salmon Stage) I vs. III (p=0.026) and ISS (International Staging System) Stage I vs. III (p=0.019), β2m (p=0.029) and percentage of plasma cells (p < 0.001) is seen. No statistically significant correlation is seen between Ki-67 and hemoglobin, platelet count, total leukocyte count, total protein, albumin, S. calcium, S. creatinine, S. LDH, blood urea and pattern of infiltration. Conclusion: Ki-67 index correlated with other known prognostic parameters. However, it is not determined routinely in patients with MM due to little information available regarding its relevance and paucity of studies done to correlate with other known prognostic factors in MM patients. To the best of our knowledge, this is the first study in India using Dual IHC staining for Ki-67 and CD138 in MM patients. Routine determination of Ki-67 will help to identify patients who may benefit with more aggressive therapy. Recommendation: In this study follow up of patients is not included, and the sample size is small. Studying with larger sample size and long follow up is advocated to prognosticate Ki-67 as a marker of survival in patients with multiple myeloma.

Keywords: bone marrow, dual IHC, Ki-67, multiple myeloma

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4471 In-Situ Quasistatic Compression and Microstructural Characterization of Aluminium Foams of Different Cell Topology

Authors: M. A. Islam, P. J. Hazell, J. P. Escobedo, M. Saadatfar

Abstract:

Quasistatic compression and micro structural characterization of closed cell aluminium foams of different pore size and cell distributions has been carried out. Metallic foams have good potential for lightweight structures for impact and blast mitigation and therefore it is important to find out the optimized foam structure (i.e. cell size, shape, relative density, and distribution) to maximize energy absorption. In this paper, we present results for two different aluminium metal foams of density 0.5 g/cc and 0.7 g/cc respectively that have been tested in quasi-static compression. The influence of cell geometry and cell topology on quasistatic compression behavior has been investigated using computed tomography (micro-CT) analysis. The compression behavior and micro structural characterization will be presented.

Keywords: metal foams, micro-CT, cell topology, quasistatic compression

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4470 Fabrication of Immune-Affinity Monolithic Array for Detection of α-Fetoprotein and Carcinoembryonic Antigen

Authors: Li Li, Li-Ru Xia, He-Ye Wang, Xiao-Dong Bi

Abstract:

In this paper, we presented a highly sensitive immune-affinity monolithic array for detection of α-fetoprotein (AFP) and carcinoembryonic antigen (CEA). Firstly, the epoxy functionalized monolith arrays were fabricated using UV initiated copolymerization method. Scanning electron microscopy (SEM) image showed that the poly(BABEA-co-GMA) monolith exhibited a well-controlled skeletal and well-distributed porous structure. Then, AFP and CEA immune-affinity monolithic arrays were prepared by immobilization of AFP and CEA antibodies on epoxy functionalized monolith arrays. With a non-competitive immune response format, the presented AFP and CEA immune-affinity arrays were demonstrated as an inexpensive, flexible, homogeneous and stable array for detection of AFP and CEA.

Keywords: chemiluminescent detection, immune-affinity, monolithic copolymer array, UV-initiated copolymerization

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4469 Predictive Value of Hepatitis B Core-Related Antigen (HBcrAg) during Natural History of Hepatitis B Virus Infection

Authors: Yanhua Zhao, Yu Gou, Shu Feng, Dongdong Li, Chuanmin Tao

Abstract:

The natural history of HBV infection could experience immune tolerant (IT), immune clearance (IC), HBeAg-negative inactive/quienscent carrier (ENQ), and HBeAg-negative hepatitis (ENH). As current biomarkers for discriminating these four phases have some weaknesses, additional serological indicators are needed. Hepatits B core-related antigen (HBcrAg) encoded with precore/core gene contains denatured HBeAg, HBV core antigen (HBcAg) and a 22KDa precore protein (p22cr), which was demonstrated to have a close association with natural history of hepatitis B infection, but no specific cutoff values and diagnostic parameters to evaluate the diagnostic efficacy. This study aimed to clarify the distribution of HBcrAg levels and evaluate its diagnostic performance during the natural history of infection from a Western Chinese perspective. 294 samples collected from treatment-naïve chronic hepatitis B (CHB) patients in different phases (IT=64; IC=72; ENQ=100, and ENH=58). We detected the HBcrAg values and analyzed the relationship between HBcrAg and HBV DNA. HBsAg and other clinical parameters were quantitatively tested. HBcrAg levels of four phases were 9.30 log U/mL, 8.80 log U/mL, 3.00 log U/mL, and 5.10 logU/mL, respectively (p < 0.0001). Receiver operating characteristic curve analysis demonstrated that the area under curves (AUCs) of HBcrAg and quantitative HBsAg at cutoff values of 9.25 log U/mL and 4.355 log IU/mL for distinguishing IT from IC phases were 0.704 and 0.694, with sensitivity 76.39% and 59.72%, specificity 53.13% and 79.69%, respectively. AUCs of HBcrAg and quantitative HBsAg at cutoff values of 4.15 log U/mlmL and 2.395 log IU/mlmL for discriminating between ENQ and ENH phases were 0.931 and 0.653, with sensitivity 87.93% and 84%, specificity 91.38% and 39%, respectively. Therefore, HBcrAg levels varied significantly among four natural phases of HBV infection. It had higher predictive performance than quantitative HBsAg for distinguishing between ENQ-patients and ENH-patients and similar performance with HBsAg for the discrimination between IT and IC phases, which indicated that HBcrAg could be a potential serological marker for CHB.

Keywords: chronic hepatitis B, hepatitis B core-related antigen, hepatitis B surface antigens, hepatitis B virus

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4468 Air Conditioning Variation of 1kW Open-Cathode Proton Exchange Membrane (PEM) Fuel Cell

Authors: Mohammad Syahirin Aisha, Khairul Imran Sainan

Abstract:

The PEM fuel cell is a device that generate electric by electrochemical reaction between hydrogen fuel and oxygen in the fuel cell stack. PEM fuel cell consists of an anode (hydrogen supply), a cathode (oxygen supply) and an electrolyte that allow charges move between the two positions of the fuel cell. The only product being developed after the reaction is water (H2O) and heat as the waste which does not emit greenhouse gasses. The performance of fuel cell affected by numerous parameters. This study is restricted to cathode parameters that affect fuel cell performance. At the anode side, the reactant is not going through any changes. Experiments with variation in air velocity (3m/s, 6m/s and 9m/s), temperature (10oC, 20oC, 35oC) and relative humidity (50%, 60%, and 70%) have been carried out. The experiments results are presented in the form of fuel cell stack power output over time, which demonstrate the impacts of the various air condition on the execution of the PEM fuel cell. In this study, the experimental analysis shows that with variation of air conditions, it gives different fuel cell performance behavior. The maximum power output of the experiment was measured at an ambient temperature of 25oC with relative humidity and 9m/s velocity of air.

Keywords: air-breathing PEM fuel cell, cathode side, performance, variation in air condition

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4467 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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4466 DNA Double-Strand Break–Capturing Nuclear Envelope Tubules Drive DNA Repair

Authors: Mitra Shokrollahi, Mia Stanic, Anisha Hundal, Janet N. Y. Chan, Defne Urman, Chris A. Jordan, Anne Hakem, Roderic Espin, Jun Hao, Rehna Krishnan, Philipp G. Maass, Brendan C. Dickson, Manoor P. Hande, Miquel A. Pujana, Razqallah Hakem, Karim Mekhail

Abstract:

Current models suggest that DNA double-strand breaks (DSBs) can move to the nuclear periphery for repair. It is unclear to what extent human DSBs display such repositioning. Here we show that the human nuclear envelope localizes to DSBs in a manner depending on DNA damage response (DDR) kinases and cytoplasmic microtubules acetylated by α-tubulin acetyltransferase-1 (ATAT1). These factors collaborate with the linker of nucleoskeleton and cytoskeleton complex (LINC), nuclear pore complex (NPC) protein NUP153, the nuclear lamina and kinesins KIF5B and KIF13B to generate DSB-capturing nuclear envelope tubules (dsbNETs). dsbNETs are partly supported by nuclear actin filaments and the circadian factor PER1 and reversed by kinesin KIFC3. Although dsbNETs promote repair and survival, they are also co-opted during poly (ADP-ribose) polymerase (PARP) inhibition to restrain BRCA1-deficient breast cancer cells and are hyper-induced in cells expressing the aging-linked lamin A mutant progerin. In summary, our results advance understanding of nuclear structure-function relationships, uncover a nuclear-cytoplasmic DDR and identify dsbNETs as critical factors in genome organization and stability.

Keywords: DNA damage response, genome stability, nuclear envelope, cancer, age-related disorders

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4465 Developing a Deep Understanding of the Immune Response in Hepatitis B Virus Infected Patients Using a Knowledge Driven Approach

Authors: Hanan Begali, Shahi Dost, Annett Ziegler, Markus Cornberg, Maria-Esther Vidal, Anke R. M. Kraft

Abstract:

Chronic hepatitis B virus (HBV) infection can be treated with nucleot(s)ide analog (NA), for example, which inhibits HBV replication. However, they have hardly any influence on the functional cure of HBV, which is defined by hepatitis B surface antigen (HBsAg) loss. NA needs to be taken life-long, which is not available for all patients worldwide. Additionally, NA-treated patients are still at risk of developing cirrhosis, liver failure, or hepatocellular carcinoma (HCC). Although each patient has the same components of the immune system, immune responses vary between patients. Therefore, a deeper understanding of the immune response against HBV in different patients is necessary to understand the parameters leading to HBV cure and to use this knowledge to optimize HBV therapies. This requires seamless integration of an enormous amount of diverse and fine-grained data from viral markers, e.g., hepatitis B core-related antigen (HBcrAg) and hepatitis B surface antigen (HBsAg). The data integration system relies on the assumption that profiling human immune systems requires the analysis of various variables (e.g., demographic data, treatments, pre-existing conditions, immune cell response, or HLA-typing) rather than only one. However, the values of these variables are collected independently. They are presented in a myriad of formats, e.g., excel files, textual descriptions, lab book notes, and images of flow cytometry dot plots. Additionally, patients can be identified differently in these analyses. This heterogeneity complicates the integration of variables, as data management techniques are needed to create a unified view in which individual formats and identifiers are transparent when profiling the human immune systems. The proposed study (HBsRE) aims at integrating heterogeneous data sets of 87 chronically HBV-infected patients, e.g., clinical data, immune cell response, and HLA-typing, with knowledge encoded in biomedical ontologies and open-source databases into a knowledge-driven framework. This new technique enables us to harmonize and standardize heterogeneous datasets in the defined modeling of the data integration system, which will be evaluated in the knowledge graph (KG). KGs are data structures that represent the knowledge and data as factual statements using a graph data model. Finally, the analytic data model will be applied on top of KG in order to develop a deeper understanding of the immune profiles among various patients and to evaluate factors playing a role in a holistic profile of patients with HBsAg level loss. Additionally, our objective is to utilize this unified approach to stratify patients for new effective treatments. This study is developed in the context of the project “Transforming big data into knowledge: for deep immune profiling in vaccination, infectious diseases, and transplantation (ImProVIT)”, which is a multidisciplinary team composed of computer scientists, infection biologists, and immunologists.

Keywords: chronic hepatitis B infection, immune response, knowledge graphs, ontology

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4464 Ultrasensitive Hepatitis B Virus Detection in Blood Using Nano-Porous Silicon Oxide: Towards POC Diagnostics

Authors: N. Das, N. Samanta, L. Pandey, C. Roy Chaudhuri

Abstract:

Early diagnosis of infection like Hep-B virus in blood is important for low cost medical treatment. For this purpose, it is desirable to develop a point of care device which should be able to detect trace quantities of the target molecule in blood. In this paper, we report a nanoporous silicon oxide sensor which is capable of detecting down to 1fM concentration of Hep-B surface antigen in blood without the requirement of any centrifuge or pre-concentration. This has been made possible by the presence of resonant peak in the sensitivity characteristics. This peak is observed to be dependent only on the concentration of the specific antigen and not on the interfering species in blood serum. The occurrence of opposite impedance change within the pores and at the bottom of the pore is responsible for this effect. An electronic interface has also been designed to provide a display of the virus concentration.

Keywords: impedance spectroscopy, ultrasensitive detection in blood, peak frequency, electronic interface

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4463 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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4462 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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4461 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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4460 Modelling and Simulation of Light and Temperature Efficient Interdigitated Back- Surface-Contact Solar Cell with 28.81% Efficiency Rate

Authors: Mahfuzur Rahman

Abstract:

Back-contact solar cells improve optical properties by moving all electrically conducting parts to the back of the cell. The cell's structure allows silicon solar cells to surpass the 25% efficiency barrier and interdigitated solar cells are now the most efficient. In this work, the fabrication of a light, efficient and temperature resistant interdigitated back contact (IBC) solar cell is investigated. This form of solar cell differs from a conventional solar cell in that the electrodes are located at the back of the cell, eliminating the need for grids on the top, allowing the full surface area of the cell to receive sunlight, resulting in increased efficiency. In this project, we will use SILVACO TCAD, an optoelectronic device simulator, to construct a very thin solar cell with dimensions of 100x250um in 2D Luminous. The influence of sunlight intensity and atmospheric temperature on solar cell output power is highly essential and it has been explored in this work. The cell's optimum performance with 150um bulk thickness provides 28.81% efficiency with an 87.68% fill factor rate making it very thin, flexible and resilient, providing diverse operational capabilities.

Keywords: interdigitated, shading, recombination loss, incident-plane, drift-diffusion, luminous, SILVACO

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4459 Capability of a Single Antigen to Induce Both Protective and Disease Enhancing Antibody: An Obstacle in the Creation of Vaccines and Passive Immunotherapies

Authors: Parul Kulshreshtha, Subrata Sinha, Rakesh Bhatnagar

Abstract:

This study was conducted by taking B. anthracis as a model pathogen. On infecting a host, B. anthracis secretes three proteins, namely, protective antigen (PA, 83kDa), edema factor (EF, 89 kDa) and lethal factor (LF, 90 kDa). These three proteins are the components of two anthrax toxins. PA binds to the cell surface receptors, namely, tumor endothelial marker (TEM) 8 and capillary morphogenesis protein (CMG) 2. TEM8 and CMG2 interact with LDL-receptor related protein (LRP) 6 for endocytosis of EF and LF. On entering the cell, EF acts as a calmodulin-dependent adenylate cyclase that causes a prolonged increase of cytosolic cyclic adenosine monophosphate (cAMP). LF is a metalloprotease that cleaves most isoforms of mitogen-activated protein kinase kinases (MAPKK/MEK) close to their N-terminus. By secreting these two toxins, B.anthracis ascertains death of the host. Once the systemic levels of the toxins rise, antibiotics alone cannot save the host. Therefore, toxin-specific inhibitors have to be developed. In this wake, monoclonal antibodies have been developed for the neutralization of toxic effects of anthrax toxins. We created hybridomas by using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor of B. anthracis) to obtain anti-toxin antibodies. Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immunized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies from all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H8 and H10) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). The protective efficacy of H7, H8, H10 and H11 was investigated. H7, H8 and H10 were found to be protective. H11 was found to have disease enhancing characteristics in-vitro and in mouse model of challenge with B. anthracis. In this study the disease enhancing character of H11 monoclonal antibody and anti-rLFn polyclonal sera was investigated. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature both in-vitro and in-vivo. But combination of H11 with LETscFv (an scFv with VH and VL identical to H10 but lacking Fc region) could not abrogate the disease-enhancing character of H11 mAb. Therefore it was concluded that for suppression of disease enhancement, Fc portion was absolutely essential for interaction of H10 with H11. Our study indicates that the protective potential of an antibody depends equally on its idiotype/ antigen specificity and its isotype. A number of monoclonal and engineered antibodies are being explored as immunotherapeutics but it is absolutely essential to characterize each one for their individual and combined protective potential. Although new in the sphere of toxin-based diseases, it is extremely important to characterize the disease-enhancing nature of polyclonal as well as monoclonal antibodies. This is because several anti-viral therapeutics and vaccines have failed in the face of this phenomenon. The passive –immunotherapy thus needs to be well formulated to avoid any contraindications.

Keywords: immunotherapy, polyclonal, monoclonal, antibody-dependent disease enhancement

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