Search results for: orphan nuclear receptors
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1117

Search results for: orphan nuclear receptors

967 The Establishment and Application of TRACE/FRAPTRAN Model for Kuosheng Nuclear Power Plant

Authors: S. W. Chen, W. K. Lin, J. R. Wang, C. Shih, H. T. Lin, H. C. Chang, W. Y. Li

Abstract:

Kuosheng nuclear power plant (NPP) is a BWR/6 type NPP and located on the northern coast of Taiwan. First, Kuosheng NPP TRACE model were developed in this research. In order to assess the system response of Kuosheng NPP TRACE model, startup tests data were used to evaluate Kuosheng NPP TRACE model. Second, the over pressurization transient analysis of Kuosheng NPP TRACE model was performed. Besides, in order to confirm the mechanical property and integrity of fuel rods, FRAPTRAN analysis was also performed in this study.

Keywords: TRACE, safety analysis, BWR/6, FRAPTRA

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966 Mechanisms of O-1602 Induced Endothelium-Independent Vasorelaxation of Rat Small Mesenteric Artery

Authors: Yousuf Al Suleimani, Ahmed Al Mahruqi

Abstract:

A typical cannabinoid O-1602 induces vasorelaxation and activates the orphan G protein-coupled receptor GPR55 in human endothelial cells. The aim of this study is to characterize the mechanisms of endothelium-independent relaxation of O-1602 in the rat small mesenteric artery using wire myograph. In endothelium-denuded vessels, O-1602 partially produced concentration-dependent vasorelaxation. In vessels depleted of intracellular Ca2+ (by EGTA and methoxamine), CaCl2 produced concentration-dependent contraction. Preincubation with O-1602 (at 10 µM and 30 µM) abolished the contractile responses (P<0.01). The putative antagonist at novel “endothelial anandamide receptor” O-1918 (10 µM) significantly reversed the inhibitory effect of O-1602 on CaCl2-induced vasoconstriction. It is likely that the mechanism of endothelium-independent vasorelaxation to O-1602 is mediated by interfering with Ca2+ entry via an O-1918-sensitive pathway.

Keywords: O-1602, endothelium, vasorelaxation, calcium

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965 Incorporating Spatial Transcriptome Data into Ligand-Receptor Analyses to Discover Regional Activation in Cells

Authors: Eric Bang

Abstract:

Interactions between receptors and ligands are crucial for many essential biological processes, including neurotransmission and metabolism. Ligand-receptor analyses that examine cell behavior and interactions often utilize cell type-specific RNA expressions from single-cell RNA sequencing (scRNA-seq) data. Using CellPhoneDB, a public repository consisting of ligands, receptors, and ligand-receptor interactions, the cell-cell interactions were explored in a specific scRNA-seq dataset from kidney tissue and portrayed the results with dot plots and heat maps. Depending on the type of cell, each ligand-receptor pair was aligned with the interacting cell type and calculated the positori probabilities of these associations, with corresponding P values reflecting average expression values between the triads and their significance. Using single-cell data (sample kidney cell references), genes in the dataset were cross-referenced with ones in the existing CellPhoneDB dataset. For example, a gene such as Pleiotrophin (PTN) present in the single-cell data also needed to be present in the CellPhoneDB dataset. Using the single-cell transcriptomics data via slide-seq and reference data, the CellPhoneDB program defines cell types and plots them in different formats, with the two main ones being dot plots and heat map plots. The dot plot displays derived measures of the cell to cell interaction scores and p values. For the dot plot, each row shows a ligand-receptor pair, and each column shows the two interacting cell types. CellPhoneDB defines interactions and interaction levels from the gene expression level, so since the p-value is on a -log10 scale, the larger dots represent more significant interactions. By performing an interaction analysis, a significant interaction was discovered for myeloid and T-cell ligand-receptor pairs, including those between Secreted Phosphoprotein 1 (SPP1) and Fibronectin 1 (FN1), which is consistent with previous findings. It was proposed that an effective protocol would involve a filtration step where cell types would be filtered out, depending on which ligand-receptor pair is activated in that part of the tissue, as well as the incorporation of the CellPhoneDB data in a streamlined workflow pipeline. The filtration step would be in the form of a Python script that expedites the manual process necessary for dataset filtration. Being in Python allows it to be integrated with the CellPhoneDB dataset for future workflow analysis. The manual process involves filtering cell types based on what ligand/receptor pair is activated in kidney cells. One limitation of this would be the fact that some pairings are activated in multiple cells at a time, so the manual manipulation of the data is reflected prior to analysis. Using the filtration script, accurate sorting is incorporated into the CellPhoneDB database rather than waiting until the output is produced and then subsequently applying spatial data. It was envisioned that this would reveal wherein the cell various ligands and receptors are interacting with different cell types, allowing for easier identification of which cells are being impacted and why, for the purpose of disease treatment. The hope is this new computational method utilizing spatially explicit ligand-receptor association data can be used to uncover previously unknown specific interactions within kidney tissue.

Keywords: bioinformatics, Ligands, kidney tissue, receptors, spatial transcriptome

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964 SEM Detection of Folate Receptor in a Murine Breast Cancer Model Using Secondary Antibody-Conjugated, Gold-Coated Magnetite Nanoparticles

Authors: Yasser A. Ahmed, Juleen M Dickson, Evan S. Krystofiak, Julie A. Oliver

Abstract:

Cancer cells urgently need folate to support their rapid division. Folate receptors (FR) are over-expressed on a wide range of tumor cells, including breast cancer cells. FR are distributed over the entire surface of cancer cells, but are polarized to the apical surface of normal cells. Targeting of cancer cells using specific surface molecules such as folate receptors may be one of the strategies used to kill cancer cells without hurting the neighing normal cells. The aim of the current study was to try a method of SEM detecting FR in a murine breast cancer cell model (4T1 cells) using secondary antibody conjugated to gold or gold-coated magnetite nanoparticles. 4T1 cells were suspended in RPMI medium witth FR antibody and incubated with secondary antibody for fluorescence microscopy. The cells were cultured on 30mm Thermanox coverslips for 18 hours, labeled with FR antibody then incubated with secondary antibody conjugated to gold or gold-coated magnetite nanoparticles and processed to scanning electron microscopy (SEM) analysis. The fluorescence microscopy study showed strong punctate FR expression on 4T1 cell membrane. With SEM, the labeling with gold or gold-coated magnetite conjugates showed a similar pattern. Specific labeling occurred in nanoparticle clusters, which are clearly visualized in backscattered electron images. The 4T1 tumor cell model may be useful for the development of FR-targeted tumor therapy using gold-coated magnetite nano-particles.

Keywords: cancer cell, nanoparticles, cell culture, SEM

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963 The Diverse and Flexible Coping Strategies Simulation for Maanshan Nuclear Power Plant

Authors: Chin-Hsien Yeh, Shao-Wen Chen, Wen-Shu Huang, Chun-Fu Huang, Jong-Rong Wang, Jung-Hua Yang, Yuh-Ming Ferng, Chunkuan Shih

Abstract:

In this research, a Fukushima-like conditions is simulated with TRACE and RELAP5. Fukushima Daiichi Nuclear Power Plant (NPP) occurred the disaster which caused by the earthquake and tsunami. This disaster caused extended loss of all AC power (ELAP). Hence, loss of ultimate heat sink (LUHS) happened finally. In order to handle Fukushima-like conditions, Taiwan Atomic Energy Council (AEC) commanded that Taiwan Power Company should propose strategies to ensure the nuclear power plant safety. One of the diverse and flexible coping strategies (FLEX) is a different water injection strategy. It can execute core injection at 20 Kg/cm2 without depressurization. In this study, TRACE and RELAP5 were used to simulate Maanshan nuclear power plant, which is a three loops PWR in Taiwan, under Fukushima-like conditions and make sure the success criteria of FLEX. Reducing core cooling ability is due to failure of emergency core cooling system (ECCS) in extended loss of all AC power situation. The core water level continues to decline because of the seal leakage, and then FLEX is used to save the core water level and make fuel rods covered by water. The result shows that this mitigation strategy can cool the reactor pressure vessel (RPV) as soon as possible under Fukushima-like conditions, and keep the core water level higher than Top of Active Fuel (TAF). The FLEX can ensure the peak cladding temperature (PCT) below than the criteria 1088.7 K. Finally, the FLEX can provide protection for nuclear power plant and make plant safety.

Keywords: TRACE, RELAP5/MOD3.3, ELAP, FLEX

Procedia PDF Downloads 224
962 The Analysis and Simulation of TRACE in the Ultimate Response Guideline for Chinshan BWR/4 Nuclear Power Plant

Authors: J. R. Wang, H. T. Lin, H. C. Chen, C. Shih, S. W. Chen, S. C. Chiang, C. C. Liu

Abstract:

In this research, TRACE model of Chinshan BWR/4 Nuclear Power Plant (NPP) has been developed for the simulation and analysis of Ultimate Response Guideline (URG). The main actions of URG are the depressurization and low pressure water injection of reactor and containment venting. This research focuses to verify the URG efficiency under Fukushima-like conditions. Trace analysis results show that the URG can keep the PCT below the criteria 1088.7 K under Fukushima-like conditions. It indicated that Chinshan NPP was safe.

Keywords: BWR, trace, safety analysis, URG

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961 Analysis of Two-Phase Flow Instabilities in Conventional Channel of Nuclear Power Reactor

Authors: M. Abdur Rashid Sarkar, Riffat Mahmud

Abstract:

Boiling heat transfer plays a crucial role in cooling nuclear reactor for safe electricity generation. A two phase flow is susceptible to thermal-hydrodynamic instabilities, which may cause flow oscillations of constant amplitude or diverging amplitude. These oscillations may induce boiling crisis, disturb control systems, or cause mechanical damage. Based on their mechanisms, various types of instabilities can be classified for a nuclear reactor. From a practical engineering point of view one of the major design difficulties in dealing with multiphase flow is that the mass, momentum, and energy transfer rates and processes may be quite sensitive to the geometric configuration of the heat transfer surface. Moreover, the flow within each phase or component will clearly depend on that geometric configuration. The complexity of this two-way coupling presents a major challenge in the study of multiphase flows and there is much that remains to be done. Yet, the parametric effects on flow instability such as the effect of aspect ratio, pressure drop, channel length, its orientation inlet subcooling and surface roughness etc. have been analyzed. Another frequently occurring instability, known as the Kelvin–Helmholtz instability has been briefly reviewed. Various analytical techniques for predicting parametric effect on the instability are analyzed in terms of their applicability and accuracy.

Keywords: two phase flows, boiling crisis, thermal-hydrodynamic instabilities, water cooled nuclear reactors, kelvin–helmholtz instability

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960 Impact of America's Anti-Ballistic Missile System (ABMS) on Power Dynamics of the World

Authors: Fehmeen Anwar, Ujala Liaqat

Abstract:

For over half a century, U.S. and the Soviet Union have been at daggers drawn with each other. Both leading powers of the world have been struggling hard to surpass each other in military and other technological fields. This neck-to-neck competition turned in favour of U.S. in the early 1990s when USSR had to face economic stagnation and later dismemberment of several of its states. The predominance of U.S. is still evident to date, rather it continues to grow. With this proposed defence program i.e. Anti-Ballistic Missile System, the U.S. will have a considerable chance of intercepting any nuclear strike by Russia, which re-asserts U.S. dominance in the region and creating a security dilemma for Russia and other states. The question is whether America’s recent nuclear deterrence project is merely to counter nuclear threats from Iran and North Korea or is it purely directed towards Russia, thus ensuring complete military supremacy in the world. Although U.S professes to direct its Anti-Ballistic Missile System (ABMS) against the axis of evil (Iran and North Korea), yet the deployment of this system in the East European territory undermines the Russian nuclear strategic capability, as this enables U.S. to initiate an attack and guard itself from retaliatory strike, thus disturbing the security equilibrium in Europe. The implications of this program can lead to power imbalance which can lead to the emergence of fundamentally different paradigm of international politics.

Keywords: Anti-Ballistic Missile System (ABMS), cold-war, axis of evil, power dynamics

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959 Investigation of Cost Effective Double Layered Slab for γ-Ray Shielding

Authors: Kulwinder Singh Mann, Manmohan Singh Heer, Asha Rani

Abstract:

The safe storage of radioactive materials has become an important issue. Nuclear engineering necessitates the safe handling of radioactive materials emitting high energy gamma-rays. Hazards involved in handling radioactive materials insist suitable shielded enclosures. With overgrowing use of nuclear energy for meeting the increasing demand of power, there is a need to investigate the shielding behavior of cost effective shielded enclosure (CESE) made from clay-bricks (CB) and fire-bricks (FB). In comparison to the lead-bricks (conventional-shielding), the CESE are the preferred choice in nuclear waste management. The objective behind the present investigation is to evaluate the double layered transmission exposure buildup factors (DLEBF) for gamma-rays for CESE in energy range 0.5-3MeV. For necessary computations of shielding parameters, using existing huge data regarding gamma-rays interaction parameters of all periodic table elements, two computer programs (GRIC-toolkit and BUF-toolkit) have been designed. It has been found that two-layered slabs show effective shielding for gamma-rays in orientation CB followed by FB than the reverse. It has been concluded that the arrangement, FB followed by CB reduces the leakage of scattered gamma-rays from the radioactive source.

Keywords: buildup factor, clay bricks, fire bricks, nuclear wastage management, radiation protective double layered slabs

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958 Determination of Critical Organ Doses for Liver Scintigraphy Using Cr-51

Authors: O. Maranci, A. B. Tugrul

Abstract:

Scintigraphy is an imaging method of nuclear events provoked by collisions or charged current interactions with radiation. It is used for diagnostic test used in nuclear medicine via radiopharmaceuticals emitting radiation which is captured by gamma cameras to form two-dimensional images. Liver scintigraphy is widely used in nuclear medicine.Tc-99m and Cr-51 gamma radioisotopes can be used for this purpose. Cr-51 usage is more important for patients’ organ dose that has higher energy and longer half-life as compared to Tc-99m. In this study, it is aimed to determine the required dose for critical organs of patient through liver scintigraphy via Cr-51 gamma radioisotope. Experimental studies were conducted on patients even though conducting experimental studies on patients is extremely difficult for determination of critical organ doses. Torso phantom was utilized to simulate the liver scintigraphy by using 20 mini packages of Cr-51 that were placed on the organ. The radioisotope was produced by irradiation in central thimble of TRIGA MARK II Reactor at 250 KW power. As the results of the study, critical organ doses were determined and evaluated with different critic organs.

Keywords: critical organ doses, liver, scintigraphy, TRIGA Mark-II

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957 Conserved Stem-Loop Structure at the End of Short Interspersed Nuclear Elements (SINE) and Long Interspersed Nuclear Elements (LINE) Pairs of Different Species

Authors: Daria Grechishnikova, Maria Poptsova

Abstract:

Transposable elements play an important role in the evolution of various species from bacteria to human. Long Interspersed Nuclear Elements (LINEs) and Short Interspersed Nuclear Elements (SINEs) are two major classes of retrotransposons that occupy a considerable part of any genome and their copy numbers can range form several hundreds to a million. Both LINEs and SINEs multiply through a copy-and-paste mechanism. LINEs encode proteins, which make them capable of self-propagation while SINEs are parasitic and require the machinery of LINEs to multiply. The mechanisms how LINE and SINE RNA is recognized by the LINE-encoded reverse transcriptase (RT) remain unclear. For some SINE-LINE pairs, it was shown that they share a common 3’-end with a stem-loop structure. Majority of the SINE-LINE pairs do not have a common 3’-end. Recently we have shown that in the human genome Alu-L1 pairs have structurally similar stem-loop structure at the 3’-end. Here we extended our analysis to a wide range of species and analyzed LINEs from 161 different species from Repbase and 217 SINE sequences from SINEBase. It appeared that all of the analyzed sequences contained stem-loop structures at the 3’-end. Here we conclude that it is very likely that a common evolutionary mechanism of transposon RNA recognition requires the presence of stem-loop structures at their 3’-end.

Keywords: LINE, SINE, mechanisms of retrotransposition, retrotransposons, stem-loop, stem-loop structures, transposons

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956 Effect of 8-OH-DPAT on the Behavioral Indicators of Stress and on the Number of Astrocytes after Exposure to Chronic Stress

Authors: Ivette Gonzalez-Rivera, Diana B. Paz-Trejo, Oscar Galicia-Castillo, David N. Velazquez-Martinez, Hugo Sanchez-Castillo

Abstract:

Prolonged exposure to stress can cause disorders related with dysfunction in the prefrontal cortex such as generalized anxiety and depression. These disorders involve alterations in neurotransmitter systems; the serotonergic system—a target of the drugs that are commonly used as a treatment to these disorders—is one of them. Recent studies suggest that 5-HT1A receptors play a pivotal role in the serotonergic system regulation and in stress responses. In the same way, there is increasing evidence that astrocytes are involved in the pathophysiology of stress. The aim of this study was to examine the effects of 8-OH-DPAT, a selective agonist of 5-HT1A receptors, in the behavioral signs of anxiety and anhedonia as well as in the number of astrocytes in the medial prefrontal cortex (mPFC) after exposure to chronic stress. They used 50 male Wistar rats of 250-350 grams housed in standard laboratory conditions and treated in accordance with the ethical standards of use and care of laboratory animals. A protocol of chronic unpredictable stress was used for 10 consecutive days during which the presentation of stressors such as motion restriction, water deprivation, wet bed, among others, were used. 40 rats were subjected to the stress protocol and then were divided into 4 groups of 10 rats each, which were administered 8-OH-DPAT (Tocris, USA) intraperitoneally with saline as vehicle in doses 0.0, 0.3, 1.0 and 2.0 mg/kg respectively. Another 10 rats were not subjected to the stress protocol or the drug. Subsequently, all the rats were measured in an open field test, a forced swimming test, sucrose consume, and a cero maze test. At the end of this procedure, the animals were sacrificed, the brain was removed and the tissue of the mPFC (Bregma: 4.20, 3.70, 2.70, 2.20) was processed in immunofluorescence staining for astrocytes (Anti-GFAP antibody - astrocyte maker, ABCAM). Statistically significant differences were found in the behavioral tests of all groups, showing that the stress group with saline administration had more indicators of anxiety and anhedonia than the control group and the groups with administration of 8-OH-DPAT. Also, a dose dependent effect of 8-OH-DPAT was found on the number of astrocytes in the mPFC. The results show that 8-OH-DPAT can modulate the effect of stress in both behavioral and anatomical level. Also they indicate that 5-HT1A receptors and astrocytes play an important role in the stress response and may modulate the therapeutic effect of serotonergic drugs, so they should be explored as a fundamental part in the treatment of symptoms of stress and in the understanding of the mechanisms of stress responses.

Keywords: anxiety, prefrontal cortex, serotonergic system, stress

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955 Radiation Protection and Licensing for an Experimental Fusion Facility: The Italian and European Approaches

Authors: S. Sandri, G. M. Contessa, C. Poggi

Abstract:

An experimental nuclear fusion device could be seen as a step toward the development of the future nuclear fusion power plant. If compared with other possible solutions to the energy problem, nuclear fusion has advantages that ensure sustainability and security. In particular considering the radioactivity and the radioactive waste produced, in a nuclear fusion plant the component materials could be selected in order to limit the decay period, making it possible the recycling in a new reactor after about 100 years from the beginning of the decommissioning. To achieve this and other pertinent goals many experimental machines have been developed and operated worldwide in the last decades, underlining that radiation protection and workers exposure are critical aspects of these facilities due to the high flux, high energy neutrons produced in the fusion reactions. Direct radiation, material activation, tritium diffusion and other related issues pose a real challenge to the demonstration that these devices are safer than the nuclear fission facilities. In Italy, a limited number of fusion facilities have been constructed and operated since 30 years ago, mainly at the ENEA Frascati Center, and the radiation protection approach, addressed by the national licensing requirements, shows that it is not always easy to respect the constraints for the workers' exposure to ionizing radiation. In the current analysis, the main radiation protection issues encountered in the Italian Fusion facilities are considered and discussed, and the technical and legal requirements are described. The licensing process for these kinds of devices is outlined and compared with that of other European countries. The following aspects are considered throughout the current study: i) description of the installation, plant and systems, ii) suitability of the area, buildings, and structures, iii) radioprotection structures and organization, iv) exposure of personnel, v) accident analysis and relevant radiological consequences, vi) radioactive wastes assessment and management. In conclusion, the analysis points out the needing of a special attention to the radiological exposure of the workers in order to demonstrate at least the same level of safety as that reached at the nuclear fission facilities.

Keywords: fusion facilities, high energy neutrons, licensing process, radiation protection

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954 Rapid Method for Low Level 90Sr Determination in Seawater by Liquid Extraction Technique

Authors: S. Visetpotjanakit, N. Nakkaew

Abstract:

Determination of low level 90Sr in seawater has been widely developed for the purpose of environmental monitoring and radiological research because 90Sr is one of the most hazardous radionuclides released from atmospheric during the testing of nuclear weapons, waste discharge from the generation nuclear energy and nuclear accident occurring at power plants. A liquid extraction technique using bis-2-etylhexyl-phosphoric acid to separate and purify yttrium followed by Cherenkov counting using a liquid scintillation counter to determine 90Y in secular equilibrium to 90Sr was developed to monitor 90Sr in the Asia Pacific Ocean. The analytical performance was validated for the accuracy, precision, and trueness criteria. Sr-90 determination in seawater using various low concentrations in a range of 0.01 – 1 Bq/L of 30 liters spiked seawater samples and 0.5 liters of IAEA-RML-2015-01 proficiency test sample was performed for statistical evaluation. The results had a relative bias in the range from 3.41% to 12.28%, which is below accepted relative bias of ± 25% and passed the criteria confirming that our analytical approach for determination of low levels of 90Sr in seawater was acceptable. Moreover, the approach is economical, non-laborious and fast.

Keywords: proficiency test, radiation monitoring, seawater, strontium determination

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953 An Operators’ Real-sense-based Fire Simulation for Human Factors Validation in Nuclear Power Plants

Authors: Sa-Kil Kim, Jang-Soo Lee

Abstract:

On March 31, 1993, a severe fire accident took place in a nuclear power plant located in Narora in North India. The event involved a major fire in the turbine building of NAPS unit-1 and resulted in a total loss of power to the unit for 17 hours. In addition, there was a heavy ingress of smoke in the control room, mainly through the intake of the ventilation system, forcing the operators to vacate the control room. The Narora fire accident provides us lessons indicating that operators could lose their mind and predictable behaviors during a fire. After the Fukushima accident, which resulted from a natural disaster, unanticipated external events are also required to be prepared and controlled for the ultimate safety of nuclear power plants. From last year, our research team has developed a test and evaluation facility that can simulate external events such as an earthquake and fire based on the operators’ real-sense. As one of the results of the project, we proposed a unit real-sense-based facility that can simulate fire events in a control room for utilizing a test-bed of human factor validation. The test-bed has the operator’s workstation shape and functions to simulate fire conditions such as smoke, heat, and auditory alarms in accordance with the prepared fire scenarios. Furthermore, the test-bed can be used for the operators’ training and experience.

Keywords: human behavior in fire, human factors validation, nuclear power plants, real-sense-based fire simulation

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952 Dynamic Environmental Impact Study during the Construction of the French Nuclear Power Plants

Authors: A. Er-Raki, D. Hartmann, J. P. Belaud, S. Negny

Abstract:

This paper has a double purpose: firstly, a literature review of the life cycle analysis (LCA) and secondly a comparison between conventional (static) LCA and multi-level dynamic LCA on the following items: (i) inventories evolution with time (ii) temporal evolution of the databases. The first part of the paper summarizes the state of the art of the static LCA approach. The different static LCA limits have been identified and especially the non-consideration of the spatial and temporal evolution in the inventory, for the characterization factors (FCs) and into the databases. Then a description of the different levels of integration of the notion of temporality in life cycle analysis studies was made. In the second part, the dynamic inventory has been evaluated firstly for a single nuclear plant and secondly for the entire French nuclear power fleet by taking into account the construction durations of all the plants. In addition, the databases have been adapted by integrating the temporal variability of the French energy mix. Several iterations were used to converge towards the real environmental impact of the energy mix. Another adaptation of the databases to take into account the temporal evolution of the market data of the raw material was made. An identification of the energy mix of the time studied was based on an extrapolation of the production reference values of each means of production. An application to the construction of the French nuclear power plants from 1971 to 2000 has been performed, in which a dynamic inventory of raw material has been evaluated. Then the impacts were characterized by the ILCD 2011 characterization method. In order to compare with a purely static approach, a static impact assessment was made with the V 3.4 Ecoinvent data sheets without adaptation and a static inventory considering that all the power stations would have been built at the same time. Finally, a comparison between static and dynamic LCA approaches was set up to determine the gap between them for each of the two levels of integration. The results were analyzed to identify the contribution of the evolving nuclear power fleet construction to the total environmental impacts of the French energy mix during the same period. An equivalent strategy using a dynamic approach will further be applied to identify the environmental impacts that different scenarios of the energy transition could bring, allowing to choose the best energy mix from an environmental viewpoint.

Keywords: LCA, static, dynamic, inventory, construction, nuclear energy, energy mix, energy transition

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951 History and Its Significance in Modern Visual Graphic: Its Niche with Respect to India

Authors: Hemang Madhusudan Anglay, Akash Gaur

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Value of visual perception in today’s context is vulnerable. Visual Graphic broadly and conveniently expresses culture, language and science of art that satisfactorily is a mould to cast various expressions. It is one of the essential parts of communication design which relatively can be used to approach the above areas of expressions. In between the receptors and interpreters, there is an expanse of comprehension and cliché in relation to the use of Visual Graphics. There are pedagogies, commodification and honest reflections where Visual Graphic is a common area of interest. The traditional receptors amidst the dilemma of this very situation find themselves in the pool of media, medium and interactions. Followed by a very vague interpretation the entire circle of communication becomes a question of comprehension vs cliché. Residing in the same ‘eco-system’ these communities who make pedagogies and multiply its reflections sometimes with honesty and sometimes on commercial values tend to function differently. With the advent of technology, which is a virtual space allows the user to access various forms of content. This diminishes the core characteristics and creates a vacuum even though it satisfies the user. The symbolic interpretation of visual form and structure is transmitted in a culture by the means of contemporary media. Starting from a very individualistic approach, today it is beyond Print & Electronic media. The expected outcome will be a study of Ahmedabad City, situated in the Gujarat State of India. It is identity with respect to socio-cultural as well as economic changes. The methodology will include process to understand the evolution and narratives behind it that will encompass diverse community, its reflection and it will sum up the salient features of communication through combination of visual and graphic that is relevant in Indian context trading its values to global scenario.

Keywords: communication, culture, graphic, visual

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950 Quantum Modelling of AgHMoO4, CsHMoO4 and AgCsMoO4 Chemistry in the Field of Nuclear Power Plant Safety

Authors: Mohamad Saab, Sidi Souvi

Abstract:

In a major nuclear accident, the released fission products (FPs) and the structural materials are likely to influence the transport of iodine in the reactor coolant system (RCS) of a pressurized water reactor (PWR). So far, the thermodynamic data on cesium and silver species used to estimate the magnitude of FP release show some discrepancies, data are scarce and not reliable. For this reason, it is crucial to review the thermodynamic values related to cesium and silver materials. To this end, we have used state-of-the-art quantum chemical methods to compute the formation enthalpies and entropies of AgHMoO₄, CsHMoO₄, and AgCsMoO₄ in the gas phase. Different quantum chemical methods have been investigated (DFT and CCSD(T)) in order to predict the geometrical parameters and the energetics including the correlation energy. The geometries were optimized with TPSSh-5%HF method, followed by a single point calculation of the total electronic energies using the CCSD(T) wave function method. We thus propose with a final uncertainty of about 2 kJmol⁻¹ standard enthalpies of formation of AgHMoO₄, CsHMoO₄, and AgCsMoO₄.

Keywords: nuclear accident, ASTEC code, thermochemical database, quantum chemical methods

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949 Cytotoxicological Evaluation of a Folate Receptor Targeting Drug Delivery System Based on Cyclodextrins

Authors: Caroline Mendes, Mary McNamara, Orla Howe

Abstract:

For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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948 Structural Characterization of TIR Domains Interaction

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

Abstract:

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

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

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947 Using HABIT to Establish the Chemicals Analysis Methodology for Maanshan Nuclear Power Plant

Authors: J. R. Wang, S. W. Chen, Y. Chiang, W. S. Hsu, J. H. Yang, Y. S. Tseng, C. Shih

Abstract:

In this research, the HABIT analysis methodology was established for Maanshan nuclear power plant (NPP). The Final Safety Analysis Report (FSAR), reports, and other data were used in this study. To evaluate the control room habitability under the CO2 storage burst, the HABIT methodology was used to perform this analysis. The HABIT result was below the R.G. 1.78 failure criteria. This indicates that Maanshan NPP habitability can be maintained. Additionally, the sensitivity study of the parameters (wind speed, atmospheric stability classification, air temperature, and control room intake flow rate) was also performed in this research.

Keywords: PWR, HABIT, Habitability, Maanshan

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946 Using HABIT to Estimate the Concentration of CO2 and H2SO4 for Kuosheng Nuclear Power Plant

Authors: Y. Chiang, W. Y. Li, J. R. Wang, S. W. Chen, W. S. Hsu, J. H. Yang, Y. S. Tseng, C. Shih

Abstract:

In this research, the HABIT code was used to estimate the concentration under the CO2 and H2SO4 storage burst conditions for Kuosheng nuclear power plant (NPP). The Final Safety Analysis Report (FSAR) and reports were used in this research. In addition, to evaluate the control room habitability for these cases, the HABIT analysis results were compared with the R.G. 1.78 failure criteria. The comparison results show that the HABIT results are below the criteria. Additionally, some sensitivity studies (stability classification, wind speed and control room intake rate) were performed in this study.

Keywords: BWR, HABIT, habitability, Kuosheng

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945 Appliance of the Analytic Hierarchy Process Methodology for the Selection of a Small Modular Reactors to Enhance Maritime Traffic Decarbonisation

Authors: Sara Martín, Ying Jie Zheng, César Hueso

Abstract:

International shipping is considered one of the largest sources of pollution in the world, accounting for 812 million tons of CO2 emissions in the year 2018. Current maritime decarbonisation is based on the implementation of new fuel alternatives, such as LNG, biofuels, and methanol, among others, which are less polluting as well as less efficient. Despite being a carbon-free and highly-developed technology, nuclear propulsion is hardly discussed as an alternative. Scientifically, it is believed that Small Modular Reactors (SMR) could be a promising solution to decarbonized maritime traffic due to their small dimensions and safety capabilities. However, as of today, there are no merchant ships powered by nuclear systems. Therefore, this project aims to understand the challenges of the development of nuclear-fuelled vessels by analysing all SMR designs to choose the most suitable one. In order not to fall into subjectivities, the Analytic Hierarchy Process (AHP) will be used to make the selection. This multiple-criteria evaluation technique analyses complex decisions by pairwise comparison of a number of evaluation criteria that can be applied to each SMR. The state-of-the-art 72 SMRs presented by the International Atomic Energy Agency (IAEA) will be analysed and ranked by a global parameter, calculated by applying the AHP methodology. The main target of the work is to find an adequate SMR system to power a ship. Top designs will be described in detail, and conclusions will be drawn from the results. This project has been conceived as an effort to foster the near-term development of zero-emission maritime traffic.

Keywords: international shipping, decarbonization, SMR, AHP, nuclear-fuelled vessels

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944 Prognostic Value of Tumor Markers in Younger Patients with Breast Cancer

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

Abstract:

Background: Breast cancer occupies the first place among the cancer in women in the world. It is urgent today to study the role of molecular markers which are capable of predicting the dynamics and outcome of the disease. The aim of this study is to define the prognostic value of the content of estrogen receptor (ER), progesterone receptor (PgR), and amplification of HER-2 / neu oncoprotein by studying 3 and 5-year overall and relapse-free survival in 470 patients with primary operable and 280 patients with locally–advanced breast cancer. Materials and methods: Study results of 3 and 5-year overall and relapse-free survival, depending on the content of RE, PgR in primary operable patients showed that ER positive (+) and PgR (+) survival was 100 (96.2%) and 97.3 (94.6%), for ER negative (-) and PgR (-) - 69.2 (60.3%) and 65.4 (57.7%), for ER positive (+) and negative PgR (-) 87.4 (80.1%) and 81.5 (79.3%), for ER negative (-) and positive PgR (+) - 97.4 (93.4%) and 90.4 (88.5%), respectively. Survival results depended also on the level of HER-2 / neu expression. In patients with HER-2 / neu negative the survival rates were as follows: 98.6 (94.7%) and 96.2 (92.3%). In group of patients with the level of HER-2 / neu (2+) expression these figures were: 45.3 (44.3%) and 45.1 (40.2%), and in group of patients with the level of HER-2 / neu (3+) expression - 41.2 (33.1%) and 34.3 (29.4%). The combination of ER negative (-), PgR (-), HER-2 / neu (-) they were 27.2 (25.4%) and 19.5 (15.3%), respectively. In patients with locally-advanced breast cancer the results of 3 and 5-year OS and RFS for ER (+) and PgR (+) were 76.3 (69.3%) and 62.2 (61.4%), for ER (-) and RP (-) 29.1 (23.7%) and 18.3 (12.6%), for ER (+) and PgR (-) 61.2 (47.2%) and 39.4 (25.6%), for ER (-) and PgR (+) 54.3 (43.1%) and 41.3 (18.3%), respectively. The level of HER-2 / neu expression also affected the survival results. Therefore, in HER-2/ neu negative patients the survival rate was 74.1 (67.6%) and 65.1 (57.3%), with the level of expression (2+) 20.4 (14.2%) and 8.6 (6.4%), with the level of expression (3+) 6.2 (3.1%) and 1.2 (1.5%), respectively. The combination for ER, PgR, HER-2 / neu negative was 22.1 (14.3%) and 8.4 (1.2%). Conclusion: Thus, the presence of steroid hormone receptors in breast tumor tissues at primary operable and locally- advanced process as the lack of HER-2/neu oncoprotein correlates with the highest rates of 3- and 5-year overall and relapse-free survival. The absence of steroid hormone receptors as well as of HER-2/neu overexpression in malignant breast tissues significantly degrades the 3- and 5-year overall and relapse-free survival. Tumors with ER, PgR and HER-2/neu negative have the most unfavorable prognostics.

Keywords: breast cancer, estrogen receptor, oncoprotein, progesterone receptor

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943 Combining the Production of Radiopharmaceuticals with the Department of Radionuclide Diagnostics

Authors: Umedov Mekhroz, Griaznova Svetlana

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In connection with the growth of oncological diseases, the design of centers for diagnostics and the production of radiopharmaceuticals is the most relevant area of healthcare facilities. The design of new nuclear medicine centers should be carried out from the standpoint of solving the following tasks: the availability of medical care, functionality, environmental friendliness, sustainable development, improving the safety of drugs, the use of which requires special care, reducing the rate of environmental pollution, ensuring comfortable conditions for the internal microclimate, adaptability. The purpose of this article is to substantiate architectural and planning solutions, formulate recommendations and principles for the design of nuclear medicine centers and determine the connections between the production and medical functions of a building. The advantages of combining the production of radiopharmaceuticals and the department of medical care: less radiation activity is accumulated, the cost of the final product is lower, and there is no need to hire a transport company with a special license for transportation. A medical imaging department is a structural unit of a medical institution in which diagnostic procedures are carried out in order to gain an idea of the internal structure of various organs of the body for clinical analysis. Depending on the needs of a particular institution, the department may include various rooms that provide medical imaging using radiography, ultrasound diagnostics, and the phenomenon of nuclear magnetic resonance. The production of radiopharmaceuticals is an object intended for the production of a pharmaceutical substance containing a radionuclide and intended for introduction into the human body or laboratory animal for the purpose of diagnosis, evaluation of the effectiveness of treatment, or for biomedical research. The research methodology includes the following subjects: study and generalization of international experience in scientific research, literature, standards, teaching aids, and design materials on the topic of research; An integrated approach to the study of existing international experience of PET / CT scan centers and the production of radiopharmaceuticals; Elaboration of graphical analysis and diagrams based on the system analysis of the processed information; Identification of methods and principles of functional zoning of nuclear medicine centers. The result of the research is the identification of the design principles of nuclear medicine centers with the functions of the production of radiopharmaceuticals and the department of medical imaging. This research will be applied to the design and construction of healthcare facilities in the field of nuclear medicine.

Keywords: architectural planning solutions, functional zoning, nuclear medicine, PET/CT scan, production of radiopharmaceuticals, radiotherapy

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942 Modeling of Cf-252 and PuBe Neutron Sources by Monte Carlo Method in Order to Develop Innovative BNCT Therapy

Authors: Marta Błażkiewicz, Adam Konefał

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Currently, boron-neutron therapy is carried out mainly with the use of a neutron beam generated in research nuclear reactors. This fact limits the possibility of realization of a BNCT in centers distant from the above-mentioned reactors. Moreover, the number of active nuclear reactors in operation in the world is decreasing due to the limited lifetime of their operation and the lack of new installations. Therefore, the possibilities of carrying out boron-neutron therapy based on the neutron beam from the experimental reactor are shrinking. However, the use of nuclear power reactors for BNCT purposes is impossible due to the infrastructure not intended for radiotherapy. Therefore, a serious challenge is to find ways to perform boron-neutron therapy based on neutrons generated outside the research nuclear reactor. This work meets this challenge. Its goal is to develop a BNCT technique based on commonly available neutron sources such as Cf-252 and PuBe, which will enable the above-mentioned therapy in medical centers unrelated to nuclear research reactors. Advances in the field of neutron source fabrication make it possible to achieve strong neutron fluxes. The current stage of research focuses on the development of virtual models of the above-mentioned sources using the Monte Carlo simulation method. In this study, the GEANT4 tool was used, including the model for simulating neutron-matter interactions - High Precision Neutron. Models of neutron sources were developed on the basis of experimental verification based on the activation detectors method with the use of indium foil and the cadmium differentiation method allowing to separate the indium activation contribution from thermal and resonance neutrons. Due to the large number of factors affecting the result of the verification experiment, the 10% discrepancy between the simulation and experiment results was accepted.

Keywords: BNCT, virtual models, neutron sources, monte carlo, GEANT4, neutron activation detectors, gamma spectroscopy

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941 Development of an Systematic Design in Evaluating Force-On-Force Security Exercise at Nuclear Power Plants

Authors: Seungsik Yu, Minho Kang

Abstract:

As the threat of terrorism to nuclear facilities is increasing globally after the attacks of September 11, we are striving to recognize the physical protection system and strengthen the emergency response system. Since 2015, Korea has implemented physical protection security exercise for nuclear facilities. The exercise should be carried out with full cooperation between the operator and response forces. Performance testing of the physical protection system should include appropriate exercises, for example, force-on-force exercises, to determine if the response forces can provide an effective and timely response to prevent sabotage. Significant deficiencies and actions taken should be reported as stipulated by the competent authority. The IAEA(International Atomic Energy Agency) is also preparing force-on-force exercise program documents to support exercise of member states. Currently, ROK(Republic of Korea) is implementing exercise on the force-on-force exercise evaluation system which is developed by itself for the nuclear power plant, and it is necessary to establish the exercise procedure considering the use of the force-on-force exercise evaluation system. The purpose of this study is to establish the work procedures of the three major organizations related to the force-on-force exercise of nuclear power plants in ROK, which conduct exercise using force-on-force exercise evaluation system. The three major organizations are composed of licensee, KINAC (Korea Institute of Nuclear Nonproliferation and Control), and the NSSC(Nuclear Safety and Security Commission). Major activities are as follows. First, the licensee establishes and conducts an exercise plan, and when recommendations are derived from the result of the exercise, it prepares and carries out a force-on-force result report including a plan for implementation of the recommendations. Other detailed tasks include consultation with surrounding units for adversary, interviews with exercise participants, support for document evaluation, and self-training to improve the familiarity of the MILES (Multiple Integrated Laser Engagement System). Second, KINAC establishes a force-on-force exercise plan review report and reviews the force-on-force exercise plan report established by licensee. KINAC evaluate force-on-force exercise using exercise evaluation system and prepare training evaluation report. Other detailed tasks include MILES training, adversary consultation, management of exercise evaluation systems, and analysis of exercise evaluation results. Finally, the NSSC decides whether or not to approve the force-on-force exercise and makes a correction request to the nuclear facility based on the exercise results. The most important part of ROK's force-on-force exercise system is the analysis through the exercise evaluation system implemented by KINAC after the exercise. The analytical method proceeds in the order of collecting data from the exercise evaluation system and analyzing the collected data. The exercise application process of the exercise evaluation system introduced in ROK in 2016 will be concretely set up, and a system will be established to provide objective and consistent conclusions between exercise sessions. Based on the conclusions drawn up, the ultimate goal is to complement the physical protection system of licensee so that the system makes licensee respond effectively and timely against sabotage or unauthorized removal of nuclear materials.

Keywords: Force-on-Force exercise, nuclear power plant, physical protection, sabotage, unauthorized removal

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940 Nanoparticulated (U,Gd)O2 Characterization

Authors: A. Fernandez Zuvich, I. Gana Watkins, H. Zolotucho, H. Troiani, A. Caneiro, M. Prado, A. L. Soldati

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The study of actinide nanoparticles (NPs) has attracted the attention of the scientific community not only because the lack of information about their ecotoxicological effects but also because the use of NPs could open a new way in the production of nuclear energy. Indeed, it was recently demonstrated that UO2 NPs sintered pellets exhibit closed porosity with improved fission gas retention and radiation-tolerance , ameliorated mechanical properties, and less detriment of the thermal conductivity upon use, making them an interesting option for new nuclear fuels. In this work, we used a combination of diffraction and microscopy tools to characterize the morphology, the crystalline structure and the composition of UO2 nanoparticles doped with 10%wt Gd2O3. The particles were synthesized by a modified sol-gel method at low temperatures. X-ray Diffraction (XRD) studies determined the presence of a unique phase with the cubic structure and Fm3m spatial group, supporting that Gd atoms substitute U atoms in the fluorite structure of UO2. In addition, Field Emission Gun Scanning (FEG-SEM) and Transmission (FEG-TEM) Electron Microscopy images revealed the presence of micrometric agglomerates of nanoparticles, with rounded morphology and an average crystallite size < 50 nm. Energy Dispersive Spectroscopy (EDS) coupled to TEM determined the presence of Gd in all the analyzed crystallites. Besides, FEG-SEM-EDS showed a homogeneous concentration distribution at the micrometer scale indicating that the small size of the crystallites compensates the variation in composition by averaging a large number of crystallites. These techniques, as combined tools resulted thus essential to find out details of morphology and composition distribution at the sub-micrometer scale, and set a standard for developing and analyzing nanoparticulated nuclear fuels.

Keywords: actinide nanoparticles, burnable poison, nuclear fuel, sol-gel

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939 The New Insight about Interspecies Transmission of Iranian H9N2 Influenza Viruses from Avian to Human

Authors: Masoud Soltanialvar, Ali Bagherpour

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Documented cases of human infection with H9N2 avian influenza viruses, first detected in 1999 in Hong Kong and China, indicate that these viruses can be directly transmitted from birds to humans. In this study, we characterized the mutation in the Hemagglutinin (HA) genes and proteins that correlates with a shift in affinity of the Hemagglutinin (HA) protein from the “avian” type sialic receptors to the “human” type in 10 Iranian isolates. We delineated the genomes and receptor binding profile of HA gene of some field isolates and established their phylogenetic relationship to the other Asian H9N2 sub lineages. A total of 1200 tissue samples collected from 40 farms located in various states of Iran during 2008 – 2010 as part of a program to monitor Avian Influenza Viruses (AIV) infection. To determine the genetic relationship of Iranian viruses, the Hemagglutinin (HA) genes from ten isolates were amplified and sequenced (by RT-PCR method). Nucleotide sequences (orf) of the (HA) genes were used for phylogenetic tree construction. Deduced amino acid sequences showed the presence of L226 (234 in H9 numbering) in all ten Iranian isolates which indicates a preference to binding of α (2–6) sialic acid receptors, so these Iranian H9N2 viruses have the potential to infect human beings. These isolates showed high degree of homology with 2 human H9N2 isolates A/HK/1073/99, A/HK/1074/99. Phylogenetic analysis of showed that all the HA genes of the Iranian H9N2 viruses fall into a single group within a G1-like sublineage which had contributed as donor of six internal genes to H5N1 highly pathogenic avian influenza. The results of this study indicated that all Iranian viruses have the potential to emerge as highly pathogenic influenza virus, and considering the homology of these isolates with human H9N2 strains, it seems that the potential of these avian influenza isolates to infect human should not be overlooked.

Keywords: influenza virus, hemagglutinin, neuraminidase, Iran

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938 Scientific and Regulatory Challenges of Advanced Therapy Medicinal Products

Authors: Alaa Abdellatif, Gabrièle Breda

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Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patients

Keywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation

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