Search results for: receptor activator of nuclear factor kappa-B ligand

Authors: Chargui Abderrahman, Nehdi Afef , BelaïD Amine , Djerbi Nadir, Tauc Michel, Hofman Paul, Mograbi Baharia, El May MichèLe

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K63-linked ubiquitination — i.e. conjugation of a chain of ubiquitins (Ub) linked through lys63 — has emerged as a key mechanism regulating signalling transduction pathways. Although critical, very little information is currently available about how subversion of K63 ubiquitination might contribute to cancers and inflammatory diseases. The present study provides the first evidence that Cadmium (Cd), a widespread environmental carcinogen and toxicant, is a powerful activator of K63 ubiquitination. Indeed, Cd induces accumulation of K63 polyUb proteins. Importantly, Cd-induced ubiquitination does not stem on oxidative damage or proteasome impairment. Rather, we demonstrate that Cd not only activates K63 ubiquitination but also amplifies their accumulation by overloading the capacity of autophagy pathway. At molecular level, Cd-induced ubiquitination is correlated with stabilization of HIF-1 and the activation of NF-B, two transcription factors. Strikingly, prolonged cell exposure to high Cd concentrations induces an exaggerated K63 ubiquitination that fosters aggresome formation, thus precluding these proteins from interacting with their downstream nuclear targets. We therefore propose that the aberrant activation of K63 ubiquitination by the carcinogen Cadmium could promote cell proliferation and inflammation at low levels while high levels committed cell to death.

Keywords: cadmium, environmental exposure, Lysine-63-ubiquitination, kidney, apoptosis, proliferation, autophagy

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Authors: Islam Nowisser, Noha Farag, Mohamed El Azizi

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Helicobacter pylori is a highly important human pathogen which inhabits about 50% of the population worldwide. Infection with this bacteria is very hard to treat, with high probability of recurrence. H. pylori causes severe gastric diseases, including peptic ulcer, gastritis, and gastric cancer, which has been linked to chronic inflammation. The infection has been reported to be associated with high levels of pro-inflammatory cytokines, especially IL-1β and TNF-α. The aim of the current study is to investigate the molecular mechanisms by which H. pylori activates NLRP3 inflammasome and its contribution to Il-1 β production in an innate cellular model. H. pylori PMSS1 and G27 standard strains, as well as the PMSS1 isogenic mutant strain PMSS1ΔVacA and G27ΔVacA, G27ΔCagA in addition to clinical isolates obtained from biopsy samples from the antrum and corpus mucosa of chronic gastritis patients, were used to establish infection in RAW-264.7 macrophages. The production levels of TNF-α and IL-1β was assessed using ELISA. Since expression of these cytokines is often regulated by the transcription factor complex, nuclear factor-kB (NF-kB), the activation of NF-κB in H. pylori infected cells was also evaluated by luciferase assay. Genomic DNA was extracted from bacterial cultures of H. pylori clinical isolates as well as the standard strains and their corresponding mutants, where they were evaluated for the cagA pathogenicity island and vacA expression. The correlation between these findings and expression of the cagA Pathogenicity Island and vacA in the bacteria was also investigated. The results showed IL-1β, and TNF-α production significantly increased in raw macrophages following H. pylori infection. The cagA+ and vacA+ H. pylori strains induced significant production of IL-1β compared to cagA- and vacA- strains. The activation pattern of NF-κB was correlated in the isolates to their cagA and vacA expression profiles. A similar finding could not be confirmed for TNF-α production. Our study shows the ability of H. pylori to activate NF-kB and induce significant IL-1β production as a possible mechanism for the augmented inflammatory response seen in subjects infected with cagA+ and vacA+ H. pylori strains that would lead to the progression to more severe form of the disease.

Keywords: Helicobacter pylori, IL-1β, inflammatory cytokines, nuclear factor KB, TNF-α

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Authors: Ananya Govindarajan

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Tetrahymena thermophila is a single-cell, eukaryotic organism that belongs to the Protozoa Kingdom. Tetrahymena thermophila is often used in signal transduction pathway studies because of its ability to model sensory input and the effects of environmental conditions such as chemicals and temperature. The recently discovered G37 chemorepellent receptor showed increased responsiveness to all chemorepellents. Investigating the mutant G37 Tetrahymena gene in various test solutions, including ferric chloride, ferrous sulfate, hydrogen peroxide, tetrazolium blue, potassium chloride, and dithiothreitol were performed to determine the role of oxidants and reducing agents with the mutant and wild-type cells (CU427) to assess the role of the receptor. Behavioral assays and recordings processed by ImageJ indicated that ferric chloride, hydrogen peroxide, and tetrazolium blue yielded little to no chemorepellent responses from G37 cells (<20% ARs). CU427 cells were over-responsive based on the mean percent of cells (>50% ARs). Reducing agents elicited chemorepellent responses from both G37 and CU427, in addition to potassium chloride. Cell responses were classified as over-responsive (>50% ARs). Dithiothreitol yielded unexpected results as G37 (37.0% ARs) and CU427 (38.1% ARs) had relatively similar responses and were only responsive and not over-responsive to the reducing agent test chemical solution. Ultimately, this indicates that the G37 receptor is more interactive with molecules that are reducing agents or non-oxidant compounds; G37 may be unable to sense and respond to oxidants effectively, further elucidating the pathways of the G37 strain and nature of this receptor. Results also indicate that the CSF most likely contained an oxidant, like ferric chloride. This research can be further applied to neuronal influences and how specific compounds may affect human neurons individually and their excitability as the responses model action potentials and membrane potential.

Keywords: tetrahymena thermophila, signal transduction, chemosensory, oxidant, reducing agent

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Authors: Surapong Vongvatcharanon, Fardeela Binalee, Wandee Udomuksorn, Ekkasit Kumarnsit, Uraporn Vongvatcharanon

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Hypogonadism is characterized by a decline in sex hormone levels, especially testosterone. It has been shown to be an important contributor to the decrease in muscle mass, muscle strength and performance, a condition known as sarcopenia. Preparations from Butea superba Roxb. (red Kwao Krua) have been reported to have androgenic properties. The active compounds are proposed to be flavonoids and flavonoid glycosides. Treatment with B. superba has been shown to improve erectile dysfunction in males. Parvalbumin (PV) is a relaxing factor and identified in fast twitch fibers. Alterations of the PV levels affects skeletal muscle functions. This study aimed to investigate the effects of orhchidectomy, testosterone replacement and different doses of Butea superba Roxb. on the structure, performance, levels of parvalbumin, parvalbumin and androgen receptor immunoreactivities in the extensor digitorum longus (EDL) and gastrocnemius muscles of orchidectomized rats. Twelve-week old male Wistar rats were randomly divided into 6 groups; sham-operated (SHAM), orchidectomized (BS-0), orchidectomized group that was treated with testosterone replacement of 6 µg/kg (TP) or an orchidectomized group that was treated with various doses of an extract from Butea superba Roxb.; 5 mg/kg (BS-5), 50 mg/kg (BS-50) and 500 mg/kg (BS-500) all for 90 days. The testosterone level, epididymis, seminal vesicle, prostate gland, vas deference weight, muscle fiber size, strength and endurance in both the EDL and gastrocnemius muscle were decreased in the BS-0 group but increased in the testosterone replacement group. Treatment with the B. superba Roxb. extract replacement group improved muscle fiber size, strength and endurance, but not total testosterone levels, or the epididymis, seminal vesicle, prostate gland, vas deference weight. Furthermore, the parvalbumin level, parvalbumin and androgen receptor immunoreactivities were reduced in the BS-0 group but increased in the testosterone replacement group and the B. superba Roxb. extract groups for both the EDL and gastrocnemius muscle. This study indicated that the reduction of testosterone level led to a decrease of the androgen receptor density resulting in a decline in the muscle mass and parvalbumin levels. The decrease of parvalbumin levels affected muscle performance. Testosterone replacement increased the androgen receptor density and led to an increase of muscle mass and parvalbumin levels. The increase in the parvalbumin levels may result in an improvement of muscle performance. This may explain one mechanism of testosterone on muscle mass and strength in the testosterone dependent sarcopenia. The B. superba Roxb. extract groups also had improved muscle mass, strength and endurance, parvalbumin level, parvalbumin and androgen immunoreactivities compared to the BS-O group . Butea superba Roxb. Extracts contains a flavonoid (3, 7, 3'-Trihydroxy-4'-methoxyflavone), flavonoiglycoside (3, 3'-dihydroxy-4'-methoxyflavone-7-O-β-D-glucopyranoside) and isoflavanolignans (butesuperins A and butesuperins B) all known to inhibit the cAMP phosphodiesterase enzyme. Therefore, cAMP signaling may have adaptive effects on skeletal muscle by increasing muscle mass, strength and endurance.

Keywords: Butea superba, parvalbumin, skeletal muscle, orchidectomy

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Authors: Youjeong Hwang

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Purpose: Insulin-like growth factor-I (IGF-I) promotes B-cell development, immunoglobulin formation, and interleukin-6 (IL-6) production, then regulate the immune response and inflammation. As IGF-I and their receptor also exist in the periodontal tissue, they may affect the immune response caused by periodontal pathogens in aggressive periodontitis (AgP) patients. The function of IGF is regulated by IGF binding proteins (IGFBPs), and IGFBP-3 is known to most abundant in plasma. The aim of the present study was to assess the concentration of IGF-I and IGFBP-3 in plasma and gingival crevicular fluid (GCF) in AgP patients and to find out their association. Methods: Nine patients with AgP (test group) and nine healthy subjects (control group) were included in this study. None of the subjects had a history of systemic disease, smoking or steroids medication. GCF samples were collected by microcapillary pipettes and plasma samples were obtained by venipuncture. Probing pocket depth (PD), clinical attachment level (CAL) and bleeding on probing (BOP) were recorded. Samples were assayed for IGF-I and IGFBP-3 levels using ELISA. Results: Mean IGF-I level in GCF was higher in the test group than control. Mean IGF-I level in plasma and IGFBP-3 level in GCF and plasma in control group were higher than that of the test group. However, there was no statistical significance (p > 0.05). The mean level of IGF-I and IGFBP-3 in GCF was lower than those in plasma. Mean IGF-I level in plasma showed a negative correlation with PD and CAL (p < 0.05) in both groups. The levels of IGF-I and IGFBP-3 in GCF seemed to be negatively correlated with BOP in the test group (p < 0.05). Conclusions: The difference in the level of IGF-I and IGFBP-3 between AgP and healthy subjects was not significant. Further studies that explain the mechanism of the protective role of IGF-I with more samples are needed.

Keywords: aggressive periodontitis, pathogenesis, insulin-like growth factor, insulin-like growth factor binding protein

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Authors: Milica Karadzic, Lidija Jevric, Sanja Podunavac-Kuzmanovic, Strahinja Kovacevic, Sinisa Markov, Aleksandar Okljesa, Andrea Nikolic, Marija Sakac, Katarina Penov Gasi

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This study considered the microbiological activity determination and molecular docking study for selected steroid derivatives of biomedical importance. Minimal inhibitory concentration (MIC) was determined for steroid derivatives against Staphylococcus aureus using macrodilution method. Some of the investigated steroid derivatives express bacteriostatic effect against Staphylococcus aureus. Molecular docking approaches are the most widely used techniques for predicting the binding mode of a ligand. Molecular docking study was done for steroid derivatives for androgen receptor negative prostate cancer cell line (PC-3) toward Human Cytochrome P450 CYP17A1. The molecules that had the smallest experimental IC50 values confirmed their ability to dock into active place using suitable molecular docking procedure. The binding disposition of those molecules was thoroughly investigated. Microbiological analysis and molecular docking study were conducted with aim to additionally characterize selected steroid derivatives for future investigation regarding their biological activity and to estimate the binding-affinities of investigated derivatives. This article is based upon work from COST Action (TD1305), supported by COST (European Cooperation and Science and Technology).

Keywords: binding affinity, minimal inhibitory concentration, molecular docking, pc-3 cell line, staphylococcus aureus, steroids

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Authors: D. S. Gomes, A. T. Silva

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Analysis of the uncertainty quantification related to nuclear safety margins applied to the nuclear reactor is an important concept to prevent future radioactive accidents. The nuclear fuel performance code may involve the tolerance level determined by traditional deterministic models producing acceptable results at burn cycles under 62 GWd/MTU. The behavior of nuclear fuel can simulate applying a series of material properties under irradiation and physics models to calculate the safety limits. In this study, theoretical predictions of nuclear fuel failure under transient conditions investigate extended radiation cycles at 75 GWd/MTU, considering the behavior of fuel rods in light-water reactors under reactivity accident conditions. The fuel pellet can melt due to the quick increase of reactivity during a transient. Large power excursions in the reactor are the subject of interest bringing to a treatment that is known as the Fuchs-Hansen model. The point kinetic neutron equations show similar characteristics of non-linear differential equations. In this investigation, the multivariate logistic regression is employed to a probabilistic forecast of fuel failure. A comparison of computational simulation and experimental results was acceptable. The experiments carried out use the pre-irradiated fuels rods subjected to a rapid energy pulse which exhibits the same behavior during a nuclear accident. The propagation of uncertainty utilizes the Wilk's formulation. The variables chosen as essential to failure prediction were the fuel burnup, the applied peak power, the pulse width, the oxidation layer thickness, and the cladding type.

Keywords: logistic regression, reactivity-initiated accident, safety margins, uncertainty propagation

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Authors: Taimur Khan, Zakirullah, Muhammad Shahab

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The SARS-CoV-2 variant BA.2.86 (Omicron) has emerged with unique mutations that may increase its transmission and infectivity. This study investigates how these mutations alter the Omicron receptor-binding domain's interaction network and dynamic properties (RBD) compared to the wild-type virus, focusing on its binding affinity to the human ACE2 (hACE2) receptor. Protein-protein docking and all-atom molecular dynamics simulations were used to analyze structural and dynamic differences. Despite the structural similarity to the wild-type virus, the Omicron variant exhibits a distinct interaction network involving new residues that enhance its binding capacity. The dynamic analysis reveals increased flexibility in the RBD, particularly in loop regions crucial for hACE2 interaction. Mutations significantly alter the secondary structure, leading to greater flexibility and conformational adaptability compared to the wild type. Binding free energy calculations confirm that the Omicron RBD has a higher binding affinity (-70.47 kcal/mol) to hACE2 than the wild-type RBD (-61.38 kcal/mol). These results suggest that the altered interaction network and enhanced dynamics of the Omicron variant contribute to its increased infectivity, providing insights for the development of targeted therapeutics and vaccines.

Keywords: SARS-CoV-2, molecular dynamic simulation, receptor binding domain, vaccine

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Authors: J. R. Wang, H. T. Lin, Y. Chiang, H. C. Chen, C. Shih

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Kuosheng Nuclear Power Plant (NPP) is located on the northern coast of Taiwan. Its nuclear steam supply system is a type of BWR/6 designed and built by General Electric on a twin unit concept. First, the methodology of Kuosheng NPP SPU (Stretch Power Uprate) safety analysis TRACE/SNAP model was developed in this research. Then, in order to estimate the safety of Kuosheng NPP under the more severe condition, the SBO (Station Blackout) + LOCA (Loss-of-Coolant Accident) transient analysis of Kuosheng NPP SPU TRACE/SNAP model was performed. Besides, the animation model of Kuosheng NPP was presented using the animation function of SNAP with TRACE/SNAP analysis results.

Keywords: TRACE, safety analysis, BWR/6, severe accident

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Authors: Yudhitya Kusumawati, Yuki Mitsuya, Tomooki Shiba, Mitsuru Uesaka

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After the Fukushima Daiichi nuclear power reactor incident, there are a lot of unaccountable nuclear fuel debris in the reactor core area, which is subject to safeguard and criticality safety. Before the actual precise analysis is performed, preliminary on-site screening and mapping of nuclear debris activity need to be performed to provide a reliable data on the nuclear debris mass-extraction planning. Through a collaboration project with Japan Atomic Energy Agency, an on-site nuclear debris screening system by using dual energy X-Ray inspection and neutron energy resonance analysis has been established. By using the compact and mobile pulsed neutron source constructed from 3.95 MeV X-Band electron linac, coupled with Tungsten as electron-to-photon converter and Beryllium as a photon-to-neutron converter, short-distance neutron Time of Flight measurement can be performed. Experiment result shows this system can measure neutron energy spectrum up to 100 eV range with only 2.5 meters Time of Flightpath in regards to the X-Band accelerator’s short pulse. With this, on-site neutron Time of Flight measurement can be used to identify the nuclear debris isotope contents through Neutron Resonance Transmission Analysis (NRTA). Some preliminary NRTA experiments have been done with Tungsten sample as dummy nuclear debris material, which isotopes Tungsten-186 has close energy absorption value with Uranium-238 (15 eV). The results obtained shows that this system can detect energy absorption in the resonance neutron area within 1-100 eV. It can also detect multiple elements in a material at once with the experiment using a combined sample of Indium, Tantalum, and silver makes it feasible to identify debris containing mixed material. This compact neutron Time of Flight measurement system is a great complementary for dual energy X-Ray Computed Tomography (CT) method that can identify atomic number quantitatively but with 1-mm spatial resolution and high error bar. The combination of these two measurement methods will able to perform on-site nuclear debris screening at Fukushima Daiichi reactor core area, providing the data for nuclear debris activity mapping.

Keywords: neutron source, neutron resonance, nuclear debris, time of flight

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Authors: Mengistu G. Woldu, Hani Y. Zaki, Areeg Faggad, Badreldin E. Abdalla

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Background: Type 2 diabetes mellitus (T2DM) is a complex, degenerative, and multi-factorial disease, which is culpable for huge mortality and morbidity worldwide. Even though relatively significant numbers of studies are conducted on the genetics domain of this disease in the developed world, there is huge information gap in the sub-Saharan Africa region in general and in Eritrea in particular. Objective: The principal aim of this study was to investigate the association of common variants of the Insulin Receptor Substrate 1 (IRS1) and Transcription Factor 7-Like 2 (TCF7L2) genes with T2DM in the Eritrean population. Method: In this cross-sectional case control study 200 T2DM patients and 112 non-diabetes subjects were participated and genotyping of the IRS1 (rs13431179, rs16822615, 16822644rs, rs1801123) and TCF7L2 (rs7092484) tag SNPs were carries out using PCR-RFLP method of analysis. Haplotype analyses were carried out using Plink version 1.07, and Haploview 4.2 software. Linkage disequilibrium (LD), and Hardy-Weinberg equilibrium (HWE) analyses were performed using the Plink software. All descriptive statistical data analyses were carried out using SPSS (Version-20) software. Throughout the analysis p-value ≤0.05 was considered statistically significant. Result: Significant association was found between rs13431179 SNP of the IRS1 gene and T2DM under the recessive model of inheritance (OR=9.00, 95%CI=1.17-69.07, p=0.035), and marginally significant association found in the genotypic model (OR=7.50, 95%CI=0.94-60.06, p=0.058). The rs7092484 SNP of the TCF7L2 gene also showed markedly significant association with T2DM in the recessive (OR=3.61, 95%CI=1.70-7.67, p=0.001); and allelic (OR=1.80, 95%CI=1.23-2.62, p=0.002) models. Moreover, eight haplotypes of the IRS1 gene found to have significant association withT2DM (p=0.013 to 0.049). Assessments made on the interactions of genotypes of the rs13431179 and rs7092484 SNPs with various parameters demonstrated that high density lipoprotein (HDL), low density lipoprotein (LDL), waist circumference (WC), and systolic blood pressure (SBP) are the best T2DM onset predicting models. Furthermore, genotypes of the rs7092484 SNP showed significant association with various atherogenic indexes (Atherogenic index of plasma, LDL/HDL, and CHLO/HDL); and Eritreans carrying the GG or GA genotypes were predicted to be more susceptible to cardiovascular diseases onset. Conclusions: Results of this study suggest that IRS1 (rs13431179) and TCF7L2 (rs7092484) gene polymorphisms are associated with increased risk of T2DM in Eritreans.

Keywords: IRS1, SNP, TCF7L2, type 2 diabetes

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Authors: Mehrdad HassanZadeh Dugoori, Iman Mohammadali Tajrishi

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Since Iran's nuclear program became public in 2002, the International Atomic Energy Agency (IAEA) has been unable to confirm Tehran's assertions that its nuclear activities are exclusively for peaceful purposes and that it has not sought to develop nuclear weapons. The United Nations Security Council has adopted six resolutions since 2006 requiring Iran to stop enriching uranium - which can be used for civilian purposes, but also to build nuclear bombs, which Iran never follow this strategy- and co-operate with the IAEA. Four resolutions have included progressively expansive sanctions to persuade Tehran to comply. The US and EU have imposed additional sanctions on Iranian oil exports and banks since 2012. In this article we reassess the sanction dimensions of Iran and the influences. Then according to the last agreement between P5+1 and Iran in 15 July 2015, we mention reconstruction strategies for oil export markets of Iran and the operational program for one million barrel of crude oil sales per day. These strategies are the conclusion of focus group and brain storming with Iran's oil and gas managers during content analysis.

Keywords: post-sanction, oil market, reconstruction, marketing, strategy

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Authors: Soujanya Pasumarthi

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Inverse docking is a relatively new technique that has been used to identify potential receptor targets of small molecules. Our docking software package MDock is well suited for such an application as it is both computationally efficient, yet simultaneously shows adequate results in binding affinity predictions and enrichment tests. As a validation study, we present the first stage results of an inverse-docking study which seeks to identify potential direct targets of PRIMA-1. PRIMA-1 is well known for its ability to restore mutant p53's tumor suppressor function, leading to apoptosis in several types of cancer cells. For this reason, we believe that potential direct targets of PRIMA-1 identified in silico should be experimentally screened for their ability to inhibitcancer cell growth. The highest-ranked human protein of our PRIMA-1 docking results is oxidosqualene cyclase (OSC), which is part of the cholesterol synthetic pathway. The results of two followup experiments which treat OSC as a possible anti-cancer target are promising. We show that both PRIMA-1 and Ro 48-8071, a known potent OSC inhibitor, significantly reduce theviability of BT-474 breast cancer cells relative to normal mammary cells. In addition, like PRIMA-1, we find that Ro 48-8071 results in increased binding of mutant p53 to DNA in BT- 474cells (which highly express p53). For the first time, Ro 48-8071 is shown as a potent agent in killing human breast cancer cells. The potential of OSC as a new target for developing anticancer therapies is worth further investigation.

Keywords: inverse docking, in silico screening, protein-ligand interactions, molecular docking

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Authors: Altab Hossain, Shakerul Islam, Golamur R. Khan, Abu Zafar M. Salahuddin

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An effective identification of breakdowns is of premier importance for the safe and reliable operation of Nuclear Power Plants (NPP) and its associated facilities. A great number of monitoring and diagnosis methodologies are applied and used worldwide in areas such as industry, automobiles, hospitals, and power plant to detect and reduce human disasters. The potential consequences of several hazardous activities may harm the society using nuclear and its associated facilities. Hence, one of the most popular and effective methods to ensure safety and monitor the entire nuclear facility and imply risk-free operation without human interference during the hazardous situation is using a robot. Therefore, in this study, an advanced autonomous robot has been designed and developed that can monitor several parameters in the NPP to ensure the safety and do some risky job in case of nuclear disaster. The robot consisted of autonomous track following unit, data processing and transmitting unit can follow a straight line and take turn as the bank greater than 90 degrees. The developed robot can analyze various parameters such as temperature, altitude, radiation, obstacle, humidity, detecting fire, measuring distance, ultrasonic scan and taking the heat of any particular object. It has an ability to broadcast live stream and can record the document to its own server memory. There is a separate control unit constructed with a baseboard which processes the recorded data and a transmitter which transmits the processed data. To make the robot user-friendly, the code is developed such a way that a user can control any of robotic arm as per types of work. To control at any place and without the track, there is an advanced code has been developed to take manual overwrite. Through this process, administrator who has logged in permission to Dynamic Host Client Protocol (DHCP) can make the handover of the control of the robot. In this process, this robot is provided maximum nuclear security from being hacked. Not only NPP, this robot can be used to maximize the real-time monitoring system of any nuclear facility as well as nuclear material transportation and decomposition system.

Keywords: nuclear power plant, radiation, dynamic host client protocol, nuclear security

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Authors: K. S. Bang, S. H. Yu, J. C. Lee, K. S. Seo, S. H. Lee

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Dual purpose casks are used for storage and transport of spent nuclear fuel assemblies. Therefore, they satisfy the requirements prescribed in the Korea NSSC Act 2013-27, the IAEA Safety Standard Series No. SSR-6, and US 10 CFR Part 71. These regulatory guidelines classify the dual purpose cask as a Type B package, and state that a Type B package must be able to withstand a temperature of 800°C for a period of 30 min. Therefore, a fire test was conducted using a one-sixth slice of a real cask to estimate the thermal integrity of the dual purpose cask at a temperature of 800°C. The neutron shield reached a maximum temperature of 183°C, which indicates that dual purpose cask was properly insulated from the heat of the flames. The temperature rise of the basket during the fire test was 29°C. Therefore, the integrity of a spent nuclear fuel is estimated to be maintained. The temperature was lower when a cooling pin was installed. The neutron shielding was therefore protected adequately by cooling pin. As a result, the thermal integrity of the dual purpose cask was maintained and the cask is judged to be sufficiently safe for temperatures under 800°C.

Keywords: dual purpose cask, spent nuclear fuel, pool fire test, integrity

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Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

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Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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Authors: Anita Khadka, Gregory Epiphaniou, Carsten Maple

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There is a dramatic surge in the adoption of machine learning (ML) techniques in many areas, including the nuclear industry (such as fault diagnosis and fuel management in nuclear power plants), autonomous systems (including self-driving vehicles), space systems (space debris recovery, for example), medical surgery, network intrusion detection, malware detection, to name a few. With the application of learning methods in such diverse domains, artificial intelligence (AI) has become a part of everyday modern human life. To date, the predominant focus has been on developing underpinning ML algorithms that can improve accuracy, while factors such as resiliency and robustness of algorithms have been largely overlooked. If an adversarial attack is able to compromise the learning method or data, the consequences can be fatal, especially but not exclusively in safety-critical applications. In this paper, we present an in-depth analysis of five adversarial attacks and three defence methods on a crack detection ML model. Our analysis shows that it can be dangerous to adopt machine learning techniques in security-critical areas such as the nuclear industry without rigorous testing since they may be vulnerable to adversarial attacks. While common defence methods can effectively defend against different attacks, none of the three considered can provide protection against all five adversarial attacks analysed.

Keywords: adversarial machine learning, attacks, defences, nuclear industry, crack detection

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Authors: Paola Leon, Hugo Garcia, Adan Leon, Samuel Munoz

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The enhanced oil recovery by steam injection was considered a process that only generated physical recovery mechanisms. However, there is evidence of the occurrence of a series of chemical reactions, which are called aquathermolysis, which generates hydrogen sulfide, carbon dioxide, methane, and lower molecular weight hydrocarbons. These reactions can be favored by the addition of a catalyst during steam injection; in this way, it is possible to generate the original oil in situ upgrading through the production increase of molecules of lower molecular weight. This additional effect could increase the oil recovery factor and reduce costs in transport and refining stages. Therefore, this research has focused on the experimental evaluation of the catalytic aquathermolysis on a Colombian heavy oil with 12,8°API. The effects of three different catalysts, reaction time, and temperature were evaluated in a batch microreactor. The changes in the Colombian heavy oil were quantified through nuclear magnetic resonance 1H-NMR. The relaxation times interpretation and the absorption intensity allowed to identify the distribution of the functional groups in the base oil and upgraded oils. Additionally, the average number of aliphatic carbons in alkyl chains, the number of substituted rings, and the aromaticity factor were established as average structural parameters in order to simplify the samples' compositional analysis. The first experimental stage proved that each catalyst develops a different reaction mechanism. The aromaticity factor has an increasing order of the salts used: Mo > Fe > Ni. However, the upgraded oil obtained with iron naphthenate tends to form a higher content of mono-aromatic and lower content of poly-aromatic compounds. On the other hand, the results obtained from the second phase of experiments suggest that the upgraded oils have a smaller difference in the length of alkyl chains in the range of 240º to 270°C. This parameter has lower values at 300°C, which indicates that the alkylation or cleavage reactions of alkyl chains govern at higher reaction temperatures. The presence of condensation reactions is supported by the behavior of the aromaticity factor and the bridge carbons production between aromatic rings (RCH₂). Finally, it is observed that there is a greater dispersion in the aliphatic hydrogens, which indicates that the alkyl chains have a greater reactivity compared to the aromatic structures.

Keywords: catalyst, upgrading, aquathermolysis, steam

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Authors: D: Gupta, M. Radhakrishnan, Y. Kurhe, D. Thangaraj

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Depression is among the leading causes of death worldwide. The current pharmacotherapy is associated with poor compliance, resistance and relapse, which necessitate the development of novel compounds with better efficacy. The present study designed and synthesized EQC-34 (N-cyclohexyl-3-ethoxyquinoxalin-2-carboxamide) as novel serotonin type-3 (5HT3) antagonist and evaluated its antidepressant-like effects using neurobehavioral mouse model. 5HT3 antagonism (as pA2 value) was determined on the longitudinal smooth muscle of guinea-pig ileum against 2-methyl-5HT (a 5HT3 agonist). The doses were calculated by dose response of basal locomotor activity. Consequently, effects of EQC-34 on neurobehavioral parameters were measured in forced swim (FST) and tail suspension test (TST). The possible mechanism was estimated by interaction study with fluoxetine (a selective serotonin reuptake inhibitor) and mCPBG (1-(m-chlorophenyl)-biguanide, a selective 5HT3 agonist), and confirmed by potentiation of head twitch response by 5hydroxy-L-tryptophan (5HTP). EQC-34 (1-4 mg/kg, i.p.) produced significant decreased behavioral despair effects in FST and TST. It potentiated fluoxetine response, while mCPBG reduced EQC-34 activity in FST. Further, EQC-34 potentiated 5HTP induced head twitch response. EQC-34 revealed potential antidepressant-like effects, which may involve 5HT3 receptor mediated facilitation of 5HT neurotransmission, thereby reversing the pathological deficiency of monoamines (5HT) observed in depression. Thus, it may be further investigated as promising agent to improve therapeutics of depression.

Keywords: depression, forced swim test, 5HT3 receptor antagonist, serotonin

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Authors: Aurélia Jandot

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With the oil and economic crises which began in the 1970’s, it has progressively appeared necessary to convince the French “general public“ that a use of new energy sources was essential. In this field, nuclear energy represented the future and concentrated lots of hopes. However, the discourse about nuclear energy has progressively seen negative arguments growing in the French media. The gradual changes in the perception of nuclear energy will be studied here through the arguments given in the main French weekly newsmagazines, which had a great impact on the readers, thus on the “general public“, from the 1970’s to the end of the 1980’s. Indeed, to understand better these changes will be taken into account the major international events, the reorientations of the French domestic policy, and the evolutions of the nuclear technology. As this represents a considerable amount of copies and thus of information, will be selected here the main articles which emphasize the “mental images“ aiming to direct the thought of the readers, and which have led the public awareness and acceptance to evolve. From the 1970’s to the end of the 1980’s, two dichotomous trends are in confrontation : one is promoting the perception of the nuclear energy, the other is discrediting it. Moreover, these two trends are organized in two axes. The first axis is about the engineerings evolutions, such as the main French media represent them, with its approximations, its exaggerations, its fictions sometimes. Is added the will to make accessible to the “general public“ some concepts which are quite difficult to understand for the largest number. The second axis rests on the way the major accidents of the period are approached, including those of Three Mile Island and Chernobyl. Thanks to these accidents and because of the international relations evolutions, the ecologist movements and their impacts have progressively grown, with evident consequences on the public perception of nuclear energy and on the way the successive governments can implement new power plants in France. Then, in both cases, over the period considered, the language has changed, as the perceptible objectives of the communication, allowing to discern the deepest intentions of the newsmagazines editing. This is all these changes that will be emphasized, over a period where the nuclear energy technology, to there a field for specialists, bearing mystery and secret, has become a social issue seemingly open to all.

Keywords: social issues, public acceptance, mediatization, discourse changes

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Authors: S. S. Nafee, A. M. Al-Ramady, S. A. Shaheen

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Evaluated nuclear decay data for the 217Po nuclide ispresented in the present work. These data include recommended values for the half-life T1/2, α-, β--, and γ-ray emission energies and probabilities. Decay data from 221Rn α and 217Bi β—decays are presented. Q(α) has been updated based on the recent published work of the Atomic Mass Evaluation AME2012. In addition, the logft values were calculated using the Logft program from the ENSDF evaluation package. Moreover, the total internal conversion electrons has been calculated using Bricc program. Meanwhile, recommendation values or the multi-polarities have been assigned based on recently measurement yield a better intensity balance at the 254 keV and 264 keV gamma transitions.

Keywords: nuclear decay data evaluation, mass evaluation, total converison coefficients, atomic mass evaluation

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Authors: Amr A. Fouad, Waleed H. Albuali, Iyad Jresat

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The protective effect of hesperidin was investigated in rats exposed to liver injury induced by a single intraperitoneal injection of cyclophosphamide (CYP) at a dose of 150 mg kg-1. Hesperidin treatment (100 mg kg-1/day, orally) was applied for seven days, starting five days before CYP administration. Hesperidin significantly decreased the CYP-induced elevations of serum alanine aminotransferase, and hepatic malondialdehyde and myeloperoxidase activity, significantly prevented the depletion of hepatic glutathione peroxidase activity resulted from CYP administration. Also, hesperidin ameliorated the CYP-induced liver tissue injury observed by histopathological examination. In addition, hesperidin decreased the CYP-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, Fas ligand, and caspase-9 in liver tissue. It was concluded that hesperidin may represent a potential candidate to protect against CYP-induced hepatotoxicity.

Keywords: hesperidin, cyclophosphamide, liver, rats

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Authors: Hu-Jiang Shi, Li-Juan Zhu

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The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in affective behaviors is a topic of debate, and the underlying mechanisms remain largely unclear. Here, we elucidate that the interaction between hippocampal neuronal nitric oxide synthase (nNOS) and carboxy-terminal PDZ ligand of nNOS (CAPON) contributes to the disruption of hippocampal excitation-inhibition (E/I) balance, which is responsible for the anxiety- and depressive-like behaviors caused by chronic stress-related 5-HT2CR signaling deficiency. In detail, activation or inhibition of 5-HT2CR by CP809101 or SB242084 modulates nNOS-CAPON interaction by influencing intracellular Ca²⁺ release. Notably, the dissociation of nNOS-CAPON abolishes SB242084-induced anxiety- and depressive-like behaviors, as well as the reduction in extracellular signal-regulated kinase (ERK)/cAMP-response element binding protein (CREB)/synapsin signaling and SNARE complex assembly. Furthermore, nNOS-CAPON blockers restore the impairments caused by SB242084, including the reduction in SNARE assembly-mediated γ-aminobutyric acid (GABA) vesicle release and a consequent shift of the E/I balance toward excitation in CA3 pyramidal neurons. Conclusively, our findings disclose the regulatory role of 5-HT2CR in anxiety- and depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.

Keywords: 5-HT2CR, anxiety, depression, nNOS-CAPON coupling, excitation-inhibition balance, neurotransmitter release

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Authors: Rabia Göçmen, Gülşah Kanbur, Sinan Sefa Parlat

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In this study, in the breeding Japanese quails (coturnix coturnix japonica), it was aimed to study the effects of cellular insulin receptor stimulation on the performance, some blood parameters, and hatchability features. In the study, a total of 84 breeding quails were used, which are in 6 weeks age, and whose 24 are male and 60 female. In the trial, rations which contain 2900 kcal/kg metabolic energy; crude protein of 20%, and water whose pH is calibrated to 7.45 were administered as ad-libitum, to the animals, as metformin source, metformin-HCl was used and as chrome resource, Chromium Picolinate. Trial groups were formed as control group (basal ration), metformin group (basal ration, added metformin at the level of fodder of 20 mg/kg), and chromium picolinate group (basal ration, added fodder of 1500 ppb Cr. When regarded to the results of performance at the end of trial, it is seen that live weight gain, fodder consumption, egg weight, fodder evaluation coefficient, and egg production were affected at the significant level (p < 0.05). When the results are evaluated in terms of incubation features at the end of trial, it was identified that incubation yield and hatchability are not affected by the treatments but in the groups, in which metformin and chromium picolinate are added to ration, that fertility rose at the significant level compared to control group (p < 0,05). According to the results of blood parameters and hormone at the end of the trial, while the level of plasma glucose level was not affected by treatments (p > 0.05), with the addition of metformin and chromium picolinate to ration, plasma, total control, cholesterol, HDL, LDL, and triglyceride levels were significantly affected from insulin receptor stimulators added to ration (p<0,05). Hormone level of Plasma T3 and T4 were also affected at the significant level from insulin receptor stimulators added to ration (p < 0,05).

Keywords: cholesterol, chromium picolinate, hormone, metformin, performance, quail

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Authors: Fangtian Fan, Zhaoguo Liu, Yin Lu

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Early recurrence (ER) (< 1 year) after liver resection is one of the most important factors that impacts the prognosis of patients with hepatocellular carcinoma (HCC). However, the molecular mechanisms and predictive indexes of ER after curative resection remain largely unknown. The present study aimed to exploit the role of EGFR signaling in EMT and early recurrence of HCC after curative resection and elucidate the molecular mechanisms. Our results showed that nuclear beta-catenin / PKM2 was a independent predictor of early recurrence after curative resection in EGFR-overexpressed HCC. Mechanistic investigation indicated that nuclear accumulation of beta-catenin and PKM2 induced by EGFR signal promoted HCC cell invasion and proliferation, which were required for early recurrence of HCC. These effects were mediated by PI3K/AKT and ERK pathways rather than the canonical Wnt signaling. In conclusions, EGFR signal induced-nuclear translocation of beta-catenin and PKM2 promotes HCC malignancy and indicates early recurrence after curative resection.

Keywords: beta-catenin, early recurrence, hepatocellular carcinoma, malignancy, PKM2

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Authors: Piyush V. Surjagade, Jiamei Deng, Paul Doney, S. R. Shimjith, A. John Arul

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In sophisticated and complex systems such as nuclear power plants, maintaining the system's stability in the presence of uncertainties and disturbances and obtaining a fast dynamic response are the most challenging problems. Thus, to ensure the satisfactory and safe operation of nuclear power plants, this work proposes a new fast, robust optimal switching control strategy for pressurized water reactor-type nuclear power plants. The proposed control strategy guarantees a substantial degree of robustness, fast dynamic response over the entire operational envelope, and optimal performance during the nominal operation of the plant. To improve the robustness, obtain a fast dynamic response, and make the system optimal, a bank of controllers is designed. Various controllers, like a baseline proportional-integral-derivative controller, an optimal linear quadratic Gaussian controller, and a robust adaptive L1 controller, are designed to perform distinct tasks in a specific situation. At any instant of time, the most suitable controller from the bank of controllers is selected using the switching logic unit that designates the controller by monitoring the health of the nuclear power plant or transients. The proposed switching control strategy optimizes the overall performance and increases operational safety and efficiency. Simulation studies have been performed considering various uncertainties and disturbances that demonstrate the applicability and effectiveness of the proposed switching control strategy over some conventional control techniques.

Keywords: switching control, robust control, optimal control, nuclear power control

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Authors: Yousuf Al Suleimani, Ahmed Al Mahruqi

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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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Authors: Shannen Lorraine, Paul Maragh, Tara Dasgupta, Kamaluddin Abdur-Rashid

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(R)-(4,4',6,6'-tetramethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine) (R-Ph-Garphos), and (S)-(4,4',6,6'-tetramethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine) (S-Ph-Garphos) are novel, nucleophilic, chiral atropisomeric ligands. The research explored the synthesis of chiral transition metal complexes containing these ligands and their applications in various asymmetric catalytic transformations. Herein, the transition metal complexes having ruthenium(II), rhodium(I) and iridium(I) metal centres will be discussed. These are air stable complexes and were characterized by CHN analysis, 1H, 13C, and 31P NMR spectroscopy, and polarimetry. Currently, there is an emphasis on 'greener' catalysts and the need for 'green' solvents in asymmetric catalysis. As such, the Ph-Garphos ligands were demethylated thereby introducing hydroxyl moieties unto the ligand scaffold. The facile tunability of the biaryl diphosphines led to the preparation of the (R)-(4,4',6,6'-tetrahydroxybiphenyl-2,2'-diyl)bis(diphenylphosphine) (R-Ph-Garphos-OH), and (S)-(4,4',6,6'-tetrahydroxybiphenyl-2,2'-diyl)bis(diphenylphosphine) (S-Ph-Garphos-OH) ligands. These were successfully characterized by CHN analysis, 1H, 13C, and 31P NMR spectroscopy, and polarimetry. The use of the Ph-Garphos and Ph-Garphos-OH ligands and their transition metal complexes in asymmetric hydrogenations will be reported. Additionally, the scope of the research will highlight the applicability of the Ph-Garphos-OH ligand and its transitional metal complexes as 'green' catalysts.

Keywords: catalysis, asymmetric hydrogenation, diphosphine transition metal complexes, Ph-Garphos ligands

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Authors: A. Elmajdoub, A. El-Mahmoudy

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The present study was designed to investigate the neurotransmitters that mediate the excitatory response of the circular muscle of final branches of mesenteric artery in bovine calves. Mesentery was dissected and the iliac branches were separated and used. The final mesenteric branches of diameter 400 micrometers and less responded strongly to norepinephrine and moderately to ATP. However, the mesenteric branches of wider diameters were gradually less responsive to norepinephrine and those of diameter 700 micrometers were exclusively nonresponsive. These arteries were strongly responsive to ATP (100 µM). Norepinephrine response was sensitive to phentolamine (3 µM) and prazosin (5 µM) indicating that it is mediated by α1 receptor; while ATP response was sensitive to suramin (200 µM), PPADS (50 µM), but not to cibacron blue (100 µM) indicating that it is mediated via P2X receptor. Further confirmatory experiments were performed including application of α1 and P2X receptor specific agonists which are methoxamine and α,β-methylene ATP. Methoxamine (1 µM) showed effects similar to norepinephrine in final branches and was without effect in wider branches. α,β-methylene ATP (1 µM), exhibited more pronounced effects on both wide and narrow branches but in parallel manner to that of ATP. Agonists for α2 and P2Y receptors as clonidine (10 µM) and 2-meThio ATP (10 µM), respectively, were without effect indicating that involvement of these receptors is unlikely. The neuropeptide-Y (200 nM) did not have any effects on either the narrow or the wide rings. Conclusion: These data may imply that in the most peripheral mesenteric arteries a strong vasopressor power represented by norepinephrine and ATP integration is needed for maintaining peripheral resistance; on the other hand a mild vasopressor power mediated only by ATP is enough to maintain the vascular tone in the relatively central mesenteric branches.

Keywords: ATP, calves, mesenteric artery, norepinephrine

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Authors: Anirban Dey, Sukanta Kumar Dash, Bishnupada Mandal

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Carbondioxide (CO2) is a major greenhouse gas responsible for global warming and fossil fuel power plants are the main emitting sources. Therefore the capture of CO2 is essential to maintain the emission levels according to the standards. Carbon capture and storage (CCS) is considered as an important option for stabilization of atmospheric greenhouse gases and minimizing global warming effects. There are three approaches towards CCS: Pre combustion capture where carbon is removed from the fuel prior to combustion, Oxy-fuel combustion, where coal is combusted with oxygen instead of air and Post combustion capture where the fossil fuel is combusted to produce energy and CO2 is removed from the flue gases left after the combustion process. Post combustion technology offers some advantage as existing combustion technologies can still be used without adopting major changes on them. A number of separation processes could be utilized part of post –combustion capture technology. These include (a) Physical absorption (b) Chemical absorption (c) Membrane separation (d) Adsorption. Chemical absorption is one of the most extensively used technologies for large scale CO2 capture systems. The industrially important solvents used are primary amines like Monoethanolamine (MEA) and Diglycolamine (DGA), secondary amines like diethanolamine (DEA) and Diisopropanolamine (DIPA) and tertiary amines like methyldiethanolamine (MDEA) and Triethanolamine (TEA). Primary and secondary amines react fast and directly with CO2 to form stable carbamates while Tertiary amines do not react directly with CO2 as in aqueous solution they catalyzes the hydrolysis of CO2 to form a bicarbonate ion and a protonated amine. Concentrated Piperazine (PZ) has been proposed as a better solvent as well as activator for CO2 capture from flue gas with a 10 % energy benefit compared to conventional amines such as MEA. However, the application of concentrated PZ is limited due to its low solubility in water at low temperature and lean CO2 loading. So following the performance of PZ its derivative 2-Aminoethyl piperazine (AEP) which is a cyclic amine can be explored as an activator towards the absorption of CO2. Vapour liquid equilibrium (VLE) in CO2 capture systems is an important factor for the design of separation equipment and gas treating processes. For proper thermodynamic modeling accurate equilibrium data for the solvent system over a wide range of temperatures, pressure and composition is essential. The present work focuses on the determination of VLE data for (AEP + H2O) system at 40 °C for various composition range.

Keywords: absorption, aminoethyl piperazine, carbondioxide, vapour liquid equilibrium

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