Search results for: mixed ligand complexes

Authors: P. Hooshangitabrizi, I. Contreras, N. Bhuiyan

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This work presents an online scheduling problem which accommodates multiple requests of patients for chemotherapy treatments in a cancer center of a major metropolitan hospital in Canada. To solve the problem, an adaptive flexible approach is proposed which systematically combines two optimization models. The first model is intended to dynamically schedule arriving requests in the form of waiting lists whereas the second model is used to reschedule the already booked patients with the goal of finding better resource allocations when new information becomes available. Both models are created as mixed integer programming formulations. Various controllable and flexible parameters such as deviating the prescribed target dates by a pre-determined threshold, changing the start time of already booked appointments and the maximum number of appointments to move in the schedule are included in the proposed approach to have sufficient degrees of flexibility in handling arrival requests and unexpected changes. Several computational experiments are conducted to evaluate the performance of the proposed approach using historical data provided by the oncology clinic. Our approach achieves outstandingly better results as compared to those of the scheduling system being used in practice. Moreover, several analyses are conducted to evaluate the effect of considering different levels of flexibility on the obtained results and to assess the performance of the proposed approach in dealing with last-minute changes. We strongly believe that the proposed flexible adaptive approach is very well-suited for implementation at the clinic to provide better patient-care services and to utilize available resource more efficiently.

Keywords: chemotherapy scheduling, multi-appointment modeling, optimization of resources, satisfaction of patients, mixed integer programming

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Authors: Joanna Marie A. Paulino-Morente, Vaneza Valentina L. Penolio, Grace Sabado

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Ovarian cancer is extremely hard to diagnose in its early stages, and those afflicted at the time of diagnosis are typically asymptomatic and in the late stages of the disease, with metastasis to other organs. Ovarian cancers often occur sporadically, with only 5% associated with hereditary mutations. Mutations in the BRCA1 and BRCA2 tumor suppressor genes have been found to be responsible for the majority of hereditary ovarian cancers. One type of ovarian tumor is Malignant Mixed Mullerian Tumor (MMMT), which is a very rare and aggressive type, accounting for only 1% of all ovarian cancers. Reported is a case of a 43-year-old G3P3 (3003), who came into our institution due to a 2-month history of difficulty of breathing. Family history reveals that her eldest and younger sisters both died of ovarian malignancy, with her younger sister having a histopathology report of endometrioid ovarian carcinoma, left ovary stage IIIb. She still has 2 asymptomatic sisters. Physical examination pointed to pleural effusion of right lung, and presence of bilateral ovarian new growth, which had a Sassone score of 13. Admitting Diagnosis was G3P3 (3003), Ovarian New Growth, bilateral, Malignant; Pleural effusion secondary to malignancy. BRCA was requested to establish a hereditary mutation; however, the patient had no funds. Once the patient was stabilized, TAHBSO with surgical staging was performed. Intraoperatively, the pelvic cavity was occupied by firm, irregularly shaped ovaries, with a colorectal metastasis. Microscopic sections from both ovaries and the colorectal metastasis had pleomorphic tumor cells lined by cuboidal to columnar epithelium exhibiting glandular complexity, displaying nuclear atypia and increased nuclear-cytoplasmic ratio, which are infiltrating the stroma, consistent with the features of Malignant Mixed Mullerian Tumor, since MMMT is composed histologically of malignant epithelial and sarcomatous elements. In conclusion, discussed is the clinic-pathological feature of a patient with primary ovarian Malignant Mixed Mullerian Tumor, a rare malignancy comprising only 1% of all ovarian neoplasms. Also, by understanding the hereditary ovarian cancer syndromes and its relation to this patient, it cannot be overemphasized that a comprehensive family history is really fundamental for early diagnosis. The familial association of the disease, given that the patient has two sisters who were diagnosed with an advanced stage of ovarian cancer and succumbed to the disease at a much earlier age than what is reported in the general population, points to a possible hereditary syndrome which occurs in only 5% of ovarian neoplasms. In a low-resource setting, being in a third world country, the following will be recommended for monitoring and/or screening women who are at high risk for developing ovarian cancer, such as the remaining sisters of the patient: 1) Physical examination focusing on the breast, abdomen, and rectal area every 6 months. 2) Transvaginal sonography every 6 months. 3) Mammography annually. 4) CA125 for postmenopausal women. 5) Genetic testing for BRCA1 and BRCA2 will be reserved for those who are financially capable.

Keywords: BRCA, hereditary breast-ovarian cancer syndrome, malignant mixed mullerian tumor, ovarian cancer

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Authors: Neha Awasthi, Ujjwal Kumar

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Density of large carnivores is primarily dictated by the density of their prey. Therefore, optimal management of ungulates populations permits harbouring of viable large carnivore populations within protected areas. Ungulate density is likely to respond to regimes of protection and vegetation types. This has generated the need among conservation practitioners to obtain strata specific seasonal species densities for habitat management. Kanha Tiger Reserve (KTR) of 2074 km2 area comprises of two distinct management strata: The core (940 km2), devoid of human settlements and buffer (1134 km2) which is a multiple use area. In general, four habitat strata, grassland, sal forest, bamboo-mixed forest and miscellaneous forest are present in the reserve. Stratified sampling approach was used to access a) impact of human use and b) effect of habitat and season on ungulate densities. Since 2013 to 2016, ungulates were surveyed in winter and summer of each year with an effort of 1200 km walk in 200 spatial transects distributed throughout Kanha Tiger Reserve. We used a single detection function for each species within each habitat stratum for each season for estimating species specific seasonal density, using program DISTANCE. Our key results state that the core area had 4.8 times higher wild ungulate biomass compared with the buffer zone, highlighting the importance of undisturbed area. Chital was found to be most abundant, having a density of 30.1(SE 4.34)/km2 and contributing 33% of the biomass with a habitat preference for grassland. Unlike other ungulates, Gaur being mega herbivore, showed a major seasonal shift in density from bamboo-mixed and sal forest in summer to miscellaneous forest in winter. Maximum diversity and ungulate biomass were supported by grassland followed by bamboo-mixed habitat. Our study stresses the importance of inviolate core areas for achieving high wild ungulate densities and for maintaining populations of endangered and rare species. Grasslands accounts for 9% of the core area of KTR maintained in arrested stage of succession, therefore enhancing this habitat would maintain ungulate diversity, density and cater to the needs of only surviving population of the endangered barasingha and grassland specialist the blackbuck. We show the relevance of different habitat types for differential seasonal use by ungulates and attempt to interpret this in the context of nutrition and cover needs by wild ungulates. Management for an optimal habitat mosaic that maintains ungulate diversity and maximizes ungulate biomass is recommended.

Keywords: distance sampling, habitat management, ungulate biomass, diversity

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Authors: H. Yousefnia, S. Zolghadri, A. Golabi Dezfuli

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Tris (1,10-phenanthroline) lanthanum(III)] trithiocyanate is a new compound that has shown to stop DNA synthesis in CCRF-CEM and Ehrlich ascites cells leading to a cell cycle arrest in G0/G1. One other important property of the phenanthroline nucleus is its ability to act as a triplet-state photosensitizer especially in complexes with lanthanides. In Nowadays, the radiation dose assessment resource (RADAR) method is known as the most common method for absorbed dose calculation. 177Lu was produced by irradiation of a natural Lu2O3 target at a thermal neutron flux of approximately 4 × 1013 n/cm2•s. 177Lu-PL3 was prepared in the optimized condition. The radiochemical yield was checked by ITLC method. The biodistribution of the complex was investigated by intravenously injection to wild-type rats via their tail veins. In this study, the absorbed dose of 177Lu-PL3 to human organs was estimated by RADAR method. 177Lu was prepared with a specific activity of 2.6-3 GBq.mg-1 and radionuclide purity of 99.98 %. The 177Lu-PL3 complex can prepare with high radiochemical yield (> 99 %) at optimized conditions. The results show that liver and spleen have received the highest absorbed dose of 1.051 and 0.441 mSv/MBq, respectivley. The absorbed dose values for these two dose-limiting tissues suggest more biological studies special in tumor-bearing animals.

Keywords: internal dosimetry, Lutetium-177, radar, animals

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Authors: Abbas R. Ali, Daroon Hasan Khorsheed

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Twenty one samples of stream sediments were collected from the Diyala River Basin (DRB), which represent one of three major tributaries of the Tigris River at northeastern Iraq. This study is concerned with the heavy minerals (HM) analysis in the + 63μ m fraction of the Diyala River sediments, distribution pattern in the various river basin sectors, as well as comparing the present results with previous works.The metastable heavy minerals (epidote, staurolite, garnet) represent more than (30%) Whereas the ultrastable heavy minerals (pyroxene and amphibole) make only about (19 %). Opaques are present in high proportions reaching about (29%) as an average. The ultrastable (zircon, tourmaline, rutile) heavy minerals are the miner constituents (7%) in the sediments.According to the laboratory analytical data of heavy mineral distributions the studied sediments are derived from mafic and ultramafic rocks are found in northeastern Iraq that represent Walash – Nawpordan Series and Mawat complexes in Zagros zones. The presence of zircon and tourmaline in trace amounts may give an indication for the weak role of acidic rocks in the source area whereas the epidote group minerals give an indication for the role of metamorphic rocks.

Keywords: heavy minerals, mineral distribution, recent stream sediment, Diyala river, northeastern Iraq

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Authors: H. Yousefnia, S. Zolghadri

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The measurement of organ radiation exposure dose is one of the most important steps to be taken initially, for developing a new radiopharmaceutical. In this study, the dosimetric studies of a novel agent for SPECT-imaging of the bone metastasis, 111In-1,4,7,10-tetraazacyclododecane-1,4,7,10 tetraethylene phosphonic acid (111In-DOTMP) complex, have been carried out to estimate the dose in human organs based on the data derived from rats. The radiolabeled complex was prepared with high radiochemical purity in the optimal conditions. Biodistribution studies of the complex was investigated in the male Syrian rats at selected times after injection (2, 4, 24 and 48 h). The human absorbed dose estimation of the complex was made based on data derived from the rats by the radiation absorbed dose assessment resource (RADAR) method. 111In-DOTMP complex was prepared with high radiochemical purity of >99% (ITLC). Total body effective absorbed dose for 111In-DOTMP was 0.061 mSv/MBq. This value is comparable to the other 111In clinically used complexes. The results show that the dose with respect to the critical organs is satisfactory within the acceptable range for diagnostic nuclear medicine procedures. Generally, 111In-DOTMP has interesting characteristics and can be considered as a viable agent for SPECT-imaging of the bone metastasis in the near future.

Keywords: In-111, DOTMP, Internal Dosimetry, RADAR

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Authors: R. S. Yadav, J. Havlica, I. Kuřitka, Z. Kozakova, J. Masilko, M. Hajdúchová, V. Enev, J. Wasserbauer

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In this work, the effect of particle size on the structural and magnetic properties of CoFe2-xGdxO4 (x =0.1) spinel ferrite nanoparticles synthesized by starch-assisted sol-gel auto combustion method was investigated. The different sized CoFe2-xGdxO4 (x =0.1) spinel ferrite nanoparticles were achieved after annealing at different temperature 500, 700 and 900 oC. The structural phases, crystallite size and lattice parameter of synthesized ferrite nanoparticles were estimated from X-ray diffraction studies. The field emission scanning electron microscopy study demonstrated increase in particle size with increase of annealing temperature. Raman spectroscopy study indicated the change in octahedral and tetrahedral site related Raman modes in Gd3+ ions doped cobalt ferrite nanoparticles. An infrared spectroscopy study showed the presence of two absorption bands in the frequency range around 580 cm-1 (ν1) and around 340 cm-1 (ν2); which indicated the presence of tetrahedral and octahedral group complexes, respectively, within the spinel ferrite nanoparticles. Vibrating Sample magnetometer study showed that the saturation magnetization and coercivity changes with particle size of CoFe2-xGdxO4 (x =0.1) spinel ferrite.

Keywords: magnetic properties, spinel ferrite, nanoparticles, sol-gel synthesis

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Authors: Arunima Verma, Padmabati Mondal

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Serotonin-receptor binding plays a key role in several neurological and biological processes, including mood, sleep, hunger, cognition, learning, and memory. In this article, we performed molecular dynamics simulation to examine the key residues that play an essential role in the binding of serotonin to the G-protein-coupled 5-HT₁ᴮ receptor (5-HT₁ᴮ R) via electrostatic interactions. An end-point free energy calculation method (MM-PBSA) determines the stability of the 5-HT1B R due to serotonin binding. The single-point mutation of the polar or charged amino acid residues (Asp129, Thr134) on the binding sites and the calculation of binding free energy validate the importance of these residues in the stability of the serotonin-receptor complex. Principal component analysis indicates the serotonin-bound 5-HT1BR is more stabilized than the apo-receptor in terms of dynamical changes. The difference dynamic cross-correlations map shows the correlation between the transmembrane and mini-Go, which indicates signal transduction happening between mini-Go and the receptor. Allosteric communication reveals the key nodes for signal transduction in 5-HT1BR. These results provide useful insights into the signal transduction pathways and mutagenesis study to regulate the functionality of the complex. The developed protocols can be applied to study local non-covalent interactions and long-range allosteric communications in any protein-ligand system for computer-aided drug design.

Keywords: allostery, CADD, MD simulations, MM-PBSA

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Authors: Fatemeh Soltani, Simindokht Shirvani Arani, Ali Bahrami Samani, Mahdi Sadeghi, Kamal Yavari

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Cerium-141 [T1/2 = 32.501 days, Eβ (max) = 0.580 (29.8%) and 0.435(70.2%) MeV, Eγ=145.44 (48.2%) keV] possesses radionuclidic properties suitable for use in palliative therapy of bone metastases. 141Ce also has gamma energy of 145.44 keV, which resembles that of 99mTc. Therefore, the energy window is adjustable on the Tc-99m energy because of imaging studies. 141Ce can be produced through a relatively easy route that involves thermal neutron bombardment on natural CeO2 in medium flux research reactors (4–5×1013 neutrons/cm2•s). The requirement for an enriched target does not arise. Ethylenediamine tetramethylene phosphonic acid (EDTMP) was synthesized and radiolabeled with 141Ce. Complexation parameters were optimized to achieve maximum yields (>99%). The radiochemical purity of 141Ce-EDTMP was evaluated by radio-thin layer chromatography. The stability of the prepared formulation was monitored for one week at room temperature, and results showed that the preparation was stable during this period (>99%). Biodistribution studies of the complexes carried out in wild-type rats exhibited significant bone uptake with rapid clearance from blood. The properties of produced 141Ce-EDTMP suggest applying a new efficient bone pain palliative therapeutic agent to overcome metastatic bone pains.

Keywords: bone pain palliative, cerium-141, EDTMP, radiopharmaceutical

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Authors: Zixuan Zhao, Lingbin Du, Le Wang, Youqing Wang, Yi Yang, Jingjun Chen, Hengjin Dong

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Objectives: Few results from public attitudes for lung cancer screening are available both in China and abroad. This study aimed to identify preferred lung cancer screening modalities in a Chinese population and predict uptake rates of different modalities. Materials and Methods: A discrete choice experiment questionnaire was administered to 392 Chinese individuals aged 50–74 years who were at high risk for lung cancer. Each choice set had two lung screening options and an option to opt-out, and respondents were asked to choose the most preferred one. Both mixed logit analysis and stepwise logistic analysis were conducted to explore whether preferences were related to respondent characteristics and identify which kinds of respondents were more likely to opt out of any screening. Results: On mixed logit analysis, attributes that were predictive of choice at 1% level of statistical significance included the screening interval, screening venue, and out-of-pocket costs. The preferred screening modality seemed to be screening by low-dose computed tomography (LDCT) + blood test once a year in a general hospital at a cost of RMB 50; this could increase the uptake rate by 0.40 compared to the baseline setting. On stepwise logistic regression, those with no endowment insurance were more likely to opt out; those who were older and housewives/househusbands, and those with a health check habit and with commercial endowment insurance were less likely to opt out from a screening programme. Conclusions: There was considerable variance between real risk and self-perceived risk of lung cancer among respondents, and further research is required in this area. Lung cancer screening uptake can be increased by offering various screening modalities, so as to help policymakers further design the screening modality.

Keywords: lung cancer, screening, China., discrete choice experiment

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Authors: Amal Aljohani, Ahmed Iraqi

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Emitting materials with thermally activated delayed fluorescence (TADF) properties as the third generation of organic light-emitting diodes (OLEDs) have received much attention as a modern class of highly efficient emitters because such properties enable the harvesting of both singlet and triplet excitons in EL applications without the doping with complexes of scarce noble metals such as platinum and iridium. Improved molecular design of TADF molecules and applied materials exhibiting internal electroluminescence (EL) with quantum efficiencies of nearly 100% has been achieved being. A2B3 hyperbranched polymers based on new derivatives containing silane core units serving as host materials for thermally activated delayed fluorescence (TADF) guest molecules have been designed and synthesized through several steps, including the synthesis of tetrakis(4-bromophenyl)silane, bis(4-(9H-carbazol-9-yl)phenyl)bis(4-bromophenyl)silane,bis(4-(9H-carbazol-9 yl)phenyl)bis(4-methoxyphenyl)silane and bis(4-(9H-carbazol-9-yl)phenyl)bis(4hydroxyphenyl)silane. This monomer has been used successfully used along with 1,1,1-tri-(p-tosyloxymethyl)-propane to prepare A2B3 hyperbranched polymers via step-growth polymerization. The characterization and the properties of these new host polymers will be presented and discussed in this contribution.

Keywords: carbazole, organic light emitting diodes, thermally activated delayed fluorescence, donor-acceptor, host and guest interaction

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Authors: Alain Gholam

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Visual thinking routines are principles based on several theories, approaches, and strategies. Such routines promote thinking skills, call for collaboration and sharing of ideas, and above all, make thinking and learning visible. Visual thinking routines were implemented in the teaching methodology graduate course at the American University in Dubai. The study used mixed methods. It was guided by the following two research questions: 1). To what extent do visual thinking inspire learning in the classroom, and make time for students’ questions, contributions, and thinking? 2). How do visual thinking routines inspire learning in the classroom and make time for students’ questions, contributions, and thinking? Eight student teachers enrolled in the teaching methodology course at the American University in Dubai (Spring 2017) participated in the following study. First, they completed a survey that measured to what degree they believed visual thinking routines inspired learning in the classroom and made time for students’ questions, contributions, and thinking. In order to build on the results from the quantitative phase, the student teachers were next involved in a qualitative data collection phase, where they had to answer the question: How do visual thinking routines inspire learning in the classroom and make time for students’ questions, contributions, and thinking? Results revealed that the implementation of visual thinking routines in the classroom strongly inspire learning in the classroom and make time for students’ questions, contributions, and thinking. In addition, student teachers explained how visual thinking routines allow for organization, variety, thinking, and documentation. As with all original, new, and unique resources, visual thinking routines are not free of challenges. To make the most of this useful and valued resource, educators, need to comprehend, model and spread an awareness of the effective ways of using such routines in the classroom. It is crucial that such routines become part of the curriculum to allow for and document students’ questions, contributions, and thinking.

Keywords: classroom display, student engagement, thinking classroom, visual thinking routines

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Authors: Shalini Singh, Sanjay K. Srivastava, Govind, Mukhtar. A. Khan, P. K. Singh

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Nanotechnology is revolutionizing the development of biosensors. Nanomaterials and nanofabrication technologies are increasingly being used to design novel biosensors. Sensitivity and other attributes of biosensors can be improved by using nanomaterials with unique chemical, physical, and mechanical properties in their construction. Silicon is a promising biomaterial that is non-toxic and biodegradable and can be exploited in chemical and biological sensing. Present study demonstrated the streptavidin–biotin interaction on silicon surfaces with different topographies such as flat and nanostructured silicon (nanowires) surfaces. Silicon nanowires with wide range of surface to volume ratio were prepared by electrochemical etching of silicon wafer. The large specific surface of silicon nanowires can be chemically modified to link different molecular probes (DNA strands, enzymes, proteins and so on), which recognize the target analytes, in order to enhance the selectivity and specificity of the sensor device. The interaction of streptavidin with biotin was carried out on 3-aminopropyltriethoxysilane (APTS) functionalized silicon surfaces. Fourier Transform Infrared Spectroscopy (FTIR) and X-ray Photoelectron Spectroscopy (XPS) studies have been performed to characterize the surface characteristics to ensure the protein attachment. Silicon nanowires showed the enhance protein attachment, as compared to flat silicon surface due to its large surface area and good molecular penetration to its surface. The methodology developed herein could be generalized to a wide range of protein-ligand interactions, since it is relatively easy to conjugate biotin with diverse biomolecules such as antibodies, enzymes, peptides, and nucleotides.

Keywords: FTIR, silicon nanowires, streptavidin-biotin, XPS

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Authors: Maggie Mosher, Adam Carreon, Sean Smith

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A systematic literature review was conducted to explore the evidence base on the use of augmented reality (AR), virtual reality (VR), mixed reality (MR), and extended reality (XR) to present social skill instruction to school-age students with autism spectrum disorder (ASD). Specifically, the systematic review focus was on a. the participants and intervention agents using AR, VR, MR, and XR for social skill acquisition b. the social skills taught through these mediums and c. the social validity measures (i.e., goals, procedures, and outcomes) reported in these studies. Forty-one articles met the inclusion criteria. Researchers in six studies taught social skills to students through AR, in 27 studies through non-immersive VR, and in 10 studies through immersive VR. No studies used MR or XR. The primary targeted social skills were relationship skills, emotion recognition, social awareness, cooperation, and executive functioning. An intervention to improve many social skills was implemented by 73% of researchers, 17% taught a single skill, and 10% did not clearly state the targeted skill. The intervention was considered effective in 26 of the 41 studies (63%), not effective in four studies (10%), and 11 studies (27%) reported mixed results. No researchers reported information for all 17 social validity indicators. The social validity indicators reported by researchers ranged from two to 14. Social validity measures on the feelings toward and use of the technology were provided in 22 studies (54%). Findings indicated both AR and VR are promising platforms for providing social skill instruction to students with ASD. Studies utilizing this technology show a number of social validity indicators. However, the limited information provided on the various interventions, participant characteristics, and validity measures, offers insufficient evidence of the impact of these technologies in teaching social skills to students with ASD. Future research should develop a protocol for training treatment agents to assess the role of different variables (i.e., whether agents are customizing content, monitoring student learning, using intervention specific vocabulary in their day to day instruction). Sustainability may be increased by providing training in the technology to both treatment agents and participants. Providing scripts of instruction occurring within the intervention would provide the needed information to determine the primary method of teaching within the intervention. These variables play a role in maintenance and generalization of the social skills. Understanding the type of feedback provided would help researchers determine if students were able to feel rewarded for progressing through the scenarios or if students require rewarding aspects within the intervention (i.e., badges, trophies). AR has the potential to generalize instruction and VR has the potential for providing a practice environment for performance deficits. Combining these two technologies into a mixed reality intervention may provide a more cohesive and effective intervention.

Keywords: autism, augmented reality, social and emotional learning, social skills, virtual reality

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Authors: S. Benessam, T. H. Debieche, S. Amiour, A. Chine, S. Khelili

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Iron is naturally present in groundwater, it comes from the dissolution of the geological formations (clay, schist, mica-schist, gneiss…). Its chemical form and mobility in water are controlled mainly by two physicochemical parameters (Eh and pH). In order to determine its spatiotemporal evolution in groundwater, a two-monthly monitoring of the physicochemical parameters and major elements in the water of the alluvial sheet of Nil river (North-eastern Algerian) was carried out during the period from November 2013 to January 2015. The results show that iron is present in weak concentrations in the upstream part of the alluvial sheet and with raised concentrations, which can exceed the standard of potable drinking water (0.2 mg/L), in the central and downstream parts of the alluvial sheet. This variation of the concentrations is related to the important variation of Eh between the upstream part (200 mV) where the aquiver is unconfined (oxidizing medium) and the central and downstream parts (-100 mV) where the aquifer is confined (reducing medium). Iron in the oxidizing part is presented with the complexes form, where it precipitates or/and adsorbed by the geological formations. On the other hand in the reducing parts, it is released in water. In this study, one will discuss also the mobility and the chemical forms of iron according to the rains and pumping.

Keywords: groundwater, iron, mobility, speciation

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Authors: Mathumalar Loganathan, Lina Syazana, Bryony Dean Franklin

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Background: The therapeutic benefit of self-administered medication for long-term use is limited by an average 50% non-adherence rate. Patient forgetfulness is a common factor in unintentional non-adherence. With a growing ageing population, strategies to improve self-administration of medication adherence are essential. Our aim was to review systematically the effects of interventions to optimise self-administration of medication. Method: Database searched were MEDLINE, EMBASE, PsynINFO, CINAHL from 1980 to 31 October 2013. Search terms included were ‘self-administration’, ‘self-care’, ‘medication adherence’, and ‘intervention’. Two independent reviewers undertook screening and methodological quality assessment, using the Downs and Black rating scale. Results: The search strategy retrieved 6 studies that met the inclusion and exclusion criteria. Three intervention strategies were identified: self-administration medication programme (SAMP), nursing education and medication packaging (pill calendar). A nursing education programme focused on improving patients’ behavioural self-management of drug prescribing. This was the most studied area and three studies highlighting an improvement in self-administration of medication. Conclusion: Results are mixed and there is no one interventional strategy that has proved to be effective. Nevertheless, self-administration of medication programme seems to show most promise. A multi-faceted approach and clearer policy guideline are likely to be required to improve prescribing for these vulnerable patients. Mixed results were found for SAMP. Medication packaging (pill calendar) was evaluated in one study showing a significant improvement in self-administration of medication. A meta-analysis could not be performed due to heterogeneity in the outcome measures.

Keywords: self-administered medication, intervention, prescribing, older patients

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Authors: Nargiza Nuralieva

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The study delves into assessing the influence of mindfulness and mental resilience training on the cognitive performance and stress management of pilots. Employing a meticulous literature search across databases such as Medline and Google Scholar, the study used specific keywords to target a wide array of studies. Inclusion criteria were stringent, focusing on peer-reviewed studies in English that utilized designs like randomized controlled trials, with a specific interest in interventions related to mindfulness or mental resilience training for pilots and measured outcomes pertaining to cognitive performance and stress management. The initial literature search identified a pool of 123 articles, with subsequent screening resulting in the exclusion of 77 based on title and abstract. The remaining 54 articles underwent a more rigorous full-text screening, leading to the exclusion of 41. Additionally, five studies were selected from the World Health Organization's clinical trials database. A total of 11 articles from meta-analyses were retained for examination, underscoring the study's dedication to a meticulous and robust inclusion process. The interventions varied widely, incorporating mixed approaches, Cognitive behavioral Therapy (CBT)-based, and mindfulness-based techniques. The analysis uncovered positive effects across these interventions. Specifically, mixed interventions demonstrated a Standardized Mean Difference (SMD) of 0.54, CBT-based interventions showed an SMD of 0.29, and mindfulness-based interventions exhibited an SMD of 0.43. Long-term effects at a 6-month follow-up suggested sustained impacts for both mindfulness-based (SMD: 0.63) and CBT-based interventions (SMD: 0.73), albeit with notable heterogeneity.

Keywords: mindfulness, mental resilience, pilots, cognitive performance, stress management

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Authors: Achilles Kameas, Eleni Georgakakou, Anna Lisa Amodeo, Aideen Quilty, Aisling Malone, Roberta Albertazzi, Moises Carmona, Concetta Esposito, Ruben David Fernandez Carrasco, Carmela Ferrara, Francesco Garzillo, Mojca Pusnik, Maria Cristina Scarano

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While researchers, especially in academia, study and research the phenomena of inclusion of sexual minority and gender marginalized groups, seldom the European Higher Education Institutions (HEI) act on lowering the cultural and educational barriers to their proactive inclusion. The challenge in European HEIs is that gender, and sexual orientation discrimination remains an issue not adequately addressed. Following a mixed methods research design of quantitative and qualitative research techniques and tools, which is applied in five (5) European countries (Italy, Greece, Ireland, Slovenia, and Spain) and that combines desk research, evaluation, and weighting processes for a Matrix-based on Objective indicators and Survey for students and staff of the HEI to gauge the perception of inclusiveness in the HEI context, XENIA HEI Inclusiveness Index is an instrument that will allow universities to gauge and assess their inclusiveness in the domain of discrimination and exclusion based on gender identity and sexual orientation. The index will allow capturing the depth and reach of policies, programmes, and initiatives of HEIs in tackling the phenomena and dynamics of exclusion of LGBT+ (lesbian, gay, bisexual, trans, and other marginalized groups on the basis of gender and sexual identity) and cisgender women exposed to the risk of discrimination.

Keywords: gender identity, higher education, LGBT+ rights, XENIA inclusiveness index

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Authors: Judith Stein, Elfriede Friedmann

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The injection of a drug into the vitreous body for the treatment of retinal diseases like wet aged-related macular degeneration (AMD) is the most common medical intervention worldwide. We develop mathematical models for drug transport in the vitreous body of a human eye to analyse the impact of different rheological models of the vitreous on drug distribution. In addition to the convection diffusion equation characterizing the drug spreading, we use porous media modeling for the healthy vitreous with a dense collagen network and include the steady permeating flow of the aqueous humor described by Darcy's law driven by a pressure drop. Additionally, the vitreous body in a healthy human eye behaves like a viscoelastic gel through the collagen fibers suspended in the network of hyaluronic acid and acts as a drug depot for the treatment of retinal diseases. In a completely liquefied vitreous, we couple the drug diffusion with the classical Navier-Stokes flow equations. We prove the global existence and uniqueness of the weak solution of the developed initial-boundary value problem describing the drug distribution in the healthy vitreous considering the permeating aqueous humor flow in the realistic three-dimensional setting. In particular, for the drug diffusion equation, results from the literature are extended from homogeneous Dirichlet boundary conditions to our mixed boundary conditions that describe the eye with the Galerkin's method using Cauchy-Schwarz inequality and trace theorem. Because there is only a small effective drug concentration range and higher concentrations may be toxic, the ability to model the drug transport could improve the therapy by considering patient individual differences and give a better understanding of the physiological and pathological processes in the vitreous.

Keywords: coupled PDE systems, drug diffusion, mixed boundary conditions, vitreous body

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Authors: H. Shamoradifar, B. Teimuri, P. Parvaresh, S. Mohammadi

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One of the main characteristics of Heavy Water Moderated Reactors is their high production of plutonium. This article demonstrates the possibility of reduction of plutonium and other actinides in Heavy Water Research Reactor. Among the many ways for reducing plutonium production in a heavy water reactor, in this research, changing the fuel from natural Uranium fuel to Thorium-Uranium mixed fuel was focused. The main fissile nucleus in Thorium-Uranium fuels is U-233 which would be produced after neutron absorption by Th-232, so the Thorium-Uranium fuels have some known advantages compared to the Uranium fuels. Due to this fact, four Thorium-Uranium fuels with different compositions ratios were chosen in our simulations; a) 10% UO₂-90% THO₂ (enriched= 20%); b) 15% UO₂-85% THO₂ (enriched= 10%); c) 30% UO₂-70% THO₂ (enriched= 5%); d) 35% UO₂-65% THO₂ (enriched= 3.7%). The natural Uranium Oxide (UO₂) is considered as the reference fuel, in other words all of the calculated data are compared with the related data from Uranium fuel. Neutronic parameters were calculated and used as the comparison parameters. All calculations were performed by Monte Carol (MCNPX2.6) steady state reaction rate calculation linked to a deterministic depletion calculation (CINDER90). The obtained computational data showed that Thorium-Uranium fuels with four different fissile compositions ratios can satisfy the safety and operating requirements for Heavy Water Research Reactor. Furthermore, Thorium-Uranium fuels have a very good proliferation resistance and consume less fissile material than uranium fuels at the same reactor operation time. Using mixed Thorium-Uranium fuels reduced the long-lived α emitter, high radiotoxic wastes and the radio toxicity level of spent fuel.

Keywords: Heavy Water Reactor, Burn up, Minor Actinides, Neutronic Calculation

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Authors: Nimasha Malalasekera

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Working with the indigenous Adivasi (Vedda) community of Dambana in the district of Badulla in Sri Lanka, this research documents linguistic data to address language and cultural endangerment. The ancestral language of Adivasi has undergone sustained restructuration over a long historical period due to its contact with Sinhala, an Indo-Aryan language spoken by the majority Sinhalese. The Vedda language is highly endangered today. At present, all speakers of the Vedda language spoken in Dambana are Adivasi men in the parent generation, who are Sinhala-Vedda bilinguals. Adivasi women and children do not speak the Vedda language but Sinhala in everyday life. Women can understand the Vedda language and would respond to a Vedda language utterance in Sinhala. The use of the Vedda language is largely restricted to self-ascribing Adivasi men who employ it in the context of cultural tourism in Dambana to index ethnolinguistic otherness. Adivasi of Dambana often refers to this distinct linguistic code that they speak as baasapojja or language. This research employs a cooperative model of ethnographic documentation to explore the interrelations between discursive practices, linguistic structures, and linguistic (and broader sociocultural) ideologies in this community. The Vedda language has been previously identified as a dialect of Sinhala or a creole emerging in the contact between Sinhala and the ancestral Vedda language. This paper analyzes the current language endangerment context of bilingual Adivasi members that allows the birth of a mixed language. The aim of this research is to preserve ongoing linguistic innovation among this endangered language speech community. It contributes to the appreciation of creative cultural and linguistic production of a stigmatized minuscule indigenous community of South Asia that strives to assert a distinct linguistic and cultural identity from the dominant populations.

Keywords: Vedda language, language endangerment, mixed languages, indigenous identity

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Authors: Easa Almustanyir

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This study investigates the linguistic and thematic approach of translator Abdullah Khrief in the context of video translations on the X platform. The sample comprises 15 videos from Khrief's account, covering diverse content categories like science, religion, social issues, personal experiences, lifestyle, and culture. The analysis focuses on two aspects: language usage and thematic representation. Regarding language, the study examines the prevalence of English while considering the inclusion of French and German content, highlighting Khrief's multilingual versatility and ability to navigate cultural nuances. Thematically, the study explores the diverse range of topics covered, encompassing scientific, religious, social, and personal narratives, underscoring Khrief's broad subject matter expertise and commitment to knowledge dissemination. The study employs a mixed-methods approach, combining quantitative data analysis with qualitative content analysis. Statistical data on video languages, presenter genders, and content categories are analyzed, and a thorough content analysis assesses translation accuracy, cultural appropriateness, and overall quality. Preliminary findings indicate a high level of professionalism and expertise in Khrief's translations. The absence of errors across the diverse range of videos establishes his credibility and trustworthiness. Furthermore, the accurate representation of cultural nuances and sensitive topics highlights Khrief's cultural sensitivity and commitment to preserving intended meanings and emotional resonance.

Keywords: audiovisual translation, linguistic versatility, thematic diversity, cultural sensitivity, content analysis, mixed-methods approach

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Authors: Adinarayana Gorajana, Venkata Srikanth Meka, Sanjay Garg, Lim Sue May

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This study was designed to evaluate and enhance the solubility of poorly soluble drug, docetaxel through solid dispersion (SD) technique prepared using freeze drying method. Docetaxel solid dispersions were formulated with Soluplus in different weight ratios. Freeze drying method was used to prepare the solid dispersions. Solubility of the solid dispersions were evaluated respectively and the optimized of drug-solubilizers ratio systems were characterized with different analytical methods like Differential scanning calorimeter (DSC), Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) to confirm the formation of complexes between drug and solubilizers. The solubility data revealed an overall improvement in solubility for all SD formulations. The ternary combination 1:5:2 gave the highest increase in solubility that is approximately 3 folds from the pure drug, suggesting the optimum drug-solubilizers ratio system. This data corresponds with the DSC and SEM analyses, which demonstrates presence of drug in amorphous state and the dispersion in the solubilizers in molecular level. The solubility of the poorly soluble drug, docetaxel was enhanced through preparation of solid dispersion formulations employing freeze drying method. Solid dispersion with multiple carrier system shows better solubility compared to single carrier system.

Keywords: docetaxel, freeze drying, soluplus, solid dispersion technique

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Authors: So Youn Park, Yi Sle Lee, Ki Whan Hong, Chi Dae Kim

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The role of metabolism in the pathogenesis of osteoarthritis is an emerging field. Metabolic alterations may be a role in osteoarthritis (OA) pathogenesis, and these changes influence joint destruction via several cytokine. Especially, in OA patients, levels of IL-1β are elevated in the synovial fluid, synovial membrane, subchondral bone, and cartilage. The IL-1β is activated by NLRP3 inflammasomes, and NLRP3 inflammasomes are cytosolic complexes that drive the production of other inflammatory cytokines, including IL-1β. In this study, we examined that SIRT1 suppresses IL-1β through inhibiting NLRP3 inflammasomes and SIRT1 ameliorates osteoarthritis. OA fibroblasts were isolated from synovium of OA patients. IL-1β and NLRP3 were detected in synovium of OA patients by immunohistochemistry. Lipopolysaccharides (LPS) stimulated the expression of active IL-1β mRNA in OA fibroblasts and combination of LPS, and adenosine triphosphate increased more the expression of active IL-1β in OA fibroblasts. The level of IL-1β was measured by western blot and ELISA assay. NLRP3 inflammasomes complex were measured by western blot. SIRT1 did not inhibit expression of NLRP3 inflammasome. So caspase-1, apoptotic speck-like protein containing a caspase recruitment domain (ASC) and NLRP3 protein were expressed in OA fibroblasts. But SIRT1 suppressed activation of IL-1β by inhibiting activity of caspase-1 via NLRP3 inflammasome in OA fibroblasts under LPS plus ATP stimulation. These results suggest that SIRT1 is a modulator of NLRP3 inflammasomes in OA fibroblasts and ameliorate IL-1β, so expression of SIRT1 in OA fibroblast may be a potential strategy for OA inflammation treatment.

Keywords: osteoarthritis, inflammasome, SIRT1, IL-1beta

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Authors: Sirwe Ghaderpour, Nasrollah Ahmadifard, Naser Agh, Zakaria Vahabzadeh

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Rotifers are used in many hatcheries for feeding the earliest stages of fish larvae and crustaceans due to their small size, slow movements, fast reproduction, and easy cultivation. One of the disadvantages of using rotifers as live prey is their lower content of some nutrients compared to copepods, so it is necessary to increase the amounts of these nutrients by means of enrichment. Minerals are a group of micro-elements, essential to fish, that is lacking in the rotifers, for example, selenium (30 fold) and zinc (5 fold) are present in lower quantities than the minimum amounts found in copepods. In this study, the condensed Isochrysis aff. galbana (T-ISO) and Nannochloropsis oculata were suspended at concentration of 18 × 109 cell mL⁻¹ of water with 20 ppt of salinity. Four different levels (0, 1000, 2000, and 4000 mg L⁻¹) of each Na₂SeO₃ and ZnSO₄.7H₂O separately were prepared, and 1 mL of each stock was poured to the algae enrichment vessels for 1 h simultaneously. After that, the material was centrifuged (at 4000 rpm for 5 min), and the precipitated enriched algae was used for rotifer feeding. The contents of Se, Zn, Cu, and Mn were determined in enriched microalgae and rotifer by Atomic absorption. The highest content of both minerals was observed in 0.4 Zn + 0.4 Se treatment and also rotifer enriched with these enriched microalgae. The enrichment of microalgae with Zn and Se does not affect the content of Cu in the microalgae. Also, the content of Cu in rotifer fed with the enriched microalgae showed the highest Cu content in the treatments than the control. But, the enrichment with both minerals had a negative effect on the content Mn in enriched mixed microalgae except 0.4 Zn + 0.4 Se. The Mn content in enriched rotifer decreased in the treatments than the control except for 0.1 Zn + 0.1 Se. There was no significant effect on rotifer growth in combined enrichment with both minerals (p < 0.05). Overall, rotifers enrichment with Se and Zn mixed microalgae resulted in increasing Se, Zn, and Cu. This will allow Se and Zn microalgae enriched rotifers to be used as the minerals delivery method for fish larvae nutritional requirements.

Keywords: enrichment, larvae, microalgae, mineral, rotifer

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Authors: Deborah Bailey-Rodriguez, Maria Paula Valdivieso Rueda, Gemma Reynolds

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In recent years, the mental health of Higher Education (HE) students has been a growing concern. This has been further exacerbated by the stresses associated with the Covid-19 pandemic, placing students at even greater risk of developing mental health issues. Support available to students in HE tends to follow an established and traditional route. The demands for counseling services have grown, not only with the increase in student numbers but with the number of students seeking support for mental health issues, with 94% of HE institutions recently reporting an increase in the need for counseling services. One way of improving the well-being and mental health of HE students is through the use of brief interventions, such as expressive writing (EW). This intervention involves encouraging individuals to write continuously for at least 15-20 minutes for three to five sessions (often on consecutive days) about their deepest thoughts and feelings to explore significant personal experiences in a meaningful way. Given the brevity, simplicity and cost-effectiveness of EW, this intervention has considerable potential as an intervention for HE populations. The current study, therefore, employed a mixed-methods design to explore the effectiveness of EW in reducing anxiety, general stress, academic stress and depression in HE students while improving well-being. HE students at MDX were randomly assigned to one of three conditions: (1) The UniExp-EW group was required to write about their emotions and thoughts about any stressors they have faced that are directly relevant to their university experience (2) The NonUniExp-EW group was required to write about their emotions and thoughts about any stressors that are NOT directly relevant to their university experience, and (3) The Control group were required to write about how they spent their weekend, with no reference to thoughts or emotions, and without thinking about university. Participants were required to carry out the EW intervention for 15 minutes per day for four consecutive days. Baseline mental health and well-being measures were taken before the intervention via a battery of standardized questionnaires. Following completion of the intervention on day four, participants were required to complete the questionnaires a second time and again one week later. Participants were also invited to attend focus groups to discuss their experience of the intervention. This will allow an in-depth investigation into students’ perceptions of EW as an effective intervention to determine whether they would choose to use this intervention in the future. Preliminary findings will be discussed at the conference as well as a discussion of the important implications of the findings. The study is fundamental because if EW is an effective intervention for improving mental health and well-being in HE students, its brevity and simplicity mean it can be easily implemented and can be freely available to students. Improving the mental health and well-being of HE students can have knock-on implications for improving academic skills and career development.

Keywords: expressive writing, higher education, psychology in education, mixed-methods, mental health, academic stress

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Authors: Yeidy Sorani Montenegro Camacho, Samir Bensaid, Nunzio Russo, Debora Fino

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LiFeO2 nano-powders were prepared via solution combustion synthesis (SCS) method and were used as carbon gasification catalyst in a reduced atmosphere. The gasification of soot with CO2 and H2O in the presence of CO and H2 (syngas atmosphere) were also investigated under atmospheric conditions using a fixed-bed micro-reactor placed in an electric, PID-regulated oven. The catalytic bed was composed of 150 mg of inert silica, 45 mg of carbon (Printex-U) and 5 mg of catalyst. The bed was prepared by ball milling the mixture at 240 rpm for 15 min to get an intimate contact between the catalyst and soot. A Gas Hourly Space Velocity (GHSV) of 38.000 h-1 was used for the tests campaign. The furnace was heated up to the desired temperature, a flow of 120 mL/min was sent into the system and at the same time the concentrations of CO, CO2 and H2 were recorded at the reactor outlet using an EMERSON X-STREAM XEGP analyzer. Catalytic and non-catalytic soot gasification reactions were studied in a temperature range of 120°C – 850°C with a heating rate of 5 °C/min (non-isothermal case) and at 650°C for 40 minutes (isothermal case). Experimental results show that the gasification of soot with H2O and CO2 are inhibited by the H2 and CO, respectively. The soot conversion at 650°C decreases from 70.2% to 31.6% when the CO is present in the feed. Besides, the soot conversion was 73.1% and 48.6% for H2O-soot and H2O-H2-soot gasification reactions, respectively. Also, it was observed that the carbon gasification in mixed atmosphere, i.e., when simultaneous carbon gasification with CO2 and steam take place, with H2 and CO as co-reagents; the gasification reaction is strongly inhibited by CO and H2, as well has been observed in single atmospheres for the isothermal and non-isothermal reactions. Further, it has been observed that when CO2 and H2O react with carbon at the same time, there is a passive cooperation of steam and carbon dioxide in the gasification reaction, this means that the two gases operate on separate active sites without influencing each other. Finally, despite the extreme reduced operating conditions, it has been demonstrated that the 32.9% of the initial carbon was gasified using LiFeO2-catalyst, while in the non-catalytic case only 8% of the soot was gasified at 650°C.

Keywords: soot gasification, nanostructured catalyst, reducing environment, syngas

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Authors: E. Gil, A. Zepeda, J. Rivera, C. Ben-Youssef, S. Rincón

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Water pollution has become one of the most serious environmental problems. Multiple methods have been proposed for the removal of Pb(II) from contaminated water. Among these, adsorption processes have shown to be more efficient, cheaper and easier to handle with respect to other treatment methods. However, research for adsorbents with high adsorption capacities is still necessary. For this purpose, we proposed in this work the study of metal-organic Framework [Co2(btec)(bipy)(DMF)2]n (MOF-Co) as adsorbent material of Pb (II) in aqueous media. MOF-Co was synthesized by a simple method. Firstly 4, 4’ dipyridyl, 1,2,4,5 benzenetetracarboxylic acid, cobalt (II) and nitrate hexahydrate were first mixed each one in N,N dimethylformamide (DMF) and then, mixed in a reactor altogether. The obtained solution was heated at 363 K in a muffle during 68 h to complete the synthesis. It was washed and dried, obtaining MOF-Co as the final product. MOF-Co was characterized before and after the adsorption process by Fourier transforms infrared spectra (FTIR) and X-ray photoelectron spectroscopy (XPS). The Pb(II) in aqueous media was detected by Absorption Atomic Spectroscopy (AA). In order to evaluate the adsorption process in the presence of Pb(II) in aqueous media, the experiments were realized in flask of 100 ml the work volume at 200 rpm, with different MOF-Co quantities (0.0125 and 0.025 g), pH (2-6), contact time (0.5-6 h) and temperature (298,308 and 318 K). The kinetic adsorption was represented by pseudo-second order model, which suggests that the adsorption took place through chemisorption or chemical adsorption. The best adsorption results were obtained at pH 5. Langmuir, Freundlich and BET equilibrium isotherms models were used to study the adsorption of Pb(II) with 0.0125 g of MOF-Co, in the presence of different concentration of Pb(II) (20-200 mg/L, 100 mL, pH 5) with 4 h of reaction. The correlation coefficients (R2) of the different models show that the Langmuir model is better than Freundlich and BET model with R2=0.97 and a maximum adsorption capacity of 833 mg/g. Therefore, the Langmuir model can be used to best describe the Pb(II) adsorption in monolayer behavior on the MOF-Co. This value is the highest when compared to other materials such as the graphene/activated carbon composite (217 mg/g), biomass fly ashes (96.8 mg/g), PVA/PAA gel (194.99 mg/g) and MOF with Ag12 nanoparticles (120 mg/g).

Keywords: adsorption, heavy metals, metal-organic frameworks, Pb(II)

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Authors: Ismail Celik, Gulgun Ayhan Kilcigil, Berna Guven, Zumra Kara, Arzu Onay-Besikci

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Epidermal Growth Factor Receptor is the cell-surface receptor of the ErbB (erythroblastic leukemia viral oncogene homologue receptors) family of tyrosine kinases. It plays a vital role in regulating the proliferation and differentiation of cells. However, a variety of mechanisms, such as EGFR expression, mutation, and ligand-dependent receptor dimerization, are associated with the development of various activated EGFR tumors. EGFR is highly expressed in most solid tumors, including breast, head and neck cancer, non-small cell lung cancer (NSCLC), renal, ovarian, and colon cancers. Thus, specific EGFR inhibition plays one of the key roles in cancer treatment. The compounds used in the treatment as tyrosine kinase inhibitors are known to contain the benzimidazole isosterium indole, pazopanib, and axitinibin indazole rings. In addition, benzimidazoles have been shown to exhibit protein kinase inhibitory activity in addition to their different biological activities.Based on these data, it was planned and synthesized of some oxadiazole bearing benzimidazole derivatives [N-cyclohexyl-5-((2-phenyl/substitutedphenyl-1H-benzo[d]imidazole-1-yl) methyl)-1,3,4-oxadiazole-2-amine]. EGFR kinase inhibitory efficiency of the synthesized compounds was determined by comparing them with a known kinase inhibitor erlotinib in vitro, and two of the compounds bearing phenyl (19a) and 3,4-dibenzyloxyphenyl (21a) ring exhibited significant activities.

Keywords: benzimidazole, EGFR kinase inhibitory, oxadiazole, synthesis

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Authors: Mayank, Navneet Kaur, Narinder Singh

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The V599 mutations in the BRAF protein are extremely oncogenic, responsible for countless of malignant conditions. Along with wild type, V599E, V599D, and V599R are the important mutated variants of the BRAF proteins. The BRAF inhibitory anticancer agents are continuously developing, and sorafenib is a BRAF inhibitor that is under clinical use. The crystal structure of sorafenib bounded to wild type, and V599 is known, showing a similar interaction pattern in both the case. The mutated 599th residue, in both the case, is also found not interacting directly with the co-crystallized sorafenib molecule. However, the IC50 value of sorafenib was found extremely different in both the case, i.e., 22 nmol/L for wild and 38 nmol/L for V599E protein. Molecular docking study and MMGBSA binding energy results also revealed a significant difference in the binding pattern of sorafenib in both the case. Therefore, to explore the role of distinctively situated 599th residue, we have further conducted comprehensive computational studies. The molecular dynamics simulation, residue interaction network (RIN) analysis, and residue correlation study results revealed the importance of the 599th residue on the therapeutic outcome and overall dynamic of the BRAF protein. Therefore, although the position of 599th residue is very much distinctive from the ligand-binding cavity of BRAF, still it has exceptional control over the overall functional outcome of the protein. The insight obtained here may seem extremely important and guide us while designing ideal BRAF inhibitory anticancer molecules.

Keywords: BRAF, oncogenic, sorafenib, computational studies

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