Search results for: strand jacking

Authors: Ahmed M. Debela, Mayreli Ortiz , Ciara K. O´Sullivan

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The completion of the human genome Project (HGP) has paved the way for mapping the diversity in the overall genome sequence which helps to understand the genetic causes of inherited diseases and susceptibility to drugs or environmental toxins. Arrayed primer extension (APEX) is a microarray based minisequencing strategy for screening disease causing mutations. It is derived from Sanger DNA sequencing and uses fluorescently dideoxynucleotides (ddNTPs) for termination of a growing DNA strand from a primer with its 3´- end designed immediately upstream of a site where single nucleotide polymorphism (SNP) occurs. The use of DNA polymerase offers a very high accuracy and specificity to APEX which in turn happens to be a method of choice for multiplex SNP detection. Coupling the high specificity of this method with the high sensitivity, low cost and compatibility for miniaturization of electrochemical techniques would offer an excellent platform for detection of mutation as well as sequencing of DNA templates. We are developing an electrochemical APEX for the analysis of SNPs found in the MYH7 gene for group of cardiomyopathy patients. ddNTPs were labeled with four different redox active compounds with four distinct potentials. Thiolated oligonucleotide probes were immobilised on gold and glassy carbon substrates which are followed by hybridisation with complementary target DNA just adjacent to the base to be extended by polymerase. Electrochemical interrogation was performed after the incorporation of the redox labelled dedioxynucleotide. The work involved the synthesis and characterisation of the redox labelled ddNTPs, optimisation and characterisation of surface functionalisation strategies and the nucleotide incorporation assays.

Keywords: array based primer extension, labelled ddNTPs, electrochemical, mutations

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Authors: Carmela Perta

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Among the studies flourished in the field of historical sociolinguistics, mainly in the strand devoted to English history, during its Medieval and early modern phases, multilingual texts had been analysed using theories and models coming from contact linguistics, thus applying synchronic models and approaches to the past. This is true also in the case of contact phenomena which would transcend the writing level involving the language systems implicated in contact processes to the point of perceiving a new variety. This is the case for medieval administrative-commercial texts in which, according to some Scholars, the degree of fusion of Anglo-Norman, Latin and middle English is so high a mixed code emerges, and there are recurrent patterns of mixed forms. Interesting is a collection of multilingual business writings by John Balmayn, an Englishman overseeing a large shipment in Tuscany, namely the Cantelowe accounts. These documents display various analogies with multilingual texts written in England in the same period; in fact, the writer seems to make use of the above-mentioned patterns, with Middle English, Latin, Anglo-Norman, and the newly added Italian. Applying an atomistic yet dynamic approach to the study of contact phenomena, we will investigate these documents, trying to explore the nature of the switching forms they contain from an intra-writer variation perspective. After analysing the accounts and the type of multilingualism in them, we will take stock of the assumed mixed code nature, comparing the characteristics found in this genre with modern assumptions. The aim is to evaluate the possibility to consider the switching forms as core elements of a mixed code, used as professional variety among merchant communities, or whether such texts should be analysed from a switching perspective.

Keywords: historical sociolinguistics, historical code switching, letters, medieval england

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Authors: Sajjad Shojaeidoust, Mohsen Ghanbarzadeh, Abdolhamid Habibi

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Exercise-induced bronchospasm (EIB) is a transitory condition of airflow obstruction that is associated with physical activities. It is noted that high ventilation can lead to an increase in the heat and reduce in the moisture in airways resistance of trachea. Also causes of pathophysiological mechanism are EIB. Accordingly, studying some parameters of pulmonary function (FVC, FEV1) among active people seems quintessential. The aim of this study was to analyze bronchospasm following the implementation of a program of maximum aerobic exercise in active men at Chamran University of Ahwaz. Method: In this quasi-experimental study, the population consisted of all students at Chamran University. Among from 55 participants, of which, 15 were randomly selected as the experimental group. In this study, the size of the maximum oxygen consumption was initially measured, and then, based on the maximum oxygen consumed, the active individuals were identified. After five minutes’ warm-up, Strand treadmill exercise test was taken (one session) and pulmonary parameters were measured at both pre- and post-tests (spirometer). After data normalization using KS and non-normality of the data, the Wilcoxon test was used to analyze the data. The significance level for all statistical surveys was considered p≤0/05. Results: The results showed that the ventilation factors and bronchospasm (FVC, FEV1) in the pre-test and post-test resulted in no significant difference among the active people (p≥0/05). Discussion and conclusion: Based on the results observed in this study, it appears that pulmonary indices in active individuals increased after aerobic test. The increase in this indicator in active people is due to increased volume and elasticity of the lungs as well. In other words, pulmonary index is affected by rib muscles. It is considered that progress over respiratory muscle strength and endurance has raised FEV1 in the active cases.

Keywords: aerobic active maximum, bronchospasm, pulmonary function, spirometer

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Authors: Narges Razmjoo, Hamid Sefidari, Michael Strand

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Biomass combustion is a growing technique for heat and power production due to the increasing stringent regulations with CO2 emissions. Grate-fired systems have been regarded as a common and popular combustion technology for burning woody biomass. However, some grate furnaces are not well optimized and may emit significant amount of unwanted compounds such as dust, NOx, CO, and unburned gaseous components. The combustion characteristics inside the fuel bed are of practical interest, as they are directly related to the release of volatiles and affect the stability and the efficiency of the fuel bed combustion. Although numerous studies have been presented on the grate firing of biomass, to the author’s knowledge, none of them have conducted a detailed experimental study within the fuel bed. It is difficult to conduct measurements of temperature and gas species inside the burning bed of the fuel in full-scale boilers. Results from such inside bed measurements can also be applied by the numerical experts for modeling the fuel bed combustion. The current work presents an experimental investigation into the combustion behavior of wet woody biomass (53 %) in a 4 MW reciprocating grate boiler, by focusing on the gas species distribution along the height of the fuel bed. The local concentrations of gases (CO, CO2, CH4, NO, and O2) inside the fuel bed were measured through a glass port situated on the side wall of the furnace. The measurements were carried out at five different heights of the fuel bed, by means of a bent stainless steel probe containing a type-k thermocouple. The sample gas extracted from the fuel bed, through the probe, was filtered and dried and then was analyzed using two infrared spectrometers. Temperatures of about 200-1100 °C were measured close to the grate, indicating that char combustion is occurring at the bottom of the fuel bed and propagates upward. The CO and CO2 concentration varied in the range of 15-35 vol % and 3-16 vol %, respectively, and NO concentration varied between 10-140 ppm. The profile of the gas concentrations distribution along the bed height provided a good overview of the combustion sub-processes in the fuel bed.

Keywords: experimental, fuel bed, grate firing, wood combustion

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Authors: Srishty Gulati, Anju Singh, Shrikant Kukreti

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The manifestation of structural polymorphism in DNA depends on the sequence and surrounding environment. Ample of folded DNA structures have been found in the cellular system out of which DNA hairpins are very common, however, are indispensable due to their role in the replication initiation sites, recombination, transcription regulation, and protein recognition. We enumerate this approach in our study, where the two base substitutions and change in temperature embark destabilization of DNA structure and misbalance the equilibrium between two structures of a sequence present at the overlapping region of the human COMT gene and MIR4761 gene. COMT and MIR4761 gene encodes for catechol-O-methyltransferase (COMT) enzyme and microRNAs (miRNAs), respectively. Environmental changes and errors during cell division lead to genetic abnormalities. The COMT gene entailed in dopamine regulation fosters neurological diseases like Parkinson's disease, schizophrenia, velocardiofacial syndrome, etc. A 19-mer deoxyoligonucleotide sequence 5'-AGGACAAGGTGTGCATGCC-3' (COMT19) is located at exon-4 on chromosome 22 and band q11.2 at the intersection of COMT and MIR4761 gene. Bioinformatics studies suggest that this sequence is conserved in humans and few other organisms and is involved in recognition of transcription factors in the vicinity of 3'-end. Non-denaturating gel electrophoresis and CD spectroscopy of COMT sequences indicate the formation of hairpin type DNA structures. Temperature-dependent CD studies revealed an unusual shift in the slipped DNA-Hairpin DNA equilibrium with the change in temperature. Also, UV-thermal melting techniques suggest that the two base substitutions on the complementary strand of COMT19 did not affect the structure but reduces the stability of duplex. This study gives insight about the possibility of existing structurally polymorphic transient states within DNA segments present at the intersection of COMT and MIR4761 gene.

Keywords: base-substitution, catechol-o-methyltransferase (COMT), hairpin-DNA, structural polymorphism

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Authors: Jaydip De

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Urban parks are open places, green fields and riverside gardens usually maintained by public or private authorities, or eventually by both jointly; and utilized for a multidimensional purpose by the citizens. These parks are indeed the lung of urban centers. In urban socio-environmental setup, parks are the nucleus of social integration, community building, and physical development. In contemporary cities, these green places seem to perform as the panacea of congested, complex and stressful urban life. The alarmingly increasing urban population and the resultant congestion of high-rises are making life wearisome in neo-liberal cities. This has made the citizen always quest for open space and fresh air. In such a circumstance, the mere existence of parks is not capable of satisfying the growing aspirations. Therefore in this endeavour, a structured attempt is so made to empirically identify the utility, visitors’ satisfaction, and future needs through the cases of two urban parks of Kolkata Metropolitan Area, India. This study is principally based upon primary information collected through visitors’ perception survey conducted at the Chinsurah ground and Chandernagore strand. The correlation between different utility categories is identified and analyzed systematically. At the same time, indices like Weighted Satisfaction Score (WSS), Facility wise Satisfaction Index (FSI), Urban Park Satisfaction Index (UPSI) and Urban Park Necessity Index (UPNI) are advocated to quantify the visitors’ satisfaction and future necessities. It is explored that the most important utilities are passive in nature. Simultaneously, satisfaction levels of visitors are average, and their requirements are centred on the daily needs of the next generation, i.e., the children. Further, considering the visitors’ opinion planning measures are promulgated for holistic development of urban parks to revitalize sustainability of citified life.

Keywords: citified life, future needs, visitors’ satisfaction, urban parks, utility

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Authors: D. Leibman, D. Wolf, A. Gal-On

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Viral diseases of tomato crops result in heavy yield losses and may even jeopardize the production of these crops. Classical tomato breeding for disease resistance against Tomato yellow leaf curl virus (TYLCV), leads to partial resistance associated with a number of recessive genes. To author’s best knowledge Pepino mosaic virus (PepMV) genetic resistance is not yet available. The generation of viral resistance by means of genetic engineering was reported and implemented for many crops, including tomato. Transgenic resistance against viruses is based, in most cases, on Post Transcriptional Gene Silencing (PTGS), an endogenous mechanism which destroys the virus genome. In this work, we developed immunity against PepMV and TYLCV in a tomato based on a PTGS mechanism. Tomato plants were transformed with a hairpin-construct-expressed transgene-derived double-strand-RNA (tr-dsRNA). In the case of PepMV, the binary construct harbored three consecutive fragments of the replicase gene from three different PepMV strains (Italian, Spanish and American), to provide resistance against a range of virus strains. In the case of TYLCV, the binary vector included three consecutive fragments of the IR, V2 and C2 viral genes constructed in a hairpin configuration. Selected transgenic lines (T0) showed a high accumulation of transgene siRNA of 21-24 bases, and T1 transgenic lines showed complete immunity to PepMV and TYLCV. Graft inoculation displayed immunity of the transgenic scion against PepMV and TYLCV. The study presents the engineering of resistance in tomato against two serious diseases, which will help in the production of high-quality tomato. However, unfortunately, these resistant plants have not been implemented due to public ignorance and opposition against breeding by genetic engineering.

Keywords: PepMV, PTGS, TYLCV, tr-dsRNA

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Authors: Shanakr Bhattarai, V. S. Tiwari, Barak Akabayov

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The plummeting number of infections and death is due to the development of drug-resistant bacteria. In addition, the number of approved antibiotic drugs by the Food and Drug Administration (FDA) is insufficient. Therefore, developing new drugs and finding novel targets for central metabolic pathways in bacteria is urgently needed. One of the promising targets is DNA replication machinery which consists of many essential proteins and enzymes. DnaG primase is an essential enzyme and a central part of the DNA replication machinery. DnaG primase synthesizes short RNA primers that initiate the Okazaki fragments by the lagging strand DNA polymerase. Therefore, it is reasonable to assume that inhibition of primase activity will stall DNA replication and prevent bacterial proliferation. We did the expression and purification of eight different bacterial DnaGs (Mycobacterium tuberculosis(Mtb), Bacillus anthracis (Ba), Mycobacterium smegmatis (Msmeg), Francisella tularencis (Ft), Vibrio cholerae (Vc) and Yersinia pestis (Yp), Staphylococcus aureus(Saureus), Escherichia coli(Ecoli)) followed by the radioactive activity assay. After obtaining the pure and active protein DnaG, we synthesized the inhibitors for them. The inhibitors were divided into five different groups, each containing five molecules, and the cocktail inhibition assay was performed against each DnaGs. The groups of molecules inhibiting the DnaGs were further tested with individual molecules belonging to inhibiting groups. Each molecule showing inhibition was titrated against the corresponding DnaGs to find IC50. We got a molecule(VS167) that acted as broad inhibitors, inhibiting all eight DnaGs. Molecules VS180 and VS186 inhibited seven DnaGs (except Saureus). Similarly, two molecules(VS 173, VS176) inhibited five DnaGs (Mtb, Ba, Ft, Yp, Ecoli). VS261 inhibited four DnaGs (Mtb, Ba, Ft, Vc). MS50 inhibited Ba and Vc DnaGs. And some of the inhibitors inhibited only one DnaGs. Thus we found the broad and specific inhibitors for different bacterial DnaGs, and their Structure-activity analysis(SAR) was done. Further, We tried to explain the similarities among the enzyme DnaGs from different bacteria based on their inhibition pattern.

Keywords: DNA replication, DnaG, okazaki fragments, antibiotic drugs

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Authors: Titus A. Beu

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Many modern gene-delivery protocols rely on condensed complexes of DNA with polycations to introduce the genetic payload into cells by endocytosis. In particular, polyethyleneimine (PEI) stands out by a high buffering capacity (enabling the efficient condensation of DNA) and relatively simple fabrication. Realistic computational studies can offer essential insights into the formation process of DNA-PEI polyplexes, providing hints on efficient designs and engineering routes. We present comprehensive computational investigations of solvated PEI and DNA-PEI polyplexes involving calculations at three levels: ab initio, all-atom (AA), and coarse-grained (CG) molecular mechanics. In the first stage, we developed a rigorous AA CHARMM (Chemistry at Harvard Macromolecular Mechanics) force field (FF) for PEI on the basis of accurate ab initio calculations on protonated model pentamers. We validated this atomistic FF by matching the results of extensive molecular dynamics (MD) simulations of structural and dynamical properties of PEI with experimental data. In a second stage, we developed a CG MARTINI FF for PEI by Boltzmann inversion techniques from bead-based probability distributions obtained from AA simulations and ensuring an optimal match between the AA and CG structural and dynamical properties. In a third stage, we combined the developed CG FF for PEI with the standard MARTINI FF for DNA and performed comprehensive CG simulations of DNA-PEI complex formation and condensation. Various technical aspects which are crucial for the realistic modeling of DNA-PEI polyplexes, such as options of treating electrostatics and the relevance of polarizable water models, are discussed in detail. Massive CG simulations (with up to 500 000 beads) shed light on the mechanism and provide time scales for DNA polyplex formation independence of PEI chain size and protonation pattern. The DNA-PEI condensation mechanism is shown to primarily rely on the formation of DNA bundles, rather than by changes of the DNA-strand curvature. The gained insights are expected to be of significant help for designing effective gene-delivery applications.

Keywords: DNA condensation, gene-delivery, polyethylene-imine, molecular dynamics.

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Authors: Marko Spasojevic, Ying Hei Chui, Yuxiang Chen

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Increasing the level of exterior insulation in residential buildings is a popular way for improving the thermal characteristic of building enclosure and reducing heat loss. However, the layout and properties of materials composing the wall have a great effect on moisture accumulation within the wall cavity, long-term durability of a wall as well as the structural performance. A one-dimensional hygrothermal modeling has been performed to investigate moisture condensation risks and the drying capacity of standard 2×4 and 2×6 light wood-frame wall assemblies including exterior low-permeance extruded polystyrene (XPS) insulation. The analysis considered two different wall configurations whereby the rigid insulation board was placed either between Oriented Strand Board (OSB) sheathing and the stud or outboard to the structural sheathing. The thickness of the insulation varied between 0 mm and 50 mm and the analysis has been conducted for eight different locations in Canada, covering climate zone 4 through zone 8. Results show that the wall configuration with low-permeance insulation inserted between the stud and OSB sheathing accumulates more moisture within the stud cavity, compared to the assembly with the same insulation placed exterior to the sheathing. On the other hand, OSB moisture contents of the latter configuration were markedly higher. Consequently, the analysis of hygrothermal performance investigated and compared moisture accumulation in both the OSB and stud cavity. To investigate the structural performance of the wall and the effect of soft insulation layer inserted between the sheathing and framing, forty nail connection specimens were tested. Results have shown that both the connection strength and stiffness experience a significant reduction as the insulation thickness increases. These results will be compared with results from a full-scale shear wall tests in order to investigate if the capacity of shear walls with insulated sheathing would experience a similar reduction in structural capacities.

Keywords: hygrothermal analysis, insulated sheathing, moisture performance, nail joints, wood shear wall

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Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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Authors: Afshan Channa, Sameeha Aleem, Harim Mohsin

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First rank symptoms (FRS) are considered to be pathognomic for Schizophrenia. However, FRS is not a distinctive feature of Schizophrenia. It has also been noticed in affective disorder, albeit not inclusive in diagnostic criteria. The presence of FRS in Mania leads to misdiagnosis of psychotic illness, further complicating the management and delay of appropriate treatment. FRS in Mania is associated with poor clinical and functional outcome. Its existence in the first episode of bipolar disorder may be a predictor of poor short-term outcome and decompensating course of illness. FRS in Mania is studied in west. However, the cultural divergence and detriments make it pertinent to study the frequency of FRS in affective disorder independently in Pakistan. Objective: The frequency of first rank symptoms in manic patients, who were under treatment at psychiatric services of tertiary care hospital. Method: The cross sectional study was done at psychiatric services of Aga Khan University Hospital, Karachi, Pakistan. One hundred and twenty manic patients were recruited from November 2014 to May 2015. The patients who were unable to comprehend Urdu or had comorbid psychiatric or organic disorder were excluded. FRS was assessed by administration of validated Urdu version of Present State Examination (PSE) tool. Result: The mean age of the patients was 37.62 + 12.51. The mean number of previous manic episode was 2.17 + 2.23. 11.2% males and 30.6% females had FRS. This association of first rank symptoms with gender in patients of mania was found to be significant with a p-value of 0.008. All-inclusive, 19.2% exhibited FRS in their course of illness. 43.5% had thought broadcasting, made feeling, impulses, action and somatic passivity. 39.1% had thought insertion, 30.4% had auditory perceptual distortion, and 17.4% had thought withdrawal. However, none displayed delusional perception. Conclusion: The study confirms the presence of FRS in mania in both male and female, irrespective of the duration of current manic illness or previous number of manic episodes. A substantial difference was established between both the genders. Being married had no protective effect on the presence of FRS.

Keywords: first rank symptoms, Mania, psychosis, present state examination

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Authors: Pansak Vandee

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The research aims to study the background and format of Tableau Vivant suite song and the singing style of Kru Luen SunTharawatin. The data is gained by content analysis and the in-depth interview from experts on Tableau Vivant suite song, as well as an analysis on singing style of Kru Luen SunTharawatin. The research results are as follows: (1) The Tableau Vivant suite song first appeared in the reign of King Rama V, composing by Prince Naris, for paralleling with the still picture presentation offered to Crown Prince Maha Vajirunahit, which was adapted from the French performance Tableau Vivant. The performance is assigned to perform by the Crown Prince’s younger brother and other young royal siblings. The 8 suite songs were played by archeological Thai orchestra (Piphat duek dam ban) and were restored once again in the reign of King Rama VII for the pleasure of the king, being sung by the Royal Entertainment Department Officers. (2) The format of Tableau Vivant suite song is a short series song, composing a double strand of 4 to 6 songs with 6 suite songs in 8 suites, in the form of a combination of suite lyric – Unnarut (the play narrated by King Rama I) and Phra Pen Chao (the homage to Brahman gods in Na Phat song); and suite song – Khom Dam Din with Khmer tone; the Three Kingdoms with Chinese tone; Rajadhirat with Burmese and Mon tone; Nitra Chakrit (the Arabian Night) with Arabian tone; Cinderella with Western tone; Phra Lor in Laotian tone. (3) The Tableau Vivant suite singing style of Kru Luen SunTharawatin is based on Phra-ya Sanor Duriyang (Cham SunTharawatin) style, which was newly created for Kru Luen, his daughter. The five suite songs Khom Dam Din, the Three Kingdoms, Rajadhirat, Nitra Chakrit (the Arabian Night), Cinderella, Phra Lor have their distinguish tones according to their language accents. The songs were recorded in the album of the Royal Institute of Thailand in 1931; but, unfortunately, the entire album was completely destroyed during the World War II in Germany.

Keywords: Krue Luen Sun Tharawatin, tableau vivant, singing style, suite song

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Authors: Asif Bilal, Fouzia Tanvir, Sibtain Ahmad

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Estrogen receptor alpha, also known as estrogen receptor-1, is highly involved in risk of mammary carcinoma. The objectives of this study were to identify non-synonymous SNPs of estrogen receptor and their association with breast cancer and to identify the chemotherapeutic responses of phytochemicals against it via in-silico study design. For this purpose, different online tools. to identify pathogenic SNPs the tools were SIFT, Polyphen, Polyphen-2, fuNTRp, SNAP2, for finding disease associated SNPs the tools SNP&GO, PhD-SNP, PredictSNP, MAPP, SNAP, MetaSNP, PANTHER, and to check protein stability Mu-Pro, I-Mutant, and CONSURF were used. Post-translational modifications (PTMs) were detected by Musitedeep, Protein secondary structure by SOPMA, protein to protein interaction by STRING, molecular docking by PyRx. Seven SNPs having rsIDs (rs760766066, rs779180038, rs956399300, rs773683317, rs397509428, rs755020320, and rs1131692059) showing mutations on I229T, R243C, Y246H, P336R, Q375H, R394S, and R394H, respectively found to be completely deleterious. The PTMs found were 96 times Glycosylation; 30 times Ubiquitination, a single time Acetylation; and no Hydroxylation and Phosphorylation were found. The protein secondary structure consisted of Alpha helix (Hh) is (28%), Extended strand (Ee) is (21%), Beta turn (Tt) is 7.89% and Random coil (Cc) is (44.11%). Protein-protein interaction analysis revealed that it has strong interaction with Myeloperoxidase, Xanthine dehydrogenase, carboxylesterase 1, Glutathione S-transferase Mu 1, and with estrogen receptors. For molecular docking we used Asiaticoside, Ilekudinuside, Robustoflavone, Irinoticane, Withanolides, and 9-amin0-5 as ligands that extract from phytochemicals and docked with this protein. We found that there was great interaction (from -8.6 to -9.7) of these ligands of phytochemicals at ESR1 wild and two mutants (I229T and R394S). It is concluded that these SNPs found in ESR1 are involved in breast cancer and given phytochemicals are highly helpful against breast cancer as chemotherapeutic agents. Further in vitro and in vivo analysis should be performed to conduct these interactions.

Keywords: breast cancer, ESR1, phytochemicals, molecular docking

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Authors: Aneena Suresh, C. S. Sidharth

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Drug related problems (DRPs) are common in chronic kidney disease (CKD) patients and end stage patients undergoing hemodialysis. To treat the co-morbid conditions of the patients, more complex therapeutic regimen is required, and it leads to development of DRPs. So, this calls for frequent monitoring of the patients. Due to the busy work schedules, physicians are unable to deliver optimal care to these patients. Addition of a clinical pharmacist in the team will improve the standard of care offered to CKD patients by minimizing DRPs. In India, the role of clinical pharmacists in the improving the health outcomes in CKD patients is poorly recognized. Therefore, this study is conducted to put an insight on the role of clinical pharmacist in improving Drug Related Problems in patients with chronic kidney disease, thereby helping them to achieve desired therapeutic outcomes in the patients. A prospective interventional study was conducted for a year in a 620 bedded tertiary care hospital in India. Data was collected using an unstructured questionnaire, medication charts, etc. DRPs were categorized using Hepler and Strand classification. Relationships between the age, weight, GFR, average no of medication taken, average no of comorbidities, and average length of hospital days with the DRPs were identified using Mann Whitney U test. The study population primarily constituted of patients above the age of 50 years with a mean age of 59.91±13.59. Our study showed that 25% of the population presented with DRPs. On an average, CKD patients are prescribed at least 8 medications for the treatment in our study. This explains the high incidence of drug interactions in patients suffering from CKD (45.65%). The least common DRPs in our study were found to be sub therapeutic dose (2%) and adverse drug reactions (2%). Out of this, 60 % of the DRPs were addressed successfully. In our study, there is an association between the DRPs with the average number of medications prescribed, the average number of comorbidities, and the length of the hospital days with p value of 0.022, 0.004, and 0.000, respectively. In the current study, 86% of the proposed interventions were accepted, and 41 % were implemented by the physician, and only 14% were rejected. Hence, it is evident that clinical pharmacist interventions will contribute significantly to diminish the DRPs in CKD patients, thereby decreasing the economic burden of healthcare costs and improving patient’s quality of life.

Keywords: chronic kidney disease, clinical pharmacist, drug related problem, intervention

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Authors: Peter Akayuure

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Geometry is considered an important strand in mathematics due to its wide-ranging utilitarian value and because it serves as a building block for understanding other aspects of undergraduate mathematics, including algebra and calculus. Matters regarding students’ geometric thinking have therefore long been pursued by mathematics researchers and educators globally via different theoretical lenses, curriculum reform efforts, and innovative instructional practices. However, so far, studies remain inconclusive about the instructional platforms that effectively promote geometric thinking. At the University of Education, Winneba, an undergraduate geometry course was designed and delivered on UEW Learning Management System (LMS) using Moodle platform. This study utilizes van Hiele’s theoretical lens to examine the entry and exit’s geometric thinking behaviours of prospective teachers who took the undergraduate geometry course in the LMS platform. The study was a descriptive survey that involved an intact class of 280 first-year students enrolled to pursue a bachelor's in mathematics education at the university. The van Hiele’s Geometric thinking test was used to assess participants’ entry and exit behaviours, while semi-structured interviews were used to obtain data for triangulation. Data were analysed descriptively and displayed in tables and charts. An Independent t-test was used to test for significant differences in geometric thinking behaviours between those who entered the university with a diploma certificate and with senior high certificate. The results show that on entry, more than 70% of the prospective teachers operated within the visualization level of van Hiele’s geometric thinking. Less than 20% reached analysis and abstraction levels, and no participant reached deduction and rigor levels. On exit, participants’ geometric thinking levels increased markedly across levels, but the difference from entry was not significant and might have occurred by chance. The geometric thinking behaviours of those enrolled with diploma certificates did not differ significant from those enrolled directly from senior high school. The study recommends that the design principles and delivery of undergraduate geometry course via LMS should be structured and tackled using van Hiele’s geometric thinking levels to serve as means of bridging the existing learning gaps of undergraduate students.

Keywords: geometric thinking, van Hiele’s, UEW learning management system, undergraduate geometry

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Authors: Ifigeneia V. Mavragani, Zacharenia Nikitaki, George Kalantzis, George Iliakis, Alexandros G. Georgakilas

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Complex DNA damage consisting of a combination of DNA lesions, such as Double Strand Breaks (DSBs) and non-DSB base lesions occurring in a small volume is considered as one of the most important biological endpoints regarding ionizing radiation (IR) exposure. Strong theoretical (Monte Carlo simulations) and experimental evidence suggests an increment of the complexity of DNA damage and therefore repair resistance with increasing linear energy transfer (LET). Experimental detection of complex (clustered) DNA damage is often associated with technical deficiencies limiting its measurement, especially in cellular or tissue systems. Our groups have recently made significant improvements towards the identification of key parameters relating to the efficient detection of complex DSBs and non-DSBs in human cellular systems exposed to IR of varying quality (γ-, X-rays 0.3-1 keV/μm, α-particles 116 keV/μm and 36Ar ions 270 keV/μm). The induction and processing of DSB and non-DSB-oxidative clusters were measured using adaptations of immunofluorescence (γH2AX or 53PB1 foci staining as DSB probes and human repair enzymes OGG1 or APE1 as probes for oxidized purines and abasic sites respectively). In the current study, Relative Biological Effectiveness (RBE) values for DSB and non-DSB induction have been measured in different human normal (FEP18-11-T1) and cancerous cell lines (MCF7, HepG2, A549, MO59K/J). The experimental results are compared to simulation data obtained using a validated microdosimetric fast Monte Carlo DNA Damage Simulation code (MCDS). Moreover, this simulation approach is implemented in two realistic clinical cases, i.e. prostate cancer treatment using X-rays generated by a linear accelerator and a pediatric osteosarcoma case using a 200.6 MeV proton pencil beam. RBE values for complex DNA damage induction are calculated for the tumor areas. These results reveal a disparity between theory and experiment and underline the necessity for implementing highly precise and more efficient experimental and simulation approaches.

Keywords: complex DNA damage, DNA damage simulation, protons, radiotherapy

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Authors: Y. Landkocz, C. Lepers, P.J. Martin, B. Fougère, F. Roy Saint-Georges. A. Verdin, F. Cazier, F. Ledoux, D. Courcot, F. Sichel, P. Gosset, P. Shirali, S. Billet

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In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and fine particles as carcinogenic to humans. Causal relationships exist between elevated ambient levels of airborne particles and increase of mortality and morbidity including pulmonary diseases, like lung cancer. However, due to a double complexity of both physicochemical Particulate Matter (PM) properties and tumor mechanistic processes, mechanisms of action remain not fully elucidated. Furthermore, because of several common properties between air pollution PM and tobacco smoke, like the same route of exposure and chemical composition, potential mechanisms of synergy could exist. Therefore, smoking could be an aggravating factor of the particles toxicity. In order to identify some mechanisms of action of particles according to their size, two samples of PM were collected: PM0.03 2.5 and PM0.33 2.5 in the urban-industrial area of Dunkerque. The overall cytotoxicity of the fine particles was determined on human bronchial cells (BEAS-2B). Toxicological study focused then on the metabolic activation of the organic compounds coated onto PM and some genetic and epigenetic changes induced on a co-culture model of BEAS-2B and alveolar macrophages isolated from bronchoalveolar lavages performed in smokers and non-smokers. The results showed (i) the contribution of the ultrafine fraction of atmospheric particles to genotoxic (eg. DNA double-strand breaks) and epigenetic mechanisms (eg. promoter methylation) involved in tumor processes, and (ii) the influence of smoking on the cellular response. Three main conclusions can be discussed. First, our results showed the ability of the particles to induce deleterious effects potentially involved in the stages of initiation and promotion of carcinogenesis. The second conclusion is that smoking affects the nature of the induced genotoxic effects. Finally, the in vitro developed cell model, using bronchial epithelial cells and alveolar macrophages can take into account quite realistically, some of the existing cell interactions existing in the lung.

Keywords: air pollution, fine and ultrafine particles, genotoxic and epigenetic alterations, smoking

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Authors: Desalegn Feyissa Desu

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Drug therapy problem is a significant challenge to provide high quality health care service for the patients. It is associated with morbidity, mortality, increased hospital stay, and reduced quality of life. Moreover, pediatric patients are quite susceptible to drug therapy problems. Thus this study aimed to assess drug therapy problem and its contributing factors among pediatric patients diagnosed with infectious disease admitted to pediatric ward of Jimma university medical center, from April 1 to June 30, 2018. Prospective observational study was conducted among pediatric patients with infectious disease admitted from April 01 to June 30, 2018. Drug therapy problems were identified by using Cipolle’s and strand’s drug related problem classification method. Patient’s written informed consent was obtained after explaining the purpose of the study. Patient’s specific data were collected using structured questionnaire. Data were entered into Epi data version 4.0.2 and then exported to statistical software package version 21.0 for analysis. To identify predictors of drug therapy problems occurrence, multiple stepwise backward logistic regression analysis was done. The 95% CI was used to show the accuracy of data analysis and statistical significance was considered at p-value < 0.05. A total of 304 pediatric patients were included in the study. Of these, 226(74.3%) patients had at least one drug therapy problem during their hospital stay. A total of 356 drug therapy problems were identified among two hundred twenty six patients. Non-compliance (28.65%) and dose too low (27.53%) were the most common type of drug related problems while disease comorbidity [AOR=3.39, 95% CI= (1.89-6.08)], Polypharmacy [AOR=3.16, 95% CI= (1.61-6.20)] and more than six days stay in hospital [AOR=3.37, 95% CI= (1.71-6.64) were independent predictors of drug therapy problem occurrence. Drug therapy problems were common in pediatric patients with infectious disease in the study area. Presence of comorbidity, polypharmacy and prolonged hospital stay were the predictors of drug therapy problem in study area. Therefore, to overcome the significant gaps in pediatric pharmaceutical care, clinical pharmacists, Pediatricians, and other health care professionals have to work in collaboration.

Keywords: drug therapy problem, pediatric, infectious disease, Ethiopia

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Authors: Francesca Giliberto

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Heritage and culture, in general, plays a central role in addressing the complexity and broad variety of global development challenges, ranging from environmental degradation and refugee and humanitarian crisis to extreme poverty, food insecurity, persisting inequalities, and unsustainable urbanisation, just to mention some examples. Nevertheless, the potential of harnessing heritage to address global challenges has remained largely under-represented and underestimated in the most recent international development agenda adopted by the United Nations in 2015 (2030 Agenda). Among the 17 sustainable development goals (SDGs) and 169 associated targets established, only target 11.4 explicitly mentions heritage, stating that efforts should be strengthened “to protect and safeguard the world’s cultural and natural heritage in order to make our cities safe, resilient, and sustainable”. However, this global target continues to reflect a rather limited approach to heritage for development. This paper will provide a critical reflection on the contribution that using (tangible and intangible) heritage in international research can make to tackling global challenges and supporting the achievement of all the SDGs. It will present key findings and insights from the heritage strand of PRAXIS, a research project from the University of Leeds, which focuses on Arts and Humanities research across 300+ projects funded through the Global Challenges Research Fund and Newton Fund. In particular, this paper will shed light on successful practices and lessons learned from 87 research projects funded through the Global Challenges Research Fund and Newton Fund portfolios in 49 countries eligible for Official Development Assistance (ODA) between 2014 and 2021. Research data were collected through a desk assessment of project data available on UKRI Gateway to Research, online surveys, and qualitative interviews with research principal investigators and partners. The findings of this research provide evidence of how heritage and heritage research can foster innovative, interdisciplinary, inclusive, and transformative sustainable development and the achievement of the SDGs in ODA countries and beyond. This paper also highlights current challenges and research gaps that still need to be overcome to rethink current approaches and transform our development models to be more integrated, human-centred, and sustainable.

Keywords: global challenges, heritage, international research, sustainable development

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Authors: Ane Escobar, Paula Angelomé, Mihaela Delcea, Marek Grzelczak, Sergio Enrique Moya

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The antibacterial capacity of bone-anchoring implants can be improved by the use of antibiotics that can be delivered to the media after the surgery. Mesoporous films have shown great potential in drug delivery for orthopedic applications, since pore size and thickness can be tuned to produce different surface area and free volume inside the material. This work shows the synthesis of mesoporous titania films (MTF) by sol-gel chemistry and evaporation-induced self-assembly (EISA) on top of glass substrates. Pores with a diameter of 12nm were observed by Transmission Electron Microscopy (TEM). A film thickness of 100 nm was measured by Scanning Electron Microscopy (SEM). Gentamicin was used to study the antibiotic delivery from the film by means of High-performance liquid chromatography (HPLC). The Staphilococcus aureus strand was used to evaluate the effectiveness of the penicillin loaded films toward inhibiting bacterial colonization. MC3T3-E1 pre-osteoblast cell proliferation experiments proved that MTFs have a good biocompatibility and are a suitable surface for MC3T3-E1 cell proliferation. Moreover, images taken by Confocal Fluorescence Microscopy using labeled vinculin, showed good adhesion of the MC3T3-E1 cells to the MTFs, as well as complex actin filaments arrangement. In order to improve cell proliferation Bone Morphogenetic Protein-2 (BMP-2) was adsorbed on top of the mesoporous film. The deposition of the protein was proved by measurements in the contact angle, showing an increment in the hydrophobicity while the protein concentration is higher. By measuring the dehydrogenase activity in MC3T3-E1 cells cultured in dually functionalized mesoporous titatina films with gentamicin and BMP-2 is possible to find an improvement in cell proliferation. For this purpose, the absorption of a yellow-color formazan dye, product of a water-soluble salt (WST-8) reduction by the dehydrogenases, is measured. In summary, this study proves that by means of the surface modification of MTFs with proteins and loading of gentamicin is possible to achieve an antibacterial effect and a cell growth improvement.

Keywords: antibacterial, biocompatibility, bone morphogenetic protein-2, cell proliferation, gentamicin, implants, mesoporous titania films, osteoblasts

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Authors: Nidia Thalia Alva Rangel, Ferran Padros Blazquez, Ma. Ines Gomez Del Campo Del Paso

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Happiness has been since antiquity a concept of interest around the world. Positive psychology is the science that begins to study happiness in a more precise and controlled way, obtaining wide amount of research which can be applied. One of the central constructs of Positive Psychology is Carol Ryff’s psychological well-being model as eudaimonic happiness, which comprehends six dimensions: autonomy, environmental mastery, personal growth, positive relations with others, purpose in life, and self-acceptance. Humanistic psychology is a clear precedent of Positive Psychology, which has studied human development topics and it features a great variety of intervention techniques nevertheless has little evidence with controlled research. Therefore, the present research had the aim to evaluate the efficacy of a humanistic intervention program to increase psychological well-being in healthy adults through a mixed methods study. Before and after the intervention, it was applied Carol Ryff’s psychological well-being scale (PWBS) and the Symptom Check List 90 as pretest and posttest. In addition, a questionnaire of five open questions was applied after each session. The intervention program was designed in experiential workshop format, based on the foundational attitudes defined by Carl Rogers: congruence, unconditional positive regard and empathy, integrating humanistic intervention strategies from gestalt, psychodrama, logotherapy and psychological body therapy, with the aim to strengthen skills in the six dimensions of psychological well-being model. The workshop was applied to six volunteer adults in 12 sessions of 2 hours each. Finally, quantitative data were analyzed with Wilcoxon statistic test through the SPSS program, obtaining as results differences statistically significant in pathology symptoms between prettest and postest, also levels of dimensions of psychological well-being were increased, on the other hand for qualitative strand, by open questionnaires it showed how the participants were experiencing the techniques and changing through the sessions. Thus, the humanistic psychology program was effective to increase psychological well-being. Working to promote well-being prompts to be an effective way to reduce pathological symptoms as a secondary gain. Experiential workshops are a useful tool for small groups. There exists the need for research to count with more evidence of humanistic psychology interventions in different contexts and impulse the application of Positive Psychology knowledge.

Keywords: happiness, humanistic psychology, positive psychology, psychological well-being, workshop

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Authors: Y. Landkocz, P. Gosset, A. Héliot, C. Corbière, C. Vendeville, V. Keravec, S. Billet, A. Verdin, C. Monteil, D. Préterre, J-P. Morin, F. Sichel, T. Douki, P. J. Martin

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Air Pollution produced by automobile traffic is one of the main sources of pollutants in urban atmosphere and is largely due to exhausts of the diesel engine powered vehicles. The International Agency for Research on Cancer, which is part of the World Health Organization, classified in 2012 diesel engine exhaust as carcinogenic to humans (Group 1), based on sufficient evidence that exposure is associated with an increased risk for lung cancer. Amongst the strategies aimed at limiting exhausts in order to take into consideration the health impact of automobile pollution, filtration of the emissions and use of biofuels are developed, but their toxicological impact is largely unknown. Diesel exhausts are indeed complex mixtures of toxic substances difficult to study from a toxicological point of view, due to both the necessary characterization of the pollutants, sampling difficulties, potential synergy between the compounds and the wide variety of biological effects. Here, we studied the potential indirect genotoxicity of emission of Diesel engines through on-line exposure of rats in inhalation chambers to a subchronic high but realistic dose. Following exposure to standard gasoil +/- rapeseed methyl ester either upstream or downstream of a particle filter or control treatment, rats have been sacrificed and their lungs collected. The following indirect genotoxic parameters have been measured: (i) telomerase activity and telomeres length associated with rTERT and rTERC gene expression by RT-qPCR on frozen lungs, (ii) γH2AX quantification, representing double-strand DNA breaks, by immunohistochemistry on formalin fixed-paraffin embedded (FFPE) lung samples. These preliminary results will be then associated with global cellular response analyzed by pan-genomic microarrays, monitoring of oxidative stress and the quantification of primary DNA lesions in order to identify biological markers associated with a potential pro-carcinogenic response of diesel or biodiesel, with or without filters, in a relevant system of in vivo exposition.

Keywords: diesel exhaust exposed rats, γH2AX, indirect genotoxicity, lung carcinogenicity, telomerase activity, telomeres length

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Authors: Elena Maria Scalisi

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The increasing production and the use of TiO₂ nanoparticles (NPs) have inevitably led to their release into the environment, thereby posing a threat to organisms and also for human. Human exposure to TiO₂-NPs may occur during both manufacturing and use. TiO₂-NPs are common in consumer products for dermal application, toothpaste, food colorants, and nutritional supplements, then oral exposure may occur during use of such products. Into the body, TiO₂-NPs thanks to their small size (<100 nm), can, through testicular blood barrier inducing effect on testis and then on male reproductive health. The nanoscale size of TiO₂ increase the surface-to-volume ratio making them more reactive in a cell, then TiO₂ NPs increase their ability to produce reactive oxygen species (ROS). In male germ cells, ROS may have important implications in maintaining the normal functions of mature spermatozoa at physiological levels, moreover, in spermatozoa they are important signaling molecules for their hyperactivation and acrosome reaction. Nevertheless, an excess of ROS by external inputs such as NPs can increased the oxidative stress (OS), which results in damage DNA and apoptosis. The aim of our study has been investigate the impact of TiO₂ NPs on human spermatozoa, evaluating DNA damage and the expression of proteins involved in cell stress. According WHO guidelines 2021, we have exposed human spermatozoa in vitro to TiO₂ NP at concentrations 50 ppm, 100 ppm, 250 ppm, and 500 ppm for 1 hour (at 37°C and CO₂ at 5%). DNA damage was evaluated by Sperm Chromatin Dispersion Test (SCD) and TUNEL assay; moreover, we have evaluated the expression of biomarkers of oxidative stress like Heat Shock Protein 70 (HSP70) and Metallothioneins (MTs). Also, sperm parameters as motility viability have been evaluated. Our results not report a significant reduction in motility of spermatozoa at the end of the exposure. On the contrary, the progressive motility was increased at the highest concentration (500 ppm) and was statistically significant compared to control (p <0.05). Also, viability was not changed by exposure to TiO₂-NPs (p <0.05). However, increased DNA damage was observed at all concentrations, and the TUNEL assay highlighted the presence of single strand breaks in the DNA. The spermatozoa responded to the presence of TiO₂-NPs with the expression of Hsp70, which have a protective function because they allow the maintenance of cellular homeostasis in stressful/ lethal conditions. A positivity for MTs was observed mainly for the concentration of 4 mg/L. Although the biological and physiological function of the metallothionein (MTs) in the male genital organs is unclear, our results highlighted that the MTs expressed by spermatozoa maintain their biological role of detoxification from metals. Our results can give additional information to the data in the literature on the toxicity of TiO₂-NPs and reproduction.

Keywords: human spermatozoa, DNA damage, TiO₂-NPs, biomarkers

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Authors: Kyung Jin Kim, Jiwon Kwak, Jae-Hoon Lee, Soo Suk Lee

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MicroRNAs (miRNA) are a class of endogenous, single-stranded, small, and non-protein coding RNA molecules typically 20-25 nucleotides long. They are thought to regulate the expression of other genes in a broad range by binding to 3’- untranslated regions (3’-UTRs) of specific mRNAs. The detection of miRNAs is very important for understanding of the function of these molecules and in the diagnosis of variety of human diseases. However, detection of miRNAs is very challenging because of their short length and high sequence similarities within miRNA families. So, a simple-to-use, low-cost, and highly sensitive method for the detection of miRNAs is desirable. In this study, we demonstrate a novel bi-directional extension (BDE) assay. In the first step, a specific linear RT primer is hybridized to 6-10 base pairs from the 3’-end of a target miRNA molecule and then reverse transcribed to generate a cDNA strand. After reverse transcription, the cDNA was hybridized to the 3’-end which is BDE sequence; it played role as the PCR template. The PCR template was amplified in an SYBR green-based quantitative real-time PCR. To prove the concept, we used human brain total RNA. It could be detected quantitatively in the range of seven orders of magnitude with excellent linearity and reproducibility. To evaluate the performance of BDE assay, we contrasted sensitivity and specificity of the BDE assay against a commercially available poly (A) tailing method using miRNAs for let-7e extracted from A549 human epithelial lung cancer cells. The BDE assay displayed good performance compared with a poly (A) tailing method in terms of specificity and sensitivity; the CT values differed by 2.5 and the melting curve showed a sharper than poly (A) tailing methods. We have demonstrated an innovative, cost-effective BDE assay that allows improved sensitivity and specificity in detection of miRNAs. Dynamic range of the SYBR green-based RT-qPCR for miR-145 could be represented quantitatively over a range of 7 orders of magnitude from 0.1 pg to 1.0 μg of human brain total RNA. Finally, the BDE assay for detection of miRNA species such as let-7e shows good performance compared with a poly (A) tailing method in terms of specificity and sensitivity. Thus BDE proves a simple, low cost, and highly sensitive assay for various miRNAs and should provide significant contributions in research on miRNA biology and application of disease diagnostics with miRNAs as targets.

Keywords: bi-directional extension (BDE), microRNA (miRNA), poly (A) tailing assay, reverse transcription, RT-qPCR

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Authors: Ali Mashayekh, Mahdiye Khorasani, Thomas weyh

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The demand for battery electric vehicles (BEV) is steadily increasing, and it can be assumed that electric mobility will dominate the market for individual transportation in the future. Regarding BEVs, the focus of state-of-the-art research and development is on vehicle batteries since their properties primarily determine vehicles' characteristic parameters, such as price, driving range, charging time, and lifetime. State-of-the-art battery packs consist of invariable configurations of battery cells, connected in series and parallel. A promising alternative is battery systems based on multilevel inverters, which can alter the configuration of the battery cells during operation via semiconductor switches. The main benefit of such topologies is that a three-phase AC voltage can be directly generated from the battery pack, and no separate power inverters are required. Therefore, modular battery systems based on different multilevel inverter topologies and reconfigurable battery systems are currently under investigation. Another advantage of the multilevel concept is that the possibility to reconfigure the battery pack allows battery cells with different states of charge (SoC) to be connected in parallel, and thus low-loss balancing can take place between such cells. In contrast, in conventional battery systems, parallel connected (hard-wired) battery cells are discharged via bleeder resistors to keep the individual SoCs of the parallel battery strands balanced, ultimately reducing the vehicle range. Different multilevel inverter topologies and reconfigurable batteries have been described in the available literature that makes the before-mentioned advantages possible. However, what has not yet been described is how an intelligent operating algorithm needs to look like to keep the SoCs of the individual battery strands of a modular battery system with integrated power electronics balanced. Therefore, this paper suggests an SoC balancing approach for Battery Modular Multilevel Management (BM3) converter systems, which can be similarly used for reconfigurable battery systems or other multilevel inverter topologies with parallel connectivity. The here suggested approach attempts to simultaneously utilize all converter modules (bypassing individual modules should be avoided) because the parallel connection of adjacent modules reduces the phase-strand's battery impedance. Furthermore, the presented approach tries to reduce the number of switching events when changing the switching state combination. Thereby, the ohmic battery losses and switching losses are kept as low as possible. Since no power is dissipated in any designated bleeder resistors and no designated active balancing circuitry is required, the suggested approach can be categorized as a proactive balancing approach. To verify the algorithm's validity, simulations are used.

Keywords: battery management system, BEV, battery modular multilevel management (BM3), SoC balancing

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Authors: Anuranjani Kumar, Madhu Bala

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Ionising radiation exposure induces generation of free radicals and the oxidative DNA damage. SBL-1, a radioprotective leaf extract prepared from leaves Hippophae rhamnoides L. (Common name; Seabuckthorn), showed > 90% survival in mice population that was treated with lethal dose (10 Gy) of ⁶⁰Co gamma irradiation. In this study, early effects of pre-treatment with or without SBL-1 in blood peripheral blood lymphocytes (PBMCs) were investigated by cell viability assays (trypan blue and MTT). The quantitative in vitro study of Hoescht/PI staining was performed to check the apoptosis/necrosis in PBMCs irradiated at 2 Gy with or without pretreatment of SBL-1 (at different concentrations) up to 24 and 48h. Comet assay was performed in vivo, to detect the DNA strands breaks and its repair mechanism on peripheral blood lymphocytes at lethal dose (10 Gy). For this study, male mice (wt. 28 ± 2g) were administered radioprotective dose (30mg/kg body weight) of SBL-1, 30 min prior to irradiation. Animals were sacrificed at 24h and 48h. Blood was drawn through cardiac puncture, and blood lymphocytes were separated using histopaque column. Both neutral and alkaline comet assay were performed using standardized technique. In irradiated animals, alkaline comet assay revealed single strand breaks (SSBs) that showed significant (p < 0.05) increase in percent DNA in tail and Olive tail moment (OTM) at 24 h while at 48h the percent DNA in tail further increased significantly (p < 0.02). The double strands breaks (DSBs) increased significantly (p < 0.01) at 48 h in neutral assay, in comparison to untreated control. The animals pre-treated with SBL-1 before irradiation showed significantly (p < 0.05) less DSBs at 48 h treatment in comparison to irradiated group of animals. The SBL-1 alone treated group itself showed no toxicity. The antioxidant potential of SBL-1 were also investigated by in vitro biochemical assays such as DPPH (p < 0.05), ABTS, reducing ability (p < 0.09), hydroxyl radical scavenging (p < 0.05), ferric reducing antioxidant power (FRAP), superoxide radical scavenging activity (p < 0.05), hydrogen peroxide scavenging activity (p < 0.05) etc. SBL-1 showed strong free radical scavenging power that plays important role in the studies of radiation-induced injuries. The SBL-1 treated PBMCs showed significant (p < 0.02) viability in trypan blue assay at 24-hour incubation.

Keywords: radiation, SBL-1, SSBs, DSBs, FRAP, PBMCs

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Authors: Razan Salem

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Gender plays a vital role in the stock markets because men and women differ in their behavior when investing in stocks. Accordingly, the role of gender differences in investment behavior is an increasingly important strand in the field of behavioral finance research. The investment behaviors of women relative to men have been examined in the behavioral finance literature, mainly for comparison purposes. Women's roles in the stock market have not been examined in the behavioral finance literature, however, particularly with respect to the Arab region. This study aims to contribute towards a better understanding of the investment behavior of Arab women (in regards to their risk tolerance, investment confidence, and investment literacy levels) relative to Arab men; using a sample from Arab women and men investors living in Saudi Arabia and Jordan. In order to achieve the study's main aim, the researcher used non-parametric tests, as Mann-Whitney U test, along with frequency distribution analysis to analyze the study’s primary data. The researcher distributed close-ended online questionnaires to a sample of 550 Arab male and female individuals investing in stocks in both Saudi Arabia and Jordan. The results confirm that the sample Arab women invest less in stocks compared to Arab men due to their risk-averse behaviors and limited confidence levels. The results also reveal that due to Arab women’s very low investment literacy levels, they fear from taking the risk and invest often in stocks relative to Arab men. Overall, the study’s main variables (risk tolerance, investment confidence, and investment literacy levels) have a combined effect on the investment behavior of Arab women and their limited participation in the stock market. Hence, this study is one of the very first studies that indicate the combined effect of the three main variables (which are usually studied separately in the existing literature) on the investment behavior of women, particularly Arab women. This study makes three important contributions to the growing literature on gender differences in investment behavior. First, while the behavioral finance literature documents evidence on gender differences in investment behaviors in many developed countries, there are very limited studies that investigate such differences in Arab countries. Arab women investors, generally, are ignored from the behavioral finance literature due probably to cultural barriers and data collection difficulties. Thus, this study extends the literature to include Arab women and their investment behaviors when trading stock relative to Arab men. Moreover, the study associates women investment literacy and confidence levels with their financial risk behaviors and participation in the stock market. This study provides direct evidence on Arab women's investment behaviors when trading stocks. Overall, studying Arab women investors is important to investigate whether the investment behavior identified for Western women investors are also found in Arab women investors.

Keywords: Arab women, gender differences, investment behavior, stock markets

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Authors: Malcolm Richardson, Gabriele Richardson

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This paper illustrates how historical problems can be studied successfully using GIS even in cases in which data, in the modern sense, is fragmentary. The overall problem under investigation is how early (1300-1500) English schools of Common Law moved from apprenticeship training in random individual London inns run in part by clerks of the royal chancery to become what is widely called 'the Third University of England,' a recognized system of independent but connected legal inns. This paper focuses on the preparatory legal inns, called the Inns of Chancery, rather than the senior (and still existing) Inns of Court. The immediate problem studied in this paper is how the junior legal inns were organized, staffed, and located from 1292 to about 1500, and what maps tell us about the role of the chancery clerks as managers of legal inns. The authors first uncovered the names of all chancery clerks of the period, most of them unrecorded in histories, from archival sources in the National Archives, Kew. Then they matched the names with London property leases. Using ArcGIS, the legal inns and their owners were plotted on a series of maps covering the period 1292 to 1500. The results show a distinct pattern of ownership of the legal inns and suggest a narrative that would help explain why the Inns of Chancery became serious centers of learning during the fifteenth century. In brief, lower-ranking chancery clerks, always looking for sources of income, discovered by 1370 that legal inns could be a source of income. Since chancery clerks were intimately involved with writs and other legal forms, and since the chancery itself had a long-standing training system, these clerks opened their own legal inns to train fledgling lawyers, estate managers, and scriveners. The maps clearly show growth patterns of ownership by the chancery clerks for both legal inns and other London properties in the areas of Holborn and The Strand between 1450 and 1417. However, the maps also show that a royal ordinance of 1417 forbidding chancery clerks to live with lawyers, law students, and other non-chancery personnel had an immediate effect, and properties in that area of London leased by chancery clerks simply stop after 1417. The long-term importance of the patterns shown in the maps is that while the presence of chancery clerks in the legal inns likely created a more coherent education system, their removal forced the legal profession, suddenly without a hostelry managerial class, to professionalize the inns and legal education themselves. Given the number and social status of members of the legal inns, the effect on English education was to free legal education from the limits of chancery clerk education (the clerks were not practicing common lawyers) and to enable it to become broader in theory and practice, in fact, a kind of 'finishing school' for the governing (if not noble) class.

Keywords: GIS, law, London, education

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Authors: Evelyn Kropfreiter, Roland Bernhard

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There has been an increased interest in school-based whole-child development in the Austrian education system in the last few years. Although there is a consensus among academics that teachers' beliefs are an essential component of their professional competence, there are hardly any studies in the German-speaking world examining teachers' beliefs about school-based character education. To close this gap, we are conducting a mixed methods study combining qualitative interviews and a questionnaire in Austria (doctoral thesis at the University of Salzburg). In this paper, we present preliminary insights into the quantitative strand of the project. In contrast to German-speaking countries, the Anglo-Saxon world has a long tradition of explicit character education in schools. There has been a rising interest in approaches focusing on a neo-Aristotelian form of character education in England. The Jubilee Centre strongly influences the "renaissance" of papers on neo-Aristotelian character education for Character and Virtues, founded in 2012. The quantitative questionnaire study (n = 264) is an online survey of teachers and school principals conducted in four different federal states in spring 2023. Most respondents (n = 264) from lower secondary schools (AHS-Unterstufe and Mittelschule) believe that character education in schools for 10-14-year-olds is more important for society than good exam results. Many teachers state that they consider themselves prepared to promote their students' personal development and life skills through their education and to attend further training courses. However, there are many obstacles in the education system to ensure that a comprehensive education reaches the students. Many teachers state that they consider themselves prepared to promote their students' character strengths and life skills through their education and to attend further training courses. However, there are many obstacles in the education system to ensure that a comprehensive education reaches the students. Among the most cited difficulties, teachers mention the time factor associated with an overcrowded curriculum and a strong focus on performance, which often leaves them needing more time to keep an eye on nurturing the whole person. The fact that character education is not a separate subject, and its implementation needs to be monitored also makes it challenging to implement it in everyday school life. Austrian teachers prioritize moral virtues such as compassion and honesty as character strengths in everyday school life and resilience and commitment in the next place. Our results are like those reported in other studies on teacher's beliefs about character education. They indicate that Austrian teachers want to teach character in their schools but see systemic constraints such as the curriculum, in which personality roles play a subordinate role, and the focus on performance testing in the school system and the associated lack of time as obstacles to fostering more character development in students.

Keywords: character education, life skills, teachers' beliefs, virtues

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