Search results for: receptor activation

Authors: Saâd Oukkass, Abderrahim Bouftou, Rachid Ouchn, L. Lebrun, Miloudi Hlaibi

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We invariably exist in a world steeped in colors, whether in our clothing, food, cosmetics, or even medications. However, most of the dyes we use pose significant problems, being both harmful to the environment and resistant to degradation. Among these dyes, methylene blue and acid yellow 61 stand out, commonly used to dye various materials such as cotton, wood, and silk. Fortunately, various methods have been developed to treat and remove these polluting dyes, among which membrane processes play a prominent role. These methods are praised for their low energy consumption, ease of operation, and their ability to achieve effective separation of components. Adsorption on activated carbon is also a widely employed technique, complementing the basic processes. It proves particularly effective in capturing and removing organic compounds from water due to its substantial specific surface area while retaining its properties unchanged. In the context of our study, we examined two crucial aspects. Firstly, we explored the possibility of selectively extracting methylene blue from a mixture containing another dye, acid yellow 61, using a polymer inclusion membrane (PIM) made of PVA. After characterizing the morphology and porosity of the membrane, we applied kinetic and thermodynamic models to determine the values of permeability (P), initial flux (J0), association constant (Kass), and apparent diffusion coefficient (D*). Subsequently, we measured activation parameters (activation energy (Ea), enthalpy (ΔH#ass), entropy (ΔS#)). Finally, we studied the effect of activated carbon on the processes carried out through the membrane, demonstrating a clear improvement. These results make the membrane developed in this study a potentially pivotal player in the field of membrane separation.

Keywords: dyes, methylene blue, membrane, activated carbon

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Authors: Syed Asif Hassan, Tabrej Khan

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Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

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Authors: Malvina Hoxha, Valerie Capra, Carola Buccellati, Angelo Sala, Clara Cena, Roberta Fruttero, Massimo Bertinaria, G. Enrico Rovati

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Today COXIBs are used in the treatment of arthritis and many other painful conditions in selected patients with high gastrointestinal risk and low CV risk. Previously we found a new mechanism of action of a traditional NSAID (diclofenac) and a COXIB (lumiracoxib) that possess weak competitive antagonism at the TP receptor. We hypothesize that modifying the structure of a known specific inhibitor of cyclooxygenase-2 (COXIB), so that it becomes also a more potent thromboxane antagonist will preserve the anti-inflammatory and gastrointestinal safety typical of COXIBs and prevent the cardiovascular risk associated with long term therapy.

Keywords: cyclooxygenase, inflammation, lumiracoxib, thromboxane A2

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Authors: Yi-An Liao, Lu-Wei Kuo, Yu-Jen Shih, Yao-Hui Huang

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Abstract—Imidacloprid (IMI, a widely used pesticide, iImidacloprid (IMI), a widely used pesticide, is known to affect the bee populations. A sulfate radical-based oxidation method was utilized to remove the commercial pesticide consisted of IMI, dimethylacetamide, N-methyl-2-pyrrolidone, and methanol (TOC0 = 497 ppm). The experimental results evidenced that sulfate radicals created by UV activation (254nm, 6.4 mW/cm2) of S2O82- could remove 97% of total organic carbon (TOC) from the synthetic wastewater in 4 h using 120 mM of oxidant dosage. The dose of oxidant, temperature and the light flux were the key factors to further improve the mineralization efficiency, while the ferrous ions decreased the efficacy of UV/S2O82- reaction due to the competition of UV-adsorption by complex formation of FeSO4+.s known to affect the bee populations. A sulfate radical-based oxidation method was utilized to remove the commercial pesticide consisted of IMI, dimethylacetamide, N-methyl-2-pyrrolidone, and methanol (TOC0 = 497 ppm). The experimental results evidenced that sulfate radicals created by UV activation (254nm, 6.4 mW/cm2) of S2O82- could remove 97% of total organic carbon (TOC) from the synthetic wastewater in 4 h using 120 mM of oxidant dosage. The dose of oxidant, temperature and the light flux were the key factors to further improve the mineralization efficiency, while the ferrous ions decreased the efficacy of UV/S2O82- reaction due to the competition of UV-adsorption by complex formation of FeSO4+.

Keywords: organic nitrogen, photochemical oxidation, imidacloprid, UV-persulfate, mineralization

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Authors: Hao Yang, Lei Chen, Ting Mei, Jianbang Zheng

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Currently, the uncooled PbSe photodetectors in the mid-infrared range (2-5μm) with sensitization technology extract more photoelectric response than traditional ones, and enable the room temperature (300K) photo-detection with high detectivity, which have attracted wide attentions in many fields. This technology generally contains the film fabrication with vapor phase deposition (VPD) and a sensitizing process with doping of oxygen and iodine. Many works presented in the recent years almost provide and high temperature activation method with oxygen/iodine vapor diffusion, which reveals that oxygen or iodine plays an important role in the sensitization of PbSe material. In this paper, we provide our latest experimental results and discussions in the stoichiometry of oxygen and iodine and its influence on the polycrystalline structure and photo-response. The experimental results revealed that crystal orientation was transformed from (200) to (420) by sensitization, and the responsivity of 5.42 A/W was gained by the optimal stoichiometry of oxygen and iodine with molecular density of I2 of ~1.51×1012 mm-3 and oxygen pressure of ~1Mpa. We verified that I2 plays a role in transporting oxygen into the lattice of crystal, which is actually not its major role. It is revealed that samples sensitized with iodine transform atomic proportion of Pb from 34.5% to 25.0% compared with samples without iodine from XPS data, which result in the proportion of about 1:1 between Pb and Se atoms by sublimation of PbI2 during sensitization process, and Pb/Se atomic proportion is controlled by I/O atomic proportion in the polycrystalline grains, which is very an important factor for improving responsivity of uncooled PbSe photodetector. Moreover, a novel sensitization and dopant activation method is proposed using oxygen ion implantation with low ion energy of < 500eV and beam current of ~120μA/cm2. These results may be helpful to understanding the sensitization mechanism of polycrystalline lead salt materials.

Keywords: polycrystalline PbSe, sensitization, transport, stoichiometry

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

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

Keywords: IRS1, SNP, TCF7L2, type 2 diabetes

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Authors: Liong-Rung Liu, Yu-Hui Chiu, Wen-Han Chang

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Firearm injuries are high-energy injuries. The ballistic pathways could cause severe burns or chemical damages to vessels, musculoskeletal or other major organs. The high mortality rate is accompanied by complications such as sepsis. As laws prohibit gun possession, civilian gunshot wounds (GSW) are relatively rare in Taiwan. Our hospital, Mackay Memorial Hospital, located at the center of Taipei city is surrounded by nightclubs and red-light districts. Due to this unique location, our hospital becomes the first-line trauma center managing gunshot victims in Taiwan. To author’s best knowledge, there are few published research articles regarding this unique situation. We hereby analyze the distinct characteristics and length of stay (LOS) of GSW patients in the emergency room (ER) at Mackay Memorial Hospital. A 6-year retrospective analysis of 27 patients treated for GSW injuries from January 2012 to December 2017 was performed. The patients’ records were reviewed for the following analyses, 1) wound position and the correlated clinical presentations; 2) the LOS in ED of patients receiving emergency surgery for major organ or vascular injuries. We found males (96.3%) were injured by guns more often than females (3.7%) in all age groups. The most common injured site was in the extremities. With regards to the ER LOS, the average time were 72.2 ± 34.5 minutes for patients with triage I and 207.4 ± 143.9 minutes for patients with triage II. The ED LOS of patients whose ISS score were more than 15 was 59.9 ± 25.6 minutes, and 179.4 ± 119.8 minutes for patients whose ISS score were between 9 to 15, respectively. Among these 27 patients, 10 patients had emergency surgery and their average ED stay time was 104.5 ± 33.3 minutes. Even more, the average ED stay time could be shortened to 88.8 ± 32.3 minutes in the 5 patients with trauma team activation. In conclusion, trauma team activation in severe GSW patients indeed shortens the ED LOS and might initially improve the quality of patient care. This is the result of better trauma systems, including advances in care from emergency medical services and acute care surgical management.

Keywords: gunshot, length of stay, trauma, mortality

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Authors: Yihunie Hibstie Asres, Manny Mathuthu

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Farmers may not be conscious for their farmland’s nutrients, soil organic matter, water and air because they simply concerned only for their labor availability and soil fertility losses. The composition and proportion of these components greatly influence soil physical properties, including texture, structure, and porosity, the fraction of pore space in a soil. The soil of this farmland must be able to supply adequate amount of plant nutrients, in forms which can be absorbed by the crop, within its lifespan. Deficiencies or imbalances in the supply of any of essential elements can compromise growth, affecting root development, cell division, crop quality, crop yield and resistance to disease and drought. This study was conducted to fill this knowledge gap in order to develop economically vital and environmentally accepted nutrient management strategies for the use of soils in agricultural lands. The objective of this study is to assess the elemental contents and concentration of soil samples collected from farmlands of ‘Yebrage’ using Neutron Activation Analysis (NAA) techniques regardless of oxidation state, chemical form or physical locations. NAA is used to determine the elemental composition and concentrations present in a soil. The macro/micronutrient and organic matter deficiencies have been verified in agricultural soils through increased use of soil testing and plant analysis. The challenge for agriculture over the coming decades will meet the world’s increasing demands for food in a sustainable way. Current issues and future challenges point out that as long as agriculture remains a soil-based industry, major decreases in productivity likely to be attained ensuring that plants do not have adequate and balanced supply of nutrients.

Keywords: NAA, Yebrage, Chemoga, macro/micronutrient

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Authors: Mohamed Abd Esselem Dems, Souhila Laib, Nadjia Latelli, Nadia Ouddai

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In this work, we have developed QSAR model for Relative Binding Affinity (RBA) of a large diverse set of estradiol among these derivatives, the organometallic derivatives. By dividing the dataset into a training set of 24 compounds and a test set of 6 compounds. The DFT method was used to calculate quantum chemical descriptors and physicochemical descriptors (MR and MLOGP) were performed using E-Dragon. All the validations indicated that the QSAR model built was robust and satisfactory (R2 = 90.12, Q2LOO = 86.61, RMSE = 0.272, F = 60.6473, Q2ext =86.07). We have therefore apply this model to predict the RBA, for two isomers β and α wherein Mn(CO)3 complex with the aromatic ring of estradiol, and the two isomers show little appreciation for the estrogenic receptor (RBAβ = 1.812 and RBAα = 1.741).

Keywords: DFT, estradiol, haptotropic rearrangement, QSAR, relative binding affinity

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Authors: Janneth González, George Barreto, Ludis Morales, Angélica Sabogal

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Sea anemone neurotoxins are peptides that interact with Na+ and K+ channels, resulting in specific alterations on their functions. Some of these neurotoxins (1ROO, 1BGK, 2K9E, 1BEI) are important for the treatment of nearly eighty autoimmune disorders due to their specificity for Kv1.3 channel. The aim of this study was to identify the common residues among these neurotoxins by computational methods, and establish whether there is a pattern useful for the future generation of a treatment for autoimmune diseases. Our results showed eight new key common residues between the studied neurotoxins interacting with a histidine ring and the selectivity filter of the receptor, thus showing a possible pattern of interaction. This knowledge may serve as an input for the design of more promising drugs for autoimmune treatments.

Keywords: neurotoxins, potassium channel, Kv1.3, computational methods, autoimmune diseases

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Authors: Katarzyna Wal, Wojciech Stawiński, Piotr Rutkowski

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The scientific community is paying more and more attention to the problem of air pollution. Carbon dioxide is classified as one of the most harmful gases. Its emissions are generated during fossil fuel burning, waste management, and combustion and are responsible for global warming. Clay minerals constitute a group of promising materials for the role of adsorbents. They are composed of two types of phyllosilicate sheets: tetrahedral and octahedral, which form 1:1 or 2:1 structures. Vermiculite is one of their best-known representative, which can be used as an adsorbent from water and gaseous phase. The aim of the presented work was carbon dioxide adsorption on vermiculite. Acid-activated samples (W_NO3_x) were prepared by acid treatment with different concentrations of nitric acid (1, 2, 3, 4 mol L⁻¹). Vermiculite was subjected to modification in order to increase its porosity and adsorption properties. The prepared adsorbents were characterized using the BET-specific surface area analysis, thermogravimetry (TG), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). Applied modifications significantly increase the specific surface area from 78,21 m² g⁻¹ for the unmodified sample (W_REF) to 536 m² g-1 for W_NO3_4. Obtained results showed that acid treatment tunes the material’s functional properties by increasing the contact surface and generating more active sites in its structure. The adsorption performance in terms carbon dioxide adsorption capacities follows the order of W_REF (25.91 mg g⁻¹) < W_NO3_1 (38.54 mg g⁻¹) < W_NO3_2 (44.03 mg g⁻¹) W_NO3_4 (67.51 mg g⁻¹) < W_NO3_3 (70.48 mg g⁻¹). Acid activation significantly improved the carbon dioxide adsorption properties of modified samples compared to raw material. These results demonstrate that vermiculite-based samples have the potential to be used as effective CO₂ adsorbents. Furthermore, acid treatment is a promising technique for improving the adsorption properties of clay minerals.

Keywords: adsorption, adsorbent, clay minerals, air pollution, environment

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Authors: Nahush Modak, Meena Pangarkar, Anand Pathak, Ankita Tamhane

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Background: Breast cancer is the prominent cause of cancer and mortality among women. This study was done to show the statistical analysis of a cohort of over 250 patients detected with breast cancer diagnosed by oncologists using Immunohistochemistry (IHC). IHC was performed by using ER; PR; HER2; Ki-67 antibodies. Materials and methods: Formalin fixed Paraffin embedded tissue samples were obtained by surgical manner and standard protocol was followed for fixation, grossing, tissue processing, embedding, cutting and IHC. The Ventana Benchmark XT machine was used for automated IHC of the samples. Antibodies used were supplied by F. Hoffmann-La Roche Ltd. Statistical analysis was performed by using SPSS for windows. Statistical tests performed were chi-squared test and Correlation tests with p<.01. The raw data was collected and provided by National Cancer Insitute, Jamtha, India. Result: Luminal B was the most prevailing molecular subtype of Breast cancer at our institute. Chi squared test of homogeneity was performed to find equality in distribution and Luminal B was the most prevalent molecular subtype. The worse prognostic indicator for breast cancer depends upon expression of Ki-67 and her2 protein in cancerous cells. Our study was done at p <.01 and significant dependence was observed. There exists no dependence of age on molecular subtype of breast cancer. Similarly, age is an independent variable while considering Ki-67 expression. Chi square test performed on Human epidermal growth factor receptor 2 (HER2) statuses of patients and strong dependence was observed in percentage of Ki-67 expression and Her2 (+/-) character which shows that, value of Ki depends upon Her2 expression in cancerous cells (p<.01). Surprisingly, dependence was observed in case of Ki-67 and Pr, at p <.01. This shows that Progesterone receptor proteins (PR) are over-expressed when there is an elevation in expression of Ki-67 protein. Conclusion: We conclude from that Luminal B is the most prevalent molecular subtype at National Cancer Institute, Jamtha, India. There was found no significant correlation between age and Ki-67 expression in any molecular subtype. And no dependence or correlation exists between patients’ age and molecular subtype. We also found that, when the diagnosis is Luminal A, out of the cohort of 257 patients, no patient shows >14% Ki-67 value. Statistically, extremely significant values were observed for dependence of PR+Her2- and PR-Her2+ scores on Ki-67 expression. (p<.01). Her2 is an important prognostic factor in breast cancer. Chi squared test for Her2 and Ki-67 shows that the expression of Ki depends upon Her2 statuses. Moreover, Ki-67 cannot be used as a standalone prognostic factor for determining breast cancer.

Keywords: breast cancer molecular subtypes , correlation, immunohistochemistry, Ki-67 and HR, statistical analysis

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Authors: Beata Spilakova, Daniel J. Shaw, Radek Marecek, Milan Brazdil

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Hyperscanning affords a unique insight into the brain dynamics underlying human interaction by simultaneously scanning two or more individuals’ brain responses while they engage in dyadic exchange. This provides an opportunity to observe dynamic brain activations in all individuals participating in interaction, and possible interbrain effects among them. The present research aims to provide an experimental paradigm for hyperscanning research capable of delineating among different forms of interaction. Specifically, the goal was to distinguish between two dimensions: (1) interaction structure (concurrent vs. turn-based) and (2) goal structure (competition vs cooperation). Dual-fMRI was used to scan 22 pairs of participants - each pair matched on gender, age, education and handedness - as they played the Pattern Game. In this simple interactive task, one player attempts to recreate a pattern of tokens while the second player must either help (cooperation) or prevent the first achieving the pattern (competition). Each pair played the game iteratively, alternating their roles every round. The game was played in two consecutive sessions: first the players took sequential turns (turn-based), but in the second session they placed their tokens concurrently (concurrent). Conventional general linear model (GLM) analyses revealed activations throughout a diffuse collection of brain regions: The cooperative condition engaged medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC); in the competitive condition, significant activations were observed in frontal and prefrontal areas, insula cortices and the thalamus. Comparisons between the turn-based and concurrent conditions revealed greater precuneus engagement in the former. Interestingly, mPFC, PCC and insulae are linked repeatedly to social cognitive processes. Similarly, the thalamus is often associated with a cognitive empathy, thus its activation may reflect the need to predict the opponent’s upcoming moves. Frontal and prefrontal activation most likely represent the higher attentional and executive demands of the concurrent condition, whereby subjects must simultaneously observe their co-player and place his own tokens accordingly. The activation of precuneus in the turn-based condition may be linked to self-other distinction processes. Finally, by performing intra-pair correlations of brain responses we demonstrate condition-specific patterns of brain-to-brain coupling in mPFC and PCC. Moreover, the degree of synchronicity in these neural signals related to performance on the game. The present results, then, show that different types of interaction recruit different brain systems implicated in social cognition, and the degree of inter-player synchrony within these brain systems is related to nature of the social interaction.

Keywords: brain-to-brain coupling, hyperscanning, pattern game, social interaction

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Authors: Sinarwati Mohamad Suhaili, Naomie Salim, Mohamad Nazim Jambli

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Sequence-to-sequence (seq2seq) models augmented with attention mechanisms are playing an increasingly important role in automated customer service. These models, which are able to recognize complex relationships between input and output sequences, are crucial for optimizing chatbot responses. Central to these mechanisms are neural attention weights that determine the focus of the model during sequence generation. Despite their widespread use, there remains a gap in the comparative analysis of different attention weighting functions within seq2seq models, particularly in the domain of chatbots using the Customer Support Twitter (CST) dataset. This study addresses this gap by evaluating four distinct attention-scoring functions—dot, multiplicative/general, additive, and an extended multiplicative function with a tanh activation parameter — in neural generative seq2seq models. Utilizing the CST dataset, these models were trained and evaluated over 10 epochs with the AdamW optimizer. Evaluation criteria included validation loss and BLEU scores implemented under both greedy and beam search strategies with a beam size of k=3. Results indicate that the model with the tanh-augmented multiplicative function significantly outperforms its counterparts, achieving the lowest validation loss (1.136484) and the highest BLEU scores (0.438926 under greedy search, 0.443000 under beam search, k=3). These results emphasize the crucial influence of selecting an appropriate attention-scoring function in improving the performance of seq2seq models for chatbots. Particularly, the model that integrates tanh activation proves to be a promising approach to improve the quality of chatbots in the customer support context.

Keywords: attention weight, chatbot, encoder-decoder, neural generative attention, score function, sequence-to-sequence

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Authors: Hamed Karimian, Noraziah Nordin, Mohamad Ibrahim Noordin, Syam Mohan, Mahboubeh Razavi, Najihah Mohd Hashim, Happipah Mohd Ali

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Satureja bachtiarica Bunge is a perennial medicinal plant belonging to the Lamiaceae family and endemic species in Iran. Satureja bachtiarica Bunge with the local name of Marzeh koohi is edible vegetable use as flavoring agent, anti-bacterial and to relieve cough and indigestion. In this study, the anti-cancer effect of Satureja bachtiarica Bunge on the MDA-MB-231 cell line as an Breast cancer cell model has been analyzed for the first time. Satureja bachtiarica Bunge was extracted using different solvents in the order of increasing polarity. Cytotoxicity activity of hexane extract of Satureja bachtiarica Bunge (SBHE) was observed using MTT assay. Acridine orange/Propidium iodide staining was used to detect early apoptosis; Annexin-V-FITC assay was carried out to observe the detection of cell-surface Phosphatidylserine (PS), with Annexin-Vserving as a marker for apoptotic cells. Caspase 3/7, 8 and-9 assays showed significantly activation of caspase-9 where lead intrinsic mitochondrial pathway. Bcl-2/Bax expressions and cell cycle arrest were also investigated. SBHE had exhibited significantly higher cytotoxicity against MDA-MB-231 Cell line compare to other cell lines. A significant increase in chromatin condensation in the cell nucleus was observed by fluorescence analysis. Treatment of MDA-MB-231 cells with SBHE encouraged apoptosis, by down-regulating Bcl-2 and up-regulating Bax, which lead the activation of caspase 9. Moreover, SBHE treatment significantly arrested MDA-MB-231 cells in the G1 phase. Together, the results presented in this study demonstrated that SBHE inhibited the proliferation of MDA-MB-231 cells, leading cell cycle arrest and programmed cell death, which was confirmed to be through the mitochondrial pathway.

Keywords: Satureja bachtiarica Bunge, MDA-MB-231, apoptosis, annexin-V, cell cycle

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Authors: Chro Kawyan

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Endothelin-1 (ET-1), the principal individual from the newfound mammalian endothelin group of organically dynamic peptides, was initially distinguished as a 21 buildup powerful vasoconstrictor peptide in vascular endothelial cells. However, it has since been demonstrated to have a wide range of pharmacological activities in tissues both inside and outside the cardiovascular system. Additionally, peptides that have a striking resemblance to ET-1 have been identified as the primary toxic component of snake venom. In addition, late examinations have proposed that warm blooded creatures, including people, produce three unmistakable individuals from this peptide family, ET-1, ET-2 and ET-J, which might have various profiles of organic action and may follow up on particular subtypes of endothelin receptor. Masashi Yanagisawa and Tomoh Masaki survey the ongoing status of the organic chemistry and sub-atomic science of endothelin.

Keywords: thelin, microbiology, molecular biology, cell

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Authors: Khadse Saurabh, Talele Gokul, Surana Sanjay

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In an endeavor to find a new class of anti-inflammatory agents, a series of novel benzamides (ab1-ab16) were synthesized by utilizing some arylideneoxazolones (az1-az4) having 2-acetyloxyphenyl substitution on their second position. Structures of these synthesized compounds were confirmed by IR, 1H-NMR, 13C NMR, and HRMS. Among the tested benzamide compounds 3ab1, 3ab2, 3ab11, and 3ab16 showed promising anti-inflammatory activity with lessened propensity to cause gastro-intestinal hypermotility and ulceration when compared with standard Indomethacin. Virtual screening was performed by docking the designed compounds into the ATP binding site of COX-2 receptor to predict if these compounds have analogous binding mode to the COX-2 inhibitor.

Keywords: benzamides, anti-inflammatory, gastro-intestinal hypermotility, ulcerogenic activity, docking

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Authors: Aizati N. A. Daud, Jorieke E. H. Bergman, Wilhelmina S. Kerstjens-Frederikse, Pieter Van Der Vlies, Eelko Hak, Rolf M. F. Berger, Henk Groen, Bob Wilffert

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Prenatal use of SRIs was previously associated with Congenital Heart Anomalies (CHA). The aim of the study is to explore whether pharmacogenetics plays a role in this teratogenicity using a gene-environment interaction study. A total of 33 case-mother dyads and 2 mother-only (children deceased) registered in EUROCAT Northern Netherlands were included in a case-only study. Five case-mother dyads and two mothers-only were exposed to SRIs (paroxetine=3, fluoxetine=2, venlafaxine=1, paroxetine and venlafaxine=1) in the first trimester of pregnancy. The remaining 28 case-mother dyads were not exposed to SRIs. Ten genes that encode the enzymes or proteins important in determining fetal exposure to SRIs or its mechanism of action were selected: CYPs (CYP1A2, CYP2C9, CYP2C19, CYP2D6), ABCB1 (placental P-glycoprotein), SLC6A4 (serotonin transporter) and serotonin receptor genes (HTR1A, HTR1B, HTR2A, and HTR3B). All included subjects were genotyped for 58 genetic variations in these ten genes. Logistic regression analyses were performed to determine the interaction odds ratio (OR) between genetic variations and SRIs exposure on the risk of CHA. Due to low phenotype frequencies of CYP450 poor metabolizers among exposed cases, the OR cannot be calculated. For ABCB1, there was no indication of changes in the risk of CHA with any of the ABCB1 SNPs in the children and their mothers. Several genetic variations of the serotonin transporter and receptors (SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 & rs6298, HTR3B rs1176744) were associated with an increased risk of CHA, but with too limited sample size to reach statistical significance. For SLC6A4 genetic variations, the mean genetic scores of the exposed case-mothers tended to be higher than the unexposed mothers (2.5 ± 0.8 and 1.88 ± 0.7, respectively; p=0.061). For SNPs of the serotonin receptors, the mean genetic score for exposed cases (children) tended to be higher than the unexposed cases (3.4 ± 2.2, and 1.9 ± 1.6, respectively; p=0.065). This study might be among the first to explore the potential gene-environment interaction between pharmacogenetic determinants and SRIs use on the risk of CHA. With small sample sizes, it was not possible to find a significant interaction. However, there were indications for a role of serotonin receptor polymorphisms in fetuses exposed to SRIs on fetal risk of CHA which warrants further investigation.

Keywords: gene-environment interaction, heart defects, pharmacogenetics, serotonin reuptake inhibitors, teratogenicity

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Authors: Ozlem Oral, Seval Kilic, Ozlem Yedier, Serap Dokmeci, Devrim Gozuacik

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Autophagy is a degradation pathway, activating under stress conditions. It digests macromolecules, such as abnormal proteins and long-lived organelles by engulfing them and by subsequent delivery of the cargo to lysosomes. The members of the phospholipid-dependent serine/threonine kinases, involved in many signaling pathways, which are necessary for the regulation of cellular metabolic activation. Previous studies implicate that, serine/threonine kinases have crucial roles in the mechanism of many diseases depend on the activated and/or inactivated signaling pathway. Data indicates, the signaling pathways activated by serine/threonine kinases are also involved in activation of autophagy mechanism. However, the information about the effect of serine/threonine kinases on autophagy mechanism and the roles of these effects in disease formation is limited. In this study, we investigated the effect of activated serine/threonine kinases on autophagic pathway. We performed a commonly used autophagy technique, GFP-LC3 dot formation and by using microscopy analyses, we evaluated promotion and/or inhibition of autophagy in serine/threonine kinase-overexpressed fibroblasts as well as cancer cells. In addition, we carried out confocal microscopy analyses and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. Based on the shRNA-library based screening, we identified autophagy-related proteins affected by serine/threonine kinases. We further studied the involvement of serine/threonine kinases on the molecular mechanism of newly identified autophagy proteins and found that, autophagic pathway is indirectly controlled by serine/threonine kinases via specific autophagic proteins. Our data indicate the molecular connection between two critical cellular mechanisms, which have important roles in the formation of many disease pathologies, particularly cancer. This project is supported by TUBITAK-1001-Scientific and Technological Research Projects Funding Program, Project No: 114Z836.

Keywords: autophagy, GFP-LC3 dot formation assay, serine/threonine kinases, shRNA-library screening

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Authors: Sarai Alvarado Pineda, Ricardo Maldonado Soto

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The acquisition of Verb Particle Constructions is a challenge for Spanish speakers learning English. The acquisition is particularly difficult for speakers of languages with no verb particle constructions. The purpose of the current study is to define the procedural steps in the acquisition of constructions with the particle on. There are three outstanding meanings for the particle on; Surface: The movie is based on a true story, Activation: John turn on the light, Continuity: The band played on all night. The central aim of this study is to measure how Mexican Spanish participants respond to both the three meanings mentioned above and the degree of meaning transparency/opacity of on verb particle constructions. Forty Mexican Spanish learners of English (20 basic and 20 advanced) are compared against a control group of 20 American native English speakers through a reaction time test (PsychoPy2 2015). The participants were asked to discriminate 90 items based on their knowledge of these constructions. There are 30 items per meaning divided into two groups of transparent and opaque meaning. Results revealed three major findings: Advanced students have a reaction time similar to that of native speakers (advanced 4.5s versus native 3.7s), while students with a lower level of English proficiency, show a high reaction time (7s). Likewise, there is a shorter reaction time in constructions with lower opacity in the three groups of participants, with differences between each level (basic 6.7s, advanced 4.3s, and native 3.4s). Finally, a difference in reaction time can be identified according to the meaning provided by the construction. The reaction time for the activation category (5.27s) is greater than continuity (5.04s), and this category is also slower than the surface (4.94s). The study shows that the level of sensitivity of English learners increases significantly aiming towards native speaker patterns as determined by the level of transparency of meaning of each construction as well as the degree of entrenchment of each constructional meaning.

Keywords: meaning of the particle, opacity, reaction time, verb particle constructions

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Authors: Houssam Hijazi, Laurent Cantrel, Jean-François Paul

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Periodic DFT calculations were performed to study the chemistry of CsI particles and the possible release of volatile iodine from CsI surfaces for nuclear safety interest. The results show that water adsorbs at low temperature associatively on the (011) surface of CsI, while water desorbs at higher temperatures. On the other hand, removing iodine species from the surface requires oxidizing the surface one time for each removed iodide atom. The activation energy of removing I₂ from the surface in the presence of two OH is 1,2 eV.

Keywords: aerosols, CSI, reactivity, DFT, water adsorption

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Authors: William Elnemer, Nauman Hussain, Samir Al-Ali, Henry Shu, Diane Ghanem, Babar Shafiq

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Introduction: The incidence of infection in open tibial shaft injuries varies depending on the severity of the injury, with rates ranging from 1.8% for Gustilo-Anderson type I to 42.9% for type IIIB fractures. The timely administration of antibiotics upon presentation to the emergency department (ED) is an essential component of fracture management, and evidence indicates that prompt delivery of antibiotics is associated with improved outcomes. The objective of this study is to identify factors that contribute to the expedient administration of antibiotics. Methods: This is a retrospective study of open tibial shaft fractures at an academic Level I trauma center. Current Procedural Terminology (CPT) codes identified all patients treated for open tibial shaft fractures between 2015 and 2021. Open fractures were identified by reviewing ED and provider notes, and with ballistic fractures were considered open. Chart reviews were performed to extract demographics, fracture characteristics, postoperative outcomes, time to operative room, time to antibiotic order, and delivery. Univariate statistical analysis compared patients who received early antibiotics (EA), which were delivered within one hour of ED presentation, and those who received late antibiotics (LA), which were delivered outside of one hour of ED presentation. A multivariate analysis was performed to investigate patient, fracture, and transport/ED characteristics contributing to faster delivery of antibiotics. The multivariate analysis included the dependent variables: ballistic fracture, activation of Delta Trauma, Gustilo-Andersen (Type III vs. Type I and II), AO-OTA Classification (Type C vs. Type A and B), arrival between 7 am and 11 pm, and arrival via Emergency Medical Services (EMS) or walk-in. Results: Seventy ED patients with open tibial shaft fractures were identified. Of these, 39 patients (55.7%) received EA, while 31 patients (44.3%) received LA. Univariate analysis shows that the arrival via EMS as opposed to walk-in (97.4% vs. 74.2%, respectively, p = 0.01) and activation of Delta Trauma (89.7% vs. 51.6%, respectively, p < 0.001) was significantly higher in the EA group vs. the LA group. Additionally, EA cases had significantly shorter intervals between the antibiotic order and delivery when compared to LA cases (0.02 hours vs. 0.35 hours, p = 0.007). No other significant differences were found in terms of postoperative outcomes or fracture characteristics. Multivariate analysis shows that a Delta Trauma Response, arrival via EMS, and presentation between 7 am and 11 pm were independent predictors of a shorter time to antibiotic administration (Odds Ratio = 11.9, 30.7, and 5.4, p = 0.001, 0.016, and 0.013, respectively). Discussion: Earlier antibiotic delivery is associated with arrival to the ED between 7 am and 11 pm, arrival via EMS, and a coordinated Delta Trauma activation. Our findings indicate that in cases where administering antibiotics is critical to achieving positive outcomes, it is advisable to employ a coordinated Delta Trauma response. Hospital personnel should be attentive to the rapid administration of antibiotics to patients with open fractures who arrive via walk-in or during late-night hours.

Keywords: antibiotics, emergency department, fracture management, open tibial shaft fractures, orthopaedic surgery, time to or, trauma fractures

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Authors: Milad Pirali, Sohrab Keyhani, Mohhamad Ali Sanjari, Ali Ashraf Jamshidi

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Purpose: The effect of hamstring antagonist activity on the knee extensors torque of the Anterior Cruciate Ligament reconstruction (ACLR) is not clear and persistent muscle weakness is common after ACLR. Hamstring activation when acting as antagonist is considered very important for knee strengths. Therefore the purpose of this study was to examine hamstring antagonist coactivation during maximal effort of the isokinetic knee extension in ACLR athletes with hamstring autograft. Materials and Methods: We enrolled 20 professional athletes who underwent primary ACLR (hamstring tendon autograft)with 6-24 months postoperative and 20 healthy subjects as control group. Each subjects performed maximal effort isokinetic knee extension and flexion in 60/˚ s and 180/˚ s velocities for the involved and uninvolved limb. Synchronously, surface electromyography (EMG) was recorded of vastus medialis (VM), vastus lateralis (VL), rectus femoris (RF) and biceps femoris (BF). The antagonist integrated EMG (IEMG) values were normalized to the IEMG of the same muscle during maximal isokinetic eccentric effort at the same velocities and ROM. Results: A one-way analysis of variance designs shows significantly greater IEMG coactivation of hamstring and decreased activation of Vm in ACLR when compared to uninvolved and control group leg in 60/˚ s and 180/˚ s velocities. Likewise peak torque to body weight was decreased in ACLR compared to uninvolved and control group during knee extension in both velocities (p < 0.05). Conclusions: Decreased extensors moment caused by decreased quadriceps inhibition and increased hamstring coactivation. In addition, these result indicated to decrease of motor unit recruitment in the VM (as a kinesiologicmonitore of the knee). It is appearing that strengthening of the quadriceps to be an important for rehabilitation program after ACLR for preparation in athletes endeavors. Therefore, we suggest that having more emphasis and focus on quadriceps strength and less emphasis on hamstring following ACLR.

Keywords: ACLR-coactivation, dynamometry, electromyography, isokinetic

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Authors: Lucky Malise, Hilary Rutto, Tumisang Seodigeng

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Heavy metal contamination in waste water is a very serious issue affecting a lot of industrialized countries due to the health and environmental impact of these heavy metals on human life and the ecosystem. Adsorption using activated carbon is the most promising method for the removal of heavy metals from waste water but commercial activated carbon is expensive which gives rise to the need for alternatively activated carbon derived from cheap precursors, agricultural wastes, or byproducts from other processes. In this study activated bio-carbon derived from the carbonaceous material obtained from the pyrolysis of Marula nut shells was chemically activated and used as an adsorbent for the removal of lead (II) and copper (II) ions from aqueous solution. The surface morphology and chemistry of the adsorbent before and after chemical activation with zinc chloride impregnation were studied using SEM and FTIR analysis respectively and the results obtained indicate that chemical activation with zinc chloride improves the surface morphology of the adsorbent and enhances the intensity of the surface oxygen complexes on the surface of the adsorbent. The effect of process parameters such as adsorbent dosage, pH value of the solution, initial metal concentration, contact time, and temperature on the adsorption of lead (II) and copper (II) ions onto Marula nut activated carbon were investigated, and their optimum operating conditions were also determined. The experimental data was fitted to both the Langmuir and Freundlich isotherm models, and the data fitted best on the Freundlich isotherm model for both metal ions. The adsorption kinetics were also evaluated, and the experimental data fitted the pseudo-first order kinetic model better than the pseudo second-order kinetic model. The adsorption thermodynamics were also studied and the results indicate that the adsorption of lead and copper ions is spontaneous and exothermic in nature, feasible, and also involves a dissociative mechanism in the temperature range of 25-45 °C.

Keywords: adsorption, isotherms, kinetics, marula nut shells activated carbon, thermodynamics

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Authors: Bernice Jeanne Lottering, Yi-Wen Lin

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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.

Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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

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

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Authors: Ji Su Kim, Bo Ram Choi, Ju Yeon Cho, Hyukjin Lee

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Epidermal growth factor receptor (EGFR) 19 deletion mutation gene is over-expressed in carcinoma patient. EGFR 19 deletion mutation is known as typical biomarker of non-small cell lung cancer (NSCLC), which one section in the coding exon 19 of EGFR is deleted. Therefore, there have been many attempts over the years to detect EGFR 19 deletion mutation for replacing conventional diagnostic method such as PCR and tissue biopsy. We developed a simple and facile detection platform based on Rolling Circle Amplification (RCA), which provides highly amplified products in isothermal amplification of the ligated DNA template. Limit of detection (~50 nM) and a faster detection time (~30 min) could be achieved by introducing RCA.

Keywords: EGFR19, cancer, diagnosis, rolling circle amplification (RCA), hydrogel

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Authors: Nazish Badar

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In early 2009, Pandemic type A (H1N1) Influenza virus emerged globally. Since then, it has continued circulation causing considerable morbidity and mortality. The purpose of this study was to evaluate the evolutionary changes in Influenza A (H1N1) pdm09 viruses from 2009-15 and their relevance with the current vaccine viruses. Methods: Respiratory specimens were collected with influenza-like illness and Severe Acute Respiratory Illness. Samples were processed according to CDC protocol. Sequencing and phylogenetic analysis of Haemagglutinin (HA) and neuraminidase (NA) genes was carried out comparing representative isolates from Pakistan viruses. Results: Between Jan2009 - Feb 2016, 1870 (13.2%) samples were positive for influenza A out of 14086. During the pandemic period (2009–10), Influenza A/ H1N1pdm 09 was the dominant strain with 366 (45%) of total influenza positives. In the post-pandemic period (2011–2016), a total of 1066 (59.6%) cases were positive Influenza A/ H1N1pdm 09 with co-circulation of different Influenza A subtypes. Overall, the Pakistan A(H1N1) pdm09 viruses grouped in two genetic clades. Influenza A(H1N1)pdm09 viruses only ascribed to Clade 7 during the pandemic period whereas viruses belong to clade 7 (2011) and clade 6B (2015) during the post-pandemic years. Amino acid analysis of the HA gene revealed mutations at positions S220T, I338V and P100S specially associated with outbreaks in all the analyzed strains. Sequence analyses of post-pandemic A(H1N1)pdm09 viruses showed additional substitutions at antigenic sites; S179N,K180Q (SA), D185N, D239G (CA), S202A (SB) and at receptor binding sites; A13T, S200P when compared with pandemic period. Substitution at Genetic markers; A273T (69%), S200P/T (15%) and D239G (7.6%) associated with severity and E391K (69%) associated with virulence was identified in viruses isolated during 2015. Analysis of NA gene revealed outbreak markers; V106I (23%) among pandemic and N248D (100%) during post-pandemic Pakistan viruses. Additional N-Glycosylation site; HA S179N (23%), NA I23T(7.6%) and N44S (77%) in place of N386K(77%) were only found in post-pandemic viruses. All isolates showed histidine (H) at position 275 in NA indicating sensitivity to neuraminidase inhibitors. Conclusion: This study shows that the Influenza A(H1N1)pdm09 viruses from Pakistan clustered into two genetic clades, with co-circulation of some variants. Certain key substitutions in the receptor binding site and few changes indicative of virulence were also detected in post-pandemic strains. Therefore, it is imperative to continue monitoring of the viruses for early identification of potential variants of high virulence or emergence of drug-resistant variants.

Keywords: Influenza A (H1N1) pdm09, evolutionary analysis, post pandemic period, Pakistan

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Authors: Manish Chand, Subhrojit Bagchi, R. Kumar

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A new dry tube (DT) has been installed in the tank of KAMINI research reactor, Kalpakkam India. This tube will be used for neutron activation analysis of small to large samples and testing of neutron detectors. DT tube is 375 cm height and 7.5 cm in diameter, located 35 cm away from the core centre. The experimental thermal flux at various axial positions inside the tube has been measured by irradiating the flux monitor (¹⁹⁷Au) at 20kW reactor power. The measured activity of ¹⁹⁸Au and the thermal cross section of ¹⁹⁷Au (n,γ) ¹⁹⁸Au reaction were used for experimental thermal flux measurement. The flux inside the tube varies from 10⁹ to 10¹⁰ and maximum flux was (1.02 ± 0.023) x10¹⁰ n cm⁻²s⁻¹ at 36 cm from the bottom of the tube. The Au and Zr foils without and with cadmium cover of 1-mm thickness were irradiated at the maximum flux position in the DT to find out the irradiation specific input parameters like sub-cadmium to epithermal neutron flux ratio (f) and the epithermal neutron flux shape factor (α). The f value was 143 ± 5, indicates about 99.3% thermal neutron component and α value was -0.2886 ± 0.0125, indicates hard epithermal neutron spectrum due to insufficient moderation. The measured flux profile has been validated using theoretical model of KAMINI reactor through Monte Carlo N-Particle Code (MCNP). In MCNP, the complex geometry of the entire reactor is modelled in 3D, ensuring minimum approximations for all the components. Continuous energy cross-section data from ENDF-B/VII.1 as well as S (α, β) thermal neutron scattering functions are considered. The neutron flux has been estimated at the corresponding axial locations of the DT using mesh tally. The thermal flux obtained from the experiment shows good agreement with the theoretically predicted values by MCNP, it was within ± 10%. It can be concluded that this MCNP model can be utilized for calculating other important parameters like neutron spectra, dose rate, etc. and multi elemental analysis can be carried out by irradiating the sample at maximum flux position using measured f and α parameters by k₀-NAA standardization.

Keywords: neutron flux, neutron activation analysis, neutron flux shape factor, MCNP, Monte Carlo N-Particle Code

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Authors: Viktor Soprunyuk, Wilfried Schranz, Patrick Huber

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In the present work, we show that Dynamic Mechanical Analysis (DMA) with a measurement frequency range f= 0.2 - 100 Hz is a rather powerful technique for the study of phase transitions (freezing and melting) and glass transitions of water in geometrical confinement. Inserting water into nanoporous host matrices, like e.g. Gelsil (size of pores 2.6 nm and 5 nm) or Vycor (size of pores 10 nm) allows one to study size effects occurring at the nanoscale conveniently in macroscopic bulk samples. One obtains valuable insight concerning confinement induced changes of the dynamics by measuring the temperature and frequency dependencies of the complex Young's modulus Y* for various pore sizes. Solid-liquid transitions or glass-liquid transitions show up in a softening or the real part Y' of the complex Young's modulus, yet with completely different frequency dependencies. Analysing the frequency dependent imaginary part of the Young´s modulus in the glass transition regions for different pore sizes we find a clear-cut 1/d-dependence of the calculated glass transition temperatures which extrapolates to Tg(1/d=0)=136 K, in agreement with the traditional value of water. The results indicate that the main role of the pore diameter is the relative amount of water molecules that are near an interface within a length scale of the order of the dynamic correlation length x. Thus we argue that the observed strong pore size dependence of Tg is an interfacial effect, rather than a finite size effect. We obtained similar signatures of Y* near glass transitions in different biological objects (fruits, vegetables, and bread). The values of the activation energies for these biological materials in the region of glass transition are quite similar to the values of the activation energies of supercooled water in the nanoporous confinement in this region. The present work was supported by the Austrian Science Fund (FWF, project Nr. P 28672 – N36).

Keywords: biological systems, liquids, glasses, amorphous systems, nanoporous materials, phase transition

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