Search results for: aryl hydrocarbon receptor (AhR)

Authors: Chien Y. Lin, Jung Y. Huang, Leu-Wei Lo

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A growing body of data reveals that the membrane cholesterol molecules can alter the signaling pathways of living cells. However, the understanding about how membrane cholesterol modulates receptor proteins is still lacking. Single-molecule tracking can effectively probe into the microscopic environments and thermal fluctuations of receptor proteins in a living cell. In this study we applies single-molecule optical tracking on ligand-induced dimerization process of EGFRs in the plasma membranes of two cancer cell lines (HeLa and A431) and one normal endothelial cell line (MCF12A). We tracked individual EGFR and dual receptors, diffusing in a correlated manner in the plasma membranes of live cells. We developed an energetic model by integrating the generalized Langevin equation with the Cahn-Hilliard equation to help extracting important information from single-molecule trajectories. From the study, we discovered that ligand-bound EGFRs move from non-raft areas into lipid raft domains. This ligand-induced motion is a common behavior in both cancer and normal cells. By manipulating the total amount of membrane cholesterol with methyl-β-cyclodextrin and the local concentration of membrane cholesterol with nystatin, we further found that the amount of cholesterol can affect the stability of EGFR dimers. The EGFR dimers in the plasma membrane of normal cells are more sensitive to the local concentration changes of cholesterol than EGFR dimers in the cancer cells. Our method successfully captures dynamic interactions of receptors at the single-molecule level and provides insight into the functional architecture of both the diffusing EGFR molecules and their local cellular environment.

Keywords: membrane proteins, single-molecule tracking, Cahn-Hilliard equation, EGFR dimers

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Authors: Abdolamir Allameh, Seyyed Mortaza Haghgoo, Adnan Khosravi, Esmaeil Mortaz, Mihan Pourabdollah-Toutkaboni, Sharareh Seifi

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Non-Small Cell Lung Carcinoma (NSCLC) is associated with a number of gene mutations in epidermal growth factor receptor (EGFR). The prognostic significance of mutations in exons 19 and 21, together with serum levels of EGFR, amphiregulin (AR), and Transforming Growth Factor-alpha (TGF-α) are implicated in diagnosis and treatment. The aim of this study was to examine the relationship of EGFR mutations in selected exons with the expression of relevant ligands in sera samples of NSCLC patients. For this, a group of NSCLC patients (n=98) referred to the hospital for lung surgery with a mean age of 59±10.5 were enrolled (M/F: 75/23). Blood specimen was collected from each patient. Besides, formalin fixed paraffin embedded tissues were processed for DNA extraction. Gene mutations in exons 19 and 21 were detected by direct sequencing, following DNA amplification which was done by PCR (Polymerase Chain Reaction). Also, serum levels of EGFR, AR, and TGF-α were measured by ELISA. The results of our study show that EGFR mutations were present in 37% of Iranian NSCLC patients. The most frequently identified mutations were deletions in exon 19 (72.2%) and substitutions in exon 21 (27.8%). The most frequently identified alteration, which is considered as a rare mutation, was the E872K mutation in exon 21, which was found in 90% (9 out of 10) cases. EGFR mutation detected in exon 21 was significantly (P<0.05) correlated with the levels of its ligands, EGFR and TGF-α in serum samples. Furthermore, it was found that increased serum AR (>3pg/ml) and TGF-α (>10.5 pg/ml) were associated with shorter overall survival (P<0.05). The results clearly showed a close relationship between EGFR mutations and serum EGFR and serum TGF-α. Increased serum EGFR was associated with TGF-α and AR and linked to poor prognosis of NSCLC. These findings are implicated in clinical decision-making related to EGFR-Tyrosine kinase inhibitors (TKIs).

Keywords: lung cancer, Iranian patients, epidermal growth factor, mutation, prognosis

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Authors: Srijata Mitra, Mobina Parveen, Pranab Roy, Narayan Chandra Chattopadhyay

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Chlorinated hydrocarbon can be a major pollution problem in groundwater as well as soil. Many people interact with these chemicals on daily accidentally or by professionally in the laboratory. One of the most common sources for Chlorinated hydrocarbon contamination of soil and groundwater are industrial effluents. The wide use and discharge of Trichloroethylene (TCE), a volatile chlorohydrocarbon from chemical industry, led to major water pollution in rural areas. TCE is an mainly used as an industrial metal degreaser in industries. Biotransformation of TCE to the potent carcinogen vinyl chloride (VC) by consortia of anaerobic bacteria might have role for the above purpose. For these reasons, the aim of current study was to isolate and characterized the genes involved in TCE metabolism and also to investigate the in silico study of those genes. To our knowledge, only one aromatic dioxygenase system, the toluene dioxygenase in Pseudomonas putida F1 has been shown to be involved in TCE degradation. This is first instance where Bacillus cereus group being used in biodegradation of trichloroethylene. A novel bacterial strain 2479 was isolated from oil depot site at Rajbandh, Durgapur (West Bengal, India) by enrichment culture technique. It was identified based on polyphasic approach and ribotyping. The bacterium was gram positive, rod shaped, endospore forming and capable of degrading trichloroethylene as the sole carbon source. On the basis of phylogenetic data and Fatty Acid Methyl Ester Analysis, strain 2479 should be placed within the genus Bacillus and species cereus. However, the present isolate (strain 2479) is unique and sharply different from the usual Bacillus strains in its biodegrading nature. Fujiwara test was done to estimate that the strain 2479 could degrade TCE efficiently. The gene for TCE biodegradation was PCR amplified from genomic DNA of Bacillus cereus 2479 by using todC1 gene specific primers. The 600bp amplicon was cloned into expression vector pUC I8 in the E. coli host XL1-Blue and expressed under the control of lac promoter and nucleotide sequence was determined. The gene sequence was deposited at NCBI under the Accession no. GU183105. In Silico approach involved predicting the physico-chemical properties of deduced Tce1 protein by using ProtParam tool. The tce1 gene contained 342 bp long ORF encoding 114 amino acids with a predicted molecular weight 12.6 kDa and the theoretical pI value of the polypeptide was 5.17, molecular formula: C559H886N152O165S8, total number of atoms: 1770, aliphatic index: 101.93, instability index: 28.60, Grand Average of Hydropathicity (GRAVY): 0.152. Three differentially expressed proteins (97.1, 40 and 30 kDa) were directly involved in TCE biodegradation, found to react immunologically to the antibodies raised against TCE inducible proteins in Western blot analysis. The present study suggested that cloned gene product (TCE1) was capable of degrading TCE as verified chemically.

Keywords: cloning, Bacillus cereus, in silico analysis, TCE

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Authors: M. Merabet-Khelassi, Z. Houiene, L. Aribi-Zouioueche, O. Riant

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Lipases (EC.3.1.1.3) are efficient biotools widely used for their remarkable chemo-, regio- and enantio-selectivity, especially, in kinetic resolution of racemates. They offer access to a large panel of enantiopure building blocks, such as secondary benzylic alcohols, commonly used as synthetic intermediates in pharmaceutical and agrochemical industries. Due to the stability of lipases in both water and organic solvents poor in water, they are able to catalyze both transesterifications of arylalkylcarbinols and hydrolysis of their corresponding acetates. The use of enzymatic hydrolysis in aqueous media still limited. In this presentation, we expose a practical methodology for the preparation of optically enriched acetates using a Candida antarctica lipase B-catalyzed hydrolysis in non-aqueous media in the presence of alkaline carbonate salts. The influence of several parameters which can intervene on the enzymatic efficiency such as the impact of the introduction of the carbonates salts, its amount and the nature of the alkaline earth metal are discussed. The obtained results show that the use of sodium carbonate with CAL-B enhances drastically both reactivity and selectivity of this immobilized lipase. In all cases, the resulting alcohols and remaining acetates are obtained in high ee values (up to > 99 %), and the selectivities reach (E > 500).

Keywords: alkaline-hydrolysis, enzymatic kinetic resolution, lipases, arylalkylcarbinol, non-aqueous media

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Authors: Ankush M. Dewle, Suditi Bhattacharya, Prachi R. Abhang, Savita Datar, Ajay J. Jog, Rupesh K. Srivastava, Geetanjali Tomar

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Objectives: The aim of this study was to investigate the quality of mesenchymal stem cells (MSCs) obtained from ageing gingival tissues, in order to suggest their potential role in autologous stem cell therapy for old individuals. Methods: MSCs were isolated from gingival tissues of young (18-45 years) and old (above 45 years) donors by enzymatic digestion. MSCs were analysed for cfu-f, surface marker expression by flow-cytometry and multilineage differentiation potential. The angiogenic potential was compared in a chick embryo yolk sac membrane model. The aging and differentiation markers including SA-β-galactosidase and p21 respectively were analysed by staining and flow-cytometry analysis. Additionally, osteogenic markers such as glucocorticoid receptor (GR), vitamin D receptor (VDR) were measured by flow-cytometry and RT-qPCR was performed for quantification of osteogenic gene expression. Alizarin Red S and alkaline phosphatase (ALP) activity were also quantitated. Results: Gingival MSCs (GMSCs) from both the age groups were similar in their morphology and displayed cfu-f. They had similar expression of MSC surface markers and p21, comparable rate of proliferation and differentiated to all the four lineages. GMSCs from young donors had a higher adipogenic differentiation potential as compared to the old GMSCs. Moreover, these cells did not display a significant difference in ALP activity probably due to comparable expression of GR, VDR, and osteogenic genes. Conclusions: Ageing of GMSCs occurs at a much slower rate than stem cells from other sources. Thus we suggest GMSCs as an excellent candidate for autologous stem cell therapy in degenerative diseases of elderly individuals. Clinical Significance: GMSCs could help overcome the setbacks in clinical implementation of autologous stem cell therapy for regenerative medicine in all age group of patient.

Keywords: bone regeneration, cell therapy, senescence, stem cell

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Authors: Daria Karasalihovic Sedlar, Lucija Jukic, Ivan Smajla, Marija Macenic

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This paper analyses possible geothermal energy production from a mature oil reservoir based on exploitation of underlying aquifer thermal energy for the purpose of heating public buildings. Research was conducted based on the case study of the City of Ivanic-Grad public buildings energy demand and Ivanic oil filed that is situated in the same area. Since the City of Ivanic is one of the few cities in the EU where hydrocarbon exploitation has been taking place for decades almost entirely in urban area, decommissioning of oil wells is inevitable; therefore, the research goal was to investigate how to extend the life-time of the reservoir by exploiting geothermal brine beneath the oil reservoir in an environmental friendly manner. This kind of a project is extremely complex in all segments, from documentation preparation, implementation of technological solutions, and providing ecological measures for environmentally acceptable geothermal energy production and utilization. New mining activities that will be needed for the development of geothermal project at the observed Hydrocarbon Exploitation Field Ivanic will be carried out in order to prepare wells for increasing geothermal brine production. These operations involve the conversion of existing wells (well completion for conversion of the observation wells to production ones) along with workover activities, installation of new heat exchangers, and pipelines. Since the wells are in the urban area of the City of Ivanic-Grad in high density populated area, the inhabitants will be exposed to the different environmental impacts during preparation phase of the project. For the purpose of performing workovers, it will be necessary to secure access to wellheads of existing wells. This paper gives guidelines for describing potential impacts on environment components that could occur during geothermal production preparation on existing mature oil filed, recommends possible protection measures to mitigate these impacts, and gives recommendations for environmental monitoring.

Keywords: geothermal energy production, mature oil filed, environmental impact assessment, underlying aquifer thermal energy

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Authors: Yi-Chiang Huang, Hsu-Feng Lee, Yu-Chao Tseng, Wen-Yao Huang

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Proton exchange membranes as a key component in fuel cells have been widely studying over the past few decades. As proton exchange, membranes should have some main characteristics, such as good mechanical properties, low oxidative stability and high proton conductivity. In this work, trifluoromethyl groups had been introduced on polymer backbone and phenyl side chain which can provide densely located sulfonic acid group substitution and also promotes solubility, thermal and oxidative stability. Herein, a series of novel sulfonated aromatic hydrocarbon polyelectrolytes was synthesized by polycondensation of 4,4''''-difluoro-3,3''''- bis(trifluoromethyl)-2'',3''-bis(3-(trifluoromethyl)phenyl)-1,1':4',1'':4'',1''':4''',1''''-quinquephenyl with 2'',3''',5'',6''-tetraphenyl-[1,1':4',1'': 4'',1''':4''',1''''-quinquephenyl]-4,4''''-diol and post-sulfonated was through chlorosulfonic acid to given sulfonated polymers (SFC3-X) possessing ion exchange capacities ranging from 1.93, 1.91 and 2.53 mmol/g. ¹H NMR and FT-IR spectroscopy were applied to confirm the structure and composition of sulfonated polymers. The membranes exhibited considerably dimension stability (10-27.8% in length change; 24-56.5% in thickness change) and excellent oxidative stability (weight remain higher than 97%). The mechanical properties of membranes demonstrated good tensile strength on account of the high rigidity multi-phenylated backbone. Young's modulus were ranged 0.65-0.77GPa which is much larger than that of Nafion 211 (0.10GPa). Proton conductivities of membranes ranged from 130 to 240 mS/cm at 80 °C under fully humidified which were comparable or higher than that of Nafion 211 (150 mS/cm). The morphology of membranes was investigated by transmission electron microscopy which demonstrated a clear hydrophilic/hydrophobic phase separation with spherical ionic clusters in the size range of 5-20 nm. The SFC3-1.97 single fuel cell performance demonstrates the maximum power density at 1.08W/cm², and Nafion 211 was 1.24W/cm² as a reference in this work. The result indicated that SFC3-X are good candidates for proton exchange membranes in fuel cell applications. Fuel cell of other membranes is under testing.

Keywords: fuel cells, polyelectrolyte, proton exchange membrane, sulfonated polymers

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Authors: Wojciech Górecki, Anna Sowiżdżał, Grzegorz Machowski, Tomasz Maćkowski, Bartosz Papiernik, Michał Stefaniuk

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The article shows results of the project which aims at evaluating possibilities of effective development and exploitation of natural gas from argillaceous series of the Autochthonous Miocene in the Carpathian Foredeep. To achieve the objective, the research team develop a world-trend based but unique methodology of processing and interpretation, adjusted to data, local variations and petroleum characteristics of the area. In order to determine the zones in which maximum volumes of hydrocarbons might have been generated and preserved as shale gas reservoirs, as well as to identify the most preferable well sites where largest gas accumulations are anticipated a number of task were accomplished. Evaluation of petrophysical properties and hydrocarbon saturation of the Miocene complex is based on laboratory measurements as well as interpretation of well-logs and archival data. The studies apply mercury porosimetry (MICP), micro CT and nuclear magnetic resonance imaging (using the Rock Core Analyzer). For prospective location (e.g. central part of Carpathian Foredeep – Brzesko-Wojnicz area) reprocessing and reinterpretation of detailed seismic survey data with the use of integrated geophysical investigations has been made. Construction of quantitative, structural and parametric models for selected areas of the Carpathian Foredeep is performed on the basis of integrated, detailed 3D computer models. Modeling are carried on with the Schlumberger’s Petrel software. Finally, prospective zones are spatially contoured in a form of regional 3D grid, which will be framework for generation modelling and comprehensive parametric mapping, allowing for spatial identification of the most prospective zones of unconventional gas accumulation in the Carpathian Foredeep. Preliminary results of research works indicate a potentially prospective area for occurrence of unconventional gas accumulations in the Polish part of Carpathian Foredeep.

Keywords: autochthonous Miocene, Carpathian foredeep, Poland, shale gas

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Authors: Peter David Reiss

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The concept of the psychosis prodrome has allowed for the identification of adolescent and young adult patients who have a significantly elevated risk of developing schizophrenia spectrum disorders. A number of different interventions have been tested in order to prevent or delay progression of symptoms. To date, there has been no consistent meta-analytical evidence to support efficacy of antipsychotic treatment for patients in the prodromal state, and their use remains therefore inconclusive. Although antipsychotics may manage symptoms transiently, they have not been found to prevent or delay onset of psychotic disorders. Furthermore, pharmacological intervention in high-risk individuals remains controversial, because of the antipsychotic side effect profile in a population in which only about 20 to 35 percent will eventually convert to psychosis over a two-year period, with even after two years conversion rates not exceeding 30 to 40 percent. This general estimate is additionally problematic, in that it ignores the fact that there is significant variation in individual risk among clinical high-risk cases. The current lack of reliable tests for at-risk patients makes it difficult to justify individual treatment decisions. Preventive treatment should ideally be dictated by an individual’s risk while minimizing potentially harmful medication exposure. This requires more accurate predictive assessments by using valid and accessible prognostic markers. The following will compare prediction and risk modification potential of behavioral biomarkers such as disturbances of basic sense of self and emotion awareness, neurocognitive biomarkers such as attention, working and declarative memory, and neurophysiological biomarkers such as glutamatergic abnormalities and NMDA receptor dysfunction. Identification of robust biomarkers could therefore not only provide more reliable means of psychosis prediction, but also help test and develop new clinical interventions targeted at the prodromal state.

Keywords: at-risk mental state, biomarkers, glutamatergic system, NMDA receptor, psychosis prodrome, schizophrenia

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Authors: Saad Mahmud Khan, Sarah El Hajj Chehadeh, Mehera Abdulrahman, Wael Osman, Habiba Al Safar

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Obesity is a non-communicable disease that is widely prevalent with approximately 600 million people classified as obese worldwide. Its etiology is multifactorial and involves a complex interplay between genes and the environment. Over the past few decades, obesity rates among the Emirati population have been increasing. The aim of this study was to investigate the association of candidate gene single nucleotide polymorphisms (SNPs), namely the fat mass and obesity associated (FTO) gene SNP rs9939609 and Vitamin D Receptor (VDR) gene SNP rs1544410, with obesity in the UAE population. Methods: This is a case-control study in which 414 individuals were enrolled during their routine visit to endocrinology clinics in Abu Dhabi, United Arab Emirates between the period of June 2012 and December 2013. Several biochemical tests and clinical assessments along with a lifestyle questionnaire for each participant were completed at the clinic. Genomic DNA was extracted from saliva samples of 201 obese, 114 overweight and 99 normal subjects. Genotyping for the variants was performed using TaqMan assay. Results: The mean Body Mass Index (BMI) ± SD for the obese, overweight, and normal subjects was 35.76 ± 4.54, 27.53 ± 1.45 and 22.69 ± 1.84 kg/m2, respectively. Increasing BMI values were associated with an increase in values for systolic blood pressure, diastolic blood pressure, HbA1c, and triglycerides. The SNP rs9939609 in the FTO gene was found to be significantly associated with the BMI (p=0.028), with the minor allele A having a clear additive effect on BMI values. No significant association was detected between BMI and rs1544410 of the VDR gene. Conclusions: Our study findings indicate that the minor allele A of the rs9939609 has a significant association with increasing BMI values. In addition, our findings support the fact that increasing BMI is associated with increasing risks of other comorbidities such as higher blood pressure, poorer glycemic control and higher triglycerides.

Keywords: body mass index, FTO gene, obesity, rs9939609, United Arab Emirates

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Authors: Marek Kuźniewski, Magdalena B. Kaziuk , Danuta Fedak, Paulina Dumnicka, Ewa Stępień, Beata Kuśnierz-Cabala, Władysław Sułowicz

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Background: The high prevalence of cardiovascular morbidity and mortality among patients with chronic kidney disease (CKD) is observed especially in those undergoing dialysis. Osteoprotegerin (OPG) and its ligands, receptor activator of nuclear factor kappa-B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been associated with cardiovascular complications. Our aim was to study their role as cardiovascular risk factors in stage 5 CKD patients. Methods: OPG, RANKL and TRAIL concentrations were measured in 69 hemodialyzed CKD patients and 35 healthy volunteers. In CKD patients, cardiovascular dysfunction was assessed with aortic pulse wave velocity (AoPWV), carotid artery intima-media thickness (CCA-IMT), coronary artery calcium score (CaSc) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentration. Cardiovascular and overall mortality data were collected during a 7-years follow-up. Results: OPG plasma concentrations were higher in CKD patients comparing to controls. Total soluble RANKL was lower and OPG/RANKL ratio higher in patients. Soluble TRAIL concentrations did not differ between the groups and OPG/TRAIL ratio was higher in CKD patients. OPG and OPG/TRAIL positively predicted long-term mortality (all-cause and cardiovascular) in CKD patients. OPG positively correlated with AoPWV, CCA-IMT and NT-proBNP whereas OPG/TRAIL with AoPWV and NT-proBNP. Described relationships were independent of classical and non-classical cardiovascular risk factors, with exception of age. Conclusions: Our study confirmed the role of OPG as a biomarker of cardiovascular dysfunction and a predictor of mortality in stage 5 CKD. OPG/TRAIL ratio can be proposed as a predictor of cardiovascular dysfunction and mortality.

Keywords: osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, receptor activator of nuclear factor kappa-B ligand, hemodialysis, chronic kidney disease, cardiovascular disease

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Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

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Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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Authors: Afsaneh Mohammadnejad, Marianne Nygaard, Jan Baumbach, Shuxia Li, Weilong Li, Jesper Lund, Jacob v. B. Hjelmborg, Lene Christensen, Qihua Tan

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Cognitive impairment in the elderly is a key issue affecting the quality of life. Despite a strong genetic background in cognition, only a limited number of single nucleotide polymorphisms (SNPs) have been found. These explain a small proportion of the genetic component of cognitive function, thus leaving a large proportion unaccounted for. We hypothesize that one reason for this missing heritability is the misspecified modeling in data analysis concerning phenotype distribution as well as the relationship between SNP dosage and the phenotype of interest. In an attempt to overcome these issues, we introduced a model-free method based on the generalized correlation coefficient (GCC) in a genome-wide association study (GWAS) of cognitive function in twin samples and compared its performance with two popular linear regression models. The GCC-based GWAS identified two genome-wide significant (P-value < 5e-8) SNPs; rs2904650 near ZDHHC2 on chromosome 8 and rs111256489 near CD6 on chromosome 11. The kinship model also detected two genome-wide significant SNPs, rs112169253 on chromosome 4 and rs17417920 on chromosome 7, whereas no genome-wide significant SNPs were found by the linear mixed model (LME). Compared to the linear models, more meaningful biological pathways like GABA receptor activation, ion channel transport, neuroactive ligand-receptor interaction, and the renin-angiotensin system were found to be enriched by SNPs from GCC. The GCC model outperformed the linear regression models by identifying more genome-wide significant genetic variants and more meaningful biological pathways related to cognitive function. Moreover, GCC-based GWAS was robust in handling genetically related twin samples, which is an important feature in handling genetic confounding in association studies.

Keywords: cognition, generalized correlation coefficient, GWAS, twins

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Authors: Carolin Anna Joy, Rohith K. R, Rehin Sulay, Parvathy Santhoshkumar, G.Anil Kumar, Vibin Ipe Thomas

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Ullmann coupling reactions are gaining great relevance owing to their contribution in the synthesis of biologically and pharmaceutically important compounds. Palladium and many other heavy metals have proven their excellent ability in coupling reaction, but the toxicity matters. The first-row transition metal also possess toxicity, except in the case of iron and manganese. The suitability of manganese as a catalyst is achieving great interest in oxidation, reduction, C-H activation, coupling reaction etc. In this presentation, we discuss the thermo chemistry of ligand free manganese catalyzed C-O coupling reaction between phenol and aryl halide for the synthesis of biaryl ethers using Density functional theory techniques. The mechanism involves an oxidative addition-reductive elimination step. The transition state for both the step had been studied and confirmed using Intrinsic Reaction Coordinate (IRC) calculation. The barrier height for the reaction had also been calculated from the rate determining step. The possibility of other mechanistic way had also been studied. To achieve further insight into the mechanism, substrate having various functional groups is considered in our study to direct their effect on the feasibility of the reaction.

Keywords: Density functional theory, Molecular Modeling, ligand free, biaryl ethers, Ullmann coupling

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Authors: Yong Zhou, Congping Wu, Zhigang Zou

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With the rapid societal development, energy demand has increased exponentially and is mainly based on traditional and nonrenewable energy resources, such as petroleum, fossil fuels, and coal. The combustion of carbon-containing fuels releases a large amount of CO₂, causing the greenhouse effect that contribute to climate change. Photocatalytic CO₂ reduction into solar fuels is a promising approach to simultaneously alleviate current energy and environmental issues. In this study, we report the synthesis of a series of atomically ultrathin 2D structures, which contain an ultrahigh fraction of surface atoms, benefitting for efficiency and selectivity regulation of the target products toward CO₂ photoconversion.

Keywords: Photocatalysis, CO₂, Solar fuels, Nanostructure

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Authors: Katarzyna Sobczak

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Over the last few years extensive research on the Lower Palaeozic of the Baltic region has been carried out, associated with growing interest in the unconventional hydrocarbon resources of the area. The present study contributes to this investigation by providing relevant microfacies analysis of Ordovician and Silurian carbonate and clastic deposits of the Polish part of the Baltic Syneclise, using data from the Kętrzyn IG-1, Henrykowo 1 and Babiak 1 boreholes. The analytical data, encompassing sedimentological, palaeontological, and petrographic indicators enables the interpretation of the sedimentary environments and their control factors. The main microfacies types distinguished within the studied interval are: bioclastic wackestone, bioclastic packstone, carbonate-rich mudstone, marlstone, nodular limestone and bituminous claystone. The Ordovician is represented by redeposited carbonate rocks formed in a relatively high-energy environment (middle shelf setting). The Upper Ordovician-Lower Silurian rocks of the studied basin represent sedimentary succession formed during a distinctive marine transgression. Considering the sedimentological and petrological data from the Silurian, a low-energy sedimentary environment (offshore setting) with intermittent high-energy events (tempestites) can be inferred for the sedimentary basin of NE Poland. Slow sedimentation of carbonate ooze and fine-grained siliciclastic rocks, formed under oxygen-deficient conditions of the seabed, favoured organic matter preservation. The presence of the storm beds suggests an episodic nature of seabed oxygenation. A significant part of the analysed depositional successions shows characteristics indicative of deposition from gravity flows, but lacks evidence of its turbidity origins. There is, however, evidence for storms acting as a mechanism of flow activation. The discussed Ordovician-Silurian transition of depositional environments in the Baltic area fits well to the global environmental changes encompassing the Upper Ordovician and the Lower Silurian.

Keywords: Baltic Syneclise, microfacies analysis, Ordovician, Silurian, unconventional hydrocarbons

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Authors: O. J. Olaniran, P. E. D. Love, D. J. Edwards, O. Olatunji, J. Matthews

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Cost overruns are a persistent problem in oil and gas megaprojects. Whilst the extant literature is filled with studies on incidents and causes of cost overruns, underlying theories to explain their emergence in oil and gas megaprojects are few. Yet, a way to contain the syndrome of cost overruns is to understand the bases of ‘how and why’ they occur. Such knowledge will also help to develop pragmatic techniques for better overall management of oil and gas megaprojects. The aim of this paper is to explain the development of cost overruns in hydrocarbon megaprojects through the perspective of chaos theory. The underlying principles of chaos theory and its implications for cost overruns are examined and practical recommendations proposed. In addition, directions for future research in this fertile area provided.

Keywords: chaos theory, oil and gas, cost overruns, megaprojects

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Authors: Sunil Arora, Anitya Kumar Jena, S. A. Ravi

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India is at the cusp of major reforms in the hydrocarbon sector. Oil and gas sector is highly liberalised to attract private investment and to increase domestic production. Major hydrocarbon Exploration & Production (E&P) activity here have been undertaken by Government owned companies but with easing up and reworking of hydro carbon exploration licensing policies private players have also joined the fray towards achieving energy security for India. Government of India has come up with policy and administrative reforms including Hydrocarbon Exploration and Licensing Policy (HELP), Sagarmala (port-led development with coastal connectivity), and Development of Small Discovered Fields, etc. with the intention to make industry friendly conditions for investment, ease of doing business and reduce gestation period. To harness the potential resources of Deep water and Ultra deep water, High Pressure – High Temperature (HP-HT) regions, Coal Bed Methane (CBM), Shale Hydrocarbons besides Gas Hydrates, participation shall be required from both domestic and international players. Companies engaged in E&P activities in India have traditionally been managing through their captive supply base, but with crude prices under hammer, the need is being felt to outsource non-core activities. This necessitates establishment of a robust support services to cater to E&P Industry, which is currently non-existent to meet the bourgeon challenges. This paper outlines an agenda for creating an Integrated Services Hub (ISH) under Special Economic Zone (SEZ) to facilitate complete gamut of non-core support activities of E&P industry. This responsive and proficient multi-usage facility becomes viable with better resource utilization, economies of scale to offer cost effective services. The concept envisages companies to bring-in their core technical expertise leaving complete hardware peripherals outsourced to this ISH. The Integrated Services Hub, complying with the best in class global standards, shall typically provide following Services under Single Window Solution, but not limited to: a) Logistics including supply base operations, transport of manpower and material, helicopters, offshore supply vessels, warehousing, inventory management, sourcing and procurement activities, international freight forwarding, domestic trucking, customs clearance service etc. b) Trained/Experienced pool of competent Manpower (Technical, Security etc.) will be available for engagement by companies on either short or long term basis depending upon the requirements with provisions of meeting any training requirements. c) Specialized Services through tie-up with global best companies for Crisis Management, Mud/Cement, Fishing, Floating Dry-dock besides provision of Workshop, Repair and Testing facilities, etc. d) Tools and Tackles including drill strings, etc. A pre-established Integrated Services Hub shall facilitate an early start-up of activities with substantial savings in time lines. This model can be replicated at other parts of the world to expedite E&P activities.

Keywords: integrated service hub, India, oil gas, offshore supply base

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Authors: Nadia Naseem, Farwa Batool, Nasir Mehmood, AbdulHannan Nagi

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Background: The incidence and mortality of breast cancer vary significantly in geographically distinct populations. In Pakistan, breast cancer has shown an increase in incidence in young females and is characterized by more aggressive behavior. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. This study investigated the TP53 mutations in molecular subtypes of both nodes negative and positive breast cancer in young Pakistani patients. Material and Methods: p53, Estrogen Receptor (ER), Progesterone Receptor (PR), Her-2 neu and Ki 67 expressions were analyzed immunohistochemically in a series of 75 node negative (A) and 75 node positive (B) young (aged: 19-40 years) breast cancer patients diagnosed between 2014 to 2017 at two leading hospitals of Punjab, Pakistan. Tumor tissue specimens and peripheral blood samples were examined for TP53 mutations by direct sequencing of the gene (exons 4-9). The relation of TP53 mutations to these markers and clinicopathological data was investigated. Results: Mean age of the patients was 32.4 + 9.1 SD. Invasive breast carcinoma was the most frequent histological variant (A=92%, B=94.6%). Grade 3 carcinoma was the commonest grade (A=72%, B=81.3%). Triple negative cases (ER-, PR-, Her-2) formed most of the molecular subtypes (A=44%, B=50.6%). A total of 17.2% (A: 6.6%, B: 10.6%) patients showed TP53 mutations. Mutations were significantly more frequent in triple negative cases (A: 74.8%, B: 62.2%) compared to HER2-positive patients (P < 0.0001). In the multivariate analysis of the whole patient group, the independent prognosticator were triple negative cases (P=0.021), TP53 overexpression by IHC (P=0.001) and advanced-stage disease (P=0.007). No statistically significant correlation between TP53 mutations and clinicopathological parameters was found (P < 0.05). Conclusions: It is concluded that TP53 mutations are infrequently present in breast carcinoma of young Pakistani population and there was no significant correlation between p53 mutation and early onset disease. Immunohistochemically detected TP53 expression in our resource-constrained to set up can be beneficial in predicting mutations at the younger age in our population.

Keywords: immunohistochemistry (IHC), invasive breast carcinoma (IBC), Pakistan, TP53

Procedia PDF Downloads 136

Authors: Frida Carrillo Morales, Maria Maricela Carrasco Yépez, Saúl Rojas Hernández

Abstract:

Naegleria fowleri is the causative agent of primary amebic meningoencephalitis, this disease is acute and fulminant that affects humans. It has been reported that despite the existence of therapeutic options against this disease, its mortality rate is 97%. Therefore, the need arises to have vaccines that confer protection against this disease and, in addition to developing adjuvants to enhance the immune response. In this regard, in our work group, we obtained a peptide designed from the membrane protein MP2CL5 of Naegleria fowleri called Smp145 that was shown to be immunogenic; however, it would be of great importance to enhance its immunological response, being able to co-administer it with a non-toxic adjuvant. Therefore, the objective of this work was to carry out the bioinformatic design of a peptide of the Naegleria fowleri membrane protein MP2CL5 conjugated with a non-toxic modified adjuvant from the native A1 structure of Cholera Toxin. For which different bioinformatics tools were used to obtain a model with a modification in amino acid 61 of the A1 subunit of the CT (CTA1), to which the Smp145 peptide was added and both molecules were joined with a 13-glycine linker. As for the results obtained, the modification in CTA1 bound to the peptide produces a reduction in the toxicity of the molecule in in silico experiments, likewise, the prediction in the binding of Smp145 to the receptor of B cells suggests that the molecule is directed in specifically to the BCR receptor, decreasing its native enzymatic activity. The stereochemical evaluation showed that the generated model has a high number of adequately predicted residues. In the ERRAT test, the confidence with which it is possible to reject regions that exceed the error values was evaluated, in the generated model, a high score was obtained, which determines that the model has a good structural resolution. Therefore, the design of the conjugated peptide in this work will allow us to proceed with its chemical synthesis and subsequently be able to use it in the mouse meningitis protection model caused by N. fowleri.

Keywords: immunology, vaccines, pathogens, infectious disease

Procedia PDF Downloads 69

Authors: Bruna Lima Gomes, Vanessa Caroline De Barros Bonato, Luciano Freschi, Eduardo Purgatto

Abstract:

Plant hormones are long known to be tightly associated with fruit development and are involved in controlling various aspects of fruit ripening. For fleshy fruits, ripening is characterized for changes in texture, color, aroma and other parameters that markedly contribute to its quality. Ethylene is one of the major players regulating the ripening-related processes, but emerging evidences suggest that auxin is also part of this dynamic control. Thus, the aim of this study was providing new insights into the auxin role during ripening and the hormonal interplay between auxin and ethylene. For that, tomato fruits (Micro-Tom) were collected at mature green stage and separated in four groups: one for indole-3-acetic acid (IAA) treatment, one for ethylene, one for a combination of IAA and ethylene, and one for control. Hormone solution was injected through the stylar apex, while mock samples were injected with buffer only. For ethylene treatments, fruits were exposed to gaseous hormone. Then, fruits were left to ripen under standard conditions and to assess ripening development, hue angle was reported as color indicator and ethylene production was measured by gas chromatography. The transcript levels of three ripening-related ethylene receptors (LeETR3, LeETR4 and LeETR6) were evaluated by RT-qPCR. Results showed that ethylene treatment induced ripening, stimulated ethylene production, accelerated color changes and induced receptor expression, as expected. Nonetheless, auxin treatment showed the opposite effect once fruits remained green for longer time than control group and ethylene perception has changed, taking account the reduced levels of receptor transcripts. Further, treatment with both hormones revealed that auxin effect in delaying ripening was predominant, even with higher levels of ethylene. Altogether, the data suggest that auxin modulates several aspects of the tomato fruit ripening modifying the ethylene perception. The knowledge about hormonal control of fruit development will help design new strategies for effective manipulation of ripening regarding fruit quality and brings a new level of complexity on fruit ripening regulation.

Keywords: ethylene, auxin, fruit ripening, hormonal crosstalk

Procedia PDF Downloads 446

Authors: Kukuh Suprayogi, Muhamad Natsir, Olif Kurniawan, Hot Parulian, Bayu Fitriana, Fery Mustofa

Abstract:

The new approach by utilizing the heat propagation analysis carried out by studying and evaluating the effect of the presence of hydrocarbons to the flow of heat that goes from the bottom surface to surface. Heat propagation is determined by the thermal conductivity of rocks. The thermal conductivity of rock itself is a quantity that describes the ability of a rock to deliver heat. This quantity depends on the constituent rock lithology, large porosity, and pore fluid filler. The higher the thermal conductivity of a rock, the more easily the flow of heat passing through these rocks. With the same sense, the heat flow will more easily pass through the rock when the rock is filled with water than hydrocarbons, given the nature of the hydrocarbons having more insulator against heat. The main objective of this research is to try to make the model the heat propagation calculations in degrees Celsius from the subsurface to the surface which is then compared with the surface temperature is measured directly at the point of location. In calculating the propagation of heat, we need to first determine the thermal conductivity of rocks, where the rocks at the point calculation are not composed of homogeneous but consist of strata. Therefore, we need to determine the mineral constituent and porosity values of each stratum. As for the parameters of pore fluid filler, we assume that all the pores filled with water. Once we get a thermal conductivity value of each unit of the rock, then we begin to model the propagation of heat profile from the bottom to the surface. The initial value of the temperature that we use comes from the data bottom hole temperature (BHT) is obtained from drilling results. Results of calculations per depths the temperature is displayed in plotting temperature versus depth profiles that describe the propagation of heat from the bottom of the well to the surface, note that pore fluid is water. In the technical implementation, we can identify the magnitude of the effect of hydrocarbons in reducing the amount of heat that crept to the surface based on the calculation of propagation of heat at a certain point and compared with measurements of surface temperature at that point, assuming that the surface temperature measured is the temperature that comes from the asthenosphere. This publication proves that the accumulation of hydrocarbon can be identified by analysis of heat propagation profile which could be a method for identifying the presence of hydrocarbons.

Keywords: thermal conductivity, rock, pore fluid, heat propagation

Procedia PDF Downloads 98

Authors: X. Vecino, J. M. Cruz, A. Moldes

Abstract:

The disposal and the treatment of sewage sludge is an expensive and environmentally complex problem. In this work, a lipopeptide biosurfactant extracted from corn steep liquor was used as ecofriendly and cost-competitive alternative for the mobilization and bioremediation of fluorene in sewage sludge. Results have demonstrated that this biosurfactant has the capability to mobilize fluorene to the aqueous phase, reducing the amount of fluorene in the sewage sludge from 484.4 mg/Kg up to 413.7 mg/Kg and 196.0 mg/Kg after 1 and 27 days respectively. Furthemore, once the fluorene was extracted the lipopeptide biosurfactant contained in the aqueous phase allowed the bio-degradation, up to 40.5 % of the initial concentration of this polycyclic aromatic hydrocarbon.

Keywords: fluorene, lipopeptide biosurfactant, mobilization, sewage sludge

Procedia PDF Downloads 273

Authors: Hammad T. Janjuhah, Josep Sanjuan, Mohamed K. Salah

Abstract:

Biological and chemical activities in carbonates are responsible for the complexity of the pore system. Primary porosity is generally of natural origin while secondary porosity is subject to chemical reactivity through diagenetic processes. To understand the integrated part of hydrocarbon exploration, it is necessary to understand the carbonate pore system. However, the current porosity classification scheme is limited to adequately predict the petrophysical properties of different reservoirs having various origins and depositional environments. Rock classification provides a descriptive method for explaining the lithofacies but makes no significant contribution to the application of porosity and permeability (poro-perm) correlation. The Central Luconia carbonate system (Malaysia) represents a good example of pore complexity (in terms of nature and origin) mainly related to diagenetic processes which have altered the original reservoir. For quantitative analysis, 32 high-resolution images of each thin section were taken using transmitted light microscopy. The quantification of grains, matrix, cement, and macroporosity (pore types) was achieved using a petrographic analysis of thin sections and FESEM images. The point counting technique was used to estimate the amount of macroporosity from thin section, which was then subtracted from the total porosity to derive the microporosity. The quantitative observation of thin sections revealed that the mouldic porosity (macroporosity) is the dominant porosity type present, whereas the microporosity seems to correspond to a sum of 40 to 50% of the total porosity. It has been proven that these Miocene carbonates contain a significant amount of microporosity, which significantly complicates the estimation and production of hydrocarbons. Neglecting its impact can increase uncertainty about estimating hydrocarbon reserves. Due to the diversity of geological parameters, the application of existing porosity classifications does not allow a better understanding of the poro-perm relationship. However, the classification can be improved by including the pore types and pore structures where they can be divided into macro- and microporosity. Such studies of microporosity identification/classification represent now a major concern in limestone reservoirs around the world.

Keywords: overview of porosity classification, reservoir characterization, microporosity, carbonate reservoir

Procedia PDF Downloads 132

Authors: Shreya Sara Ittycheria, K. C. Sivakumar, Shijulal Nelson Sathi, Priya Srinivas

Abstract:

hCG, a heterodimer composed of α and β subunits, is a peptide hormone having numerous biological functions. Although hCG is expressed by placenta during pregnancy, ectopic β-hCG secretion is observed in many non-trophoblastic tumors including that of breast. In-vitro and in-vivo studies done in the lab, have proved that BRCA1 defective cancers express β-hCG and when β-hCG is expressed or supplemented, it promotes tumor progression and exhibits resistance to carboplatin and ABT888, in such cancers but not in BRCA1 wild type cancers. In cancer cells, instead of binding to its regular receptor, LH-CGR, β-hCG binds with Transforming Growth Factor Receptor 2 (TGFβRII) and phosphorylates it resulting in faster tumor progression through the Smad signaling pathway. Targeting β-hCG could be a potential therapeutic strategy for managing BRCA1 defective cancers. Here, molecular docking and dynamic simulation studies were done to identify potential small molecule inhibitors against β-hCG as there are currently no such inhibitors reported. The binding sites of TGFβRII on β-hCG were identified from the top 10 predicted complexes from Z Dock. Virtual screening of selected commercially available small molecules from various libraries such as ZINC, NCI and Life Chemicals amounting to a total of 50,025 molecules were done. Four potential small molecule inhibitors were identified, RgcbPs-1, RgcbPs-2, RgcbPs-3 and RgcbPs-4 with binding affinities -60.778 kcal/mol, -45.447 kcal/mol, -65.2268 kcal/mol and -82.040 kcal/mol respectively. Further, 100ns Molecular Dynamics (MD) simulation showed that these molecules form stable complexes with β-hCG. RgcbPs-1 maintains hydrogen bonds with Q54, L52, Q46, C100, G36, C57, C38 residues, RgcbPs-2 maintains hydrogen bonds with A83 residue, RgcbPs-3 maintains hydrogen bonds with C57, Y58, R94, G101 residues and RgcbPs-4 maintains hydrogen bonds with G36, C38, T40, C57, D99, C100, G101 and L104 residues of β-hCG all of which coincide with the TGFβRII binding site on β-hCG. These results show that these two inhibitors could be used either singly or in combination for inhibiting β-hCG from binding to TGFβRII and thereby directly inhibiting the tumorigenesis pathway.

Keywords: β-hCG, breast cancer, dynamic simulations, molecular docking, small molecule inhibitors, virtual screening.

Procedia PDF Downloads 85

Authors: Vinod Kumar

Abstract:

Background: Tissue Plasminogen Activator (tPA) showed a level 1 benefit in acute stroke (within 3-6 hrs). Intracarotid sodium nitroprusside (ICSNP) has been studied in this context with a wide treatment window, fast recovery and affordability. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a)Retrograde Neurotransmission (acute cases): 1)Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2)Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b)Vasospasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c)Long-Term Potentıatıon (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Des’gn: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat stroke cases. Case-control prospective study. Mater’als And Methods: The experimental population included 82 stroke patients (10 patients were given control treatments without superfusion or with 5% dextrose superfusion, and 72 patients comprised the ICSNP group). The mean time for superfusion was 9.5 days post-stroke. Pre- and post-ICSNP status was monitored by NIHSS, MRI and TCD. Results: After 90 seconds in the ICSNP group, the mean change in the NIHSS score was a decrease of 1.44 points, or 6.55%; after 2 h, there was a decrease of 1.16 points; after 24 h, there was an increase of 0.66 points, 2.25%, compared to the control-group increase of 0.7 points, or 3.53%; at 7 days, there was an 8.61-point decrease, 44.58%, compared to the control-group increase of 2.55 points, or 22.37%; at 2 months in ICSNP, there was a 6.94-points decrease, 62.80%, compared to the control-group decrease of 2.77 points, or 8.78%. TCD was documented and improvements were noted. Conclusions: ICSNP is a swift-acting drug in the treatment of stroke, acting within 90 seconds on day 9.5 post-stroke with a small decrease after 24 hours. The drug recovers from this decrease quickly.

Keywords: brain infarcts, intracarotid sodium nitroprusside, perforators, vasodilatıons, retrograde transmission, the 10, 000-fold effect

Procedia PDF Downloads 297

Authors: Esmael Makarian, Ayub Elyasi, Fatemeh Saberi, Olusegun Stanley Tomomewo

Abstract:

Rock mechanical investigation is one of the most crucial activities in underground operations, especially in surveys related to hydrocarbon exploration and production, geothermal reservoirs, energy storage, mining, and geotechnics. There is a wide range of traditional methods for driving, collecting, and analyzing rock mechanics data. However, these approaches may not be suitable or work perfectly in some situations, such as fractured zones. Cutting-edge technologies have been provided to solve and optimize the mentioned issues. Internet of Things (IoT), Edge, and Cloud Computing technologies (ECt & CCt, respectively) are among the most widely used and new artificial intelligence methods employed for geomechanical studies. IoT devices act as sensors and cameras for real-time monitoring and mechanical-geological data collection of rocks, such as temperature, movement, pressure, or stress levels. Structural integrity, especially for cap rocks within hydrocarbon systems, and rock mass behavior assessment, to further activities such as enhanced oil recovery (EOR) and underground gas storage (UGS), or to improve safety risk management (SRM) and potential hazards identification (P.H.I), are other benefits from IoT technologies. EC techniques can process, aggregate, and analyze data immediately collected by IoT on a real-time scale, providing detailed insights into the behavior of rocks in various situations (e.g., stress, temperature, and pressure), establishing patterns quickly, and detecting trends. Therefore, this state-of-the-art and useful technology can adopt autonomous systems in rock mechanical surveys, such as drilling and production (in hydrocarbon wells) or excavation (in mining and geotechnics industries). Besides, ECt allows all rock-related operations to be controlled remotely and enables operators to apply changes or make adjustments. It must be mentioned that this feature is very important in environmental goals. More often than not, rock mechanical studies consist of different data, such as laboratory tests, field operations, and indirect information like seismic or well-logging data. CCt provides a useful platform for storing and managing a great deal of volume and different information, which can be very useful in fractured zones. Additionally, CCt supplies powerful tools for predicting, modeling, and simulating rock mechanical information, especially in fractured zones within vast areas. Also, it is a suitable source for sharing extensive information on rock mechanics, such as the direction and size of fractures in a large oil field or mine. The comprehensive review findings demonstrate that digital transformation through integrated IoT, Edge, and Cloud solutions is revolutionizing traditional rock mechanical investigation. These advanced technologies have empowered real-time monitoring, predictive analysis, and data-driven decision-making, culminating in noteworthy enhancements in safety, efficiency, and sustainability. Therefore, by employing IoT, CCt, and ECt, underground operations have experienced a significant boost, allowing for timely and informed actions using real-time data insights. The successful implementation of IoT, CCt, and ECt has led to optimized and safer operations, optimized processes, and environmentally conscious approaches in underground geological endeavors.

Keywords: rock mechanical studies, internet of things, edge computing, cloud computing, underground surveys, geological operations

Procedia PDF Downloads 38

Authors: Owonikoko Abayomi Dele

Abstract:

Epilepsy is an unresolved disease that needs urgent attention. It is a brain disorder that affects over sixty-five (65) million people around the globe. Despite the availability of commercial anti-epileptic drugs, the war against this unmet condition is yet to be resolved. Most epilepsy patients are resistant to available anti-epileptic medications thus the need for affordable novel therapy against epilepsy is a necessity. Numerous phytochemicals have been reported for their potency, efficacy and safety as therapeutic agents against many diseases. This study investigated 99 isolated phytochemicals from Chasmanthera dependens and Carissa edulis against carbonic anhydrase (ii) drug target. The absorption, distribution, metabolism, excretion and toxicity (ADMET) of the isolated compounds were examined using admet SAR-2 web server while Swiss ADME was used to analyze the oral bioavailability, drug-likeness and lead-likeness properties of the selected leads. PASS web server was used to predict the biological activities of selected leads while other important physicochemical properties and interactions of the selected leads with the active site of the target after successful molecular docking simulation with the pyrx virtual screening tool were also examined. The results of these study identified seven lead compounds; C49- alpha-carissanol (-7.6 kcal/mol), C13- Catechin (-7.4 kcal/mol), C45- Salicin (-7.4 kcal/mol), C6- Bisnorargemonine (-7.3 kcal/mol), C36- Pallidine (-7.1 kcal/mol), S4- Lacosamide (-7.1 kcal/mol), and S7- Acetazolamide (-6.4 kcal/mol) for CA II (3HS4 receptor). These leads compounds are probable inhibitors of this drug target due to the observed good binding affinities and favourable interactions with the active site of the drug target, excellent ADMET profiles, PASS Properties, drug-likeness, lead-likeness and oral bioavailability properties. The identified leads have better binding energies as compared to the binding energies of the two standards. Thus, seven identified lead compounds can be developed further towards the development of new anti-epileptic medications.

Keywords: drug-likeness, phytochemicals, carbonic anhydrases, metalloeazymes, active site, ADMET

Procedia PDF Downloads 23

Authors: V. K. Tewari, M. Hussain, H. K. D. Gupta

Abstract:

Background: Nitric Oxide Donars (NODs) (intrathecal sodium nitroprusside (ITSNP) and oral tadalafil 20mg post ITSNP) has been studied in this context in cerebral palsy patients for fast recovery. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a) Retrograde Neurotransmission (acute cases): 1) Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2) Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b) Vasopasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c) Long-Term Potentiation (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Design: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat cerebral palsy cases. Case-control prospective study. Materials and Methods: The experimental population included 82 cerebral palsy patients (10 patients were given control treatments without NOD or with 5% dextrose superfusion, and 72 patients comprised the NOD group). The mean time for superfusion was 5 months post-cerebral palsy. Pre- and post-NOD status was monitored by Gross Motor Function Classification System for Cerebral Palsy (GMFCS), MRI, and TCD studies. Results: After 7 days in the NOD group, the mean change in the GMFCS score was an increase of 1.2 points mean; after 3 months, there was an increase of 3.4 points mean, compared to the control-group increase of 0.1 points at 3 months. MRI and TCD documented the improvements. Conclusions: NOD (ITSNP boosts up the recovery and oral tadalafil maintains the recovery to a well-desired level) acts swiftly in the treatment of CP, acting within 7 days on 5 months post-cerebral palsy either of the three mechanisms.

Keywords: cerebral palsy, intrathecal sodium nitroprusside, oral tadalafil, perforators, vasodilations, retrograde transmission, the 10, 000-fold effect, long-term potantiation

Procedia PDF Downloads 351

Authors: Krystian Wójcik, Sara Wróblewska, Marcin Łojek, Katarzyna Sobień

Abstract:

Polish Geological Survey selected five of the most prospective areas for oil and gas exploration in Poland. They are dedicated to the 6th international tender round for hydrocarbon concessions, planned in 2022. The main exploration target of these areas is related to conventional and unconventional accumulations of gas and oil in the Carpathian basement, Carpathian Foredeep and Outer Carpathians (Block 413 – 414), as well as in the Carboniferous, Rotliegend, Main Dolomite (Block 208, Cybinka – Torzym, Zielona Góra West), and in the Mesozoic of the Polish Lowlands (Koło).

Keywords: concession policy, international tender, oil and gas exploration horizons, prospective areas

Procedia PDF Downloads 191