Search results for: proliferating cell nuclear antigen

Authors: Su Bin Wang, Jin Hee Ahn, Tong-Shin Chang

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The peroxisome proliferator-activated receptors (PPARs) are member of nuclear receptor superfamily that act as a ligand-activated transcription factors. Although platelets lack a nucleus, previous studies have shown that PPARγ agonists, rosiglitazone, inhibited platelet activation induced by collagen. In this study, we investigated the inhibitory effects of KR-62980, a newly synthesized PPARγ agonist, on collagen receptor-stimulated platelet activation. The specific tyrosine phosphorylations of key components (Syk, Vav1, Btk and PLCγ2) for collagen receptor signaling pathways were suppressed by KR-62980. KR-62980 also attenuated downstream responses including cytosolic calcium elevation, P-selectin surface exposure, and integrin αIIbβ3 activation. PPARγ was found to associate with multiple proteins within the LAT signaling complex in collagen-stimulated platelets. This association was prevented by KR-62980, indicating a potential mechanism for PPARγ function in collagen-stimulated platelet activation. Furthermore, KR-62980 inhibited platelet aggregation and adhesion in response to collagen in vitro and prolonged in vivo thrombotic response in carotid arteries of mice. Collectively, these data suggest that KR-62980 inhibits collagen-stimulated platelet activation and thrombus formation through modulating the collagen receptor signaling pathways.

Keywords: KR-62980, PPARγ, antiplatelet, thrombosis

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Authors: Anshul Gupta, T. Shankar

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In this paper, we had analyzed the call drop to provide a good quality of service to user. By optimizing it we can increase the coverage area and also the reduction of interference and congestion created in a network. Basically handover is the transfer of call from one cell site to another site during a call. Here we have analyzed the whole network by two method-statistic model and analytic model. In statistic model we have collected all the data of a network during busy hour and normal 24 hours and in analytic model we have the equation through which we have to find the call drop probability. By avoiding unnecessary handovers we can increase the number of calls per hour. The most important parameter is co-efficient of variation on which the whole paper discussed.

Keywords: coefficient of variation, mean, standard deviation, call drop probability, handover

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Authors: Karthick Dharmalingam, Stalin Ramakrishnan, Haseena Banu Hedayathullah Khan, Sachidanandanam Thiruvaiyaru Panchanadham, Shanthi Palanivelu

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Background: Breast cancer is arising as the most dreadful cancer affecting women worldwide. Hence, there arises a need to search and test for new drugs. Herbal formulations used in Siddha preparations are proved to be effective against various types of cancer. They also offer advantage through synergistic amplification and diminish any possible adverse effects. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio and has been used for the treatment of mammary carcinoma. Objective: To study the restorative effect of Tridham and penta galloyl glucose (a component of TD) on DMBA induced mammary carcinoma in female Sprague Dawley rats. Materials and Methods: Rats were divided into seven groups of six animals each. Group I (Control) received corn oil. Group II– mammary carcinoma was induced by DMBA dissolved in corn oil single dose orally. Group III and Group IV were induced with DMBA and subsequently treated with Tridham and penta galloyl glucose, respectively for 48 days. Group V was treated with DMBA and subsequently with a standard drug, cyclophosphamide. Group VI and Group VII were given Tridham and penta galloyl glucose alone, respectively for 48 days. After the experimental period, the animals were sacrificed by cervical decapitation. The mammary gland tissue was excised and levels of antioxidants were determined by biochemical assay. p53 and PCNA expression were accessed using immunohistochemistry. Nrf-2, Cox-2 and caspase-3 protein expression were studied by Western Blotting analysis. p21, Bcl-2, Bax, Bad and caspase-8 gene expression were studied by RT-PCR. Results: Histopathological studies confirmed induction of mammary carcinoma in DMBA induced rats and treatment with TD and PGG resulted in regression of tumour. The levels of enzymic and non-enzymic antioxidants were decreased in DMBA induced rats when compared to control rats. The levels of cell cycle inhibitory markers and apoptotic markers were decreased in DMBA induced rats when compared to control rats. These parameters were restored to near normal levels on treatment with Tridham and PGG. Conclusion: The results of the present study indicate the antineoplastic effect of Tridham and PGG are exerted through the modulation of antioxidant status and expression of cell cycle regulatory markers as well as apoptotic markers. Acknowledgment: Financial assistance provided in the form of ICMR-SRF by Indian Council of Medical Research (ICMR), India is gratefully acknowledged here.

Keywords: antioxidants, Mammary carcinoma, pentaGalloyl glucose, Tridham

Procedia PDF Downloads 279

Authors: Feng Guo

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Human brain organoids, 3D brain tissue cultures derived from human pluripotent stem cells, hold promising potential in modeling neuroinflammation for a variety of neurological diseases. However, challenges remain in generating standardized human brain organoids that can recapitulate key physiological features of a human brain. Here, this study presents a series of organoids-on-a-chip systems to generate better human brain organoids and model neuroinflammation. By employing 3D printing and microfluidic 3D cell culture technologies, the study’s systems enable the reliable, scalable, and reproducible generation of human brain organoids. Compared with conventional protocols, this study’s method increased neural progenitor proliferation and reduced heterogeneity of human brain organoids. As a proof-of-concept application, the study applied this method to model substance use disorders.

Keywords: human brain organoids, microfluidics, organ-on-a-chip, neuroinflammation

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Authors: Niki K. Burns, James R. Pearson, Paul G. Stevenson, Xavier A. Conlan

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In Australian state Victoria, synthetic cannabinoids have recently been made illegal under an amendment to the drugs, poisons and controlled substances act 1981. Identification of synthetic cannabinoids in popular brands of ‘incense’ and ‘potpourri’ has been a difficult and challenging task due to the sample complexity and changes observed in the chemical composition of the cannabinoids of interest. This study has developed analytical methodology for the targeted extraction and determination of synthetic cannabinoids available pre-ban. A simple solvent extraction and solid phase extraction methodology was developed that selectively extracted the cannabinoid of interest. High performance liquid chromatography coupled with UV‐visible and chemiluminescence detection (acidic potassium permanganate and tris (2,2‐bipyridine) ruthenium(III)) were used to interrogate the synthetic cannabinoid products. Mass spectrometry and nuclear magnetic resonance spectroscopy were used for structural elucidation of the synthetic cannabinoids. The tris(2,2‐bipyridine)ruthenium(III) detection was found to offer better sensitivity than the permanganate based reagents. In twelve different brands of herbal incense, cannabinoids were extracted and identified including UR‐144, XLR 11, AM2201, 5‐F‐AKB48 and A796‐260.

Keywords: electrospray mass spectrometry, high performance liquid chromatography, solid phase extraction, synthetic cannabinoids

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Authors: Mohammad Mardi

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Generally, the resistivity is high in oil layer and low in water layer. Yet there are intervals of oil-bearing zones showing low resistivity, high porosity, and low resistance. In the typical example, well A (depth: 4341.5-4372.0m), both Spectral Gamma Ray (SGR) and Corrected Gamma Ray (CGR) are relatively low; porosity varies from 12-22%. Above 4360 meters, the reservoir shows the conventional positive difference between deep and shallow resistivity with high resistance; below 4360m, the reservoir shows a negative difference with low resistance, especially at depths of 4362.4 meters and 4371 meters, deep resistivity is only 2Ω.m, and the CAST-V imaging map shows that there are low resistance substances contained in the pores or matrix in the reservoirs of this interval. The rock slice analysis data shows that the pyrite volume is 2-3% in the interval 4369.08m-4371.55m. A comprehensive analysis on the volume of shale (Vsh), porosity, invasion features of resistivity, mud logging, and mineral volume indicates that the possible causes for the negative difference between deep and shallow resistivities with relatively low resistance are erosional pores, caves, micritic texture and the presence of pyrite. Full-bore Drill Stem Test (DST) verified 4991.09 bbl/d in this interval. To identify and thoroughly characterize low resistivity intervals coring, Nuclear Magnetic Resonance (NMR) logging and further geological evaluation are needed.

Keywords: low resistivity pay, carbonates petrophysics, microporosity, porosity

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Authors: Gassem Alfaleh

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In Strict liability, a person can be held liable for any harm resulting from certain actions or activities without any mistake. The liability is strict because a person can be liable when he or she commits any harm with or without his intention. The duty owed is the duty to avoid causing the plaintiff any harm. However, “strict liability is imposed at the International level by two types of treaties, namely those limited to giving internal effect to treaty provisions and those that impose responsibilities on states. The basic principle of strict liability is that there is a liability on the operator or the state (when the act concerned is attributable to the state) for damage inflicted without there being a need to prove unlawful behavior”. In international human rights law, strict liability can exist when a defendant is in legal jeopardy by virtue of an internationally wrongful act, without any accompanying intent or mental state. When the defendant engages in an abnormally dangerous activity against the environment, he will be held liable for any harm it causes, even if he was not at fault. The paper will focus on these activities under international human rights law. First, the paper will define important terms in the first section of the paper. Second, it will focus on state and non-state actors in terms of strict liability. Then, the paper will cover three major areas in which states should be liable for hazardous activities: (1) nuclear energy, (2) maritime pollution, (3) Space Law, and (4) other hazardous activities which damage the environment.

Keywords: human rights, law, legal, absolute

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Authors: Moreblessings Shoko

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Polymersomes are materials which are considered as artificial counterparts of natural vesicles. The nanotechnology of such smart nanovesicles is very useful to enhance the efficiency of many therapeutic and diagnostic drugs. Those compounds show a higher stability, flexibility, and mechanical strength to the membrane compared to natural liposomes. Also, they can be designed in detail, the permeability of the membrane can be controlled by different stimuli, and the surface can be functionalized with different biological molecules to facilitate monitoring and target. For this purpose, this study demonstrates the formation of multifunctional and pH sensitive polymersomes and their functionalization with different reactive groups or biomolecules inside and outside of polymersomes´ membrane providing by crossing the membrane and docking/undocking processes for biomedical applications. Overall, they are highly versatile and thus present new opportunities for the design of targeted and selective recognition systems, for example, in mimicking cell functions and in synthetic biology.

Keywords: women, geomatics, challenges, capacity building

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Authors: G. Nitesh

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Stone column or granular pile is a proven technique to mitigate settlement in soft soil. Granular pile increases both rate of consolidation and stiffness of the ground. In this paper, a method to analyze further reduction in settlement of granular column reinforced with lime pile is presented treating the system as a unit cell and considering one-dimensional compression approach. The core of the granular pile is stiffened with a steel rod or lime column. Influence of a wide range of parameters such as area ratio of granular pile-soft soil, area ratio of lime pile-granular pile, modular ratio of granular pile and modular ratio of lime pile with respect to granular pile on settlement reduction factor, etc. are obtained and presented.

Keywords: lime pile, granular pile, soft soil, settlement

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Authors: Ali Reza Tahavvor‚ Saeed Hosseini, Behnam Amiri

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Concentric and eccentric annulus is used frequently in technical and industrial applications such as nuclear reactors, thermal storage system and etc. In this paper, computational fluid dynamics (CFD) is used to investigate two dimensional free convection of laminar flow in annulus with isotherm cylinders surface and cooler inner surface. Problem studied in thirty different cases. Due to natural convection continuity and momentum equations are coupled and must be solved simultaneously. Finite volume method is used for solving governing equations. The purpose was to obtain the eccentricity effect on Nusselt number in different Rayleight numbers, so streamlines and temperature fields must be determined. Results shown that the highest Nusselt number values occurs in degree of eccentricity equal to 0.5 upward for inner cylinder and degree of eccentricity equal to 0.3 upward for outer cylinder. Side eccentricity reduces the outer cylinder Nusselt number but increases inner cylinder Nusselt number. The trend in variation of Nusselt number with respect to eccentricity remain similar in different Rayleight numbers. Correlations are included to calculate the Nusselt number of the cylinders.

Keywords: natural convection, concentric, eccentric, Nusselt number, annulus

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Authors: Arthur Thirion

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Auxetic geometries allow the generation of a negative Poisson ratio (NPR) in conventional materials. This behaviour allows materials to have certain improved mechanical properties, including impact resistance and altered synclastic behaviour. This means these structures have significant potential when it comes to applications as chronic wound dressings. To this end, 6 different "perforated sheet" structure types were 3D printed. These structures all had variations of key geometrical features included cell length and angle. These were tested in compression and tension to assess their Poisson ratio. Both a positive and negative Poisson ratio was generated by the structures depending on the loading. The a/b ratio followed by θ has been shown to impact the Poisson ratio significantly. There is still a significant discrepancy between modelled and observed behaviour.

Keywords: auxetic materials, 3D printing, negative Poisson's ratio, tunable Poisson's ratio

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Authors: Tomás Sobrino, Lara García-Varela, Marta Aramburu-Núñez, Mónica Castro, Noemí Gómez-Lado, Mariña Rodríguez-Arrizabalaga, Antía Custodia, Juan Manuel Pías-Peleteiro, José Manuel Aldrey, Daniel Romaus-Sanjurjo, Ángeles Almeida, Pablo Aguiar, Alberto Ouro

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Introduction: Alzheimer’s disease (AD) and other tauopathies are primary causes of dementia, causing progressive cognitive deterioration that entails serious repercussions for the patients' performance of daily tasks. Currently, there is no effective approach for the early diagnosis and treatment of AD and tauopathies. This study suggests a theragnostic approach based on the importance of phosphorylated tau protein (p-Tau) in the early pathophysiological processes of AD. We have developed a novel theragnostic monoclonal antibody (mAb) to provide both diagnostic and therapeutic effects. Methods/Results: We have developed a p-Tau mAb, which was doped with deferoxamine for radiolabeling with Zirconium-89 (89Zr) for PET imaging, as well as fluorescence dies for immunofluorescence assays. The p-Tau mAb was evaluated in vitro for toxicity by MTT assay, LDH activity, propidium iodide/Annexin V assay, caspase-3, and mitochondrial membrane potential (MMP) assay in both mouse endothelial cell line (bEnd.3) and cortical primary neurons cell cultures. Importantly, non-toxic effects (up to concentrations of p-Tau mAb greater than 100 ug/mL) were detected. In vivo experiments in the tauopathy model mice (PS19) show that the 89Zr-pTau-mAb and 89Zr-Fragments-pTau-mAb are stable in circulation for up to 10 days without toxic effects. However, only less than 0.2% reached the brain, so further strategies have to be designed for crossing the Brain-Blood-Barrier (BBB). Moreover, an intraparenchymal treatment strategy was carried out. The PS19 mice were operated to implement osmotic pumps (Alzet 1004) at two different times, at 4 and 7 months, to stimulate the controlled release for one month each of the B6 antibody or the IgG1 control antibody. We demonstrated that B6-treated mice maintained their motor and memory abilities significantly compared with IgG1 treatment. In addition, we observed a significant reduction in p-Tau deposits in the brain. Conclusions /Discussion: A theragnostic pTau-mAb was developed. Moreover, we demonstrated that our p-Tau mAb recognizes very-early pathology forms of p-Tau by non-invasive techniques, such as PET. In addition, p-Tau mAb has non-toxic effects, both in vitro and in vivo. Although the p-Tau mAb is stable in circulation, only 0.2% achieve the brain. However, direct intraventricular treatment significantly reduces cognitive impairment in Alzheimer's animal models, as well as the accumulation of toxic p-Tau species.

Keywords: alzheimer's disease, theragnosis, tau, PET, immunotherapy, tauopathies

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Authors: Sarah Crawford, Gerry Lesley

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This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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Authors: G.S. Patel

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In this research paper the discussion have been made on teachers work mental stress and coping strategies. Stress Measurement scale was developed for school teachers. All the scientific steps of test construction was followed. For this test construction, different factors like teachers workplace, teachers' residential area, teachers' family life, teachers' ability and skills, economic factors and other factors to construct teachers stress measurement scale. In this research tool, situational statements have been made and teachers have to give a response in each statement on five-point rating scale what they experienced in their daily life. Special features of the test also established like validity and reliability of this test and also computed norms for its interpretation. A sample of 320 teachers of school teachers of Gujarat state was selected by Cluster sampling technique. t-test was computed for testing null hypothesis. The main findings of the present study are Urban area teachers feel more stressful situation compare to rural area teachers. Those teachers who live in the joint family feel less stress compare to teachers who live in a nuclear family. This research work is very useful to prepare list of activities to reduce teachers mental stress.

Keywords: stress measurement scale, level of stress, validity, reliability, norms

Procedia PDF Downloads 195

Authors: Raheela Akhtar, Zafar Iqbal Chaudhary, Yongqun Oliver He, Muhammad Younus, Aftab Ahmad Anjum

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Brucella abortus is an intracellular pathogen affecting macrophages. Macrophages release some components such as lysozymes (LZ), reactive oxygen species (ROS) and reactive nitrite intermediates (RNI) which are important tools against intracellular survival of Brucella. The antibrucella activity of bovine and murine macrophages was compared following stimulation with Brucella abortus lipopolysaccharides. Our results revealed that murine macrophages were ten times more potent to produce antibrucella components than bovine macrophages. The differential production of these components explained the differential Brucella killing ability of these species that was measured in terms of intramacrophagic survival of Brucella in murine and bovine macrophages.

Keywords: bovine macrophages, Brucella abortus, cell stimulation, cytokines, Murine macrophages

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Authors: A. Shishkin, V. Mironovs, D. Goljandin, A. Korjakins

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The goal of this work is to develop sustainable and durable ceramic cellular structures using widely available natural resources- clay and milled waste glass. Present paper describes method of obtaining clay ceramic foam (CCF) with addition of milled waste glass in 5, 7 and 10 wt% by direct foaming with high speed mixer-disperser (HSMD). For more efficient clay and waste glass milling and mixing, the high velocity disintegrator was used. The CCF with 5, 7, and 10 wt% were obtained at 900, 950, 1000 and 1050 °C firing temperature and they have demonstrated mechanical compressive strength for all 12 samples ranging from 3.8 to 14.3 MPa and porosity 76-65%. Obtained CCF has compressive strength 14.3 MPa and porosity 65.3%.

Keywords: ceramic foam, waste glass, clay foam, glass foam, open cell, direct foaming

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Authors: Michael Bach

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Extensive weld repair was carried out in 2009 after a leak was detected in the aluminum 5052 vessel of the National Research Universal (NRU) reactor. This was the second vessel installed since 1974. In support of the NRU vessel leak repair and fitness for service assessments, an estimate of property changes due to irradiation exposure is required to extend the service of the reactor until 2018. In order to fully evaluate the property changes in the vessel wall, an Iodine-125 rod (I rod) made from the same material and irradiated in the NRU reactor from 1974 1991, was retrieved and sectioned for microstructure characterization and mechanical testing. The different sections of the I rod were exposed to various levels of thermal neutron fluences from 0 to a maximum of 11.9 x 1022 n/cm2. The end of life thermal neutron fluence of the NRU vessel is estimated to be 2.2 x 1022 n/cm2 at 35 years of service. Tensile test and fracture toughness test was performed on the I-rod material at various axial locations. The changes in tensile properties were attributed primarily to the creation of finely dispersed Mg-Si precipitates that harden the material and reduced the ductility. Despite having a reduction in fracture toughness, the NRU vessel is still operation at the current fluence levels.

Keywords: aluminum alloy, fitness-for-service assessment , fracutre toughness, nuclear reactor, precipitate strengthening, radiation damage, tensile strength

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Authors: Elif Erdem, Nalan Kaya, Gonca Ozan, Durrin Ozlem Dabak, Enver Ozan

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This study was carried out to determine the histological and biochemical changes in the lungs of the rat pups exposed to tobacco smoke during pregnancy period and to investigate the protective effects of alpha lipoic acid, which is administered during pregnancy, on these changes. In our study, 24 six-week old Spraque-Dawley female rats weighing 160 ± 10 g were used (n:7). Rats were randomly divided into four equal groups: group I (control), group II (tobacco smoke), group III (tobacco smoke + alpha lipoic acid) and group IV (alpha lipoic acid). Rats in the group II, group III were exposed to tobacco smoke twice a day for one hour starting from eight weeks before mating and during pregnancy. In addition to tobacco smoke, 20 mg/kg of alpha lipoic acid was administered via oral gavage to the rats in the group III. Only alpha lipoic acid was administered to the rats in the group IV. Once after the delivery, all administrations were stopped. On the 7 and 21th days, the seven pups of all groups were decapitated. A portion of the lung was taken and stained with HE, PAS and Masson. In addition to immunohistochemical staining of surfactant protein A, vascular endothelial growth factor, caspase-3, TUNEL method was also used to determine apoptosis. Biochemical analyzes were performed with some part of the lung tissue specimens. In the histological evaluations performed under light microscopy, inflammatory cell increase, hemorrhagic areas, edema, interalveolar septal thickening, alveolar numbers decrease, degeneration of some bronchi and bronchial epithelium, epithelial cells that were fallen into the lumen and hyaline membrane formation were observed in tobacco smoke group. These findings were ameliorated in tobacco smoke + ALA group. Hyaline membrane formation was not detected in this group. The TUNEL positive cell numbers a significant increase was detected in the tobacco smoke group, whereas a significant decrease was detected in the tobacco smoke + ALA group. In terms of the immunoreactivity of both SP-A and VEGF, a significant decrease was observed in the tobacco smoke group, and a significant increase was observed in the tobacco smoke + ALA group. Regarding the immunoreactivity of caspase-3, there was a significant increase in the group of tobacco smoke and a significant decrease in the group of tobacco smoke + ALA. The malondialdehyde levels were determined to be significantly increased in the tobacco smoke group, and a significant decreased in the tobacco smoke + ALA. Glutathione and superoxide dismutase enzyme activities showed a significant decrease in the group of tobacco smoke and a significant increase in the tobacco smoke + ALA group. In conclusion, we suggest that the exposure to tobacco smoke during pregnancy leads to morphological, histopathological and functional changes on lung development by causing oxidative damage in lung tissues of neonatal rats and the maternal use of alpha lipoic acid can provide a protective effect on the neonatal lung development against this oxidative stress originating from tobacco smoke.

Keywords: alpha lipoic acid, lung, neonate, tobacco smoke, pregnancy

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Authors: Darshna Sharma, Suban K. Sahoo

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The detection of intracellular fluoride in human cancer cell HeLa was achieved by chemosensors derived from vitamin B6 cofactors using fluorescence imaging technique. These sensors were first synthesized by condensation of pyridoxal/pyridoxal phosphate with 2-amino(thio)phenol. The anion recognition ability was explored by experimental (UV-VIS, fluorescence and 1H NMR) and theoretical DFT [(B3LYP/6-31G(d,p)] methods in DMSO and mixed DMSO-H2O system. All the developed sensors showed both naked-eye detectable color change and remarkable fluorescence enhancement in the presence of F- and AcO-. The anion recognition was occurred through the formation of hydrogen bonded complexes between these anions and sensor, followed by the partial deprotonation of sensor. The detection limit of these sensors were down to micro(nano) molar level of F- and AcO-.

Keywords: chemosensors, fluoride, acetate, turn-on, live cells imaging, DFT

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Authors: Tanvir Hasan, Minhaz Uddin, Anwar Sadat Anik

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A pressurizer is a safety-related reactor component that maintains the reactor operating pressure to guarantee safety. Its structure is usually made of high thermal and pressure resistive material. The mechanical structure of these components should be maintained in all working settings, including transient to severe accidents conditions. The goal of this study is to examine the structural integrity and stress of the pressurizer in order to ensure its design integrity towards transient situations. For this, the finite element method (FEM) was used to analyze the mechanical stress on pressurizer components in this research. ANSYS MECHANICAL tool was used to analyze a 3D model of the pressurizer. The material for the body and safety relief nozzle is selected as low alloy steel i.e., SA-508 Gr.3 Cl.2. The model was put into ANSYS WORKBENCH and run under the boundary conditions of (internal Pressure, -17.2 MPa, inside radius, -1348mm, the thickness of the shell, -127mm, and the ratio of the outside radius to an inside radius, - 1.059). The theoretical calculation was done using the formulas and then the results were compared with the simulated results. When stimulated at design conditions, the findings revealed that the pressurizer stress analysis completely fulfilled the ASME standards.

Keywords: pressurizer, stress analysis, finite element method, nuclear reactor

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Authors: Yahia Massinissa, Melakhessou Med Akram, Mezahdia Mehdi, Marref Salah Eddine

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Cytokines are natural proteins which act as true intercellular communication signals in immune and inflammatory responses. Reverse signaling pathways that activate cytokines help to regulate different functions at the target cell, causing its activation, its proliferation, the differentiation, its survival or death. It was shown that malfunctioning of the cytokine regulation, particularly over-expression, contributes to the onset and development of certain serious diseases such as chronic rheumatoid arthritis, Crohn's disease, psoriasis, lupus. The action mode of Kinoid® technology is based on the principle vaccine: The patient's immune system is activated so that it neutralizes itself and the factor responsible for the disease. When applied specifically to autoimmune diseases, therapeutic vaccination allows the body to neutralize cytokines (proteins) overproduced through a highly targeted stimulation of the immune system.

Keywords: cytokines, Kinoid tech, auto-immune diseases, vaccination

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Authors: Bidya Dhar Sahu, Meghana Koneru, R. Shyam Sunder, Ramakrishna Sistla

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Environmental and occupational exposure to hexavalent chromium [Cr(VI)] via textile manufacture, metallurgy, spray paints, stainless steel industries, drinking water containing chromium are often known to cause acute renal injury in humans and animals. Nephrotoxicity is the major effect of chromium poisoning. In the present study, we investigated the potential renoprotective effect and underlying mechanisms of carvedilol using rat model of potassium dichromate (K2Cr2O7)-induced nephrotoxicity. Exploration of the underlying mechanisms of carvedilol revealed that carvedilol attenuated nuclear translocation and DNA binding activity of NF-κB (p65), restored antioxidant and mitochondrial respiratory enzyme activities and attenuated apoptosis related protein expressions in kidney tissues. The serum levels of TNF-α, the renal iNOS and myeloperoxidase activity were significantly decreased in carvedilol pre-treated K2Cr2O7-induced nephrotoxic rats. These results were further supported and confirmed by histological findings. In conclusion, the findings of the present study demonstrated that carvedilol is an effective chemoprotectant against K2Cr2O7-induced nephrotoxicity in rats.

Keywords: apoptosis, carvedilol, inflammation, potassium dichromate-induced nephrotoxicity, applied pharmacology

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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Authors: Soumitra Satapathi, Anubhav Raghav

Abstract:

Perovskite solar cell technology has passed through a phase of unprecedented growth in the efficiency scale from 3.8% to above 22% within a half decade. This technology has drawn tremendous research interest. It has been observed that performances of perovskite based solar cells are extremely dependent on the morphology and crystallinity of the perovskite layer. It has also been observed that device lifetime depends on the perovskite morphology; devices with larger perovskite grains degrade slowly than those of the smaller ones. Various methods of perovskite growth have been applied to achieve the most appropriate morphology necessary for high efficient solar cells. The recent progress in morphology optimization by various methods emphasizing on grain sizes, stoichiometry, and ambient compatibility as well as photophysics study in air-processed perovskite solar cells will be discussed.

Keywords: perovskite solar cells, morphology optimization, photophysics study, air-processed solar cells

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Authors: Griaznova Svetlana, Umedov Mekhroz

Abstract:

The current healthcare facilities trend is the creation of multidisciplinary large-scale centers to provide the maximum possible services in one place, minimizing the number of possible instances in the path of patient treatment. The multifunctional medical centers are mainly designed in urban infrastructure for good accessibility. However, many functions and connections define the building shape, often make it inharmonious, that greatly destroys the city's appearance. The purpose of the research is to scientifically substantiate the factors influencing the shaping, the formation of architectural solutions principles, the formation of recommendations and principles for the multifunctional medical centers' design. The result of the research is the elaboration of architectural and planning solutions principles and the determination of factors affecting the multifunctional healthcare facilities shaping. Research method: Study and generalization of international experience in scientific research, literature, standards, teaching aids, and design materials on the topic of research. An integrated approach to the study of existing international experience of multidisciplinary medical centers. Elaboration of graphical analysis and diagrams based on the system analysis of the processed information. Identification of methods and principles of functional zoning of nuclear medicine centers.

Keywords: health care, multifunctionality, form, medical center, hospital, PET, CT scan

Procedia PDF Downloads 104

Authors: Smita Pallavi, Raj Ratn Pranesh, Sumit Kumar

Abstract:

Information representation as tables is compact and concise method that eases searching, indexing, and storage requirements. Extracting and cloning tables from parsable documents is easier and widely used; however, industry still faces challenges in detecting and extracting tables from OCR (Optical Character Recognition) documents or images. This paper proposes an algorithm that detects and extracts multiple tables from OCR document. The algorithm uses a combination of image processing techniques, text recognition, and procedural coding to identify distinct tables in the same image and map the text to appropriate the corresponding cell in dataframe, which can be stored as comma-separated values, database, excel, and multiple other usable formats.

Keywords: table extraction, optical character recognition, image processing, text extraction, morphological transformation

Procedia PDF Downloads 144

Authors: Zexin Lei, Timothy Langrish

Abstract:

Lutein is a type of carotene believed to be beneficial to the eyes. This study aims to explore the possibility of using a closed cycle spray drying system to produce lutein. The system contains a spray dryer, a condenser, a heater, and a pressure seal. Hexane, ethanol, and isopropanol will be used as organic solvents to compare the extraction effects. Several physical and chemical methods of cell disruption will be compared. By continuously sweeping the system with nitrogen, the oxygen content will be controlled below 2%, reducing the concentration of organic solvent below the explosion limit and preventing lutein from being oxidized. Lutein powder will be recovered in the collection device. The volatile organic solvent will be cooled in the condenser and deposited in the bottom until it is discharged from the bottom of the condenser.

Keywords: closed cycle spray drying system, Chlorella vulgaris, organic solvent, solvent recovery

Procedia PDF Downloads 137

Authors: Meriem Mossaddek, El Mehdi Laadissi, El Mehdi Loualid, Chouaib Ennawaoui, Sohaib Bouzaid, Abdelowahed Hajjaji

Abstract:

An electrochemical system is a subset of mechatronic systems that includes a wide variety of batteries and nickel-cadmium, lead-acid batteries, and lithium-ion. Those structures have several non-linear behaviors and uncertainties in their running range. This paper studies an effective technique for modeling Lithium-Ion (Li-Ion) batteries using a Nonlinear Auto-Regressive model with exogenous input (NARX). The Artificial Neural Network (ANN) is trained to employ the data collected from the battery testing process. The proposed model is implemented on a Li-Ion battery cell. Simulation of this model in MATLAB shows good accuracy of the proposed model.

Keywords: lithium-ion battery, neural network, energy storage, battery model, nonlinear models

Procedia PDF Downloads 115

Authors: Belgheis Ebrahimi, Jun Lu

Abstract:

In recent years, there has been a growing recognition of the potential of marine-based functional foods and combination therapies in promoting a healthy lifestyle and exploring their effectiveness in preventing or treating diseases. The combination of marine bioactive compounds or extracts offers synergistic or enhancement effects through various mechanisms, including multi-target actions, improved bioavailability, enhanced bioactivity, and mitigation of potential adverse effects. Both the green-lipped mussel (GLM) and fucoidan derived from brown seaweed are rich in bioactivities. These two, mussel and fucoidan, have not been previously formulated together. This study aims to combine GLM oil from Perna canaliculus with low molecular weight fucoidan (LMWF) extracted from Undaria pinnatifida to investigate the unique mixture’s anti-inflammatory and antioxidant properties. The cytotoxicity of individual compounds and combinations was assessed using the MTT assay in (THP-1 and RAW264.7) cell lines. The anti-inflammatory activity of mussel-fucoidan was evaluated by treating LPS-stimulated human monocyte and macrophage (THP1-1) cells. Subsequently, the inflammatory cytokines released into the supernatant of these cell lines were quantified via ELISA. Antioxidant activity was determined by using the free radical scavenging assay (DPPH). DPPH assay demonstrated that the radical scavenging activity of the combinations, particularly at concentrations exceeding 1 mg/ml, showed a significantly higher percentage of inhibition when compared to the individual component. This suggests an enhancement effect when the two compounds are combined, leading to increased antioxidant activity. In terms of immunomodulatory activity, the individual compounds exhibited distinct behaviors. GLM oil displayed a higher ability to suppress the cytokine TNF- compared to LMWF. Interestingly, the LMWF fraction, when used individually, did not demonstrate TNF- suppression. However, when combined with GLM, the TNF- suppression (anti-inflammatory) activity of the combination was better than GLM or LWMF alone. This observation underscores the potential for enhancement interactions between the two components in terms of anti-inflammatory properties. This study revealed that each individual compound, LMWF, and GLM, possesses unique and notable bioactivity. The combination of these two individual compounds results in an enhancement effect, where the bioactivity of each is enhanced, creating a superior combination. This suggests that the combination of LMWF and GLM has the potential to offer a more potent and multifaceted therapeutic effect, particularly in the context of antioxidant and anti-inflammatory activities. These findings hold promise for the development of novel therapeutic interventions or supplements that harness the enhancement effects.

Keywords: combination, enhancement effect, perna canaliculus, undaria pinnatifida

Procedia PDF Downloads 81

Authors: Mohamed Tamer, Wink Michael

Abstract:

DNA intercalating agents increase the stability of DNA which can be demonstrated by measuring the melting temperature Tm. Tm can be determined in a spectrophotometer in which the cell temperature is increased gradually. The resulting absorption data comes as a sigmoidal curve from which melting temperature can be determined when half of the DNA has denatured. The current study aims to assess DNA intercalating activities of four pure bioactive isoquinoline alkaloids: sanguinarine, berberine, allocryptopine, and chelerythrine which were isolated from Chelidonium majus (Papaveraceae) by repeated silica gel column chromatography, recrystallization and preparative TLC. The isolated compounds were identified by comparing their physical properties and mass spectra with those of the published data. The results showed that sanguiarine is the most active intercalating agent with Tm value of 83.55 ± 0.49 followed by berberine, chelerythrine, and allocryptopine with Tm values 62.58 ± 0.47, 51.38 ± 0.37 and 50.94 ± 0.65, respectively, relative to 49.78 ± 1.05 of bacteriophage DNA alone and 86.09 ± 0.5 for ethidium bromide as a positive control.

Keywords: alkaloids, Chelidonium majus, DNA intercalation, Tm

Procedia PDF Downloads 501