Search results for: small molecule inhibitor
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5403

Search results for: small molecule inhibitor

5133 Evaluation of Shock Sensitivity of Nano-Scaled 1,3,5-Trinitro-1,3,5-Triazacyclohexane Using Small Scale Gap Test

Authors: Kang-In Lee, Woo-Jin Lee, Keun-Deuk Lee, Ju-Seung Chae

Abstract:

In this study, small scale gap test (SSGT) was performed to measure shock sensitivity of nano-scaled 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) samples. The shock sensitivity of energetic materials is usually evaluated by the method of large-scale gap test (LSGT) that has a higher reliability than other methods. But LSGT has the disadvantage that it takes a high cost and time by using a large amount of explosive. In this experiment, nano-scaled RDX samples were prepared by spray crystallization in two different drying methods. In addition, 30μm RDX sample produced by precipitation crystallization and 5μm RDX sample produced by fluid energy mill process were tested to compare shock sensitivity. The study of shock sensitivity measured by small-scale gap test shows that small sized RDX particles have greater insensitivity. As a result, we infer SSGT method has higher reliability compared to the literature as measurement of shock sensitivity of energetic materials.

Keywords: nano-scaled RDX, SSGT(small scale gap test), shock sensitivity, RDX

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5132 Small Farm Diversification Opportunities in Viticulture-Winemaking Sector of Georgia

Authors: E. Kharaishvili

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The paper analyses the role of small farms in socio-economic development of agriculture in Georgia and evaluates modern concepts regarding the development of the farms of this size. The scale of farms in Georgia is studied and the major problems are revealed. Opportunities and directions of diversification are discussed from the point of increasing the share of Georgian grapes and wine both on domestic and international markets. It’s shown that the size of vineyard areas is directly reflected on the grape and wine production potential. Accordingly, vineyard area and grape production dynamics is discussed. Comparative analysis of small farms in Georgia and Italy is made and the major differences are identified. Diversification is evaluated based on cost-benefit analysis on the one hand and on the other hand, from the point of promoting economic activities, protecting nature and rural area development. The paper provides proofs for the outcomes of diversification. The key hindering factors for the development of small farms are identified and corresponding conclusions are made, based on which recommendations for diversification of the farms of this size are developed.

Keywords: small farms, scale of farms, diversification, Georgia

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5131 Identification and Characterization of Inhibitors of Epoxide Hydrolase from Trichoderma reesei

Authors: Gabriel S. De Oliveira, Patricia P. Adriani, Christophe Moriseau, Bruce D. Hammock, Felipe S. Chambergo

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Epoxide hydrolases (EHs) are enzymes that are present in all living organisms and catalyze the hydrolysis of epoxides to the corresponding vicinal diols. EHs have high biotechnological interest for the drug design and chemistry transformation for industries. In this study, we describe the identification of substrates and inhibitors of epoxide hydrolase enzyme from the filamentous fungus Trichoderma reesei (TrEH), and these inhibitors showed the fungal growth inhibitory activity. We have used the cloned enzyme and expressed in E. coli to develop the screening in the library of fluorescent substrates with the objective of finding the best substrate to be used in the identification of good inhibitors for the enzyme TrEH. The substrate (3-phenyloxiranyl)-acetic acid cyano-(6-methoxy-naphthalen-2-yl)-methyl ester showed the highest specific activity and was chosen for the next steps of the study. The inhibitors screening was performed in the library with more than three thousand molecules and we could identify the 6 best inhibitors. The IC50 of these molecules were determined in nM and all the best inhibitors have urea or amide in their structure, because It has been recognized that these groups fit well in the hydrolase catalytic pocket of the epoxide hydrolases. Then the growth of T. reesei in PDA medium containing these TrEH inhibitors was tested, and fungal growth inhibition activity was demonstrated with more than 60% of inhibition of fungus growth in the assay with the TrEH inhibitor with the lowest IC50. Understanding how this EH enzyme from T. reesei responds to inhibitors may contribute for the study of fungal metabolism and drug design against pathogenic fungi.

Keywords: epoxide hydrolases, fungal growth inhibition, inhibitor, Trichoderma reesei

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5130 Cooperative Game Theory and Small Hold Farming: Towards A Conceptual Model

Authors: Abel Kahuni

Abstract:

Cooperative game theory (CGT) postulates that groups of players are crucial units of the decision-making and impose cooperative behaviour. Accordingly, cooperative games are regarded as competition between coalitions of players, rather than between individual players. However, the basic supposition in CGT is that the cooperative is formed by all players. One of the emerging questions in CGT is how to develop cooperatives and fairly allocate the payoff. Cooperative Game Theory (CGT) may provide a framework and insights into the ways small holder farmers in rural resettlements may develop competitive advantage through marketing cooperatives. This conceptual paper proposes a non-competition model for small holder farmers of homogenous agri-commodity under CGT conditions. This paper will also provide brief insights into to the theory of cooperative games in-order to generate an understanding of CGT, cooperative marketing gains and its application in small holder farming arrangements. Accordingly, the objective is to provide a basic introduction to this theory in connection with economic competitive theories in the context of small holder farmers. The key value proposition of CGT is the equitable and fair sharing of cooperative gains.

Keywords: game theory, cooperative game theory, cooperatives, competition

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5129 The Role of Climate-Smart Agriculture in the Contribution of Small-Scale Farming towards Ensuring Food Security in South Africa

Authors: Victor O. Abegunde, Melusi Sibanda

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There is need for a great deal of attention on small-scale agriculture for livelihood and food security because of the expanding global population. Small-scale agriculture has been identified as a major driving force of agricultural and rural development. However, the high dependence of the sector on natural and climatic resources has made small-scale farmers highly vulnerable to the adverse impact of climatic change thereby necessitating the need for embracing practices or concepts that will help absorb shocks from changes in climatic condition. This study examines the strategic position of small-scale farming in South African agriculture and in ensuring food security in the country, the vulnerability of small-scale agriculture to climate change and the potential of the concept of climate-smart agriculture to tackle the challenge of climate change. The study carried out a systematic review of peer-reviewed literature touching small-scale agriculture, climate change, food security and climate-smart agriculture, employing the realist review method. Findings revealed that increased productivity in the small-scale agricultural sector has a great potential of improving the food security of households in South Africa and reducing dependence on food purchase in a context of high food price inflation. Findings, however, also revealed that climate change affects small-scale subsistence farmers in terms of productivity, food security and family income, categorizing the impact on smallholder livelihoods into three major groups; biological processes, environmental and physical processes and impact on health. Analysis of the literature consistently showed that climate-smart agriculture integrates the benefits of adaptation and resilience to climate change, mitigation, and food security. As a result, farming households adopting climate-smart agriculture will be better off than their counterparts who do not. This study concludes that climate-smart agriculture could be a very good bridge linking small-scale agricultural sector and agricultural productivity and development which could bring about the much needed food security.

Keywords: climate change, climate-smart agriculture, food security, small-scale

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5128 Studies on Effect of Nano Size and Surface Coating on Enhancement of Bioavailability and Toxicity of Berberine Chloride; A p-gp Substrate

Authors: Sanjay Singh, Parameswara Rao Vuddanda

Abstract:

The aim of the present study is study the factual benefit of nano size and surface coating of p-gp efflux inhibitor on enhancement of bioavailability of Berberine chloride (BBR); a p-gp substrate. In addition, 28 days sub acute oral toxicity study was also conducted to assess the toxicity of the formulation on chronic administration. BBR loaded polymeric nanoparticles (BBR-NP) were prepared by nanoprecipitation method. BBR NP were surface coated (BBR-SCNP) with the 1 % w/v of vitamin E TPGS. For bioavailability study, total five groups (n=6) of rat were treated as follows first; pure BBR, second; physical mixture of BBR, carrier and vitamin E TPGS, third; BBR-NP, fourth; BBR-SCNP and fifth; BBR and verapamil (widely used p-gp inhibitor). Blood was withdrawn at pre-set timing points in 24 hrs study and drug was quantified by HPLC method. In oral chronic toxicity study, total four groups (n=6) were treated as follows first (control); water, second; pure BBR, third; BBR surface coated nanoparticles and fourth; placebo BBR surface coated nanoparticles. Biochemical levels of liver (AST, ALP and ALT) and kidney (serum urea and creatinine) along with their histopathological studies were also examined (0-28 days). The AUC of BBR-SCNP was significantly 3.5 folds higher compared to all other groups. The AUC of BBR-NP was 3.23 and 1.52 folds higher compared to BBR solution and BBR with verapamil group, respectively. The physical mixture treated group showed slightly higher AUC than BBR solution treated group but significantly low compared to other groups. It indicates that encapsulation of BBR in nanosize form can circumvent P-gp efflux effect. BBR-NP showed pharmacokinetic parameters (Cmax and AUC) which are near to BBR-SCNP. However, the difference in values of T1/2 and clearance indicate that surface coating with vitamin E TPGS not only avoids the P-gp efflux at its absorption site (intestine) but also at organs which are responsible for metabolism and excretion (kidney and liver). It may be the reason for observed decrease in clearance of BBR-SCNP. No toxicity signs were observed either in biochemical or histopathological examination of liver and kidney during toxicity studies. The results indicate that administration of BBR in surface coated nanoformulation would be beneficial for enhancement of its bioavailability and longer retention in systemic circulation. Further, sub acute oral dose toxicity studies for 28 days such as evaluation of intestine, liver and kidney histopathology and biochemical estimations indicated that BBR-SCNP developed were safe for long use.

Keywords: bioavailability, berberine nanoparticles, p-gp efflux inhibitor, nanoprecipitation method

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5127 Barrier Analysis of Sustainable Development of Small Towns: A Perspective of Southwest China

Authors: Yitian Ren, Liyin Shen, Tao Zhou, Xiao Li

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The past urbanization process in China has brought out series of problems, the Chinese government has then positioned small towns in essential roles for implementing the strategy 'The National New-type Urbanization Plan (2014-2020)'. As the connector and transfer station of cities and countryside, small towns are important force to narrow the gap between urban and rural area, and to achieve the mission of new-type urbanization in China. The sustainable development of small towns plays crucial role because cities are not capable enough to absorb the surplus rural population. Nevertheless, there are various types of barriers hindering the sustainable development of small towns, which led to the limited development of small towns and has presented a bottleneck in Chinese urbanization process. Therefore, this paper makes deep understanding of these barriers, thus effective actions can be taken to address them. And this paper chooses the perspective of Southwest China (refers to Sichuan province, Yunnan province, Guizhou province, Chongqing Municipality City and Tibet Autonomous Region), cause the urbanization rate in Southwest China is far behind the average urbanization level of the nation and the number of small towns accounts for a great proportion in mainland China, also the characteristics of small towns in Southwest China are distinct. This paper investigates the barriers of sustainable development of small towns which located in Southwest China by using the content analysis method, combing with the field work and interviews in sample small towns, then identified and concludes 18 barriers into four dimensions, namely, institutional barriers, economic barriers, social barriers and ecological barriers. Based on the research above, questionnaire survey and data analysis are implemented, thus the key barriers hinder the sustainable development of small towns in Southwest China are identified by using fuzzy set theory, those barriers are, lack of independent financial power, lack of construction land index, financial channels limitation, single industrial structure, topography variety and complexity, which mainly belongs to institutional barriers and economic barriers. In conclusion part, policy suggestions are come up with to improve the politic and institutional environment of small town development, also the market mechanism are supposed to be introduced to the development process of small towns, which can effectively overcome the economic barriers, promote the sustainable development of small towns, accelerate the in-situ urbanization by absorbing peasants in nearby villages, and achieve the mission of new-type urbanization in China from the perspective of people-oriented.

Keywords: barrier analysis, sustainable development, small town, Southwest China

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5126 Combined Treatment of PARP-1 Inhibitor and Carbon Ion or Gamma Exposure Reduces the Metastatic Potential in Cultured Human Cells

Authors: Priyanka Chowdhury, Asitikantha Sarma, Utpal Ghosh

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Hadron therapy using high Linear Energy Transfer (LET) ion beam is producing promising clinical results worldwide. The major advantages are its ability to kill radio-resistant tumor and its anti-metastatic activity. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been widely used as radiosensitizer, but its role in metastasis is unknown. The purpose of our study was to investigate the effect of PARP-1 depletion in combination with either Carbon Ion Beam (CIB) or gamma irradiation on metastatic potential of cultured cancerous cells. A549 cells were irradiated with CIB (0-4Gy) or gamma (0, 2, 4, 6 and 10 Gy) with and without PARP-1 inhibition. The metastatic potential of the cells was determined by cell migratory assay, expression, and activity of MMP-2 and MMP-9, expression of Cadherin, Fibronectin, and Vimentin. CIB exposure reduced migratory property and activity of MMP-2 and MMP-9 significantly. CIB with PARP-1 inhibition reduced cell migration and Matrix Metalloproteinase (MMPs) activity in a synergistic manner. Expression of MMPs was also down-regulated in CIB and combined treatment. On the contrary, MMP- 2 and MMP-9 activity was significantly increased in gamma irradiated cells but decreased upon combined treatment of gamma and PARP-1 inhibitor. MMPs expression and migration was reduced when gamma irradiation was combined with PARP-1 inhibition. Thus, our study clearly demonstrates that PARP-1 inhibition in combination with either high or low LET can significantly suppress metastatic potential in cancer cells and thereby can be a promising tool in controlling metastatic cancers.

Keywords: high LET, low LET, matrix metalloproteinase (MMP), PARP-1

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5125 Contemporary Living Spaces – Exploring, Differentiating, and Defining the Terms and Requirements of “Micro” and “Small” Homes in Bulgaria

Authors: Evgenia Dimova-Aleksandrova, Elitsa Deianova

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Dynamic changes in modern life and habitation due to demographic, urban, technology, and ecological factors affect the size of modern homes leading to a trend of decreasing their area. The current paper aims to investigate the differences between “micro” homes and “small” homes. In Bulgaria, these two types are not included in legal regulations, and therefore, a precise definition and special requirements are needed and sought in order to include their characteristic features in contemporary individual habitation. The purpose of the current study is to determine limits in built-up volume for the two types, to create a definition of the terms “micro” and “small” home, and to find methods to distinguish them. A comparative analysis will differentiate these types of habitation units, thus determining the boundaries for the built-up area for both concepts. The analysis is based on a case study from European practices and is focused on defining minimal requirements for “micro” and “small” home in the context of contemporary demands for high quality habitation in limited areas.

Keywords: Bulgaria, differentiation, micro home, requirements, small home

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5124 Critical Terrain Slope Calculation for Locating Small Hydropower Plants

Authors: C. Vrekos, C. Evagelides, N. Samarinas, G. Arampatzis

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As known, the water energy is a renewable and clean source of energy. Energy production from hydropower has been the first, and still is today a renewable source used to generate electricity. The optimal location and sizing of a small hydropower plant is a very important issue in engineering design which encourages investigation. The aim of this paper is to present a formula that can be utilized for locating the position of a small hydropower plant although there is a high dependence on economic, environmental, and social parameters. In this paper, the economic and technical side of the problem is considered. More specifically, there is a critical terrain slope that determines if the plant should be located at the end of the slope or not. Of course, this formula can be used for a first estimate and does not include detailed economic analysis. At the end, a case study is presented for the location of a small hydropower plant in order to demonstrate the validity of the proposed formula.

Keywords: critical terrain slope, economic analysis, hydropower plant locating, renewable energy

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5123 Efficacy of Comprehensive Diabetic Care Program with the Reduction of HbA1c in Overweight Type II Diabetes Mellitus Patients: A Retrospective Study

Authors: Rohit Sane, Pravin Ghadigaonkar, Purvi Ahuja, Suvarna Tirmare, Archana Kelhe, Kranti Shinde, Rahul Mandole

Abstract:

To evaluate the efficacy of Comprehensive Diabetic Care Program with the reduction of HbA1c in overweight Diabetes Mellitus Type II patients retrospectively. Methods: Retrospective study was carried out on 34 overweight type II diabetic patients (Mean Age = 54.58 ±11.38 yrs). A total of 34 patients were enrolled after screening of 68 patients (HbA1c 7-10%). The patients were on concomitant drugs namely insulin (11.76%), DPP-4 inhibitor (17.64%), Biguanide (55.88%), Sulfonylurea (52.94%), thiazolidinedione (11.76%), other medications (20.58%) and no allopathic medications (14.70%). The patients were given Comprehensive Diabetic Care Program consisting of panchkarma procedures namely snehana (external oleation), swedana (passive heat therapy) and basti (enema), which was completed in 15 sittings. During the therapy and next 90 days, the patients followed low carbohydrate and moderate protein & fat diet. The primary endpoint of this study was the evaluation of reduction in HbA1c at the end of the follow-up after 90 days. Results: Thirty-four overweight type II diabetic patients (mean age: 54.58[±11.38], HbA1c[7-10%], 67.64% male and 32.35% female) were enrolled in the study. A significant reduction was observed in HbA1c levels (14.30%, p<0.05) at the end of the 90 days follow-up as compared to baseline. Also, BMI was reduced by 5.87%. There was reduction in the usage of the concomitant drugs namely insulin (2.94%), DPP-4 inhibitor (2.94%), Biguanide (32.35%), Sulfonylurea (35.29%), thiazolidinedione (5.88%), other medications(17.64%) and no allopathic medications (32.35%). Conclusion: The results of the study highlight not only in the reduction of HbA1c, but also in BMI and drug tapering of the CDC program in the overweight type II diabetic patients with HbA1c (7-10%).

Keywords: HbA1c, low carb diet, Panchakarma therapy, Type II Diabetes

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5122 Enabling Exporting in Cameroon Using Export Promotion Programs

Authors: Morfaw Bernice Njinju

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The contribution of exporting and small businesses to an economy cannot be overemphasized. However, small firms in developing economies are characterized by resource deficiencies, which hinders their exporting abilities. As a result, export promotion programs are designed by the government as external resources that small firms can access to overcome export barriers and improve their exporting. Nevertheless, doubts still exist as to whether firms are aware of these programs and the extent to which they are utilizing it. To analyse the level of awareness and usage of these programs, the questionnaire was developed from the review of the literature. A pilot study was conducted to determine the ease of completing the questionnaire by respondent before incorporating feedback to produce the final questionnaire. Data were collected from 200 small businesses in Cameroon in the manufacturing and agricultural sector through random sampling and analysed using regression analysis. The results indicated that different programs had different levels of awareness than others. Programs to provide training to improve product quality was found to have the highest level of awareness while those providing findings had low levels of awareness. Despite these different levels of awareness, usage was very low, as firms do not want to open up to government scrutiny of their business. Implications to policy, practice, and direction for further research are also discussed.

Keywords: export promotion programs, exporting, small businesses, Cameroon

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5121 Chloride Ion Channels Play a Role in Mediating Immune Response during Pseudomonas aeruginosa Infection

Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

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5120 Segmental Dynamics of Poly(Alkyl Methacrylate) Chain in Ultra-Thin Spin-Cast Films

Authors: Hiroyuki Aoki

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Polymeric materials are often used in a form of thin film such as food wrap and surface coating. In such the applications, polymer films thinner than 100 nm have been often used. The thickness of such the ultra-thin film is less than the unperturbed size of a polymer chain; therefore, the polymer chain in an ultra-thin film is strongly constrained. However, the details on the constrained dynamics of polymer molecules in ultra-thin films are still unclear. In the current study, the segmental dynamics of single polymer chain was directly investigated by fluorescence microscopy. The individual chains of poly(alkyl methacrylate) labeled by a perylenediimide dye molecule were observed by a highly sensitive fluorescence microscope in a defocus condition. The translational and rotational diffusion of the center segment in a single polymer chain was directly analyzed. The segmental motion in a thin film with a thickness of 10 nm was found to be suppressed compared to that in a bulk state. The detailed analysis of the molecular motion revealed that the diffusion rate of the in-plane rotation was similar to the thin film and the bulk; on the other hand, the out-of-plane motion was restricted in a thin film. This result indicates that the spatial restriction in an ultra-thin film thinner than the unperturbed chain dimension alters the dynamics of individual molecules in a polymer system.

Keywords: polymer materials, single molecule, molecular motion, fluorescence microscopy, super-resolution techniques

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5119 TiO2/Clay Minerals (Palygorskite/Halloysite) Nanocomposite Coatings for Water Disinfection

Authors: Dionisios Panagiotaras, Dimitrios Papoulis, Elias Stathatos

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Microfibrous palygorskite and tubular halloysite clay mineral combined with nanocrystalline TiO2 are incorporating in the preparation of nanocomposite films on glass substrates via sol-gel route at 450 °C. The synthesis is employing nonionic surfactant molecule as pore directing agent along with acetic acid-based sol-gel route without addition of water molecules. Drying and thermal treatment of composite films ensure elimination of organic material lead to the formation of TiO2 nanoparticles homogeneously distributed on the palygorskite or halloysite surfaces. Nanocomposite films without cracks of active anatase crystal phase on palygorskite and halloysite surfaces are characterized by microscopy techniques, UV-Vis spectroscopy, and porosimetry methods in order to examine their structural properties. The composite palygorskite-TiO2 and halloysite-TiO2 films with variable quantities of palygorskite and halloysite were tested as photocatalysts in the photo-oxidation of Basic Blue 41 azo dye in water. These nanocomposite films proved to be most promising photocatalysts and highly effective to dye’s decoloration in spite of small amount of palygorskite -TiO2 or halloysite- TiO2 catalyst immobilized onto glass substrates mainly due to the high surface area and uniform distribution of TiO2 on clay minerals avoiding aggregation.

Keywords: halloysite, palygorskite, photocatalysis, titanium dioxide

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5118 Sustainable Manufacturing Framework for Small and Medium Enterprises

Authors: Rajan Deglurkar

Abstract:

The research carried out in this piece of work is on 'Framework of Sustainable Manufacturing for Small and Medium Enterprises'. It consists of elucidation of concepts about sustainable manufacturing and sustainable product development with critical review performed on seven techniques of sustainable manufacturing. The work also covers the survey about critical review of awareness in the market with respect to the manufacturers and the consumers. The factors and challenges for sustainable manufacturing implementation are reviewed and simple framework is constructed for the small and medium enterprise for successful implementation of sustainable manufacturing and sustainable product.

Keywords: sustainable development, sustainable manufacturing, resource efficiency, framework for sustainable manufacturing

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5117 Insight into the Binding Theme of CA-074Me to Cathepsin B: Molecular Dynamics Simulations and Scaffold Hopping to Identify Potential Analogues as Anti-Neurodegenerative Diseases

Authors: Tivani Phosa Mashamba-Thompson, Mahmoud E. S. Soliman

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To date, the cause of neurodegeneration is not well understood and diseases that stem from neurodegeneration currently have no known cures. Cathepsin B (CB) enzyme is known to be involved in the production of peptide neurotransmitters and toxic peptides in neurodegenerative diseases (NDs). CA-074Me is a membrane-permeable irreversible selective cathepsin B (CB) inhibitor as confirmed by in vivo studies. Due to the lack of the crystal structure, the binding mode of CA-074Me with the human CB at molecular level has not been previously reported. The main aim of this study is to gain an insight into the binding mode of CB CA-074Me to human CB using various computational tools. Herein, molecular dynamics simulations, binding free energy calculations and per-residue energy decomposition analysis were employed to accomplish the aim of the study. Another objective was to identify novel CB inhibitors based on the structure of CA-074Me using fragment based drug design using scaffold hoping drug design approach. Results showed that two of the designed ligands (hit 1 and hit 2) were found to have better binding affinities than the prototype inhibitor, CA-074Me, by ~2-3 kcal/mol. Per-residue energy decomposition showed that amino acid residues Cys29, Gly196, His197 and Val174 contributed the most towards the binding. The Van der Waals binding forces were found to be the major component of the binding interactions. The findings of this study should assist medicinal chemist towards the design of potential irreversible CB inhibitors.

Keywords: cathepsin B, scaffold hopping, docking, molecular dynamics, binding-free energy, neurodegerative diseases

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5116 Need for Standardization of Manual Inspection in Small and Medium-Scale Manufacturing Industries

Authors: Adithya Nadig

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In the field of production, characterization of surface roughness plays a vital role in assessing the quality of a manufactured product. The defined parameters for this assessment, each, have their own drawbacks in describing a profile surface. From the purview of small-scale and medium-scale industries, an increase in time spent for manual inspection of a product for various parameters adds to the cost of the product. In order to reduce this, a uniform and established standard is necessary for quantifying a profile of a manufactured product. The inspection procedure in the small and medium-scale manufacturing units at Jigani Industrial area, Bangalore, was observed. The parameters currently in use in those industries are described in the paper and a change in the inspection method is proposed.

Keywords: efficiency of quality assessment, manual areal profiling technique, manufacturing in small and medium-scale industries product-oriented inspection, standardization of manual inspection, surface roughness characterization

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5115 Audit of TPS photon beam dataset for small field output factors using OSLDs against RPC standard dataset

Authors: Asad Yousuf

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Purpose: The aim of the present study was to audit treatment planning system beam dataset for small field output factors against standard dataset produced by radiological physics center (RPC) from a multicenter study. Such data are crucial for validity of special techniques, i.e., IMRT or stereotactic radiosurgery. Materials/Method: In this study, multiple small field size output factor datasets were measured and calculated for 6 to 18 MV x-ray beams using the RPC recommend methods. These beam datasets were measured at 10 cm depth for 10 × 10 cm2 to 2 × 2 cm2 field sizes, defined by collimator jaws at 100 cm. The measurements were made with a Landauer’s nanoDot OSLDs whose volume is small enough to gather a full ionization reading even for the 1×1 cm2 field size. At our institute the beam data including output factors have been commissioned at 5 cm depth with an SAD setup. For comparison with the RPC data, the output factors were converted to an SSD setup using tissue phantom ratios. SSD setup also enables coverage of the ion chamber in 2×2 cm2 field size. The measured output factors were also compared with those calculated by Eclipse™ treatment planning software. Result: The measured and calculated output factors are in agreement with RPC dataset within 1% and 4% respectively. The large discrepancies in TPS reflect the increased challenge in converting measured data into a commissioned beam model for very small fields. Conclusion: OSLDs are simple, durable, and accurate tool to verify doses that delivered using small photon beam fields down to a 1x1 cm2 field sizes. The study emphasizes that the treatment planning system should always be evaluated for small field out factors for the accurate dose delivery in clinical setting.

Keywords: small field dosimetry, optically stimulated luminescence, audit treatment, radiological physics center

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5114 Effects of Cymbopogon citratus, Stapf (CS) or Lemon Grass Ethanol Extract on Antioxidant and Vascular Disorders Parameters in Rat

Authors: Suphaket Saenthaweesuk, Nutiya Somparn, Atcharaporn Thewmore

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The present study aims to investigate the effects of Cymbopogon citratus, Stapf (CS) or lemon grass ethanol extract on antioxidant and vascular disorders parameters in rat. The CS ethanol extract was screened for its phytochemical contents and antioxidant activity in vitro. Moreover, the extract was studied in rats to evaluate its effects in vivo. Rats were orally administered with CS at 1,000 mg/kg/day for 30 days. Phytochemical screening of CS extract indicated the presence of tannins, flavonoids and phenolic compounds. The extract contained phenolic compounds 1,400.10 ± 0.47 mg of gallic acid equivalents per gram CS extract. The free radical scavenging activity assessed by DPPH assay gave IC50 of 168.77 ± 3.32µg/mL, which is relatively lower than that of BHT with IC50 of 12.34 ± 1.14 µg/mL. In the animals, the protein expression of antioxidant enzymes, γ-glutamylcysteine ligase (γ-GCL) in liver was significantly increased. This was consistent with elevation of serum catalase (CAT) and superoxide dismutase (SOD) activities. However, Protein expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial nitric oxide synthase (eNOS) in heart and aorta were not differenced from normal control. Taken together, the present study provides evidence that CCS water extract exhibits direct antioxidant properties and can induce cytoprotective enzymes in vivo.

Keywords: antioxidant, Cymbopogon citratus Stapf, VCAM-1, γ-glutamylcysteine ligase

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5113 Socio-Cultural Factors to Support Knowledge Management and Organizational Innovation: A Study of Small and Medium-Sized Enterprises in Latvia

Authors: Madara Apsalone

Abstract:

Knowledge management and innovation is key to competitive advantage and sustainable business development in advanced economies. Small and medium-sized enterprises (SMEs) have lower capacity and more constrained resources for long-term and high-uncertainty research and development investments. At the same time, SMEs can implement organizational innovation to improve their performance and further foster other types of innovation. The purpose of this study is to analyze, how socio-cultural factors such as shared values, organizational behaviors, work organization and decision making processes can influence knowledge management and help to develop organizational innovation via an empirical study. Surveying 600 SMEs in Latvia, the author explores the contribution of different socio-cultural factors to organizational innovation and the role of knowledge management and organizational learning in this process. A conceptual model, explaining the impact of organizational team, development, result-orientation and structure is created. The study also proposes insights that contribute to theoretical and practical discussions on fostering innovation of small businesses in small economies.

Keywords: knowledge management, organizational innovation, small and medium-sized enterprises, socio-cultural factors

Procedia PDF Downloads 364
5112 Realistic Modeling of the Preclinical Small Animal Using Commercial Software

Authors: Su Chul Han, Seungwoo Park

Abstract:

As the increasing incidence of cancer, the technology and modality of radiotherapy have advanced and the importance of preclinical model is increasing in the cancer research. Furthermore, the small animal dosimetry is an essential part of the evaluation of the relationship between the absorbed dose in preclinical small animal and biological effect in preclinical study. In this study, we carried out realistic modeling of the preclinical small animal phantom possible to verify irradiated dose using commercial software. The small animal phantom was modeling from 4D Digital Mouse whole body phantom. To manipulate Moby phantom in commercial software (Mimics, Materialise, Leuven, Belgium), we converted Moby phantom to DICOM image file of CT by Matlab and two- dimensional of CT images were converted to the three-dimensional image and it is possible to segment and crop CT image in Sagittal, Coronal and axial view). The CT images of small animals were modeling following process. Based on the profile line value, the thresholding was carried out to make a mask that was connection of all the regions of the equal threshold range. Using thresholding method, we segmented into three part (bone, body (tissue). lung), to separate neighboring pixels between lung and body (tissue), we used region growing function of Mimics software. We acquired 3D object by 3D calculation in the segmented images. The generated 3D object was smoothing by remeshing operation and smoothing operation factor was 0.4, iteration value was 5. The edge mode was selected to perform triangle reduction. The parameters were that tolerance (0.1mm), edge angle (15 degrees) and the number of iteration (5). The image processing 3D object file was converted to an STL file to output with 3D printer. We modified 3D small animal file using 3- Matic research (Materialise, Leuven, Belgium) to make space for radiation dosimetry chips. We acquired 3D object of realistic small animal phantom. The width of small animal phantom was 2.631 cm, thickness was 2.361 cm, and length was 10.817. Mimics software supported efficiency about 3D object generation and usability of conversion to STL file for user. The development of small preclinical animal phantom would increase reliability of verification of absorbed dose in small animal for preclinical study.

Keywords: mimics, preclinical small animal, segmentation, 3D printer

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5111 Is Sodium Channel Nav1.7 an Ideal Therapeutically Analgesic Target? A Systematic Review

Authors: Yutong Wan, John N. Wood

Abstract:

Introduction: SCN9A encoded Nav1.7 is an ideal therapeutic target with minimal side effects for the pharmaceutical industry because SCN9A variants can cause both human gains of function pain-related mutations and loss of function pain-free mutations. This study reviews the clinical effectiveness of existing Nav1.7 inhibitors, which theoretically should be powerful analgesics. Methods: A systematic review is conducted on the effectiveness of current Nav1.7 blockers undergoing clinical trials. Studies were mainly extracted from PubMed, U.S. National Library of Medicine Clinical Trials, World Health Organization International Clinical Trials Registry, ISRCTN registry platform, and Integrated Research Approval System by NHS. Only studies with full text available and those conducted using double-blinded, placebo controlled, and randomised designs and reporting at least one analgesic measurement were included. Results: Overall, 61 trials were screened, and eight studies covering PF 05089771 (Pfizer), TV 45070 (Teva & Xenon), and BIIB074 (Biogen) met the inclusion criteria. Most studies were excluded because results were not published. All three compounds demonstrated insignificant analgesic effects, and the comparison between PF 05089771 and pregabalin/ibuprofen showed that PF 05089771 was a much weaker analgesic. All three drug candidates only have mild side effects, indicating the potentials for further investigation of Nav1.7 antagonists. Discussion: The failure of current Nav1.7 small molecule inhibitors might attribute to ignorance of the key role of endogenous systems in Nav1.7 null mutants, the lack of selectivity and blocking potency, and central impermeability. The synergistic combination of analgesic drugs, a recent UCL patent, combining a small dose of Nav1.7 blockers and opioids or enkephalinase inhibitors dramatically enhanced the analgesic effects. Conclusion: The current clinical testing Nav1.7 blockers are generally disappointing. However, the newer generation of Nav1.7 targeting analgesics has overcome the major constraints of its predecessors.

Keywords: chronic pain, Nav1.7 blockers, SCN9A, systematic review

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5110 The Localization and Function of p38α Mitogen-Activated Protein Kinase (MAPK) in Rat Oocytes

Authors: Shifu Hu, Qiong Yu, Wei Xia, Changhong Zhu

Abstract:

Background: P38α MAPK, which is a member of the canonical MAPK family, is activated in response to various extracellular stresses and plays a role in multiple cellular processes. It is well known that p38α MAPK play vital roles in oocyte maturation, but the localization and functional roles of p38α MAPK during the meiotic maturation of rat oocytes remain unknown. Study Design: In this study, western-blot and immunofluorescent staining were used to investigate the expression and subcellular localization of p38α MAPK during the meiotic maturation of rat oocytes. SB203580, a specific inhibitor of p38α MAPK, was used to study the roles of p38α MAPK in the meiotic cell cycle of rat oocytes. Results: The results found that p38α MAPK phosphorylation (p-p38α MAPK, indicative of p38α MAPK activation) was low at the germinal vesicle (GV) stage, increased 3 h after germinal vesicle breakdown (GVBD), and maintained its maximum at MI (metaphase I) or M II (metaphase II). The p-p38α MAPK mainly accumulated in the germinal vesicle and had no obvious expression in the nucleus. From GVBD to M II, p-p38α MAPK was distributed in the cytoplasm around either the chromosomes or the spindle. We used SB203580, an inhibitor of p38α MAPK, to investigate the possible functional role of p38α MAPK during rat oocyte meiotic maturation. Treatment of GV stage oocytes with 20 μM SB203580 blocked p-p38α MAPK activity, and the spindles appeared abnormal. Additionally, the rate of GVBD after 3h of culture with 20 μM SB203580 (58.8%) was significantly inhibited compared with the control (82.5%, p < 0.05), and the polar body extrusion rate after 12 h of culture with SB203580 was also significantly decreased compared with the control (40.1 vs. 73.3%, p < 0.05). Conclusions: These data indicate that p38α MAPK may play a vital role in rat oocyte meiotic maturation.

Keywords: meiotic maturation, oocyte, p38α MAPK, spindle

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5109 The Rational Design of Original Anticancer Agents Using Computational Approach

Authors: Majid Farsadrooh, Mehran Feizi-Dehnayebi

Abstract:

Serum albumin is the most abundant protein that is present in the circulatory system of a wide variety of organisms. Although it is a significant macromolecule, it can contribute to osmotic blood pressure and also, plays a superior role in drug disposition and efficiency. Molecular docking simulation can improve in silico drug design and discovery procedures to propound a lead compound and develop it from the discovery step to the clinic. In this study, the molecular docking simulation was applied to select a lead molecule through an investigation of the interaction of the two anticancer drugs (Alitretinoin and Abemaciclib) with Human Serum Albumin (HSA). Then, a series of new compounds (a-e) were suggested using lead molecule modification. Density functional theory (DFT) including MEP map and HOMO-LUMO analysis were used for the newly proposed compounds to predict the reactivity zones on the molecules, stability, and chemical reactivity. DFT calculation illustrated that these new compounds were stable. The estimated binding free energy (ΔG) values for a-e compounds were obtained as -5.78, -5.81, -5.95, -5,98, and -6.11 kcal/mol, respectively. Finally, the pharmaceutical properties and toxicity of these new compounds were estimated through OSIRIS DataWarrior software. The results indicated no risk of tumorigenic, irritant, or reproductive effects and mutagenicity for compounds d and e. As a result, compounds d and e, could be selected for further study as potential therapeutic candidates. Moreover, employing molecular docking simulation with the prediction of pharmaceutical properties helps to discover new potential drug compounds.

Keywords: drug design, anticancer, computational studies, DFT analysis

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5108 Multidrug Resistance Mechanisms among Gram Negative Clinical Isolates from Egypt

Authors: Mona T. Kashef, Omneya M. Helmy

Abstract:

Multidrug resistant (MDR) bacteria have become a significant public health threat. The prevalence rates, of Gram negative MDR bacteria, are in continuous increase. However, few data are available about these resistant strains. Since, third generation cephalosporins are one of the most commonly used antimicrobials, we set out to investigate the prevalence, different mechanisms and clonal relatedness of multidrug resistance among third generation resistant Gram negative clinical isolates. A total of 114 Gram negative clinical isolates, previously characterized as being resistant to at least one of 3rd generation cephalosporins, were included in this study. Each isolate was tested, using Kirby Bauer disk diffusion method, against its assigned categories of antimicrobials. The role of efflux pump in resistance development was tested by the efflux pump inhibitor-based microplate assay using chloropromazine as an inhibitor. Detecting different aminoglycosides, β-lactams and quinolones resistance genes was done using polymerase chain reaction. The genetic diversity of MDR isolates was investigated using Random Amplification of Polymorphic DNA technique. MDR phenotype was detected in 101 isolates (89%). Efflux pump mediated resistance was detected in 49/101 isolates. Aminoglycosides resistance genes; armA and aac(6)-Ib were detected in one and 53 isolates, respectively. The aac(6)-Ib-cr allele, that also confers resistance to floroquinolones, was detected in 28/53 isolates. β-lactam resistance genes; blaTEM, blaSHV, blaCTX-M group 1 and group 9 were detected in 52, 29, 61 and 35 isolates, respectively. Quinolone resistance genes; qnrA, qnrB and qnrS were detectable in 2, 14, 8 isolates respectively, while qepA was not detectable at all. High diversity was observed among tested MDR isolates. MDR is common among 3rd generation cephalosporins resistant Gram negative bacteria, in Egypt. In most cases, resistance was caused by different mechanisms. Therefore, new treatment strategies should be implemented.

Keywords: gram negative, multidrug resistance, RAPD typing, resistance genes

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5107 Energetics of Photosynthesis with Respect to the Environment and Recently Reported New Balanced Chemical Equation

Authors: Suprit Pradhan, Sushil Pradhan

Abstract:

Photosynthesis is a physiological process where green plants prepare their food from carbon dioxide from the atmosphere and water being absorbed from the soil in presence of sun light and chlorophyll. From this definition it is clear that four reactants (Carbon Dioxide, Water, Light and Chlorophyll) are essential for the process to proceed and the product is a sugar or carbohydrate ultimately stored as starch. The entire process has “Light Reaction” (Photochemical) and “Dark Reaction” (Biochemical). Biochemical reactions are very much complicated being catalysed by various enzymes and the path of carbon is known as “Calvin Cycle” according to the name of its discover. The overall reaction which is now universally accepted can be explained like this. Six molecules of carbon dioxide react with twelve molecules of water in presence of chlorophyll and sun light to give only one molecule of sugar (Carbohydrate) six molecules of water and six molecules of oxygen is being evolved in gaseous form. This is the accepted equation and also chemically balanced. However while teaching the subject the author came across a new balanced equation from among the students who happened to be the daughter of the author. In the new balanced equation in place of twelve water molecules in the reactant side seven molecules can be expressed and accordingly in place of six molecules of water in the product side only one molecule of water is produced. The energetics of the photosynthesis as related to the environment and the newly reported balanced chemical equation has been discussed in detail in the present research paper presentation in this international conference on energy, environmental and chemical engineering.

Keywords: biochemistry, enzyme , isotope, photosynthesis

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5106 A Fortunate Presentation of Intestinal Obstruction Secondary to a Sarcomatoid Tumour of the Small Bowel

Authors: Thampi Rawther, Sean O’Brien, Kamala Kanta Das

Abstract:

Background: Intussusception in the adult is rarely from a benign cause and is almost always pathological. Causes include carcinomas, polyps, Meckel's diverticulum, or colonic diverticulum. Common symptoms include abdominal pain, intestinal obstruction, palpable abdominal mass, GI bleeding, and anemia. Sarcomatoid carcinoma is a rare type of small intestinal malignancy exhibiting carcinomatous and sarcomatous features. It primarily affects older patients, mean age 57, and is 1.5 times more prevalent in men. Method: This is an interesting case report of a patient presenting with intussusception secondary to a sarcomatoid tumor of the small bowel. Conclusion: Surgery is the treatment of choice in adults with intussusception due to the high malignancy potential. Furthermore, surgical resection of the affected bowel is the definitive form of therapy as small bowel sarcomatoid tumors are not responsive to chemotherapy and radiotherapy. Early surgical intervention helps reduce mortality as it allows for early staging, treatment, and monitoring of the tumor. The patient was fortunate to have presented with intussusception, facilitating early surgical intervention, and was found to have a low disease stage.

Keywords: general surgery, small bowel tumour, imaging, unique

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5105 Neighbour Cell List Reduction in Multi-Tier Heterogeneous Networks

Authors: Mohanad Alhabo, Naveed Nawaz

Abstract:

The ongoing call or data session must be maintained to ensure a good quality of service. This can be accomplished by performing the handover procedure while the user is on the move. However, the dense deployment of small cells in 5G networks is a challenging issue due to the extensive number of handovers. In this paper, a neighbour cell list method is proposed to reduce the number of target small cells and hence minimizing the number of handovers. The neighbour cell list is built by omitting cells that could cause an unnecessary handover and handover failure because of short time of stay of the user in these cells. A multi-attribute decision making technique, simple additive weighting, is then applied to the optimized neighbour cell list. Multi-tier small cells network is considered in this work. The performance of the proposed method is analysed and compared with that of the existing methods. Results disclose that our method has decreased the candidate small cell list, unnecessary handovers, handover failure, and short time of stay cells compared to the competitive method.

Keywords: handover, HetNets, multi-attribute decision making, small cells

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5104 Modeling of Processes Running in Radical Clusters Formed by Ionizing Radiation with the Help of Continuous Petri Nets and Oxygen Effect

Authors: J. Barilla, M. Lokajíček, H. Pisaková, P. Simr

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The final biological effect of ionizing particles may be influenced strongly by some chemical substances present in cells mainly in the case of low-LET radiation. The influence of oxygen may be particularly important because oxygen is always present in living cells. The corresponding processes are then running mainly in the chemical stage of radio biological mechanism. The radical clusters formed by densely ionizing ends of primary or secondary charged particles are mainly responsible for final biological effect. The damage effect depends then on radical concentration at a time when the cluster meets a DNA molecule. It may be strongly influenced by oxygen present in a cell as oxygen may act in different directions: at small concentration of it the interaction with hydrogen radicals prevails while at higher concentrations additional efficient oxygen radicals may be formed. The basic radical concentration in individual clusters diminishes, which is influenced by two parallel processes: chemical reactions and diffusion of corresponding clusters. The given simultaneous evolution may be modeled and analyzed well with the help of Continuous Petri nets. The influence of other substances present in cells during irradiation may be studied, too. Some results concerning the impact of oxygen content will be presented.

Keywords: radiobiological mechanism, chemical phase, DSB formation, Petri nets

Procedia PDF Downloads 292