Search results for: solid scale inhibitors
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 8175

Search results for: solid scale inhibitors

8085 Understanding Inhibitory Mechanism of the Selective Inhibitors of Cdk5/p25 Complex by Molecular Modeling Studies

Authors: Amir Zeb, Shailima Rampogu, Minky Son, Ayoung Baek, Sang H. Yoon, Keun W. Lee

Abstract:

Neurotoxic insults activate calpain, which in turn produces truncated p25 from p35. p25 forms hyperactivated Cdk5/p25 complex, and thereby induces severe neuropathological aberrations including hyperphosphorylated tau, neuroinflammation, apoptosis, and neuronal death. Inhibition of Cdk5/p25 complex alleviates aberrant phosphorylation of tau to mitigate AD pathology. PHA-793887 and Roscovitine have been investigated as selective inhibitors of Cdk5/p25 with IC50 values 5nM and 160nM, respectively, but their mechanistic studies remain unknown. Herein, computational simulations have explored the binding mode and interaction mechanism of PHA-793887 and Roscovitine with Cdk5/p25. Docking results suggested that PHA-793887 and Rsocovitine have occupied the ATP-binding site of Cdk5 and obtained highest docking (GOLD) score of 66.54 and 84.03, respectively. Furthermore, molecular dynamics (MD) simulation demonstrated that PHA-793887 and Roscovitine established stable RMSD of 1.09 Å and 1.48 Å with Cdk5/p25, respectively. Profiling of polar interactions suggested that each inhibitor formed hydrogen bonds (H-bond) with catalytic residues of Cdk5 and could remain stable throughout the molecular dynamics simulation. Additionally, binding free energy calculation by molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) suggested that PHA-793887 and Roscovitine had lowest binding free energies of -150.05 kJ/mol and -113.14 kJ/mol, respectively with Cdk5/p25. Free energy decomposition demonstrated that polar energy by H-bond between the Glu81 of Cdk5 and PHA-793887 is the essential factor to make PHA-793887 highly selective towards Cdk5/p25. Overall, this study provided substantial evidences to explore mechanistic interactions of the selective inhibitors of Cdk5/p25 and could be used as fundamental considerations in the development of structure-based selective inhibitors of Cdk5/p25.

Keywords: Cdk5/p25 inhibition, molecular modeling of Cdk5/p25, PHA-793887 and roscovitine, selective inhibition of Cdk5/p25

Procedia PDF Downloads 115
8084 Solubility Enhancement of Poorly Soluble Anticancer Drug, Docetaxel Using a Novel Polymer, Soluplus via Solid Dispersion Technique

Authors: Adinarayana Gorajana, Venkata Srikanth Meka, Sanjay Garg, Lim Sue May

Abstract:

This study was designed to evaluate and enhance the solubility of poorly soluble drug, docetaxel through solid dispersion (SD) technique prepared using freeze drying method. Docetaxel solid dispersions were formulated with Soluplus in different weight ratios. Freeze drying method was used to prepare the solid dispersions. Solubility of the solid dispersions were evaluated respectively and the optimized of drug-solubilizers ratio systems were characterized with different analytical methods like Differential scanning calorimeter (DSC), Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) to confirm the formation of complexes between drug and solubilizers. The solubility data revealed an overall improvement in solubility for all SD formulations. The ternary combination 1:5:2 gave the highest increase in solubility that is approximately 3 folds from the pure drug, suggesting the optimum drug-solubilizers ratio system. This data corresponds with the DSC and SEM analyses, which demonstrates presence of drug in amorphous state and the dispersion in the solubilizers in molecular level. The solubility of the poorly soluble drug, docetaxel was enhanced through preparation of solid dispersion formulations employing freeze drying method. Solid dispersion with multiple carrier system shows better solubility compared to single carrier system.

Keywords: docetaxel, freeze drying, soluplus, solid dispersion technique

Procedia PDF Downloads 480
8083 Pharmacogenetics of P2Y12 Receptor Inhibitors

Authors: Ragy Raafat Gaber Attaalla

Abstract:

For cardiovascular illness, oral P2Y12 inhibitors including clopidogrel, prasugrel, and ticagrelor are frequently recommended. Each of these medications has advantages and disadvantages. In the absence of genotyping, it has been demonstrated that the stronger platelet aggregation inhibitors prasugrel and ticagrelor are superior than clopidogrel at preventing significant adverse cardiovascular events following an acute coronary syndrome and percutaneous coronary intervention (PCI). Both, nevertheless, come with a higher risk of bleeding unrelated to a coronary artery bypass. As a prodrug, clopidogrel needs to be bioactivated, principally by the CYP2C19 enzyme. A CYP2C19 no function allele and diminished or absent CYP2C19 enzyme activity are present in about 30% of people. The reduced exposure to the active metabolite of clopidogrel and reduced inhibition of platelet aggregation among clopidogrel-treated carriers of a CYP2C19 no function allele likely contributed to the reduced efficacy of clopidogrel in clinical trials. Clopidogrel's pharmacogenetic results are strongest when used in conjunction with PCI, but evidence for other indications is growing. One of the most typical examples of clinical pharmacogenetic application is CYP2C19 genotype-guided antiplatelet medication following PCI. Guidance is available from expert consensus groups and regulatory bodies to assist with incorporating genetic information into P2Y12 inhibitor prescribing decisions. Here, we examine the data supporting genotype-guided P2Y12 inhibitor selection's effects on clopidogrel response and outcomes and discuss tips for pharmacogenetic implementation. We also discuss procedures for using genotype data to choose P2Y12 inhibitor therapies as well as any unmet research needs. Finally, choosing a P2Y12 inhibitor medication that optimally balances the atherothrombotic and bleeding risks may be influenced by both clinical and genetic factors.

Keywords: inhibitors, cardiovascular events, coronary intervention, pharmacogenetic implementation

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8082 Design of Collection and Transportation System of Municipal Solid Waste in Meshkinshahr City

Authors: Ebrahim Fataei, Seyed Ali Hosseini, Zahra Arabi, Habib farhadi, Mehdi Aalipour Erdi, Seiied Taghi Seiied Safavian

Abstract:

Solid waste production is an integral part of human life and management of waste require full scientific approach and essential planning. The allocation of most management cost to collection and transportation and also the necessity of operational efficiency in this system, by limiting time consumption, and on the other hand optimum collection system and transportation is the base of waste design and management. This study was done to optimize the exits collection and transportation system of solid waste in Meshkinshahr city. So based on the analyzed data of municipal solid waste components in seven zones of Meshkinshahr city, and GIS software, applied to design storage place based on origin recycling and a route to collect and transport. It was attempted to represent an appropriate model to store, collect and transport municipal solid waste. The result shows that GIS can be applied to locate the waste container and determine a waste collection direction in an appropriate way.

Keywords: municipal solid waste management, transportation, optimizing, GIS, Iran

Procedia PDF Downloads 501
8081 Solid Dispersions of Cefixime Using β-Cyclodextrin: Characterization and in vitro Evaluation

Authors: Nagasamy Venkatesh Dhandapani, Amged Awad El-Gied

Abstract:

Cefixime, a BCS class II drug, is insoluble in water but freely soluble in acetone and in alcohol. The aqueous solubility of cefixime in water is poor and exhibits exceptionally slow and intrinsic dissolution rate. In the present study, cefixime and β-Cyclodextrin (β-CD) solid dispersions were prepared with a view to study the effect and influence of β-CD on the solubility and dissolution rate of this poorly aqueous soluble drug. Phase solubility profile revealed that the solubility of cefixime was increased in the presence of β-CD and was classified as AL-type. Effect of variable, such as drug:carrier ratio, was studied. Physical characterization of the solid dispersion was characterized by Fourier transform infrared spectroscopy (FT-IR) and Differential scanning calorimetry (DSC). These studies revealed that a distinct loss of drug crystallinity in the solid molecular dispersions is ostensibly accounting for enhancement of dissolution rate in distilled water. The drug release from the prepared solid dispersion exhibited a first order kinetics. Solid dispersions of cefixime showed a 6.77 times fold increase in dissolution rate over the pure drug.

Keywords: β-cyclodextrin, cefixime, dissolution, Kneading method, solid dispersions, release kinetics

Procedia PDF Downloads 290
8080 Preparation of Li Ion Conductive Ceramics via Liquid Process

Authors: M. Kotobuki, M. Koishi

Abstract:

Li1.5Al0.5Ti1.5 (PO4)3(LATP) has received much attention as a solid electrolyte for lithium batteries. In this study, the LATP solid electrolyte is prepared by the co-precipitation method using Li3PO4 as a Li source. The LATP is successfully prepared and the Li ion conductivities of bulk (inner crystal) and total (inner crystal and grain boundary) are 1.1 × 10-3 and 1.1 × 10-4 S cm-1, respectively. These values are comparable to the reported values, in which Li2C2O4 is used as the Li source. It is conclude that the LATP solid electrolyte can be prepared by the co-precipitation method using Li3PO4 as the Li source and this procedure has an advantage in mass production over previous procedure using Li2C2O4 because Li3PO4 is lower price reagent compared with Li2C2O4.

Keywords: co-precipitation method, lithium battery, NASICON-type electrolyte, solid electrolyte

Procedia PDF Downloads 325
8079 Drippers Scaling Inhibition of the Localized Irrigation System by Green Inhibitors Based on Plant Extracts

Authors: Driouiche Ali, Karmal Ilham

Abstract:

The Agadir region is characterized by a dry climate, ranging from arid attenuated by oceanic influences to hyper-arid. The water mobilized in the agricultural sector of greater Agadir is 95% of underground origin and comes from the water table of Chtouka. The rest represents the surface waters of the Youssef Ben Tachfine dam. These waters are intended for the irrigation of 26880 hectares of modern agriculture. More than 120 boreholes and wells are currently exploited. Their depth varies between 10 m and 200 m and the unit flow rates of the boreholes are 5 to 50 l/s. A drop in the level of the water table of about 1.5 m/year, on average, has been observed during the last five years. Farmers are thus called upon to improve irrigation methods. Thus, localized or drip irrigation is adopted to allow rational use of water. The importance of this irrigation system is due to the fact that water is applied directly to the root zone and its compatibility with fertilization. However, this irrigation system faces a thorny problem which is the clogging of pipes and drippers. This leads to a lack of uniformity of irrigation over time. This so-called scaling phenomenon, the consequences of which are harmful (cleaning or replacement of pipes), leads to considerable unproductive expenditure. The objective set by this work is the search for green inhibitors likely to prevent this phenomenon of scaling. This study requires a better knowledge of these waters, their physico-chemical characteristics and their scaling power. Thus, using the "LCGE" controlled degassing technique, we initially evaluated, on pure calco-carbonic water at 30°F, the scaling-inhibiting power of some available plant extracts in our region of Souss-Massa. We then carried out a comparative study of the efficacy of these green inhibitors. The action of the most effective green inhibitor on real agricultural waters was then studied.

Keywords: green inhibitors, localized irrigation, plant extracts, scaling inhibition

Procedia PDF Downloads 57
8078 The Enzyme Inhibitory Potentials of Different Extracts from Linaria genistifolia subsp. genistifolia

Authors: Gokhan Zengin, Abdurrahman Aktumsek

Abstract:

The key enzyme inhibitory theory is one of the most accepted strategies in the treatment of global health problems including Alzheimer’s Disease and Diabetes mellitus. For this reason, the enzyme inhibitory potentials of different solvent extracts from Linaria genistifolia subsp. genistifolia were investigated against cholinesterase, and tyrosinase. The in vitro enzyme inhibitory potentials were measured with a microplate reader. The acetone and methanol extracts exhibited the strongest enzyme inhibitory effects on cholinesterase. However, the water extract was only active on tyrosinase. The results suggested that Linaria genistifolia subsp. genistifolia could be considered as a source of natural enzyme inhibitors for the treatment of major health problems.

Keywords: enzyme inhibitors, cholinesterase, tyrosinase, linaria, Turkey

Procedia PDF Downloads 280
8077 Solid Waste Management Challenges and Possible Solution in Kabul City

Authors: Ghulam Haider Haidaree, Nsenda Lukumwena

Abstract:

Most developing nations face energy production and supply problems. This is also the case of Afghanistan whose generating capacity does not meet its energy demand. This is due in part to high security and risk caused by war which deters foreign investments and insufficient internal revenue. To address the issue above, this paper would like to suggest an alternative and affordable way to deal with the energy problem. That is by converting Solid Waste to energy. As a result, this approach tackles the municipal solid waste issue (potential cause of several diseases), contributes to the improvement of the quality of life, local economy, and so on. While addressing the solid waste problem in general, this paper samples specifically one municipality which is District-12, one of the 22 districts of Kabul city. Using geographic information system (GIS) technology, District-12 is divided into nine different zones whose municipal solid waste is respectively collected, processed, and converted into electricity and distributed to the closest area. It is important to mention that GIS has been used to estimate the amount of electricity to be distributed and to optimally position the production plant.

Keywords: energy problem, estimation of electricity, GIS zones, solid waste management system

Procedia PDF Downloads 309
8076 Performance of a Sailing Vessel with a Solid Wing Sail Compared to a Traditional Sail

Authors: William Waddington, M. Jahir Rizvi

Abstract:

Sail used to propel a vessel functions in a similar way to an aircraft wing. Traditionally, cloth and ropes were used to produce sails. However, there is one major problem with traditional sail design, the increase in turbulence and flow separation when compared to that of an aircraft wing with the same camber. This has led to the development of the solid wing sail focusing mainly on the sail shape. Traditional cloth sails are manufactured as a single element whereas solid wing sail is made of two segments. To the authors’ best knowledge, the phenomena behind the performances of this type of sail at various angles of wind direction with respect to a sailing vessel’s direction (known as the angle of attack) is still an area of mystery. Hence, in this study, the thrusts of a sailing vessel produced by wing sails constructed with various angles (22°, 24°, 26° and 28°) between the two segments have been compared to that of a traditional cloth sail made of carbon-fiber material. The reason for using carbon-fiber material is to achieve the correct and the exact shape of a commercially available mainsail. NACA 0024 and NACA 0016 foils have been used to generate two-segment wing sail shape which incorporates a flap between the first and the second segments. Both the two-dimensional and the three-dimensional sail models designed in commercial CAD software Solidworks have been analyzed through Computational Fluid Dynamics (CFD) techniques using Ansys CFX considering an apparent wind speed of 20.55 knots with an apparent wind angle of 31°. The results indicate that the thrust from traditional sail increases from 8.18 N to 8.26 N when the angle of attack is increased from 5° to 7°. However, the thrust value decreases if the angle of attack is further increased. A solid wing sail which possesses 20° angle between its two segments, produces thrusts from 7.61 N to 7.74 N with an increase in the angle of attack from 7° to 8°. The thrust remains steady up to 9° angle of attack and drops dramatically beyond 9°. The highest thrust values that can be obtained for the solid wing sails with 22°, 24°, 26° and 28° angle respectively between the two segments are 8.75 N, 9.10 N, 9.29 N and 9.19 N respectively. The optimum angle of attack for each of the solid wing sails is identified as 7° at which these thrust values are obtained. Therefore, it can be concluded that all the thrust values predicted for the solid wing sails of angles between the two segments above 20° are higher compared to the thrust predicted for the traditional sail. However, the best performance from a solid wing sail is expected when the sail is created with an angle between the two segments above 20° but below or equal to 26°. In addition, 1/29th scale models in the wind tunnel have been tested to observe the flow behaviors around the sails. The experimental results support the numerical observations as the flow behaviors are exactly the same.

Keywords: CFD, drag, sailing vessel, thrust, traditional sail, wing sail

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8075 Analysis of Solid Waste Management Practices and the Implications for Human Health and the Environment: A Case Study of Kayamandi Informal Settlement

Authors: Peter Iyobosa Asemota

Abstract:

This study on solid waste management practices addressed aspects of environmental and health impacts resulting from poor management of solid waste. The study was occasioned by the observed rate and volume of illegal and indiscriminate dumping of solid waste materials especially in informal settlements. The main focus of this study was to establish the impact of waste management practices on human health and the environment. The study, therefore, presents a critical analysis of the state of solid waste management in the study area and the implications for human health and the environment. The study was carried out in Kayamandi informal settlement within Stellenbosch municipality. The sustainable management of solid waste is very important in order to minimize the environmental and public health risks associated with improper solid waste management. There is no denying the fact that the problems of waste management will become critical as time goes on because of improper and inefficient waste management practices. Towns and cities exhibit the burdens of waste management which is a characteristics feature of most African cities. The study critically assess the implementation of waste management practices by the residents of the informal settlement; identify the factors affecting management issues in the operation of solid waste management system by the municipality; identify factors militating against the implementation of waste management policies and legislation. Furthermore, a waste assessment study was carried out to assess the generation; composition of the waste stream and also determine the attitudes and behavior of the residents with regard to waste management practices. Findings from the study revealed that Kayamandi is not different from other informal settlements with regards to waste management. People are of the opinion that solid waste management is the sole responsibility of municipal authorities and as such, the government should be responsible for bearing the cost of solid waste management.

Keywords: environment, waste, waste composition, waste stream, policy, waste categories, sanitary landfill, waste collection, integrated solid waste management

Procedia PDF Downloads 661
8074 Developing of Attitude towards Using Complementary Treatments Scale in Turkey

Authors: Ayşegül Bilge, Merve Uğuryol, Şeyda Dülgerler, Mustafa Yıldız

Abstract:

The purpose of this research is to prove the Attitude towards Using Complementary Treatments Scale reliability and validity. The research is a methodological type of research that has been planned to determine the validity and reliability of the Attitude towards Using Complementary Treatments Scale. The scale has been developed by the researchers. In the scale, there are 23 questions including complementary and modern therapies individuals apply when they have health problems 4-item Likert-type evaluation has been carried out in preparing the questionnaire. High score obtained from the scale indicates a positive attitude towards complementary therapies. In the course of validity assessment of the scale, expert opinion has been received, and the content validity of the scale has been determined by using Kendall coefficient correlation test (Wa=0.200, p = 0.460). In the course of the reliability assessment of the scale, total score correlations of 23 materials have been examined, and those under 0.20 correlation limit has been removed from the scale correlation. As a result, the scale was left to be 13 items. In the internal consistency tests of the analyses, Cronbach's alpha value has been found to be 0.79. As a result, of the validity analyses of the Attitude towards Using Complementary Treatments Scale, the content and language validity analyses has been found to be at the expected level. It has been determined to be a highly reliable scale as the result of the reliability analyses. In conclusion, Attitude towards Using Complementary Treatments Scale is a valid and reliable scale.

Keywords: alternative health care, complementary treatment, instrument development, nursing practice

Procedia PDF Downloads 368
8073 Acute Myocardial Infarction Associated with Ingestion of Herbal Mixtures Containing Acetylcholinesterase Inhibitors: A Case Study

Authors: M. Hakami, A. Jammaly, I. Attafi, M. Oraiby, M. Jeraiby

Abstract:

We reviewed an unusual case of a 65-year-old male taking an herbal mixture containing compounds with anticholinesterase activity for a long period of time, presented with acute my myocardial infarction and multiple organ dysfunction syndrome followed by death. Clinically, there are findings correlated with anticholinesterase activity, such as bilateral miosis, diaphoresis, vomiting and fasciculation without a history of any toxic ingestion or exposure. Gas chromatography–mass spectrometry screening studies identified the presence of thymol, anethole in the herbal extract and butylated hydroxytoluene in the blood sample. Hence, with this case report, we intend to highlight the necessity of evaluating the long-term use of the herbal mixture.

Keywords: cholinesterase inhibitors, thymole, anethole, butylatedhydroxytoluene, cardiac toxicity, myocardial infarction

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8072 Excessive Recruitment of Neutrophils and Elastase Release in Emphysema and COPD; Effect of Natural Protease Inhibitors

Authors: Rachid Kacem

Abstract:

Excessive recruitment of Neutrophils into the lungs is a hallmark of several chronic inflammatory disorders such as emphysema and COPD. The resulting of this recruitment is the pathogenesis of lungs which is characterized by an imbalance between leukocyte serine proteinases mainly neutrophil elastase and the physiological inhibitors. The development of emphysema and remodeling of airway tissue occurred when neutrophil migrate into the lungs with more release of elastase and other proteolytic enzymes. Many reports have demonstrated that the extracts from medicinal plants such as Nigella sativa (L.) seeds extracts have anti-elastase activity; this is mainly due to the enrichment of the extracts with many bioactive molecules mainly phenolic compounds. Neutrophil serine proteases including human neutrophil elastase are involved in many inflammatory diseases, such as chronic obstructive pulmonary disease and emphysema. Since the current therapies for these diseases are inadequate and have numerous adverse effects, there is an acute need of potential alternative therapies. The natural protease inhibitors have received increasing attention as useful tools for potential utilization in pharmacology. This work is elucidating the most important natural phenolic substances that have been reported recently for their effectiveness as natural anti-elastase molecules, and hence, to the possibility of their use in the field of pharmaceuticals.

Keywords: medicinal plants, phenols, elastase, anti-elastase, chronic obstructive pulmonary disease, COPD, emphysema

Procedia PDF Downloads 396
8071 HcDD: The Hybrid Combination of Disk Drives in Active Storage Systems

Authors: Shu Yin, Zhiyang Ding, Jianzhong Huang, Xiaojun Ruan, Xiaomin Zhu, Xiao Qin

Abstract:

Since large-scale and data-intensive applications have been widely deployed, there is a growing demand for high-performance storage systems to support data-intensive applications. Compared with traditional storage systems, next-generation systems will embrace dedicated processor to reduce computational load of host machines and will have hybrid combinations of different storage devices. The advent of flash- memory-based solid state disk has become a critical role in revolutionizing the storage world. However, instead of simply replacing the traditional magnetic hard disk with the solid state disk, it is believed that finding a complementary approach to corporate both of them is more challenging and attractive. This paper explores an idea of active storage, an emerging new storage configuration, in terms of the architecture and design, the parallel processing capability, the cooperation of other machines in cluster computing environment, and a disk configuration, the hybrid combination of different types of disk drives. Experimental results indicate that the proposed HcDD achieves better I/O performance and longer storage system lifespan.

Keywords: arallel storage system, hybrid storage system, data inten- sive, solid state disks, reliability

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8070 Selenuranes as Cysteine Protease Inhibitors: Theorical Investigation on Model Systems

Authors: Gabriela D. Silva, Rodrigo L. O. R. Cunha, Mauricio D. Coutinho-Neto

Abstract:

In the last four decades the biological activities of selenium compounds has received great attention, particularly for hypervalent derivates from selenium (IV) used as enzyme inhibitors. The unregulated activity of cysteine proteases are related to the development of several pathologies, such as neurological disorders, cardiovascular diseases, obesity, rheumatoid arthritis, cancer and parasitic infections. These enzymes are therefore a valuable target for designing new small molecule inhibitors such as selenuranes. Even tough there has been advances in the synthesis and design of new selenuranes based inhibitors, little is known about their mechanism of action. It is a given that inhibition occurs through the reaction between the thiol group of the enzyme and the chalcogen atom. However, several open questions remain about the nature of the mechanism (associative vs. dissociative) and about the nature of the reactive species in solution under physiological conditions. In this work we performed a theoretical investigation on model systems to study the possible routes of substitution reactions. Nucleophiles may be present in biological systems, our interest is centered in the thiol groups from the cysteine proteases and the hydroxyls from the aqueous environment. We therefore expect this study to clarify the possibility of a route reaction in two stages, the first consisting of the substitution of chloro atoms by hydroxyl groups and then replacing these hydroxyl groups per thiol groups in selenuranes. The structures of selenuranes and nucleophiles were optimized using density function theory along the B3LYP functional and a 6-311+G(d) basis set. Solvent was treated using the IEFPCM method as implemented in the Gaussian 09 code. Our results indicate that hydrolysis from water react preferably with selenuranes, and then, they are replaced by the thiol group. It show the energy values of -106,0730423 kcal/mol for dople substituition by hydroxyl group and 96,63078511 kcal/mol for thiol group. The solvatation and pH reduction promotes this route, increasing the energy value for reaction with hydroxil group to -50,75637672 kcal/mol and decreasing the energy value for thiol to 7,917767189 kcal/mol. Alternative ways were analyzed for monosubstitution (considering the competition between Cl, OH and SH groups) and they suggest the same route. Similar results were obtained for aliphatic and aromatic selenuranes studied.

Keywords: chalcogenes, computational study, cysteine proteases, enzyme inhibitors

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8069 QSAR, Docking and E-pharmacophore Approach on Novel Series of HDAC Inhibitors with Thiophene Linker as Anticancer Agents

Authors: Harish Rajak, Preeti Patel

Abstract:

HDAC inhibitors can reactivate gene expression and inhibit the growth and survival of cancer cells. The 3D-QSAR and Pharmacophore modeling studies were performed to identify important pharmacophoric features and correlate 3D-chemical structure with biological activity. The pharmacophore hypotheses were developed using e-pharmacophore script and phase module. Pharmacophore hypothesis represents the 3D arrangement of molecular features necessary for activity. A series of 55 compounds with well-assigned HDAC inhibitory activity was used for 3D-QSAR model development. Best 3D-QSAR model, which is a five PLS factor model with good statistics and predictive ability, acquired Q2 (0.7293), R2 (0.9811) and standard deviation (0.0952). Molecular docking were performed using Histone Deacetylase protein (PDB ID: 1t69) and prepared series of hydroxamic acid based HDAC inhibitors. Docking study of compound 43 show significant binding interactions Ser 276 and oxygen atom of dioxine cap region, Gly 151 and amino group and Asp 267 with carboxyl group of CONHOH, which are essential for anticancer activity. On docking, most of the compounds exhibited better glide score values between -8 to -10.5. We have established structure activity correlation using docking, energetic based pharmacophore modelling, pharmacophore and atom based 3D QSAR model. The results of these studies were further used for the design and testing of new HDAC analogs.

Keywords: Docking, e-pharmacophore, HDACIs, QSAR, Suberoylanilidehydroxamic acid.

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8068 Value-Added Products from Recycling of Solid Waste in Steel Plants

Authors: B. Karthik Vasan, Rachil Maliwal, Somnath Basu

Abstract:

Generation of solid waste is a major problem confronting the iron and steel industry around the world. Disposal of untreated wastes is no longer a viable solution in view of the environmental regulations becoming more and more stringent, as well as an increase in community awareness about the long-term hazards of indiscriminate waste disposal. The current work explores the possibility of converting some of the ‘problematic’ solid wastes generated during steel manufacturing operations, viz. dust from primary steelmaking, iron ore handling, and flux calcination processes, into value-added products instead of environmentally hazardous disposal practices. It was possible to develop a synthetic calcium ferrite, which helped to enhance the dissolution of calcined basic fluxes (e.g. CaO) and reduce the overall energy consumption during steel making. This, in turn, increased process efficiency and reduced greenhouse gas emissions. The preliminary results from laboratory-scale experiments clearly demonstrate the potential of utilizing these ‘waste materials’ that are generated in-house in iron and steel manufacturing plants. The energy required for synthesis of the ferrite may be reduced further by partially utilizing the waste heat from the exhaust gases. In the longer run, it would result in significant financial benefits due to reduced dependence on purchased fluxes. The synthesized ferrite is non-hygroscopic and this provides an additional benefit during its storage and transportation, relative to calcined lime (CaO) that is widely used as a basic flux across the steel making industry.

Keywords: calcium ferrite, flux, slag formation, solid waste

Procedia PDF Downloads 184
8067 Sainte Sophie Landfill: Field-Scale Assessment of Municipal Solid Waste Mechanical Characteristics

Authors: Wameed Alghazali, Shawn Kenny, Paul J. Van Geel

Abstract:

Settlement of municipal solid waste (MSW) in landfills can be represented by mechanical settlement, which is instantaneous and time-dependent creep components, and biodegradation-induced settlement. Mechanical settlement is governed by the physical characteristics of MSW and the applied overburden pressure. Several research studies used oedometers and different size compression cells to evaluate the primary and mechanical creep compression indices/ratios. However, MSW is known for its heterogeneity, which means data obtained from laboratory testing are not necessary to be a good representation of the mechanical response observed in the field. Furthermore, most of the laboratory tests found in the literature were conducted on shredded samples of MSW to obtain specimens that are suitable for the testing setup. It is believed that shredding MSW samples changes the physical and mechanical properties of the waste. In this study, settlement field data was collected during the filling stage of Ste. Sophie landfill was used to estimate the primary and mechanical creep compression ratios. The field results from Ste. Sophie landfill indicated that both the primary and mechanical creep compression ratios of MSW are not constants but decrease with the increase in the applied vertical stress.

Keywords: mechanical creep compression ratio, municipal solid waste, primary compression ratio, stress level

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8066 Sodium-glucose Co-transporter-2 Inhibitors in Heart Failure with Mildly Reduced Reduced Ejection Fraction: Future Perspectives in Patients with Neoplasia

Authors: M. A. Munteanu, A. M. Lungu, A. I. Chivescu, V. Teodorescu, E. Tufanoiu, C. Nicolae, T. I. Nanea

Abstract:

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i), which were first developed as antidiabetic medications, have demonstrated numerous positive benefits on the cardiovascular system, especially in the prevention of heart failure (HF). HF is a challenging, multifaceted disease that needs all-encompassing therapy. It should not be viewed as a limited form of heart illness but rather as a systemic disease that leads to multiple organ failure and death. SGLT2i is an extremely effective tool for treating HF by using its pleiotropic effects. In addition to its use in patients with diabetes mellitus who are at high cardiovascular risk or who have already experienced a cardiovascular event, SGLT2i administration has been shown to have positive effects on a variety of HF manifestations and stages, regardless of the patient's presence of diabetes mellitus. Material and Methods: According to the guide, 110 patients (83 males and 27 females) with heart failure with mildly reduced ejection fraction (HFmrEF), with T2D and neoplasia, were enrolled in the prospective study. The structural and functional state of the left ventricle myocardium and ejection fraction was assessed through echocardiography. Patients were randomized to receive once-daily dapagliflozin 10 mg. Results: Patients with HFmrEF were divided into 3 subgroups according to age. 7% (8) patients aged < 45 years, 35% (28) patients aged between 46-59 years, and 58% (74) patients aged> 60 years. The most prevalent comorbidities were hypertension (43.1%), coronary heart disease (40%), and obesity (33.2%). Study drug discontinuation and serious adverse events were not frequent in the subgroups, in either men or women, until now. Conclusions: SGLT-2 inhibitors are a novel class of antidiabetic agents that have demonstrated positive efficacy and safety outcomes in the setting of HFmrEF. Until now, in our study, dapagliflozin was safe and well-tolerated irrespective of sex.

Keywords: diabetes mellitus type 2, Sodium-glucose co-transporters-2 inhibitors, heart failure, neoplasia

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8065 Optimization of Maritime Platform Transport Problem of Solid, Special and Dangerous Waste

Authors: Ocotlán Díaz-Parra, Jorge A. Ruiz-Vanoye, Alejandro Fuentes-Penna, Beatriz Bernabe-Loranca, Patricia Ambrocio-Cruz, José J. Hernández-Flores

Abstract:

The Maritime Platform Transport Problem of Solid, Special and Dangerous Waste consist of to minimize the monetary value of carry different types of waste from one location to another location using ships. We offer a novel mathematical, the characterization of the problem and the use CPLEX to find the optimal values to solve the Solid, Special and Hazardous Waste Transportation Problem of offshore platforms instances of Mexican state-owned petroleum company (PEMEX). The set of instances used are WTPLib real instances and the tool CPLEX solver to solve the MPTPSSDW problem.

Keywords: oil platform, transport problem, waste, solid waste

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8064 Synthesis, Characterization and Electrical Studies of Solid Polymer Electrolyte (1-x) PANI-KAg₄I₅.xAl₂O₃

Authors: Rafiuddin

Abstract:

Solid polymer electrolytes have emerged as an area of interest in the field of solid state chemistry owing to their facile and cost-effective synthesis and number of applications in different areas of chemistry, extending over a wide range of temperatures. In the present work, polymer composite solid electrolyte comprising of Polyaniline (PANI) as polymer and potassium silver iodide (KAg4I5) using alumina (Al2O3) of different compositions having the formula (1-x) PANI- KAg4I5. x Al2O3 with x ranging from 0.0 to 0.5 was prepared by solid state reaction method. The structural elucidation and characterization was done by X- Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric- Differential Thermal Analysis (TG-DTA) and Impedance Spectroscopy. The thermal analysis shows a phase transition at 147°C attributed to β-α phase transition of AgI due to the disproportionation of KAg4I5 to AgI and KAg2I3 at temperatures higher than 36°C. The X Ray diffraction analysis also confirms the presence of both AgI and KAg2I3 in the samples. The conductivities recorded over a temperature range of 40-250° C lie in the range of 10-1 to 10-3 S cm-1. Maximum conductivity was seen in the compositon x = 0.4 i.e. 1.84 × 10-2 Scm-1 at 313 K and 1.38 × 10-1 Scm-1 at 513 K, with a minimum activation energy of 0.14 eV.

Keywords: polymer solid electrolytes, XRD, DTA, electrical conductivity, impedance spectroscopy

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8063 Solid Waste Landfilling Practices, Related Problems and Sustainable Solutions in Turkey

Authors: Nükhet Konuk, N. Gamze Turan, Yüksel Ardalı

Abstract:

Solid waste management is the most environmental problem in Turkey as a result of the rapid increase in solid waste generation caused by the rapid population growth, urbanization, rapid industrialization and economic development. The large quantity of waste generated necessitates system of collection, transportation and disposal. The landfill method for the ultimate disposal of solid waste continues to be widely accepted and used due to its economic advantages. In Turkey, most of the disposal sites open dump areas. Open dump sites may result in serious urban, sanitary and environmental problems such as an unpleasant odor and the risk of explosion as well as groundwater contamination because of leachate percolation. Unsuitable management practices also result in the loss of resources and energy, which could be recycled and produced from a large part of the solid waste. Therefore, over the past few decades, particular attention has been drawn to the sustainable solid waste management as a response to the increase in environmental problems related to the disposal of waste. The objective of this paper is to assess the situation of landfilling practices in Turkey as a developing country and to identify any gaps in the system as currently applied. The results show that approximately 25 million tons of MSW are generated annually in Turkey. The percentage of MSW disposed to sanitary landfill is only 45% whereas more than 50% of MSW is disposed without any control.

Keywords: developing countries, open dumping, solid waste management, sustainable landfilling, sustainable solid waste management

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8062 Quantitative Structure Activity Relationship Model for Predicting the Aromatase Inhibition Activity of 1,2,3-Triazole Derivatives

Authors: M. Ouassaf, S. Belaidi

Abstract:

Aromatase is an estrogen biosynthetic enzyme belonging to the cytochrome P450 family, which catalyzes the limiting step in the conversion of androgens to estrogens. As it is relevant for the promotion of tumor cell growth. A set of thirty 1,2,3-triazole derivatives was used in the quantitative structure activity relationship (QSAR) study using regression multiple linear (MLR), We divided the data into two training and testing groups. The results showed a good predictive ability of the MLR model, the models were statistically robust internally (R² = 0.982) and the predictability of the model was tested by several parameters. including external criteria (R²pred = 0.851, CCC = 0.946). The knowledge gained in this study should provide relevant information that contributes to the origins of aromatase inhibitory activity and, therefore, facilitates our ongoing quest for aromatase inhibitors with robust properties.

Keywords: aromatase inhibitors, QSAR, MLR, 1, 2, 3-triazole

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8061 Appearance and Magnitude of Dynamic Pressure in Micro-Scale of Subsonic Airflow around Symmetric Objects

Authors: Shehret Tilvaldyev, Jorge Flores-Garay, Alfredo Villanueva, Erwin Martinez, Lazaro Rico

Abstract:

The efficiency of modern transportation is severely compromised by the prevalence of turbulent drag. The high level of turbulent skin-friction occurring, e.g., on the surface of an aircraft, automobiles or the carriage of a high-speed train, is responsible for excess fuel consumption and increased carbon emissions. The environmental, political, and economic pressure to improve fuel efficiency and reduce carbon emissions associated with transportation means that reducing turbulent skin-friction drag is a pressing engineering problem. The dynamic pressure of subsonic airflow around solid objects creates lift, but also induces drag force. This paper is presenting the results of laboratory experiments, investigating appearance and magnitude of dynamic pressure in micro scale of subsonic air flow around right cylinder and symmetrical airfoil.

Keywords: airflow, dynamic pressure, micro scale, symmetric object

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8060 Constitutive Model for Analysis of Long-Term Municipal Solid Waste Landfill Settlement

Authors: Irena Basaric Ikodinovic, Dragoslav Rakic, Mirjana Vukicevic, Sanja Jockovic, Jovana Jankovic Pantic

Abstract:

Large long-term settlement occurs at the municipal solid waste landfills over an extended period of time which may lead to breakage of the geomembrane, damage of the cover systems, other protective systems or facilities constructed on top of a landfill. Also, municipal solid waste is an extremely heterogeneous material and its properties vary over location and time within a landfill. These material characteristics require the formulation of a new constitutive model to predict the long-term settlement of municipal solid waste. The paper presents a new constitutive model which is formulated to describe the mechanical behavior of municipal solid waste. Model is based on Modified Cam Clay model and the critical state soil mechanics framework incorporating time-dependent components: mechanical creep and biodegradation of municipal solid waste. The formulated constitutive model is optimized and defined with eight input parameters: five Modified Cam Clay parameters, one parameter for mechanical creep and two parameters for biodegradation of municipal solid waste. Thereafter, the constitutive model is implemented in the software suite for finite element analysis (ABAQUS) and numerical analysis of the experimental landfill settlement is performed. The proposed model predicts the total settlement which is in good agreement with field measured settlement at the experimental landfill.

Keywords: constitutive model, finite element analysis, municipal solid waste, settlement

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8059 Study of the Clogging of Localized Irrigation Pipelines at the Agricultural Region of Agadir

Authors: Ali Driouiche, Abdallah Hadfi

Abstract:

During this work on scaling phenomenon observed in the irrigation water pipes in the agricultural region of Greater Agadir, a follow-up was carried out during a year of the physico-chemical quality of these waters. Sampling was conducted from 120 sampling points, well distributed in the study area and involved 120 water samples. The parameters measured for each sample are temperature, pH, conductivity, total hardness and the concentrations of the ions HCO₃₋, Ca²⁺, Mg²⁺, Na⁺, K⁺, SO₄₋, NO₃₋, Cl₋ and OH₋. Indeed, the monitoring of the physico-chemical quality shows that the total hardness varies between 20 and 65 °F and the complete alkalimetric title varies from 14 °F to 42 °F. For the kinetic study of the scaling power, an object of this work, 6 samples which have high hardness were selected from the 120 samples analyzed. This study was carried out using the controlled degassing method Laboratoire de Chimie et de Génie de l’Environnement (LCGE) where it was developed) and showed that the studied waters are calcifying. The germination time Tg varies between 16 and 34 minutes. The highlighting of new scale inhibitors to prevent the formation of scale in the pipelines of the agricultural sector of Greater Agadir will also be discussed.

Keywords: agadir, clogging pipes, localized irrigation, scaling power

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8058 Drug Delivery to Solid Tumor: Effect of Dynamic Capillary Network Induced by Tumor

Authors: Mostafa Sefidgar, Kaamran Raahemifar, Hossein Bazmara, Madjid Soltani

Abstract:

The computational methods provide condition for investigation related to the process of drug delivery, such as convection and diffusion of drug in extracellular matrices, and drug extravasation from microvascular. The information of this process clarifies the mechanisms of drug delivery from the injection site to absorption by a solid tumor. In this study, an advanced numerical method is used to solve fluid flow and solute transport equations simultaneously to show how capillary network structure induced by tumor affects drug delivery. The effect of heterogeneous capillary network induced by tumor on interstitial fluid flow and drug delivery is investigated by this multi scale method. The sprouting angiogenesis model is used for generating capillary network induced by tumor. Fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network and fluid flow in normal and tumor tissues. The Starling’s law is used for closing this system of equations and coupling the intravascular and extravascular flows. Finally, convection-diffusion-reaction equation is used to simulate drug delivery. The dynamic approach which changes the capillary network structure based on signals sent by hemodynamic and metabolic stimuli is used in this study for more realistic assumption. The study indicates that drug delivery to solid tumors depends on the tumor induced capillary network structure. The dynamic approach generates the irregular capillary network around the tumor and predicts a higher interstitial pressure in the tumor region. This elevated interstitial pressure with irregular capillary network leads to a heterogeneous distribution of drug in the tumor region similar to in vivo observations. The investigation indicates that the drug transport properties have a significant role against the physiological barrier of drug delivery to a solid tumor.

Keywords: solid tumor, physiological barriers to drug delivery, angiogenesis, microvascular network, solute transport

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8057 Replacing an Old PFN System with a Solid State Modulator without Changing the Klystron Transformer

Authors: Klas Elmquist, Anders Larsson

Abstract:

Until the year 2000, almost all short pulse modulators in the accelerator world were made with the pulse forming network (PFN) technique. The pulse forming network systems have since then been replaced with solid state modulators that have better efficiency, better stability, and lower cost of ownership, and they are much smaller. In this paper, it is shown that it is possible to replace a pulse forming network system with a solid-state system without changing the klystron tank and the klystron transformer. The solid-state modulator uses semiconductors switching at 1 kV level. A first pulse transformer transforms the voltage up to 10 kV. The 10 kV pulse is finally fed into the original transformer that is placed under the klystron. A flatness of 0.8 percent and stability of 100 PPM is achieved. The test is done with a CPI 8262 type of klystron. It is also shown that it is possible to run such a system with long cables between the transformers. When using this technique, it will be possible to keep original sub-systems like filament systems, vacuum systems, focusing solenoid systems, and cooling systems for the klystron. This will substantially reduce the cost of an upgrade and prolong the life of the klystron system.

Keywords: modulator, solid-state, PFN-system, thyratron

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8056 Mutational Analysis of JAK2V617F in Tunisian CML Patients with TKI-Resistance

Authors: R. Frikha, H. Kamoun

Abstract:

Background:Chronicmyeloidleukemia (CML), a hematologicaldisease, ischaracterized by t (9; 22) and relatedoncogene BCR-ABL formation. Although Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML, resistanceoccurs and possibly médiates by mutation in severalgenesindependently of the bcr-abl1 kinase mechanism. it has been reportedthat JAK2V617F/BCR-ABL double positivitymaybe a potential marker of resistance in CML. Aims: This studywasinvestigated the JAK2V617F mutation in TKI-resistant CML patients. Methods: A retrospectivestudywasconducted in the Hospital University of Sfax, south of Tunisia, including all CML TKI-resistant patients. A Sanger sequencingwasperformedusing a high-fidelity DNA polymerase. Results:Nineresistant CP-CML patients wereenrolled in thisstudy. The JAK2V617F mutation wasdetectedin 3 patients with TKI resistance. Conclusion:Despite the limit of ourstudy, ourfinding highlights the high frequency of JAK2V617F/BCR-ABL double positivity as an important marker of resistance. So; the combination of JAK and TKI inhibitorsmightbe effective and potentiallybeguided by molecular monitoring of minimal residual disease1.

Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, resistance, JAK2V617F, BCR-ABL

Procedia PDF Downloads 35