Search results for: small molecule inhibitors
Commenced in January 2007
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Edition: International
Paper Count: 5575

Search results for: small molecule inhibitors

4525 Empirical Study for the Project and the Project Management Dimensions Comparison between SMEs and Large Companies

Authors: Amina Oukennou, Zitouni Beidouri, Otmane Bouksour

Abstract:

Small to Medium-sized enterprises are a very important component of the economy. They are present in the whole industries all over the world. They are considered as the engine for future growth in the economy. Project management is an economical international factor impacting all types of enterprises including the SMEs. This paper has the aim of measuring the weight of using projects and project management in Moroccan SMEs in comparison with the large companies. The study is based on interviews with experts: project managers, managers, directors, and consultants. They were asked questions measuring the weight of using projects, the level of using project management, and the resources employed. Eighteen Moroccan companies from a range of industries and sizes were consulted. All the companies consider projects as a key element in their strategy. Most of them affirm the great usefulness of the approach 'project', especially for the external activities. The main differences lie in the duration and the size of used projects. Despite the commonly shared idea about the importance of the project management, the interviewed persons believe that the project management knowledge has the same importance or less than the technical knowledge. All the companies affirm the need for a simpler version of project management. The content varies from one company to another.

Keywords: project dimension, project management, small to medium-sized entreprise, Morocco

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4524 Separation of Lanthanides Ions from Mineral Waste with Functionalized Pillar[5]Arenes: Synthesis, Physicochemical Characterization and Molecular Dynamics Studies

Authors: Ariesny Vera, Rodrigo Montecinos

Abstract:

The rare-earth elements (REEs) or rare-earth metals (REMs), correspond to seventeen chemical elements composed by the fifteen lanthanoids, as well as scandium and yttrium. Lanthanoids corresponds to lanthanum and the f-block elements, from cerium to lutetium. Scandium and yttrium are considered rare-earth elements because they have ionic radii similar to the lighter f-block elements. These elements were called rare earths because they are simply more difficult to extract and separate individually than the most metals and, generally, they do not accumulate in minerals, they are rarely found in easily mined ores and are often unfavorably distributed in common ores/minerals. REEs show unique chemical and physical properties, in comparison to the other metals in the periodic table. Nowadays, these physicochemical properties are utilized in a wide range of synthetic, catalytic, electronic, medicinal, and military applications. Because of their applications, the global demand for rare earth metals is becoming progressively more important in the transition to a self-sustaining society and greener economy. However, due to the difficult separation between lanthanoid ions, the high cost and pollution of these processes, the scientists search the development of a method that combines selectivity and quantitative separation of lanthanoids from the leaching liquor, while being more economical and environmentally friendly processes. This motivation has favored the design and development of more efficient and environmentally friendly cation extractors with the incorporation of compounds as ionic liquids, membrane inclusion polymers (PIM) and supramolecular systems. Supramolecular chemistry focuses on the development of host-guest systems, in which a host molecule can recognize and bind a certain guest molecule or ion. Normally, the formation of a host-guest complex involves non-covalent interactions Additionally, host-guest interactions can be influenced among others effects by the structural nature of host and guests. The different macrocyclic hosts for lanthanoid species that have been studied are crown ethers, cyclodextrins, cucurbituryls, calixarenes and pillararenes.Among all the factors that can influence and affect lanthanoid (III) coordination, perhaps the most basic of them is the systematic control using macrocyclic substituents that promote a selective coordination. In this sense, macrocycles pillar[n]arenes (P[n]As) present a relatively easy functionalization and they have more π-rich cavity than other host molecules. This gives to P[n]As a negative electrostatic potential in the cavity which would be responsible for the selectivity of these compounds towards cations. Furthermore, the cavity size, the linker, and the functional groups of the polar headgroups could be modified in order to control the association of lanthanoid cations. In this sense, different P[n]As systems, specifically derivatives of the pentamer P[5]A functionalized with amide, amine, phosphate and sulfate derivatives, have been designed in terms of experimental synthesis and molecular dynamics, and the interaction between these P[5]As and some lanthanoid ions such as La³+, Eu³+ and Lu³+ has been studied by physicochemical characterization by 1H-NMR, ITC and fluorescence in the case of Eu³+ systems. The molecular dynamics study of these systems was developed in hexane as solvent, also taking into account the lanthanoid ions mentioned above, and the respective comparison studies between the different ions.

Keywords: lanthanoids, macrocycles, pillar[n]arenes, rare-earth metal extraction, supramolecular chemistry, supramolecular complexes.

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4523 Using Hybrid Method for Inactivation of Microorganism and Enzymes in a Berry Juice

Authors: Golnoosh Torabian, P. Valtchev, F. Dehghani

Abstract:

The need for efficient nutraceutical products has been dramatically changing the approach of the industrial processes. The development of novel mild processes is highly demanded for the production of such products; especially when both quality and safety need to be guaranteed during their long shelf life. Within this research, for the first time, we investigated the effect of supercritical carbon dioxide treatment for the inactivation of microbes and enzymes in a berry juice possessing therapeutic effect. We demonstrated that a complete inactivation of microbes can be achieved at optimized conditions of treatment. However, the bottle neck of the process was represented by the unpromising inactivation of the degradative enzyme by supercritical carbon dioxide treatment. However, complete enzyme inactivation was achieved by applying two strategies: the first was optimizing juicing method by adding a mechanical step and the second strategy was addition of natural inhibitors to the juice. Overall these results demonstrate that our hybrid process has a significant effect on the inactivation of microorganism and enzymes in the fresh juice. The developed process opens the possibility for the evolution of new products with optimal nutritional and sensorial characteristics, as well as offering a competitive cost and an environmentally friendly alternative for pasteurization and extension of shelf life in a wide range of natural therapeutic products.

Keywords: hybrid method, berry juice, pasteurization, enzymes inactivation

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4522 Curcumin Attenuates Angiogenesis in Liver Fibrosis and Inhibits Angiogenic Properties of Hepatic Stellate Cells

Authors: Feng Zhang, Li Chen, Desong Kong, Xiaoping Zhang, Xiaojing Zhu, Yin Lu, Shizhong Zheng

Abstract:

Sinusoidal pathological angiogenesis is a novel therapeutic target for liver fibrosis. We demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells (LSECs) were not impaired by curcumin. Further investigations showed that curcumin inhibited VEGF expression in hepatic stellate cells (HSCs) by disrupting PDGF-βR/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin via blocking PDGF-βR/FAK/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of PPARγ was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPARγ activation-dependent mechanism. PPARγ could be a target molecule for reducing pathological angiogenesis during liver fibrosis.

Keywords: angiogenesis, hepatic stellate cell, curcumin, peroxisome proliferator-activated receptor-γ

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4521 LncRNA-miRNA-mRNA Networks Associated with BCR-ABL T315I Mutation in Chronic Myeloid Leukemia

Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

Abstract:

Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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4520 Triggering Supersonic Boundary-Layer Instability by Small-Scale Vortex Shedding

Authors: Guohua Tu, Zhi Fu, Zhiwei Hu, Neil D Sandham, Jianqiang Chen

Abstract:

Tripping of boundary-layers from laminar to turbulent flow, which may be necessary in specific practical applications, requires high amplitude disturbances to be introduced into the boundary layers without large drag penalties. As a possible improvement on fixed trip devices, a technique based on vortex shedding for enhancing supersonic flow transition is demonstrated in the present paper for a Mach 1.5 boundary layer. The compressible Navier-Stokes equations are solved directly using a high-order (fifth-order in space and third-order in time) finite difference method for small-scale cylinders suspended transversely near the wall. For cylinders with proper diameter and mount location, asymmetry vortices shed within the boundary layer are capable of tripping laminar-turbulent transition. Full three-dimensional simulations showed that transition was enhanced. A parametric study of the size and mounting location of the cylinder is carried out to identify the most effective setup. It is also found that the vortex shedding can be suppressed by some factors such as wall effect.

Keywords: boundary layer instability, boundary layer transition, vortex shedding, supersonic flows, flow control

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4519 Alternative Acidizing Fluids and Their Impact on the Southern Algerian Shale Formations

Authors: Rezki Akkal, Mohamed Khodja, Slimane Azzi

Abstract:

Acidification is a technique used in oil reservoirs to improve annual production, reduce the skin and increase the pressure of an oil well while eliminating the formation damage that occurs during the drilling process, completion and, amongst others, to create new channels allowing the easy circulation of oil around a producing well. This is achieved by injecting an acidizing fluid at a relatively low pressure to prevent fracturing formation. The treatment fluid used depends on the type and nature of the reservoir rock traversed as well as its petrophysical properties. In order to understand the interaction mechanisms between the treatment fluids used for the reservoir rock acidizing, several candidate wells for stimulation were selected in the large Hassi Messaoud deposit in southern Algeria. The stimulation of these wells is completed using different fluids composed mainly of HCl acid with other additives such as corrosion inhibitors, clay stabilizers and iron controllers. These treatment fluids are injected over two phases, namely with clean tube (7.5% HCl) and matrix aidizing with HCl (15%). The stimulation results obtained are variable according to the type of rock traversed and its mineralogical composition. These results show that there has been an increase in production flow and head pressure respectively from 1.99 m3 / h to 3.56 m3 / h and from 13 Kgf / cm2 to 20 kgf / cm2 in the sands formation having good petrophysical properties of (porosity = 16%) and low amount of clay (Vsh = 6%).

Keywords: acidizing, Hassi-Messaoud reservoir, tube clean, matrix stimulation

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4518 Dual-use UAVs in Armed Conflicts: Opportunities and Risks for Cyber and Electronic Warfare

Authors: Piret Pernik

Abstract:

Based on strategic, operational, and technical analysis of the ongoing armed conflict in Ukraine, this paper will examine the opportunities and risks of using small commercial drones (dual-use unmanned aerial vehicles, UAV) for military purposes. The paper discusses the opportunities and risks in the information domain, encompassing both cyber and electromagnetic interference and attacks. The paper will draw conclusions on a possible strategic impact to the battlefield outcomes in the modern armed conflicts by the widespread use of dual-use UAVs. This article will contribute to filling the gap in the literature by examining based on empirical data cyberattacks and electromagnetic interference. Today, more than one hundred states and non-state actors possess UAVs ranging from low cost commodity models, widely are dual-use, available and affordable to anyone, to high-cost combat UAVs (UCAV) with lethal kinetic strike capabilities, which can be enhanced with Artificial Intelligence (AI) and Machine Learning (ML). Dual-use UAVs have been used by various actors for intelligence, reconnaissance, surveillance, situational awareness, geolocation, and kinetic targeting. Thus they function as force multipliers enabling kinetic and electronic warfare attacks and provide comparative and asymmetric operational and tactical advances. Some go as far as argue that automated (or semi-automated) systems can change the character of warfare, while others observe that the use of small drones has not changed the balance of power or battlefield outcomes. UAVs give considerable opportunities for commanders, for example, because they can be operated without GPS navigation, makes them less vulnerable and dependent on satellite communications. They can and have been used to conduct cyberattacks, electromagnetic interference, and kinetic attacks. However, they are highly vulnerable to those attacks themselves. So far, strategic studies, literature, and expert commentary have overlooked cybersecurity and electronic interference dimension of the use of dual use UAVs. The studies that link technical analysis of opportunities and risks with strategic battlefield outcomes is missing. It is expected that dual use commercial UAV proliferation in armed and hybrid conflicts will continue and accelerate in the future. Therefore, it is important to understand specific opportunities and risks related to the crowdsourced use of dual-use UAVs, which can have kinetic effects. Technical countermeasures to protect UAVs differ depending on a type of UAV (small, midsize, large, stealth combat), and this paper will offer a unique analysis of small UAVs both from the view of opportunities and risks for commanders and other actors in armed conflict.

Keywords: dual-use technology, cyber attacks, electromagnetic warfare, case studies of cyberattacks in armed conflicts

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4517 Optimal Design of RC Pier Accompanied with Multi Sliding Friction Damping Mechanism Using Combination of SNOPT and ANN Method

Authors: Angga S. Fajar, Y. Takahashi, J. Kiyono, S. Sawada

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The structural system concept of RC pier accompanied with multi sliding friction damping mechanism was developed based on numerical analysis approach. However in the implementation, to make design for such kind of this structural system consumes a lot of effort in case high of complexity. During making design, the special behaviors of this structural system should be considered including flexible small deformation, sufficient elastic deformation capacity, sufficient lateral force resistance, and sufficient energy dissipation. The confinement distribution of friction devices has significant influence to its. Optimization and prediction with multi function regression of this structural system expected capable of providing easier and simpler design method. The confinement distribution of friction devices is optimized with SNOPT in Opensees, while some design variables of the structure are predicted using multi function regression of ANN. Based on the optimization and prediction this structural system is able to be designed easily and simply.

Keywords: RC Pier, multi sliding friction device, optimal design, flexible small deformation

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4516 A Study on the False Alarm Rates of MEWMA and MCUSUM Control Charts When the Parameters Are Estimated

Authors: Umar Farouk Abbas, Danjuma Mustapha, Hamisu Idi

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It is now a known fact that quality is an important issue in manufacturing industries. A control chart is an integrated and powerful tool in statistical process control (SPC). The mean µ and standard deviation σ parameters are estimated. In general, the multivariate exponentially weighted moving average (MEWMA) and multivariate cumulative sum (MCUSUM) are used in the detection of small shifts in joint monitoring of several correlated variables; the charts used information from past data which makes them sensitive to small shifts. The aim of the paper is to compare the performance of Shewhart xbar, MEWMA, and MCUSUM control charts in terms of their false rates when parameters are estimated with autocorrelation. A simulation was conducted in R software to generate the average run length (ARL) values of each of the charts. After the analysis, the results show that a comparison of the false alarm rates of the charts shows that MEWMA chart has lower false alarm rates than the MCUSUM chart at various levels of parameter estimated to the number of ARL0 (in control) values. Also noticed was that the sample size has an advert effect on the false alarm of the control charts.

Keywords: average run length, MCUSUM chart, MEWMA chart, false alarm rate, parameter estimation, simulation

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4515 Reducing Total Harmonic Content of 9-Level Inverter by Use of Cuckoo Algorithm

Authors: Mahmoud Enayati, Sirous Mohammadi

Abstract:

In this paper, a novel procedure to find the firing angles of the multilevel inverters of supply voltage and, consequently, to decline the total harmonic distortion (THD), has been presented. In order to eliminate more harmonics in the multilevel inverters, its number of levels can be lessened or pulse width modulation waveform, in which more than one switching occur in each level, be used. Both cases complicate the non-algebraic equations and their solution cannot be performed by the conventional methods for the numerical solution of nonlinear equations such as Newton-Raphson method. In this paper, Cuckoo algorithm is used to compute the optimal firing angle of the pulse width modulation voltage waveform in the multilevel inverter. These angles should be calculated in such a way that the voltage amplitude of the fundamental frequency be generated while the total harmonic distortion of the output voltage be small. The simulation and theoretical results for the 9-levels inverter offer the high applicability of the proposed algorithm to identify the suitable firing angles for declining the low order harmonics and generate a waveform whose total harmonic distortion is very small and it is almost a sinusoidal waveform.

Keywords: evolutionary algorithms, multilevel inverters, total harmonic content, Cuckoo Algorithm

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4514 To Compare the Visual Outcome, Safety and Efficacy of Phacoemulsification and Small-Incision Cataract Surgery (SICS) at CEITC, Bangladesh

Authors: Rajib Husain, Munirujzaman Osmani, Mohammad Shamsal Islam

Abstract:

Purpose: To compare the safety, efficacy and visual outcome of phacoemulsification vs. manual small-incision cataract surgery (SICS) for the treatment of cataract in Bangladesh. Objectives: 1. To assess the Visual outcome after cataract surgery 2. To understand the post-operative complications and early rehabilitation 3. To identified which surgical procedure more attractive to the patients 4. To identify which surgical procedure is occurred fewer complications. 5. To find out the socio-economic and demographic characteristics of study patients Setting: Chittagong Eye Infirmary and Training Complex, Chittagong, Bangladesh. Design: Retrospective, randomised comparison of 300 patients with visually significant cataracts. Method: The present study was designed as a retrospective hospital-based research. The sample size was 300 and study period was from July, 2012 to July, 2013 and assigned randomly to receive either phacoemulsification or manual small-incision cataract surgery (SICS). Preoperative and post-operative data were collected through a well designed collection format. Three follow-up were done; i) during discharge ii) 1-3 weeks & iii) 4-11 weeks post operatively. All preoperative and surgical complications, uncorrected and best-corrected visual acuity (BCVA) and astigmatism were taken into consideration for comparison of outcome Result: Nearly 95% patients were more than 40 years of age. About 52% patients were female, and 48% were male. 52% (N=157) patients came to operate their first eye where 48% (N=143) patients were visited again to operate their second eye. Postoperatively, five eyes (3.33%) developed corneal oedema with >10 Descemets folds, and six eyes (4%) had corneal oedema with <10 Descemets folds for Phacoemulsification surgeries. For SICS surgeries, seven eyes (4.66%) developed corneal oedema with >10 Descemets folds and eight eyes (5.33%) had corneal oedema with < 10 descemets folds. However, both the uncorrected and corrected (4-11 weeks) visual acuities were better in the eyes that had phacoemulsification (p=0.02 and p=0.03), and there was less astigmatism (p=0.001) at 4-11 weeks in the eye that had phacoemulsification. Best-corrected visual acuity (BCVA) of final follow-up 95% (N=253) had a good outcome, borderline 3.10% (N=40) and poor outcome was 1.6% (N=7). The individual surgeon outcome were closer, 95% (BCVA) in SICS and 96% (BCVA) in Phacoemulsification at 4-11 weeks follow-up respectively. Conclusion: outcome of cataract surgery both Phacoemulsification and SICS in CEITC was more satisfactory according to who norms. Both Phacoemulsification and manual small-incision cataract surgery (SICS) shows excellent visual outcomes with low complication rates and good rehabilitation. Phacoemulsification is significantly faster, and modern technology based surgical procedure for cataract treatment.

Keywords: phacoemulsification, SICS, cataract, Bangladesh, visual outcome of SICS

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4513 Effect of Building Construction Sizes on Project Delivery Methods in Nigeria

Authors: Nuruddeen Usman, Mohammad Sani

Abstract:

The performance of project delivery methods has been an issue of concern to various stakeholders in the construction industry. The contracting system of project delivery is the traditional system used in the delivery of most public projects in Nigeria. The direct labor system is used most times as an alternative to the traditional system. There were so many complain about the performance of contracting system and the suitability of direct labor as an alternative to the delivery of public projects. Therefore, this paper is aimed at investigating the effect of project size on the project delivery methods in the completed public buildings. Questionnaires were self-administered to managerial staff in the study area and analyzed using descriptive statistics. The findings reveals that contracting system was choosing for large size building construction project delivery with higher frequency (F) of 40 (76.9%) against direct labor with 12 (23.1%). While the small size project, the result revealed a frequency (F) of 26 (50%) for contracting system and direct labor system respectively. Base on the research findings, the contracting system, was recommended for all sizes of building construction project delivery while direct labor system can only use as an alternative for small size building construction projects delivery.

Keywords: construction size, contracting system, direct labour, effect

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4512 Albumin-Induced Turn-on Fluorescence in Molecular Engineered Fluorescent Probe for Biomedical Application

Authors: Raja Chinnappan, Huda Alanazi, Shanmugam Easwaramoorthi, Tanveer Mir, Balamurugan Kanagasabai, Ahmed Yaqinuddin, Sandhanasamy Devanesan, Mohamad S. AlSalhi

Abstract:

Serum albumin (SA) is a highly rich water-soluble protein in plasma. It is known to maintain the living organisms' health and help to maintain the proper liver function, kidney function, and plasma osmolality in the body. Low levels of serum albumin are an indication of liver failure and chronic hepatitis. Therefore, it is important to have a low-cost, accurate and rapid method. In this study, we designed a fluorescent probe, triphenylamine rhodanine-3-acetic acid (mRA), which triggers the fluorescence signal upon binding with serum albumin (SA). mRA is a bifunctional molecule with twisted intramolecular charge transfer (TICT)-induced emission characteristics. An aqueous solution of mRA has an insignificant fluorescence signal; however, when mRA binds to SA, it undergoes TICT and turns on the fluorescence emission. A SA dose-dependent fluorescence signal was performed, and the limit of detection was found to be less than ng/mL. The specific binding of SA was tested from the cross-reactivity study using similar structural or functional proteins.

Keywords: serum albumin, fluorescent sensing probe, liver diseases, twisted intramolecular charge transfer

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4511 The Role of High Performance Liquid Chromatography in Identification of Rat Liver Microsomes Responsible for the in vitro Metabolite Formation of Dipyrone

Authors: Salem Abdalla

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Objective: Dipyrone is a widely used, well tolerated analgesic drug which, however, is compromised by agranulocytosis as an adverse effect. Subsequent to no enzymatic hydrolysis, the primary metabolic step is N-demethylation of 4-methylaminoantipyrine (4-MAA) to 4-aminoantipyrine (4-AA). The aim of the present study was to identify the cytochrome P-450 enzyme (CYP) mediating this reaction. Methods: We identified the relevant CYP using virus expressed isolated rat liver microsomes with chemical inhibition studies. The substrate of 4-methylaminantipyrine was employed at six different concentrations (25, 50, 100, 400, 800, and 1200 µmol/l) with varying concentrations of selective inhibitors of CYP1A2 (furafylline, fluvoxamine), CYP3A4 (ketoconazole), CYP2A6 (coumarin), CYP2D6 (quinidine), CYP2C19 (omeprazole, fluvoxamine, tranylcypromine), CYP2C9 (sulfaphenazole), and CYP1A1 (alpha-naphthoflavone). 4-MAA and 4-AA were analyzed by HPLC, and enzyme kinetic parameters (Km and Vmax) were determined by regression (Sigma plot 9.0). Results: The N-demethylation of 4-MAA by microsomes prepared from baculovirus-expressing human CYP was pronounced with CYP2C19. Intrinsic clearances of the most active enzymes were 0.092, 0.027, and 0.026 for the CYP enzymes 2C19, 2D6, and 1A2, respectively. Metabolism by rat liver microsomes was strongly inhibited by omeprazole (IC50 of 0.05). Conclusion: The enzyme CYP2C19 apparently has an important role in N-demethylation of 4-methylaminoantipyrine which should be further analyzed in clinical studies and which may also be interesting concerning the agranulocytosis.

Keywords: dipyrone, 4-methylaminoantipyrine (4-MAA), 4- aminoantipyrine (4-AA), metabolism, human CYP2C19

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4510 Total Knee Arthroplasty in a Haemophilia: A Patient with High Titre of Inhibitor Using Recombinant Factor VIIa

Authors: Mohammad J. Mortazavi, Arvin Najafi, Pejman Mansouri

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Hemophilia A is simply described as deficiency of factor VIII(FVIII) and patients with this disorder have bleeding complications in different organs. By using the recombinant factor VIII in these patients, elective orthopedic surgeries have been done approximately in 40 last years. About 10-30 % of these patients have bleeding complications in their surgeries even by using recombinant factor VIII because of their inhibitor against FVIII molecule. Preoperative haemostatic management in these patients is challenging. We treated a 28-year-old male patient with hemophilia A with FVIII inhibitor which had been detected when he was14 years old (with the titer 54 Bethesda unit(BU)) scheduled for total knee arthroplasty (TKA). We use 90 µg/kg rFVIIa just before the surgery and every 2 hours during surgery. The patient did not have any significant hemorrhage during the surgery and after that. For the 2 days after surgery, the rFVIIa repeated every 2 hours as the same as preoperative dosage(90 µg/kg) and for another 2 days of postoperative admission it continued every 4 hours. After 4th day, the rFVIIa continued every 6 hours with the same dosage until the sixth day from the surgery, and finally the patient were discharged about two weeks after surgery. Seven days after the discharge, he came back for the follow up visit. On the follow up examination, the site of the surgery had neither infection hemarthroses signs.

Keywords: hemophilia, factor VIII inhibitor, total knee replacement, rFVIIa

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4509 Effectiveness of Homoeopathic Medicine Conium Maculatum 200 C for Management of Pyuria

Authors: Amir Ashraf

Abstract:

Homoeopathy is an alternative system of medicine discovered by German physician Samuel Hahnemann in 1796. It has been used by several people for various health conditions globally for more than last 200 years. In India, homoeopathy is considered as a major system of alternative medicine. Homoeopathy is found effective in various medical conditions including Pyuria. Pyuria is the condition in which pus cells are found in urine. Homoeopathy is very useful for reducing pus cells, and homeopathically potentized Conium Mac (Hemlock) is an important remedy commonly used for reducing pyuria. Aim: To reduce the amount pus cells found in urine using Conium Mac 200C. Methods: Design. Small N Design. Samples: Purposive Sampling with 5 cases diagnosed as pyuria. Tools: Personal Data Schedule and ICD-10 Criteria for Pyuria. Techniques: Potentized homoeopathic medicine, Conium Mac 200th potency is used. Statistical Analysis: The statistical analyses were done using non-parametric tests. Results: There is significant pre/post difference has been identified. Conclusion: Homoeopathic potency, Conium Mac 200 C is effective in reducing the increased level of pus cells found in urine samples.

Keywords: homoeopathy, alternative medicine, Pyuria, Conim Mac, small N design, non-parametric tests, homeopathic physician, Ashirvad Hospital, Kannur

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4508 Contemplating Charge Transport by Modeling of DNA Nucleobases Based Nano Structures

Authors: Rajan Vohra, Ravinder Singh Sawhney, Kunwar Partap Singh

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Electrical charge transport through two basic strands thymine and adenine of DNA have been investigated and analyzed using the jellium model approach. The FFT-2D computations have been performed for semi-empirical Extended Huckel Theory using atomistic tool kit to contemplate the charge transport metrics like current and conductance. The envisaged data is further evaluated in terms of transmission spectrum, HOMO-LUMO Gap and number of electrons. We have scrutinized the behavior of the devices in the range of -2V to 2V for a step size of 0.2V. We observe that both thymine and adenine can act as molecular devices when sandwiched between two gold probes. A prominent observation is a drop in HLGs of adenine and thymine when working as a device as compared to their intrinsic values and this is comparative more visible in case of adenine. The current in the thymine based device exhibit linear increase with voltage in spite of having low conductance. Further, the broader transmission peaks represent the strong coupling of electrodes to the scattering molecule (thymine). Moreover, the observed current in case of thymine is almost 3-4 times than that of observed for adenine. The NDR effect has been perceived in case of adenine based device for higher bias voltages and can be utilized in various future electronics applications.

Keywords: adenine, DNA, extended Huckel, thymine, transmission spectra

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4507 Feed Value of Selected Nigerian Browse Plants: Chemical Composition and in vitro Digestibility

Authors: Isaac Samuel

Abstract:

A study was conducted to determine the in-vitro degradation of selected Nigerian browse plants consumed by small ruminants on free range in northern guinea savannah region of Nigeria using in vitro gas production, proximate composition, fibre components, methane gas production and dry matter degradation as tools. The leaves samples of the selected browse plants were collected, processed and incubated using in vitro gas dry matter degradation techniques. Results obtained showed variation in the rate of degradation. The result obtained from chemical analysis showed that the CP content of A. occidentale (26.49%) was higher than F. thonningi (23.58%), M. indica (20.58%) and T. catappa (18.61%). Both ADF and NDF of A. occidentale (40.00 and 50.00) were as well higher than F. thonningi (20.00 and 40.00), M. indica (20.00 and 40.00) and T.catappa (20.00 and 42.00). Results from in vitro gas production however showed that T. catappa (23.67ml/DM) has a significantly higher (p<0.05) value than F.thonningi (20.67ml/DM), A. occidentale (16.67ml/DM), and M. indica(14.00ml/DM) at 72 hours of incubation. Methane gas production and in vitro gas production can be used to predict dry matter degradation and nutritive value of feedstuff for small ruminants. A. occidentale with the least methane gas production and highest crude protein (CP) content might have the most nutritive value among the browse plants investigated.

Keywords: in vitro, degradation, browse, gas production

Procedia PDF Downloads 361
4506 Essential Oil Encapsulated into Succinic Acid Modified Beta-Cyclodextrin: Characterization, Docking Study, and Antifungal Activity

Authors: Amine Ez-Zoubi, Abdellah Farah

Abstract:

Because of their effectiveness and environmental safety, many essential oils have been investigated as biopesticides. Nevertheless, the encapsulation process is necessary to improve its physical, chemical, and biological properties. Therefore, the purpose of this paper was to study the physicochemical characteristics, and antifungal activity of the Artemisia Herba-Alba essential oil (HAEO) encapsulated in succinic acid modified β-CD (SACD). A yellowish oil was obtained from plant A. Herba-Alba using hydrodistillation and GC-MS was used to identify the chemical composition, in which α-Thujone (65.0%) was the main component in HAEO. The succinic acid has been esterified via the hydroxyl groups in β-CD to produce SACD. In addition, the inclusion complex formation of HAEO and SACD was generated according to the co-precipitation method and was analyzed by several techniques. The antifungal activity in vitro was examined against Botrytis cinerea by direct contact with a potato dextrose agar culture medium. At a 0.1 % concentration, the HAEO in encapsulated form showed higher potential for the control of B. cinerea when compared to the EO in free form (38.34 to 12%). Thus, these results produced evidence that the encapsulation of EOs in SACD can be useful for the development of B.cinerea inhibitors and a promising alternative biopesticide.

Keywords: Artemisia Herba-Alba essential oil, succinic acid modified β-cyclodextrin, inclusion complex, co-precipitation, Botrytis cinerea, direct contact

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4505 Understanding Nanocarrier Efficacy in Drug Delivery Systems Using Molecular Dynamics

Authors: Maedeh Rahimnejad, Bahman Vahidi, Bahman Ebrahimi Hoseinzadeh, Fatemeh Yazdian, Puria Motamed Fath, Roghieh Jamjah

Abstract:

Introduction: The intensive labor and high cost of developing new vehicles for controlled drug delivery highlights the need for a change in their discovery process. Computational models can be used to accelerate experimental steps and control the high cost of experiments. Methods: In this work, to better understand the interaction of anti-cancer drug and the nanocarrier with the cell membrane, we have done molecular dynamics simulation using NAMD. We have chosen paclitaxel for the drug molecule and dipalmitoylphosphatidylcholine (DPPC) as a natural phospholipid nanocarrier. Results: Next, center of mass (COM) between molecules and the van der Waals interaction energy close to the cell membrane has been analyzed. Furthermore, the simulation results of the paclitaxel interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane have been compared. Discussion: Analysis by molecular dynamics (MD) showed that not only the energy between the nanocarrier and the cell membrane is low, but also the center of mass amount decreases in the nanocarrier and the cell membrane system during the interaction; therefore they show significantly better interaction in comparison to the individual drug with the cell membrane.

Keywords: anti-cancer drug, center of mass, interaction energy, molecular dynamics simulation, nanocarrier

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4504 Mining the Proteome of Fusobacterium nucleatum for Potential Therapeutics Discovery

Authors: Abdul Musaweer Habib, Habibul Hasan Mazumder, Saiful Islam, Sohel Sikder, Omar Faruk Sikder

Abstract:

The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1499 proteins of Fusobacterium nucleatum, which has no homolog in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the KEGG Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the 3-D structure of these three proteins. Finally, determination of ligand binding sites of the key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against Fusobacterium nucleatum.

Keywords: colorectal cancer, drug target, Fusobacterium nucleatum, homology modeling, ligands

Procedia PDF Downloads 393
4503 Application of Single Subject Experimental Designs in Adapted Physical Activity Research: A Descriptive Analysis

Authors: Jiabei Zhang, Ying Qi

Abstract:

The purpose of this study was to develop a descriptive profile of the adapted physical activity research using single subject experimental designs. All research articles using single subject experimental designs published in the journal of Adapted Physical Activity Quarterly from 1984 to 2013 were employed as the data source. Each of the articles was coded in a subcategory of seven categories: (a) the size of sample; (b) the age of participants; (c) the type of disabilities; (d) the type of data analysis; (e) the type of designs, (f) the independent variable, and (g) the dependent variable. Frequencies, percentages, and trend inspection were used to analyze the data and develop a profile. The profile developed characterizes a small portion of research articles used single subject designs, in which most researchers used a small sample size, recruited children as subjects, emphasized learning and behavior impairments, selected visual inspection with descriptive statistics, preferred a multiple baseline design, focused on effects of therapy, inclusion, and strategy, and measured desired behaviors more often, with a decreasing trend over years.

Keywords: adapted physical activity research, single subject experimental designs, physical education, sport science

Procedia PDF Downloads 469
4502 Bcl-2: A Molecule to Detect Oral Cancer and Precancer

Authors: Vandana Singh, Subash Singh

Abstract:

Introduction: Oral squamous cell carcinoma is the most common malignant tumor of the oral cavity. Normally the death of cell and the growth are active processes and depend not only on external factors but also on the expression of genes like Bcl-2, which activate and inhibit apoptosis. The term Bcl-2 is an acronym for B-cell lymphoma/ leukemia -2 genes. Objectives: An attempt was made to evaluate Bcl-2 oncoprotein expression in patients with oral precancer and cancer and to assess possible correlation between Bcl-2 oncoprotein expression and clinicopathological features of oral precancer and cancer. Material and Methods: This is a selective prospective clinical and immunohistochemical study. Clinicopathological examination is correlated with immunohistochemical findings. The immunolocalization of Bcl-2 protein is performed using the labeled streptavidin biotin (LSAB) method. To visualize the reaction, 3, 3-diaminobenzidine (DAB) is used. Results: Bcl-2 expression was positive in 11 [36.66 %, low Bcl-2 expression 3 (10.00 %), moderate Bcl-2 expression 7 (23.33 %), and high Bcl-2 expression 1 (3.33 %)] oral cancer cases and in 14 [87.50 %, low expression 8 (50 %), moderate expression 6 (37.50 %)] precancer cases. Conclusion: On the basis of the results of our study we conclude that positive Bcl-2 expression may be an indicator of poor prognosis in oral cancer and precancer. Relevance: It has been reported that there is deregulation of Bcl-2 expression during progression from oral epithelial dysplasia to squamous cell carcinoma. It can be used for revealing progression of epithelial dysplasia to malignancy and as a prognostic marker in oral precancer and cancer.

Keywords: BcL-2, immunohistochemistry, oral cancer, oral precancer

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4501 National Directorate of Employment Training and Agricultural-Small and Medium Enterprises Performance in Nigeria

Authors: Festus M. Epetimehin

Abstract:

This study was conducted to identify the effect of National Directorate of Employment (NDE) training on the profit of Agricultural-Small and Medium Enterprises (SMEs) and to evaluate the factors that influenced farmers' participation in NDE training, as well as the type and frequency of training farmers and other agro-allied entrepreneurs in Nigeria. Using a multi-stage sampling procedure, a total of 384 respondents were sampled, including 192 beneficiaries and 192 non-beneficiaries in Oyo and Lagos States, respectively. Data were analysed using Binary Logit regression and Propensity Score Matching techniques. According to the binary logit analysis, respondents’ gender, availability to extension services, and the location of respondent’s operation were determinant factors influencing NDE training enrolment. All identified factors are related to the probability of respondents’ involvement in a positive way. Propensity score matching revealed that Agricultural-SMEs who participated in the NDE program boosted their profit by N341,072.18. The positive outcome of the effect implies that NDE training enhances Agri-SME performance in Nigeria. The study concluded that greater funding should be provided for the NDE for performance-enhancing training of the Agri-SMEs.

Keywords: PSM, binary logit model, Agri-SME

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4500 Gravitational Water Vortex Power Plant: Experimental-Parametric Design of a Hydraulic Structure Capable of Inducing the Artificial Formation of a Gravitational Water Vortex Appropriate for Hydroelectric Generation

Authors: Henrry Vicente Rojas Asuero, Holger Manuel Benavides Muñoz

Abstract:

Approximately 80% of the energy consumed worldwide is generated from fossil sources, which are responsible for the emission of a large volume of greenhouse gases. For this reason, the global trend, at present, is the widespread use of energy produced from renewable sources. This seeks safety and diversification of energy supply, based on social cohesion, economic feasibility and environmental protection. In this scenario, small hydropower systems (P ≤ 10MW) stand out due to their high efficiency, economic competitiveness and low environmental impact. Small hydropower systems, along with wind and solar energy, are expected to represent a significant percentage of the world's energy matrix in the near term. Among the various technologies present in the state of the art, relating to small hydropower systems, is the Gravitational Water Vortex Power Plant, a recent technology that excels because of its versatility of operation, since it can operate with jumps in the range of 0.70 m-2.00 m and flow rates from 1 m3/s to 20 m3/s. Its operating system is based on the utilization of the energy of rotation contained within a large water vortex artificially induced. This paper presents the study and experimental design of an optimal hydraulic structure with the capacity to induce the artificial formation of a gravitational water vortex trough a system of easy application and high efficiency, able to operate in conditions of very low head and minimum flow. The proposed structure consists of a channel, with variable base, vortex inductor, tangential flow generator, coupled to a circular tank with a conical transition bottom hole. In the laboratory test, the angular velocity of the water vortex was related to the geometric characteristics of the inductor channel, as well as the influence of the conical transition bottom hole on the physical characteristics of the water vortex. The results show angular velocity values of greater magnitude as a function of depth, in addition the presence of the conical transition in the bottom hole of the circular tank improves the water vortex formation conditions while increasing the angular velocity values. Thus, the proposed system is a sustainable solution for the energy supply of rural areas near to watercourses.

Keywords: experimental model, gravitational water vortex power plant, renewable energy, small hydropower

Procedia PDF Downloads 294
4499 Kluyveromyces marxianus ABB S8 as Yeast-Based Technology to Manufacture Low FODMAP Baking Good

Authors: Jordi Cuñé, Carlos de Lecea, Laia Marti

Abstract:

Small molecules known as fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) are quickly fermented in the large intestine after being poorly absorbed in the small intestine. There is proof that individuals suffering from functional gastrointestinal disorders, like irritable bowel syndrome (IBS), observe an improvement while following a diet low in FODMAPs. Because wheat has a relatively high fructan content, it is a key source of FODMAPs in our diet. A yeast-based method was created in this study to lower the amounts of FODMAP in (whole wheat) bread. In contrast to fermentation by regular baker yeast, the combination of Kluyveromyces marxianus ABB S7 with Saccharomyces cerevisiae allowed a reduction of fructan content by 60% without implying the appearance of other substrates categorized as FODMAP (excess fructose or polyols). The final FODMAP content in the developed whole wheat bread would allow its classification as a safe product for sensitive people, according to international consensus. Cocultures of S. cerevisiae and K. marxianus were established in order to ensure sufficient CO₂ generation; larger quantities of gas were produced due to the strains' synergistic relationship. Thus, this method works well for lowering the levels of FODMAPs in bread.

Keywords: Kluyveromyces marxianus, bakery, bread, FODMAP, IBS, functional gastro intestinal disorders

Procedia PDF Downloads 51
4498 Design for Metal Additive Manufacturing: An Investigation of Key Design Application on Electron Beam Melting

Authors: Wadea Ameen, Abdulrahman Al-Ahmari, Osama Abdulhameed

Abstract:

Electron beam melting (EBM) is one of the modern additive manufacturing (AM) technologies. In EBM, the electron beam melts metal powder into a fully solid part layer by layer. Since EBM is a new technology, most designers are unaware of the capabilities and the limitations of EBM technology. Also, many engineers are facing many challenges to utilize the technology because of a lack of design rules for the technology. The aim of this study is to identify the capabilities and the limitations of EBM technology in fabrication of small features and overhang structures and develop a design rules that need to be considered by designers and engineers. In order to achieve this objective, a series of experiments are conducted. Several features having varying sizes were designed, fabricated, and evaluated to determine their manufacturability limits. In general, the results showed the capabilities and limitations of the EBM technology in fabrication of the small size features and the overhang structures. In the end, the results of these investigation experiments are used to develop design rules. Also, the results showed the importance of developing design rules for AM technologies in increasing the utilization of these technologies.

Keywords: additive manufacturing, design for additive manufacturing, electron beam melting, self-supporting overhang

Procedia PDF Downloads 153
4497 Elaboration and Characterization of Self-Compacting Mortar Based Biopolymer

Authors: I. Djefour, M. Saidi, I. Tlemsani, S. Toubal

Abstract:

Lignin is a molecule derived from wood and also generated as waste from the paper industry. With a view to its valorization and protection of the environment, we are interested in its use as a superplasticizer-type adjuvant in mortars and concretes to improve their mechanical strengths. The additives of the concrete have a very strong influence on the properties of the fresh and / or hardened concrete. This study examines the development and use of industrial waste and lignin extracted from a renewable natural source (wood) in cementitious materials. The use of these resources is known at present as a definite resurgence of interest in the development of building materials. Physicomechanical characteristics of mortars are determined by optimization quantity of the natural superplasticizer. The results show that the mechanical strengths of mortars based on natural adjuvant have improved by 20% (64 MPa) for a W/C ratio = 0.4, and the amount of natural adjuvant of dry extract needed is 40 times smaller than commercial adjuvant. This study has a scientific impact (improving the performance of the mortar with an increase in compactness and reduction of the quantity of water), ecological use of the lignin waste generated by the paper industry) and economic reduction of the cost price necessary to elaboration of self-compacting mortars and concretes).

Keywords: biopolymer (lignin), industrial waste, mechanical resistances, self compacting mortars (SCM)

Procedia PDF Downloads 168
4496 mKDNAD: A Network Flow Anomaly Detection Method Based On Multi-teacher Knowledge Distillation

Authors: Yang Yang, Dan Liu

Abstract:

Anomaly detection models for network flow based on machine learning have poor detection performance under extremely unbalanced training data conditions and also have slow detection speed and large resource consumption when deploying on network edge devices. Embedding multi-teacher knowledge distillation (mKD) in anomaly detection can transfer knowledge from multiple teacher models to a single model. Inspired by this, we proposed a state-of-the-art model, mKDNAD, to improve detection performance. mKDNAD mine and integrate the knowledge of one-dimensional sequence and two-dimensional image implicit in network flow to improve the detection accuracy of small sample classes. The multi-teacher knowledge distillation method guides the train of the student model, thus speeding up the model's detection speed and reducing the number of model parameters. Experiments in the CICIDS2017 dataset verify the improvements of our method in the detection speed and the detection accuracy in dealing with the small sample classes.

Keywords: network flow anomaly detection (NAD), multi-teacher knowledge distillation, machine learning, deep learning

Procedia PDF Downloads 128