Search results for: tetracycline resistance genes
Commenced in January 2007
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Edition: International
Paper Count: 3951

Search results for: tetracycline resistance genes

2451 Record Peak Current Density in AlN/GaN Double-Barrier Resonant Tunneling Diodes on Free-Standing Gan Substrates by Modulating Barrier Thickness

Authors: Fang Liu, Jia Jia Yao, Guan Lin Wu, Ren Jie Liu, Zhuang Guo

Abstract:

Leveraging plasma-assisted molecular beam epitaxy (PA-MBE) on c-plane free-standing GaN substrates, this work demonstrates high-performance AlN/GaN double-barrier resonant tunneling diodes (RTDs) featuring stable and repeatable negative differential resistance (NDR) characteristics at room temperature. By scaling down the barrier thickness of AlN and the lateral mesa size of collector, a record peak current density of 1551 kA/cm2 is achieved, accompanied by a peak-to-valley current ratio (PVCR) of 1.24. This can be attributed to the reduced resonant tunneling time under thinner AlN barrier and the suppressed external incoherent valley current by reducing the dislocation number contained in the RTD device with the smaller size of collector. Statistical analysis of the NDR performance of RTD devices with different AlN barrier thicknesses reveals that, as the AlN barrier thickness decreases from 1.5 nm to 1.25 nm, the average peak current density increases from 145.7 kA/cm2 to 1215.1 kA/cm2, while the average PVCR decreases from 1.45 to 1.1, and the peak voltage drops from 6.89 V to 5.49 V. The peak current density obtained in this work represents the highest value reported for nitride-based RTDs to date, while maintaining a high PVCR value simultaneously. This illustrates that an ultra-scaled RTD based on a vertical quantum-well structure and lateral collector size is a valuable approach for the development of nitride-based RTDs with excellent NDR characteristics, revealing their great potential applications in high-frequency oscillation sources and high-speed switch circuits.

Keywords: GaN resonant tunneling diode, peak current density, peak-to-valley current ratio, negative differential resistance

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2450 Prevalence and Risk Factors of Faecal Carriage Fluoroquinolone-Resistant Escherichia coli among Hospitalized Patients in Ado-Ekiti, Nigeria

Authors: C. A. Ologunde

Abstract:

Escherichia coli have been a major microorganisms associated with, and isolated from feacal samples either in adult or children all over the world. Strains of these organisms are resistant to cephalosporins and fluoroquinolone (FQ) antimicrobial agents among hospitalized patients and FQs are the most frequently prescribed antimicrobial class in hospitals, and the level of resistant of E. coli to these antimicrobial agents is a risk factor that should be assessed. Hence, this study was conducted to determine the prevalence and risk factors for colonization with fluoroquinolone (FQ)-resistant E. coli in hospitalized patients in Ado-Ekiti. Rectal swabs were obtained from patients in hospitals in the study area and FQ-resistant E. coli were isolated and identified by means of Nalidixic acid multi-disk and a 1-step screening procedure. Species identification and FQ resistance were confirmed by automated testing (Vitek, bioMerieux, USA). Individual colonies were subjected to pulse-field gel electrophoresis (PAGE) to determine macro-restriction polymorphism after digestion of chromosomal DNA. FQ-resistant E. coli was detected in the stool sample of 37(62%) hospitalized patient. With multivariable analyses, the use of FQ before hospitalization was the only independent risk factor for FQ-resistant E. coli carriage and was consistent for FQ exposures for the 3-12 months of study. Pulsed-field gel electrophoresis of FQ-resistant E. coli identified conal spread of 1(one) strain among 18 patients. Loss (9 patients) or acquisition (10 residents) of FQ-resistant E. coli was documented and was associated with de novo colonization with genetically distinct strains. It was concluded that FQ-resistant E. coli carriage was associated with clonal spread. The differential effects of individual fluoroquinolone on antimicrobial drug resistance are an important area for future study, as hospitals manipulate their formularies with regard to use of individual fluoroquinolone, often for economic reasons.

Keywords: E. coli, fluoroquinolone, risk factors, feacal carriage, hospitalized patients, Ado-Ekiti

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2449 Development of Environmentally Clean Construction Materials Using Industrial Waste from Kazakhstan

Authors: Galiya Zhanzakovna Alzhanova, Yelaman Kanatovich Aibuldinov, Zhanar Baktybaevna Iskakova, Gaziz Galymovich Abdiyussupov, Madi Toktasynuly Omirzak, Aizhan Doldashevna Gazizova

Abstract:

The sustainable use of industrial waste has recently increased due to increased environmental problems in landfills. One of the best ways to utilise waste is as a road base material. Industrial waste is a less costly and more efficient way to strengthen local soils than by introducing new additive materials. This study explored the feasibility of utilising red mud, blast furnace slag, and lime production waste to develop environmentally friendly construction materials for stabilising natural loam. Four different ratios of red mud (20, 30, and 40%), blast furnace slag (25, 30, and 35%), lime production waste (4, 6, and 8%), and varied amounts of natural loam were combined to produce nine different mixtures. The results showed that the sample with 40% red mud, 35% blast furnace slag, and 8% lime production waste had the highest strength. The sample's measured compressive strength for 90 days was 7.38 MPa, its water resistance for the same period was 7.12 MPa, and its frost resistance for the same period was 7.35 MP; low linear expansion met the requirements of the Kazakh regulations for first-class building materials. The study of mineral composition showed that there was no contamination with heavy metals or dangerous substances. Road base materials made of red mud, blast furnace slag, lime production waste, and natural loam mix can be employed because of their durability and environmental performance. The chemical and mineral composition of raw materials was determined using X-ray diffraction, X-ray fluorescence, scanning electron microscopy, energy dispersive spectroscopy, atomic absorption spectroscopy, and axial compressive strength were examined.

Keywords: blast furnace slag, lime production waste, natural loam stabilizing, red mud, road base material

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2448 Long-Term Durability of Roller-Compacted Concrete Pavement

Authors: Jun Hee Lee, Young Kyu Kim, Seong Jae Hong, Chamroeun Chhorn, Seung Woo Lee

Abstract:

Roller-compacted concrete pavement (RCCP), an environmental friendly pavement of which load carry capacity benefitted from both hydration and aggregate interlock from roller compacting, demonstrated a superb structural performance for a relatively small amount of water and cement content. Even though an excellent structural performance can be secured, it is required to investigate roller-compacted concrete (RCC) under environmental loading and its long-term durability under critical conditions. In order to secure long-term durability, an appropriate internal air-void structure is required for this concrete. In this study, a method for improving the long-term durability of RCCP is suggested by analyzing the internal air-void structure and corresponding durability of RCC. The method of improving the long-term durability involves measurements of air content, air voids, and air-spacing factors in RCC that experiences changes in terms of type of air-entraining agent and its usage amount. This test is conducted according to the testing criteria in ASTM C 457, 672, and KS F 2456. It was found that the freezing-thawing and scaling resistances of RCC without any chemical admixture was quite low. Interestingly, an improvement of freezing-thawing and scaling resistances was observed for RCC with appropriate the air entraining (AE) agent content; Relative dynamic elastic modulus was found to be more than 80% for those mixtures. In RCC with AE agent mixtures, large amount of air was distributed within a range of 2% to 3%, and an air void spacing factor ranging between 200 and 300 μm (close to 250 μm, recommended by PCA) was secured. The long-term durability of RCC has a direct relationship with air-void spacing factor, and thus it can only be secured by ensuring the air void spacing factor through the inclusion of the AE in the mixture.

Keywords: durability, RCCP, air spacing factor, surface scaling resistance test, freezing and thawing resistance test

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2447 The Effect of Aging of ZnO, AZO, and GZO films on the Microstructure and Photoelectric Property

Authors: Zue-Chin Chang

Abstract:

RF magnetron sputtering is used on the ceramic targets, each of which contains zinc oxide (ZnO), zinc oxide doped with aluminum (AZO) and zinc oxide doped with gallium (GZO). The XRD analysis showed a preferred orientation along the (002) plane for ZnO, AZO, and GZO films. The AZO film had the best electrical properties; it had the lowest resistivity of 6.6 × 10-4 cm, the best sheet resistance of 2.2 × 10-1 Ω/square, and the highest carrier concentration of 4.3 × 1020 cm-3, as compared to the ZnO and GZO films.

Keywords: aging, films, microstructure, photoelectric property

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2446 Fluvial Stage-Discharge Rating of a Selected Reach of Jamuna River

Authors: Makduma Zahan Badhan, M. Abdul Matin

Abstract:

A study has been undertaken to develop a fluvial stage-discharge rating curve for Jamuna River. Past Cross-sectional survey of Jamuna River reach within Sirajgonj and Tangail has been analyzed. The analysis includes the estimation of discharge carrying capacity, possible maximum scour depth and sediment transport capacity of the selected reaches. To predict the discharge and sediment carrying capacity, stream flow data which include cross-sectional area, top width, water surface slope and median diameter of the bed material of selected stations have been collected and some are calculated from reduced level data. A well-known resistance equation has been adopted and modified to a simple form in order to be used in the present analysis. The modified resistance equation has been used to calculate the mean velocity through the channel sections. In addition, a sediment transport equation has been applied for the prediction of transport capacity of the various sections. Results show that the existing drainage sections of Jamuna channel reach under study have adequate carrying capacity under existing bank-full conditions, but these reaches are subject to bed erosion even in low flow situations. Regarding sediment transport rate, it can be estimated that the channel flow has a relatively high range of bed material concentration. Finally, stage­ discharge curves for various sections have been developed. Based on stage-discharge rating data of various sections, water surface profile and sediment-rating curve of Jamuna River have been developed and also the flooding conditions have been analyzed from predicted water surface profile.

Keywords: discharge rating, flow profile, fluvial, sediment rating

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2445 The Effect of Vitamin D Supplements and Aerobic Exercise on Hunger and Serum Insulin Levels in Adolescents With Metabolic Syndrome

Authors: Vahab Behmanesh

Abstract:

Metabolic syndrome is defined as having at least three of the five metabolic risk factors, including abdominal obesity, high blood pressure, high triglycerides, low HDL, and insulin resistance. Lifestyle changes towards reducing physical activity, unhealthy eating habits Especially the high-fat and high-carbohydrate diet is directly related to metabolic syndrome, and due to the epidemic of overweight and sedentary life, metabolic syndrome is a serious problem worldwide. On the other hand, vitamin D deficiency is considered as one of the most common problems in the world, which is related to the dysfunction of beta cells and insulin resistance, and therefore, vitamin D deficiency is considered as a factor in the occurrence of metabolic syndrome. 40 subjects (age: 16.12 ± 4.4 years and body mass index 25.61 ± 4.4 kg/m2) were randomly assigned to groups of aerobic exercise and placebo, aerobic exercise and vitamin D and placebo (no exercise) were divided. Vitamin D was taken at a dose of 50,000 units per week in a double-blind format for eight weeks, and the daily aerobic exercise program was performed for 50 to 60 minutes, three doses per week, with an intensity of 50-60% of the maximum heart rate. From one-way analysis of variance, Factorial variance analysis (2x2) repeated measurement and correlated t-test were used for data analysis. Aerobic exercise and vitamin D intake reduced all metabolic risk indicators and blood insulin (P < 0.05). However, the subjective feeling of hunger did not change significantly (P < 0.05). Regarding waist circumference and blood glucose, the effect of exercise combined with vitamin D consumption was greater than the corresponding effect in the vitamin D group (P < 0.05). Aerobic exercises and vitamin D intake are safe and effective for improving cardiometabolic health, Imam adds vitamin D to the exercise program has more benefits for weight and blood sugar control, which suggests prescribing it for patients with metabolic syndrome.

Keywords: vitamin D, aerobic exercise, metabolic control, adolescents

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2444 Triplet Shear Tests on Retrofitted Brickwork Masonry Walls

Authors: Berna Istegun, Erkan Celebi

Abstract:

The main objective of this experimental study is to assess the shear strength and the crack behavior of the triplets built of perforated brickwork masonry elements. In order to observe the influence of shear resistance and energy dissipating before and after retrofitting applications by using the reinforcing system, static-cyclic shear tests were employed in the structural mechanics laboratory of Sakarya University. The reinforcing system is composed of hybrid multiaxial seismic fabric consisting of alkali resistant glass and polypropylene fibers. The plaster as bonding material used in the specimen’s retrofitting consists of expanded glass granular. In order to acquire exact measuring data about the failure behavior of the two mortar joints under shear stressing, vertical load-controlled cylinder having force capacity of 50 kN and loading rate of 1.5 mm/min. with an internal inductive displacement transducers is carried out perpendicular to the triplet specimens. In this study, a total of six triplet specimens with textile reinforcement were prepared for these shear bond tests. The three of them were produced as single-sided reinforced triplets with seismic fabric, while the others were strengthened on both sides. In addition, three triplet specimens without retrofitting and plaster were also tested as reference samples. The obtained test results were given in the manner of force-displacement relationships, ductility coefficients and shear strength parameters comparatively. It is concluded that two-side seismic textile applications on masonry elements with relevant plaster have considerably increased the sheer force resistance and the ductility capacity.

Keywords: expanded glass granular, perforated brickwork, retrofitting, seismic fabric, triplet shear tests

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2443 Fabrication of Highly Conductive Graphene/ITO Transparent Bi-Film through Chemical Vapor Deposition (CVD) and Organic Additives-Free Sol-Gel Techniques

Authors: Bastian Waduge Naveen Harindu Hemasiri, Jae-Kwan Kim, Ji-Myon Lee

Abstract:

Indium tin oxide (ITO) remains the industrial standard transparent conducting oxides with better performances. Recently, graphene becomes as a strong material with unique properties to replace the ITO. However, graphene/ITO hybrid composite material is a newly born field in the electronic world. In this study, the graphene/ITO composite bi-film was synthesized by a two steps process. 10 wt.% tin-doped, ITO thin films were produced by an environmentally friendly aqueous sol-gel spin coating technique with economical salts of In(NO3)3.H2O and SnCl4 without using organic additives. The wettability and surface free energy (97.6986 mJ/m2) enhanced oxygen plasma treated glass substrates were used to form voids free continuous ITO film. The spin-coated samples were annealed at 600 0C for 1 hour under low vacuum conditions to obtained crystallized, ITO film. The crystal structure and crystalline phases of ITO thin films were analyzed by X-ray diffraction (XRD) technique. The Scherrer equation was used to determine the crystallite size. Detailed information about chemical composition and elemental composition of the ITO film were determined by X-ray photoelectron spectroscopy (XPS) and energy dispersive X-ray spectroscopy (EDX) coupled with FE-SEM respectively. Graphene synthesis was done under chemical vapor deposition (CVD) method by using Cu foil at 1000 0C for 1 min. The quality of the synthesized graphene was characterized by Raman spectroscopy (532nm excitation laser beam) and data was collected at room temperature and normal atmosphere. The surface and cross-sectional observation were done by using FE-SEM. The optical transmission and sheet resistance were measured by UV-Vis spectroscopy and four point probe head at room temperature respectively. Electrical properties were also measured by using V-I characteristics. XRD patterns reveal that the films contain the In2O3 phase only and exhibit the polycrystalline nature of the cubic structure with the main peak of (222) plane. The peak positions of In3d5/2 (444.28 eV) and Sn3d5/2 (486.7 eV) in XPS results indicated that indium and tin are in the oxide form only. The UV-visible transmittance shows 91.35 % at 550 nm with 5.88 x 10-3 Ωcm specific resistance. The G and 2D band in Raman spectroscopy of graphene appear at 1582.52 cm-1 and 2690.54 cm-1 respectively when the synthesized CVD graphene on SiO2/Si. The determined intensity ratios of 2D to G (I2D/IG) and D to G (ID/IG) were 1.531 and 0.108 respectively. However, the above-mentioned G and 2D peaks appear at 1573.57 cm-1 and 2668.14 cm-1 respectively when the CVD graphene on the ITO coated glass, the positions of G and 2D peaks were red shifted by 8.948 cm-1 and 22.396 cm-1 respectively. This graphene/ITO bi-film shows modified electrical properties when compares with sol-gel derived ITO film. The reduction of sheet resistance in the bi-film was 12.03 % from the ITO film. Further, the fabricated graphene/ITO bi-film shows 88.66 % transmittance at 550 nm wavelength.

Keywords: chemical vapor deposition, graphene, ITO, Raman Spectroscopy, sol-gel

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2442 Anti-Melanogenic Effect of Fisetin through Activating Connective Tissue Growth Factor in vivo Mice Model

Authors: Ryeong-Hyeon Kim, Ah-Reum Lee, Seong-Soo Roh, Gyo-Nam Kim

Abstract:

Appropriate regulation of melanogenesis is important for the management of skin pigmentation-related disease. Although several beneficial effects of fisetin (3,7,3’,4’-tetrahydroxyflavone) have been reported, the precise role and molecular mechanisms of fisetin in skin health both remain unclear. Here, we induced melanogenesis of HRM2 mice (n=7/group) by UVB irradiation for 20 days. UVB-induced HRM2 mice showed that the significantly increased melanin accumulation, however, fisetin treatment (25mg and 50mg/kg of body weight) dose-dependently and significantly inhibits UVB-induced melanogenesis. In line with this, fisetin treatment effectively down-regulated m RNA and expression levels of tyrosinase, TRP2, and MITF. In addition, our inhibitor assay revealed the down-regulated melanogenic marker genes by fisetin treatment were mediated with connective tissue growth factor (CCN2)/TGF-β signaling pathway. Useful information is provided for development of functional foods using fisetin for skin health.

Keywords: connective tissue growth factor, fisetin, melanogenesis, skin, TGF-beta

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2441 Slope Stability and Landslides Hazard Analysis, Limitations of Existing Approaches, and a New Direction

Authors: Alisawi Alaa T., Collins P. E. F.

Abstract:

The analysis and evaluation of slope stability and landslide hazards are landslide hazards are critically important in civil engineering projects and broader considerations of safety. The level of slope stability risk should be identified due to its significant and direct financial and safety effects. Slope stability hazard analysis is performed considering static and/or dynamic loading circumstances. To reduce and/or prevent the failure hazard caused by landslides, a sophisticated and practical hazard analysis method using advanced constitutive modeling should be developed and linked to an effective solution that corresponds to the specific type of slope stability and landslides failure risk. Previous studies on slope stability analysis methods identify the failure mechanism and its corresponding solution. The commonly used approaches include used approaches include limit equilibrium methods, empirical approaches for rock slopes (e.g., slope mass rating and Q-slope), finite element or finite difference methods, and district element codes. This study presents an overview and evaluation of these analysis techniques. Contemporary source materials are used to examine these various methods on the basis of hypotheses, the factor of safety estimation, soil types, load conditions, and analysis conditions and limitations. Limit equilibrium methods play a key role in assessing the level of slope stability hazard. The slope stability safety level can be defined by identifying the equilibrium of the shear stress and shear strength. The slope is considered stable when the movement resistance forces are greater than those that drive the movement with a factor of safety (ratio of the resistance of the resistance of the driving forces) that is greater than 1.00. However, popular and practical methods, including limit equilibrium approaches, are not effective when the slope experiences complex failure mechanisms, such as progressive failure, liquefaction, internal deformation, or creep. The present study represents the first episode of an ongoing project that involves the identification of the types of landslides hazards, assessment of the level of slope stability hazard, development of a sophisticated and practical hazard analysis method, linkage of the failure type of specific landslides conditions to the appropriate solution and application of an advanced computational method for mapping the slope stability properties in the United Kingdom, and elsewhere through geographical information system (GIS) and inverse distance weighted spatial interpolation(IDW) technique. This study investigates and assesses the different assesses the different analysis and solution techniques to enhance the knowledge on the mechanism of slope stability and landslides hazard analysis and determine the available solutions for each potential landslide failure risk.

Keywords: slope stability, finite element analysis, hazard analysis, landslides hazard

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2440 In vivo Evaluation of LAB Probiotic Potential with the Zebrafish Animal Model

Authors: Iñaki Iturria, Pasquale Russo, Montserrat Nacher-Vázquez, Giuseppe Spano, Paloma López, Miguel Angel Pardo

Abstract:

Introduction: It is known that some Lactic Acid Bacteria (LAB) present an interesting probiotic effect. Probiotic bacteria stimulate host resistance to microbial pathogens and thereby aid in immune response, and modulate the host's immune responses to antigens with a potential to down-regulate hypersensitivity reactions. Therefore, probiotic therapy is valuable against intestinal infections and may be beneficial in the treatment of Inflammatory Bowel Disease (IBD). Several in vitro tests are available to evaluate the probiotic potential of a LAB strain. However, an in vivo model is required to understand the interaction between the host immune system and the bacteria. During the last few years, zebrafish (Danio rerio) has gained interest as a promising vertebrate model in this field. This organism has been extensively used to study the interaction between the host and the microbiota, as well as the host immune response under several microbial infections. In this work, we report on the use of the zebrafish model to investigate in vivo the colonizing ability and the immunomodulatory effect of probiotic LAB. Methods: Lactobacillus strains belonging to different LAB species were fluorescently tagged and used to colonize germ-free zebrafish larvae gastrointestinal tract (GIT). Some of the strains had a well-documented probiotic effect (L. acidophilus LA5); while others presented an exopolysaccharide (EPS) producing phenotype, thus allowing evaluating the influence of EPS in the colonization and immunomodulatory effect. Bacteria colonization was monitored for 72 h by direct observation in real time using fluorescent microscopy. CFU count per larva was also evaluated at different times. The immunomodulatory effect was assessed analysing the differential expression of several innate immune system genes (MyD88, NF-κB, Tlr4, Il1β and Il10) by qRT- PCR. The anti-inflammatory effect was evaluated using a chemical enterocolitis zebrafish model. The protective effect against a pathogen was also studied. To that end, a challenge test was developed using a fluorescently tagged pathogen (Vibrio anguillarum-GFP+). The progression of the infection was monitored up to 3 days using a fluorescent stereomicroscope. Mortality rates and CFU counts were also registered. Results and conclusions: Larvae exposed to EPS-producing bacteria showed a higher fluorescence and CFU count than those colonized with no-EPS phenotype LAB. In the same way, qRT-PCR results revealed an immunomodulatory effect on the host after the administration of the strains with probiotic activity. A downregulation of proinflammatory cytoquines as well as other cellular mediators of inflammation was observed. The anti-inflammatory effect was found to be particularly marked following exposure to LA% strain, as well as EPS producing strains. Furthermore, the challenge test revealed a protective effect of probiotic administration. As a matter of fact, larvae fed with probiotics showed a decrease in the mortality rate ranging from 20 to 35%. Discussion: In this work, we developed a promising model, based on the use of gnotobiotic zebrafish coupled with a bacterial fluorescent tagging in order to evaluate the probiotic potential of different LAB strains. We have successfully used this system to monitor in real time the colonization and persistence of exogenous LAB within the gut of zebrafish larvae, to evaluate their immunomodulatory effect and for in vivo competition assays. This approach could bring further insights into the complex microbial-host interactions at intestinal level.

Keywords: gnotobiotic, immune system, lactic acid bacteria, probiotics, zebrafish

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2439 Awning: An Unsung Trait in Rice (Oryza Sativa L.)

Authors: Chamin Chimyang

Abstract:

The fast-changing global trend and declining forest region have impacted agricultural lands; animals, especially birds, might become one of the major pests in the near future and go neglected or unreported in many kinds of literature and events, which is mainly because of bird infestation being a pocket-zone problem. This bird infestation can be attributed to the balding of the forest region and the decline in their foraging hotspot due to anthropogenic activity. There are many ways to keep away the birds from agricultural fields, both conventional and non-conventional. But the question here is whether the traditional approach of bird scarring methods such as scare-crows are effective enough. There are many traits in rice that are supposed to keep the birds away from foraging in paddy fields, and the selection of such traits might be rewarding, such as the angle of the flag leaf from the stem, grain size, novelty of any trait in that particular region and also an awning. Awning, as such, is a very particular trait on which negative selection was imposed to such an extent that there has been a decline in the nucleotide responsible for the said trait. Thus, in this particular session, histology, genetics, genes behind the trait and how awns might be one of the solutions to the problem stated above will be discussed in detail.

Keywords: bird infestation, awning, negative selection, domestication

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2438 A Comparative Study of the Tribological Behavior of Bilayer Coatings for Machine Protection

Authors: Cristina Diaz, Lucia Perez-Gandarillas, Gonzalo Garcia-Fuentes, Simone Visigalli, Roberto Canziani, Giuseppe Di Florio, Paolo Gronchi

Abstract:

During their lifetime, industrial machines are often subjected to chemical, mechanical and thermal extreme conditions. In some cases, the loss of efficiency comes from the degradation of the surface as a result of its exposition to abrasive environments that can cause wear. This is a common problem to be solved in industries of diverse nature such as food, paper or concrete industries, among others. For this reason, a good selection of the material is of high importance. In the machine design context, stainless steels such as AISI 304 and 316 are widely used. However, the severity of the external conditions can require additional protection for the steel and sometimes coating solutions are demanded in order to extend the lifespan of these materials. Therefore, the development of effective coatings with high wear resistance is of utmost technological relevance. In this research, bilayer coatings made of Titanium-Tantalum, Titanium-Niobium, Titanium-Hafnium, and Titanium-Zirconium have been developed using magnetron sputtering configuration by PVD (Physical Vapor Deposition) technology. Their tribological behavior has been measured and evaluated under different environmental conditions. Two kinds of steels were used as substrates: AISI 304, AISI 316. For the comparison with these materials, titanium alloy substrate was also employed. Regarding the characterization, wear rate and friction coefficient were evaluated by a tribo-tester, using a pin-on-ball configuration with different lubricants such as tomato sauce, wine, olive oil, wet compost, a mix of sand and concrete with water and NaCl to approximate the results to real extreme conditions. In addition, topographical images of the wear tracks were obtained in order to get more insight of the wear behavior and scanning electron microscope (SEM) images were taken to evaluate the adhesion and quality of the coating. The characterization was completed with the measurement of nanoindentation hardness and elastic modulus. Concerning the results, thicknesses of the samples varied from 100 nm (Ti-Zr layer) to 1.4 µm (Ti-Hf layer) and SEM images confirmed that the addition of the Ti layer improved the adhesion of the coatings. Moreover, results have pointed out that these coatings have increased the wear resistance in comparison with the original substrates under environments of different severity. Furthermore, nanoindentation hardness results showed an improvement of the elastic strain to failure and a high modulus of elasticity (approximately 200 GPa). As a conclusion, Ti-Ta, Ti-Zr, Ti-Nb, and Ti-Hf are very promising and effective coatings in terms of tribological behavior, improving considerably the wear resistance and friction coefficient of typically used machine materials.

Keywords: coating, stainless steel, tribology, wear

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2437 Studies on the Characterization and Machinability of Duplex Stainless Steel 2205 during Dry Turning

Authors: Gaurav D. Sonawane, Vikas G. Sargade

Abstract:

The present investigation is a study of the effect of advanced Physical Vapor Deposition (PVD) coatings on cutting temperature residual stresses and surface roughness during Duplex Stainless Steel (DSS) 2205 turning. Austenite stabilizers like nickel, manganese, and molybdenum reduced the cost of DSS. Surface Integrity (SI) plays an important role in determining corrosion resistance and fatigue life. Resistance to various types of corrosion makes DSS suitable for applications with critical environments like Heat exchangers, Desalination plants, Seawater pipes and Marine components. However, lower thermal conductivity, poor chip control and non-uniform tool wear make DSS very difficult to machine. Cemented carbide tools (M grade) were used to turn DSS in a dry environment. AlTiN and AlTiCrN coatings were deposited using advanced PVD High Pulse Impulse Magnetron Sputtering (HiPIMS) technique. Experiments were conducted with cutting speed of 100 m/min, 140 m/min and 180 m/min. A constant feed and depth of cut of 0.18 mm/rev and 0.8 mm were used, respectively. AlTiCrN coated tools followed by AlTiN coated tools outperformed uncoated tools due to properties like lower thermal conductivity, higher adhesion strength and hardness. Residual stresses were found to be compressive for all the tools used for dry turning, increasing the fatigue life of the machined component. Higher cutting temperatures were observed for coated tools due to its lower thermal conductivity, which results in very less tool wear than uncoated tools. Surface roughness with uncoated tools was found to be three times higher than coated tools due to lower coefficient of friction of coating used.

Keywords: cutting temperature, DSS2205, dry turning, HiPIMS, surface integrity

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2436 Carbon based Smart Materials: Functional Carbon for Lightweight Automotive Component 3D Printing

Authors: Mohammad M. Garmabia, Peyman Shahia, Jimi Tjonga, Mohini Saina

Abstract:

Flame retardant composite filaments with functional carbon in the composition were fabricated, and printed parts showed enhancedcrash resistance pproperties and imporved EMI shielding. The negligible mass difference after prolonged immersion in automobile chemicals revealed the outstanding performance of parts for under-the-hood high-temperature applications.

Keywords: FDM, crash worthy, EMI Shield, lightweight, automotive parts

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2435 Functionalized Nano porous Ceramic Membranes for Electrodialysis Treatment of Harsh Wastewater

Authors: Emily Rabe, Stephanie Candelaria, Rachel Malone, Olivia Lenz, Greg Newbloom

Abstract:

Electrodialysis (ED) is a well-developed technology for ion removal in a variety of applications. However, many industries generate harsh wastewater streams that are incompatible with traditional ion exchange membranes. Membrion® has developed novel ceramic-based ion exchange membranes (IEMs) offering several advantages over traditional polymer membranes: high performance in low pH, chemical resistance to oxidizers, and a rigid structure that minimizes swelling. These membranes are synthesized with our patented silane-based sol-gel techniques. The pore size, shape, and network structure are engineered through a molecular self-assembly process where thermodynamic driving forces are used to direct where and how pores form. Either cationic or anionic groups can be added within the membrane nanopore structure to create cation- and anion-exchange membranes. The ceramic IEMs are produced on a roll-to-roll manufacturing line with low-temperature processing. Membrane performance testing is conducted using in-house permselectivity, area-specific resistance, and ED stack testing setups. Ceramic-based IEMs show comparable performance to traditional IEMs and offer some unique advantages. Long exposure to highly acidic solutions has a negligible impact on ED performance. Additionally, we have observed stable performance in the presence of strong oxidizing agents such as hydrogen peroxide. This stability is expected, as the ceramic backbone of these materials is already in a fully oxidized state. This data suggests ceramic membranes, made using sol-gel chemistry, could be an ideal solution for acidic and/or oxidizing wastewater streams from processes such as semiconductor manufacturing and mining.

Keywords: ion exchange, membrane, silane chemistry, nanostructure, wastewater

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2434 Sensing of Cancer DNA Using Resonance Frequency

Authors: Sungsoo Na, Chanho Park

Abstract:

Lung cancer is one of the most common severe diseases driving to the death of a human. Lung cancer can be divided into two cases of small-cell lung cancer (SCLC) and non-SCLC (NSCLC), and about 80% of lung cancers belong to the case of NSCLC. From several studies, the correlation between epidermal growth factor receptor (EGFR) and NSCLCs has been investigated. Therefore, EGFR inhibitor drugs such as gefitinib and erlotinib have been used as lung cancer treatments. However, the treatments result showed low response (10~20%) in clinical trials due to EGFR mutations that cause the drug resistance. Patients with resistance to EGFR inhibitor drugs usually are positive to KRAS mutation. Therefore, assessment of EGFR and KRAS mutation is essential for target therapies of NSCLC patient. In order to overcome the limitation of conventional therapies, overall EGFR and KRAS mutations have to be monitored. In this work, the only detection of EGFR will be presented. A variety of techniques has been presented for the detection of EGFR mutations. The standard detection method of EGFR mutation in ctDNA relies on real-time polymerase chain reaction (PCR). Real-time PCR method provides high sensitive detection performance. However, as the amplification step increases cost effect and complexity increase as well. Other types of technology such as BEAMing, next generation sequencing (NGS), an electrochemical sensor and silicon nanowire field-effect transistor have been presented. However, those technologies have limitations of low sensitivity, high cost and complexity of data analyzation. In this report, we propose a label-free and high-sensitive detection method of lung cancer using quartz crystal microbalance based platform. The proposed platform is able to sense lung cancer mutant DNA with a limit of detection of 1nM.

Keywords: cancer DNA, resonance frequency, quartz crystal microbalance, lung cancer

Procedia PDF Downloads 229
2433 Genetic Diversity and Discovery of Unique SNPs in Five Country Cultivars of Sesamum indicum by Next-Generation Sequencing

Authors: Nam-Kuk Kim, Jin Kim, Soomin Park, Changhee Lee, Mijin Chu, Seong-Hun Lee

Abstract:

In this study, we conducted whole genome re-sequencing of 10 cultivars originated from five countries including Korea, China, India, Pakistan and Ethiopia with Sesamum indicum (Zhongzho No. 13) genome as a reference. Almost 80% of the whole genome sequences of the reference genome could be covered by sequenced reads. Numerous SNP and InDel were detected by bioinformatic analysis. Among these variants, 266,051 SNPs were identified as unique to countries. Pakistan and Ethiopia had high densities of SNPs compared to other countries. Three main clusters (cluster 1: Korea, cluster 2: Pakistan and India, cluster 3: Ethiopia and China) were recovered by neighbor-joining analysis using all variants. Interestingly, some variants were detected in DGAT1 (diacylglycerol O-acyltransferase 1) and FADS (fatty acid desaturase) genes, which are known to be related with fatty acid synthesis and metabolism. These results can provide useful information to understand the regional characteristics and develop DNA markers for origin discrimination of sesame.

Keywords: Sesamum indicum, NGS, SNP, DNA marker

Procedia PDF Downloads 323
2432 A Study on Factors Affecting (Building Information Modelling) BIM Implementation in European Renovation Projects

Authors: Fatemeh Daneshvartarigh

Abstract:

New technologies and applications have radically altered construction techniques in recent years. In order to anticipate how the building will act, perform, and appear, these technologies encompass a wide range of visualization, simulation, and analytic tools. These new technologies and applications have a considerable impact on completing construction projects in today's (architecture, engineering and construction)AEC industries. The rate of changes in BIM-related topics is different worldwide, and it depends on many factors, e.g., the national policies of each country. Therefore, there is a need for comprehensive research focused on a specific area with common characteristics. Therefore, one of the necessary measures to increase the use of this new approach is to examine the challenges and obstacles facing it. In this research, based on the Delphi method, at first, the background and related literature are reviewed. Then, using the knowledge obtained from the literature, a primary questionnaire is generated and filled by experts who are selected using snowball sampling. It covered the experts' attitudes towards implementing BIM in renovation projects and their view of the benefits and obstacles in this regard. By analyzing the primary questionnaire, the second group of experts is selected among the participants to be interviewed. The results are analyzed using Theme analysis. Six themes, including Management support, staff resistance, client willingness, Cost of software and implementation, the difficulty of implementation, and other reasons, are obtained. Then a final questionnaire is generated from the themes and filled by the same group of experts. The result is analyzed by the Fuzzy Delphi method, showing the exact ranking of the obtained themes. The final results show that management support, staff resistance, and client willingness are the most critical barrier to BIM usage in renovation projects.

Keywords: building information modeling, BIM, BIM implementation, BIM barriers, BIM in renovation

Procedia PDF Downloads 157
2431 Prevalence of Mycobacterium Tuberculosis Infection and Rifampicin Resistance among Presumptive Tuberculosis Cases Visiting Tuberculosis Clinic of Adare General Hospital, Southern Ethiopia

Authors: Degineh Belachew Andarge, Tariku Lambiyo Anticho, Getamesay Mulatu Jara, Musa Mohammed Ali

Abstract:

Introduction: Tuberculosis (TB) is a communicable chronic disease causedby Mycobacterium tuberculosis (MTB). About one-third of the world’s population is latently infected with MTB. TB is among the top 10 causes of mortality throughout the globe from a single pathogen. Objective: The aim of this study was to determine the prevalence of tuberculosis,rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosis, and associated factors among presumptive tuberculosis cases attending the tuberculosis clinic of Adare General Hospital located in Hawassa city. Methods: A hospital-based cross-sectional study was conducted among 321 tuberculosis suspected patients from April toJuly 2018. Socio-demographic, environmental, and behavioral data were collected using a structured questionnaire. Sputumspecimens were analyzed using GeneXpert. Data entry was made using Epi info version 7 and analyzed by SPSS version 20. Logistic regression models were used to determine the risk factors. A p-value less than 0.05 was taken as a cut point. Results: In this study, the prevalence of Mycobacterium tuberculosis was 98 (30.5%) with 95% confidence interval (25.5–35.8), and the prevalence of rifampicin-resistant/multidrug-resistantMycobacterium tuberculosis among the 98 Mycobacteriumtuberculosis confirmed cases was 4 (4.1%). The prevalence of rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosisamong the tuberculosis suspected patients was 1.24%. Participants who had a history of treatment with anti-tuberculosisdrugs were more likely to develop rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosis. Conclusions: This study identified relatively high rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosis amongtuberculosis suspected patients in the study area. Early detection of drug-resistant Mycobacterium tuberculosis should be givenenough attention to strengthen the management of tuberculosis cases and improve direct observation therapy short-course and eventually minimize the spread of rifampicin-resistant tuberculosis strain in the community.

Keywords: rifampicin resistance, mycobacterium tuberculosis, risk factors, prevalence of TB

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2430 Microarray Gene Expression Data Dimensionality Reduction Using PCA

Authors: Fuad M. Alkoot

Abstract:

Different experimental technologies such as microarray sequencing have been proposed to generate high-resolution genetic data, in order to understand the complex dynamic interactions between complex diseases and the biological system components of genes and gene products. However, the generated samples have a very large dimension reaching thousands. Therefore, hindering all attempts to design a classifier system that can identify diseases based on such data. Additionally, the high overlap in the class distributions makes the task more difficult. The data we experiment with is generated for the identification of autism. It includes 142 samples, which is small compared to the large dimension of the data. The classifier systems trained on this data yield very low classification rates that are almost equivalent to a guess. We aim at reducing the data dimension and improve it for classification. Here, we experiment with applying a multistage PCA on the genetic data to reduce its dimensionality. Results show a significant improvement in the classification rates which increases the possibility of building an automated system for autism detection.

Keywords: PCA, gene expression, dimensionality reduction, classification, autism

Procedia PDF Downloads 557
2429 Signal Processing of the Blood Pressure and Characterization

Authors: Hadj Abd El Kader Benghenia, Fethi Bereksi Reguig

Abstract:

In clinical medicine, blood pressure, raised blood hemodynamic monitoring is rich pathophysiological information of cardiovascular system, of course described through factors such as: blood volume, arterial compliance and peripheral resistance. In this work, we are interested in analyzing these signals to propose a detection algorithm to delineate the different sequences and especially systolic blood pressure (SBP), diastolic blood pressure (DBP), and the wave and dicrotic to do their analysis in order to extract the cardiovascular parameters.

Keywords: blood pressure, SBP, DBP, detection algorithm

Procedia PDF Downloads 429
2428 Analysis of Rock Cutting Progress with a New Axe-Shaped PDC Cutter to Improve PDC Bit Performance in Elastoplastic Formation

Authors: Fangyuan Shao, Wei Liu, Deli Gao

Abstract:

Polycrystalline diamond compact (PDC) bits have occupied a large market of unconventional oil and gas drilling. The application of PDC bits benefits from the efficient rock breaking of PDC cutters. In response to increasingly complex formations, many shaped cutters have been invited, but many of them have not been solved by the mechanism of rock breaking. In this paper, two kinds of PDC cutters: a new axe-shaped (NAS) cutter and cylindrical cutter (benchmark) were studied by laboratory experiments. NAS cutter is obtained by optimizing two sides of axe-shaped cutter with curved surfaces. All the cutters were put on a vertical turret lathe (VTL) in the laboratory for cutting tests. According to the cutting distance, the VTL tests can be divided into two modes: single-turn rotary cutting and continuous cutting. The cutting depth of cutting (DOC) was set at 1.0 mm and 2.0 mm in the former mode. The later mode includes a dry VTL test for thermal stability and a wet VTL test for wear resistance. Load cell and 3D optical profiler were used to obtain the value of cutting forces and wear area, respectively. Based on the findings of the single-turn rotary cutting VTL tests, the performance of A NAS cutter was better than the benchmark cutter on elastoplastic material cutting. The cutting forces (normal forces, tangential force, and radial force) and special mechanical energy (MSE) of a NAS cutter were lower than that of the benchmark cutter under the same condition. It meant that a NAS cutter was more efficient on elastoplastic material breaking. However, the wear resistance of a new axe-shaped cutter was higher than that of a benchmark cutter. The results of the dry VTL test showed that the thermal stability of a NAS cutter was higher than that of a benchmark cutter. The cutting efficiency can be improved by optimizing the geometric structure of the PDC cutter. The change of thermal stability may be caused by the decrease of the contact area between cutter and rock at given DOC. The conclusions of this paper can be used as an important reference for PDC cutters designers.

Keywords: axe-shaped cutter, PDC cutter, rotary cutting test, vertical turret lathe

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2427 Biosynthesis of a Nanoparticle-Antibody Phthalocyanine Photosensitizer for Use in Targeted Photodynamic Therapy of Cervical Cancer

Authors: Elvin P. Chizenga, Heidi Abrahamse

Abstract:

Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

Procedia PDF Downloads 119
2426 Alternative Splicing of an Arabidopsis Gene, At2g24600, Encoding Ankyrin-Repeat Protein

Authors: H. Sakamoto, S. Kurosawa, M. Suzuki, S. Oguri

Abstract:

In Arabidopsis, several genes encoding proteins with ankyrin repeats and trans-membrane domains (AtANKTM) have been identified as mediators of biotic and abiotic stress responses. It has been known that the expression of an AtANKTM gene, At2g24600, is induced in response to abiotic stress and that there are four splicing variants derived from this locus. In this study, by RT-PCR and sequencing analysis, an unknown splicing variant of the At2g24600 transcript was identified. Based on differences in the predicted amino acid sequences, the five splicing variants are divided into three groups. The three predicted proteins are highly homologous, yet have different numbers of ankyrin repeats and trans-membrane domains. It is generally considered that ankyrin repeats mediate protein-protein interaction and that the number of trans-membrane domains affects membrane topology of proteins. The protein variants derived from the At2g24600 locus may have different molecular functions each other.

Keywords: alternative splicing, ankyrin repeats, trans-membrane domains, arabidopsis

Procedia PDF Downloads 368
2425 Stability Design by Geometrical Nonlinear Analysis Using Equivalent Geometric Imperfections

Authors: S. Fominow, C. Dobert

Abstract:

The present article describes the research that deals with the development of equivalent geometric imperfections for the stability design of steel members considering lateral-torsional buckling. The application of these equivalent imperfections takes into account the stiffness-reducing effects due to inelasticity and residual stresses, which lead to a reduction of the load carrying capacity of slender members and structures. This allows the application of a simplified design method, that is performed in three steps. Application of equivalent geometric imperfections, determination of internal forces using geometrical non-linear analysis (GNIA) and verification of the cross-section resistance at the most unfavourable location. All three verification steps are closely related and influence the results. The derivation of the equivalent imperfections was carried out in several steps. First, reference lateral-torsional buckling resistances for various rolled I-sections, slenderness grades, load shapes and steel grades were determined. This was done either with geometric and material non-linear analysis with geometrical imperfections and residual stresses (GMNIA) or for standard cases based on the equivalent member method. With the aim of obtaining identical lateral-torsional buckling resistances as the reference resistances from the application of the design method, the required sizes for equivalent imperfections were derived. For this purpose, a program based on the FEM method has been developed. Based on these results, several proposals for the specification of equivalent geometric imperfections have been developed. These differ in the shape of the applied equivalent geometric imperfection, the model of the cross-sectional resistance and the steel grade. The proposed design methods allow a wide range of applications and a reliable calculation of the lateral-torsional buckling resistances, as comparisons between the calculated resistances and the reference resistances have shown.

Keywords: equivalent geometric imperfections, GMNIA, lateral-torsional buckling, non-linear finite element analysis

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2424 The Mechanical and Comfort Properties of Cotton/Micro-Tencel Lawn Fabrics

Authors: Abdul Basit, Shahid Latif, Shah Mehmood

Abstract:

Lawn fabric was usually prepared from originally of linen but at present chiefly cotton. Lawn fabric is worn in summer. Cotton Lawn is a lightweight pure cloth which is heavier than voile. It is so fine that it is somewhat transparent. It is soft and superb to wear thus it is perfect for summer clothes or for regular wear in hotter climates. Tencel (Lyocell) fiber is considered as the fiber of the future as Tencel fibers are absorbent, soft, and extremely strong when wet or dry, and resistant to wrinkles. Fibers are more absorbent than cotton, softer than silk and cooler than linen. High water absorption and water vapor absorption give more heat capacity and heat balancing effect for thermo-regulation. This thermo-regulation is analogous with the action of phase-change-materials. The thermal wear properties result in cool and dry touch that gives cooling effect in sportswear, and the warmth properties (when used as an insulation layer). These cooling and warming effects are adaptive to the environment giving comfort in a broad range of climatic conditions. In this work, single yarns of Ne 80s were made. Yarns were made from conventional ring spinning. Different yarns of 100% cotton, 100% micro-Tencel and Cotton:micro-Tencel blends (67:33, 50:50:33:67) were made. The mechanical and comfort properties of the woven fabrics were compared. The mechanical properties include the tensile and tear strength, bending length, pilling and abrasion resistance whereas comfort properties include the air permeability, moisture management and thermal resistance. It is found that as the content of the micro-Tencel is increased, the mechanical and comfort properties of the woven fabric are also increased.

Keywords: combed cotton, comfort properties , mechanical properties, micro-Tencel

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2423 Developments and Implementation of Biomaterials in Textile Coating and Finishing

Authors: David De Smet, Myriam Vanneste

Abstract:

There is a constant need for the improvement of materials applied in textile industries. Nowadays there is a tendency for “bio, eco, natural and environmental friendly” consciousness of the consumer resulting in various textile labels. Materials, totally based on CO2-neutral renewable resources (biopolymers), respond very well to this tendency. Proteins and PLA were evaluated as binders for textile coatings. Much attention is paid to the functionalization of textiles, therefore bio-additves are examined to introduce abrasion resistance, antimicrobial and flame retardant properties.

Keywords: biomaterial, textile, coating, finishing

Procedia PDF Downloads 707
2422 A Computational Approach to Screen Antagonist’s Molecule against Mycobacterium tuberculosis Lipoprotein LprG (Rv1411c)

Authors: Syed Asif Hassan, Tabrej Khan

Abstract:

Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

Procedia PDF Downloads 267