Search results for: multi drug resistance tuberculosis (MDR-TB)
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 8856

Search results for: multi drug resistance tuberculosis (MDR-TB)

6096 Analysis of Bridge-Pile Foundation System in Multi-layered Non-Linear Soil Strata Using Energy-Based Method

Authors: Arvan Prakash Ankitha, Madasamy Arockiasamy

Abstract:

The increasing demand for adopting pile foundations in bridgeshas pointed towardsthe need to constantly improve the existing analytical techniques for better understanding of the behavior of such foundation systems. This study presents a simplistic approach using the energy-based method to assess the displacement responses of piles subjected to general loading conditions: Axial Load, Lateral Load, and a Bending Moment. The governing differential equations and the boundary conditions for a bridge pile embedded in multi-layered soil strata subjected to the general loading conditions are obtained using the Hamilton’s principle employing variational principles and minimization of energies. The soil non-linearity has been incorporated through simple constitutive relationships that account for degradation of soil moduli with increasing strain values.A simple power law based on published literature is used where the soil is assumed to be nonlinear-elastic and perfectly plastic. A Tresca yield surface is assumed to develop the soil stiffness variation with different strain levels that defines the non-linearity of the soil strata. This numerical technique has been applied to a pile foundation in a two - layered soil strata for a pier supporting the bridge and solved using the software MATLAB R2019a. The analysis yields the bridge pile displacements at any depth along the length of the pile. The results of the analysis are in good agreement with the published field data and the three-dimensional finite element analysis results performed using the software ANSYS 2019R3. The methodology can be extended to study the response of the multi-strata soil supporting group piles underneath the bridge piers.

Keywords: pile foundations, deep foundations, multilayer soil strata, energy based method

Procedia PDF Downloads 131
6095 Assessing the Risk of Condensation and Moisture Accumulation in Solid Walls: Comparing Different Internal Wall Insulation Options

Authors: David Glew, Felix Thomas, Matthew Brooke-Peat

Abstract:

Improving the thermal performance of homes is seen as an essential step in achieving climate change, fuel security, fuel poverty targets. One of the most effective thermal retrofits is to insulate solid walls. However, it has been observed that applying insulation to the internal face of solid walls reduces the surface temperature of the inner wall leaf, which may introduce condensation risk and may interrupt seasonal moisture accumulation and dissipation. This research quantifies the extent to which the risk of condensation and moisture accumulation in the wall increases (which can increase the risk of timber rot) following the installation of six different types of internal wall insulation. In so doing, it compares how risk is affected by both the thermal resistance, thickness, and breathability of the insulation. Thermal bridging, surface temperatures, condensation risk, and moisture accumulation are evaluated using hygrothermal simulation software before and after the thermal upgrades. The research finds that installing internal wall insulation will always introduce some risk of condensation and moisture. However, it identifies that risks were present prior to insulation and that breathable materials and insulation with lower resistance have lower risks than alternative insulation options. The implications of this may be that building standards that encourage the enhanced thermal performance of solid walls may be introducing moisture risks into homes.

Keywords: condensation risk, hygrothermal simulation, internal wall insulation, thermal bridging

Procedia PDF Downloads 158
6094 Nitriding of Super-Ferritic Stainless Steel by Plasma Immersion Ion Implantation in Radio Frequency and Microwave Plasma System

Authors: H. Bhuyan, S. Mändl, M. Favre, M. Cisternas, A. Henriquez, E. Wyndham, M. Walczak, D. Manova

Abstract:

The 470 Li-24 Cr and 460Li-21 Cr are two alloys belonging to the next generation of super-ferritic nickel free stainless steel grades, containing titanium (Ti), niobium (Nb) and small percentage of carbon (C) and nitrogen (N). The addition of Ti and Nb improves in general the corrosion resistance while the low interstitial content of C and N assures finer precipitates and greater ductility compared to conventional ferritic grades. These grades are considered an economic alternative to AISI 316L and 304 due to comparable or superior corrosion. However, since 316L and 304 can be nitrided to improve the mechanical surface properties like hardness and wear; it is hypothesize that the tribological properties of these super-ferritic stainless steels grades can also be improved by plasma nitriding. Thus two sets of plasma immersion ion implantation experiments have been carried out, one with a high pressure capacitively coupled radio frequency plasma at PUC Chile and the other using a low pressure microwave plasma at IOM Leipzig, in order to explore further improvements in the mechanical properties of 470 Li-24 Cr and 460Li-21 Cr steel. Nitrided and unnitrided substrates have been subsequently investigated using different surface characterization techniques including secondary ion mass spectroscopy, scanning electron microscopy, energy dispersive x-ray analysis, Vickers hardness, wear resistance, as well as corrosion test. In most of the characterizations no major differences have been observed for nitrided 470 Li-24 Cr and 460Li-21 Cr. Due to the ion bombardment, an increase in the surface roughness is observed for higher treatment temperature, independent of the steel types. The formation of chromium nitride compound takes place only at a treatment temperature around 4000C-4500C, or above. However, corrosion properties deteriorate after treatment at higher temperatures. The physical characterization results show up to 25 at.% of nitrogen for a diffusion zone of 4-6 m, and a 4-5 times increase in hardness for different experimental conditions. The samples implanted with temperature higher than 400 °C presented a wear resistance around two orders of magnitude higher than the untreated substrates. The hardness is apparently affected by the different roughness of the samples and their different profile of nitrogen.

Keywords: ion implantation, plasma, RF and microwave plasma, stainless steel

Procedia PDF Downloads 461
6093 Graphene Reinforced Magnesium Metal Matrix Composites for Biomedical Applications

Authors: Khurram Munir, Cuie Wen, Yuncang Li

Abstract:

Magnesium (Mg) metal matrix composites (MMCs) reinforced with graphene nanoplatelets (GNPs) have been developed by powder metallurgy (PM). In this study, GNPs with different concentrations (0.1-0.3 wt.%) were dispersed into Mg powders by high-energy ball-milling processes. The microstructure and resultant mechanical properties of the fabricated nanocomposites were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), Raman spectroscopy (RS), compression and nano-wear tests. The corrosion resistance of the fabricated composites was evaluated by electrochemical tests and hydrogen evolution measurements. Finally, the biological response of Mg-GNPs composites was assessed using osteoblast-like SaOS2 cells. The results indicate that GNPs are excellent candidates as reinforcements in Mg matrices for the manufacture of biodegradable Mg-based composite implants. GNP addition improved the mechanical properties of Mg via synergetic strengthening modes. Moreover, retaining the structural integrity of GNPs during PM processing improved the ductility, compressive strength, and corrosion resistance of the Mg-GNP composites as compared to monolithic Mg. Cytotoxicity assessments did not reveal any significant toxicity with the addition of GNPs to Mg matrices. This study demonstrates that Mg-xGNPs with x < 0.3 wt.%, may constitute novel biodegradable implant materials for load-bearing applications.

Keywords: magnesium-graphene composites, strengthening mechanisms, In vitro cytotoxicity, biocorrosion

Procedia PDF Downloads 155
6092 Silymarin Reverses Scopolamine-Induced Memory Deficit in Object Recognition Test in Rats: A Behavioral, Biochemical, Histopathological and Immunohistochemical Study

Authors: Salma A. El-Marasy, Reham M. Abd-Elsalam, Omar A. Ahmed-Farid

Abstract:

Dementia is characterized by impairments in memory and other cognitive abilities. This study aims to elucidate the possible ameliorative effect of silymarin on scopolamine-induced dementia using the object recognition test (ORT). The study was extended to demonstrate the role of cholinergic activity, oxidative stress, neuroinflammation, brain neurotransmitters and histopathological changes in the anti-amnestic effect of silymarin in demented rats. Wistar rats were pretreated with silymarin (200, 400, 800 mg/kg) or donepezil (10 mg/kg) orally for 14 consecutive days. Dementia was induced after the last drug administration by a single intraperitoneal dose of scopolamine (16 mg/kg). Then behavioral, biochemical, histopathological, and immunohistochemical analyses were then performed. Rats pretreated with silymarin counteracted scopolamine-induced non-spatial working memory impairment in the ORT and decreased acetylcholinesterase (AChE) activity, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), restored gamma-aminobutyric acid (GABA) and dopamine (DA) contents in the cortical and hippocampal brain homogenates. Silymarin dose-dependently reversed scopolamine-induced histopathological changes. Immunohistochemical analysis showed that silymarin dose-dependently mitigated protein expression of a glial fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NF-κB) in the brain cortex and hippocampus. All these effects of silymarin were similar to that of the standard anti-amnestic drug, donepezil. This study reveals that the ameliorative effect of silymarin on scopolamine-induced dementia in rats using the ORT maybe in part mediated by, enhancement of cholinergic activity, anti-oxidant and anti-inflammatory activities as well as mitigation in brain neurotransmitters and histopathological changes.

Keywords: dementia, donepezil, object recognition test, rats, silymarin, scopolamine

Procedia PDF Downloads 135
6091 Detoxification of Hazardous Organic/Inorganic Contaminants in Automobile Shredder Residue by Multi-Functioned Nano-Size Metallic Calcium Composite

Authors: Srinivasa Reddy Mallampati, Byoung Ho Lee, Yoshiharu Mitoma, Simion Cristian

Abstract:

In recent years, environmental nanotechnology has risen to the forefront and the new properties and enhanced reactivates offered by nanomaterial may offer a new, low-cost paradigm to solving complex environmental pollution problems. This study assessed the synthesis and application of multi-functioned nano-size metallic calcium (nMC) composite for detoxification of hazardous inorganic (heavy metals (HMs)/organic chlorinated/brominated compound (CBCs) contaminants in automobile shredder residue (ASR). ASR residues ball milled with nMC composite can achieve about 90-100% of HMs immobilization and CBCs decomposition. The results highlight the low quantity of HMs leached from ASR residues after treatment with nMC, which was found to be lower than the standard regulatory limit for hazardous waste landfills. The use of nMC composite in a mechanochemical process to treat hazardous ASR (dry conditions) is a simple and innovative approach to remediate hazardous inorganic/organic cross-contaminates in ASR.

Keywords: nano-sized metallic calcium, automobile shredder residue, organic/inorganic contaminants, immobilization, detoxification

Procedia PDF Downloads 221
6090 Method to Assessing Aspect of Sustainable Development-Walkability

Authors: Amna Ali Nasser Al-Saadi, Riken Homma, Kazuhisa Iki

Abstract:

Need to generate objective communication between researchers, Practitioners and policy makers are top concern of sustainability. Despite the fact that many places have successes in achieving some aspects of sustainable urban development, there are no scientific facts to convince policy makers in the rest of the world to apply their guides and manuals. This is because each of them was developed to fulfill the need of specific city. The question is, how to learn the lesson from each case study? And how distinguish between the potential criteria and negative one? And how quantify their effects in the future development? Walkability has been found as a solution to achieve healthy life style as well as social, environmental and economic sustainability. Moreover, it is complicated as every aspect of sustainable development. This research is stand on quantitative- comparative methodology in order to assess pedestrian oriented development. Three Analyzed Areas (AAs) were selected. One site is located in Oman in which hypotheses as motorized oriented development, while two sites are in Japan where the development is pedestrian friendly. The study used Multi-Criteria Evaluation Method (MCEM). Initially, MCEM stands on Analytic Hierarchy Process (AHP). The later was structured into main goal (walkability), objectives (functions and layout) and attributes (the urban form criteria). Secondly, the GIS were used to evaluate the attributes in multi-criteria maps. Since each criterion has different scale of measurement, all results were standardized by z-score and used to measure the co-relations among cr iteria. Different scenario was generated from each AA. After that, MCEM (AHP- OWA) based on GIS measured the walkability score and determined the priority of criteria development in the non-walker friendly environment. As results, the comparison criteria for z-score presented a measurable distinguished orientation of development. This result has been used to prove that Oman is motorized environment while Japan is walkable. Also, it defined the powerful criteria and week criteria regardless to the AA. This result has been used to generalize the priority for walkable development.

Keywords: walkability, sustainable development, multi- criteria evaluation method, gis

Procedia PDF Downloads 450
6089 Assessing the Role of Human Mobility on Malaria Transmission in South Sudan

Authors: A. Y. Mukhtar, J. B. Munyakazi, R. Ouifki

Abstract:

Over the past few decades, the unprecedented increase in mobility has raised considerable concern about the relationship between mobility and vector-borne diseases and malaria in particular. Thus, one can claim that human mobility is one of the contributing factors to the resurgence of malaria. To assess human mobility on malaria burden among hosts, we formulate a movement-based model on a network of patches. We then extend human multi-group SEIAR deterministic epidemic models into a system of stochastic differential equations (SDEs). Our quantitative stochastic model which is expressed in terms of average rates of movement between compartments is fitted to time-series data (weekly malaria data of 2011 for each patch) using the maximum likelihood approach. Using the metapopulation (multi-group) model, we compute and analyze the basic reproduction number. The result shows that human movement is sufficient to preserve malaria disease firmness in the patches with the low transmission. With these results, we concluded that the sensitivity of malaria to the human mobility is turning to be greatly important over the implications of future malaria control in South Sudan.

Keywords: basic reproduction number, malaria, maximum likelihood, movement, stochastic model

Procedia PDF Downloads 131
6088 Flexible Current Collectors for Printed Primary Batteries

Authors: Vikas Kumar

Abstract:

Portable batteries are reliable source of mobile energy to power smart wearable electronics, medical devices, communications, and others internet of thing (IoT) devices. There is a continuous increase in demand for thinner, more flexible battery with high energy density and reliability to meet the requirement. For a flexible battery, factors that affect these properties are the stability of current collectors, electrode materials and their interfaces with the corrosive electrolytes. State-of-the-art conventional and flexible batteries utilise carbon as an electrode and current collectors which cause high internal resistance (~100 ohms) and limit the peak current to ~1mA. This makes them unsuitable for a wide range of applications. Replacing the carbon parts with metallic components would reduce the internal resistance (and hence reduce parasitic loss), but significantly increases the risk of corrosion due to galvanic interactions within the battery. To overcome these challenges, low cost electroplated nickel (Ni) on copper (Cu) was studied as a potential anode current collector for a zinc-manganese oxide primary battery with different concentration of NH4Cl/ZnCl2 electrolyte. Using electrical impedance spectroscopy (EIS), we monitored the open circuit potential (OCP) of electroplated nickel (different thicknesses) in different concentration of electrolytes to optimise the thickness of Ni coating. Our results show that electroless Ni coating suffer excessive corrosion in these electrolytes. Corrosion rates of Ni coatings for different concentrations of electrolytes have been calculated with Tafel analysis. These results suggest that for electroplated Ni, channelling and/or open porosity is a major issue, which was confirmed by morphological analysis. These channels are an easy pathway for electrolyte to penetrate thorough Ni to corrode the Ni/Cu interface completely. We further investigated the incorporation of a special printed graphene layer on Ni to provide corrosion protection in this corrosive electrolyte medium. We find that the incorporation of printed graphene layer provides the corrosion protection to the Ni and enhances the chemical bonding between the active materials and current collector and also decreases the overall internal resistance of the battery system.

Keywords: corrosion, electrical impedance spectroscopy, flexible battery, graphene, metal current collector

Procedia PDF Downloads 122
6087 A Multi-Objective Methodology for Selecting Lean Initiatives in Modular Construction Companies

Authors: Saba Shams Bidhendi, Steven Goh, Andrew Wandel

Abstract:

The implementation of lean manufacturing initiatives has produced significant impacts in improving operational performance and reducing manufacturing wastes in the production process. However, selecting an appropriate set of lean strategies is critical to avoid misapplication of the lean manufacturing techniques and consequential increase in non-value-adding activities. To the author’s best knowledge, there is currently no methodology to select lean strategies that considers their impacts on manufacturing wastes and performance metrics simultaneously. In this research, a multi-objective methodology is proposed that suggests an appropriate set of lean initiatives based on their impacts on performance metrics and manufacturing wastes and within manufacturers’ resource limitation. The proposed methodology in this research suggests the best set of lean initiatives for implementation that have highest impacts on identified critical performance metrics and manufacturing wastes. Therefore, manufacturers can assure that implementing suggested lean tools improves their production performance and reduces manufacturing wastes at the same time. A case study was conducted to show the effectiveness and validate the proposed model and methodologies.

Keywords: lean manufacturing, lean strategies, manufacturing wastes, manufacturing performance, optimisation, decision making

Procedia PDF Downloads 187
6086 Evaluation of Naringenin Role in Inhibiton of Lung Tumor Progression in Mice

Authors: Vishnu Varthan Vaithiyalingamjagannathan, M. N. Sathishkumar, K. S. Lakhsmi, D. Satheeshkumar, Srividyaammayappanrajam

Abstract:

Background:Naringenin, aglycone flavonoid possess certain activities like anti-oxidant, anti-estrogenic, anti-diabetic, cardioprotective, anti-obesity,anti-inflammatory, hepatoprotective and also have anti-cancer characteristics like carcinogenic inactivation, cell cycle arrest, anti-proliferation, apoptosis, anti-angiogenesis and enhances anti-oxidant activity. Methodology:The inhibitory effect of Naringenin in lung tumor progression estimated with adenocarcinoma (A549) cell lines (in vitro) and C57BL/6 mice injected with 5 X 106A549 cell lines (in vivo) in a tri-dose manner (Naringenin 100mg/kg,150mg/kg, and 200mg/kg) compared with standard chemotherapy drug cisplatin (7mg/kg). Results:The results of the present study revealed a dose-dependent activity in Naringenin and combination with cisplatin at a higher dose which showed decreased tumor progression in mice. In vitro studies carried out for estimation of cell survival and Nitric Oxide (NO) level, shows dose dependent action of Naringenin with IC50 value of 42µg/ml. In vivo studies were carried out in C57BL/6 mice. Naringenin satisfied the condition of an anti-cancer molecule with its characteristics in fragmentation assay, Zymography assay, anti-oxidant, and myeloperoxidase studies, than cisplatin which failed in anti-oxidant and myeloperoxidase effect. Both in vitro and in vivo establishes dose dependent decrease in NO levels. But whereas, Naringenin showed adverse results in Matrix Metalloproteinase (MMP) enzymatic levels with increase in dose levels. Conclusion:From the present study, Naringenin could suppress the lung tumor progression when given individually and also in combinatorial with standard chemotherapy drug.

Keywords: naringenin, in vitro, cell line, anticancer

Procedia PDF Downloads 433
6085 Natural Bio-Active Product from Marine Resources

Authors: S. Ahmed John

Abstract:

Marine forms-bacteria, actinobacteria, cynobacteria, fungi, microalgae, seaweeds mangroves and other halophytes an extremely important oceanic resources and constituting over 90% of the oceanic biomass. The marine natural products have lead to the discovery of many compounds considered worthy for clinical applications. The marine sources have the highest probability of yielding natural products. Natural derivatives play an important role to prevent the cancer incidences as synthetic drug transformation in mangrove. 28.12% of anticancer compound extracted from the mangroves. Exchocaria agollocha has the anti cancer compounds. The present investigation reveals the potential of the Exchocaria agollocha with biotechnological applications for anti cancer, antimicrobial drug discovery, environmental remediation, and developing new resources for the industrial process. The anti-cancer activity of Exchocaria agollocha was screened from 3.906 to 1000 µg/ml of concentration with the dilution leads to 1:1 to 1:128 following methanol and chloroform extracts. The cell viability in the Exchocaria agollocha was maximum at the lower concentration where as low at the higher concentration of methanol and chloroform extracts when compare to control. At 3.906 concentration, 85.32 and 81.96 of cell viability was found at 1:128 dilution of methanol and chloroform extracts respectively. At the concentration of 31.25 following 1:16 dilution, the cell viability was 65.55 in methanol and 45.55 in chloroform extracts. However, at the higher concentration, the cell viability 22.35 and 8.12 was recorded in the extracts of methanol and chloroform. The cell viability was more in methanol when compare to chloroform extracts at lower concentration. The present findings gives current trends in screening and the activity analysis of metabolites from mangrove resources and to expose the models to bring a new sustain for tackling cancer. Bioactive compounds of Exchocaria agollocha have extensive use in treatment of many diseases and serve as a compound and templates for synthetic modification.

Keywords: bio-active product, compounds, natural products and microalgae

Procedia PDF Downloads 243
6084 Librarian Liaisons: Facilitating Multi-Disciplinary Research for Academic Advancement

Authors: Tracey Woods

Abstract:

In the ever-evolving landscape of academia, the traditional role of the librarian has undergone a remarkable transformation. Once considered as custodians of books and gatekeepers of information, librarians have the potential to take on the vital role of facilitators of cross and inter-disciplinary projects. This shift is driven by the growing recognition of the value of interdisciplinary collaboration in addressing complex research questions in pursuit of novel solutions to real-world problems. This paper shall explore the potential of the academic librarian’s role in facilitating innovative, multi-disciplinary projects, both recognising and validating the vital role that the librarian plays in a somewhat underplayed profession. Academic libraries support teaching, the strengthening of knowledge discourse, and, potentially, the development of innovative practices. As the role of the library gradually morphs from a quiet repository of books to a community-based information hub, a potential opportunity arises. The academic librarian’s role is to build knowledge across a wide span of topics, from the advancement of AI to subject-specific information, and, whilst librarians are generally not offered the research opportunities and funding that the traditional academic disciplines enjoy, they are often invited to help build research in support of the academic. This identifies that one of the primary skills of any 21st-century librarian must be the ability to collaborate and facilitate multi-disciplinary projects. In universities seeking to develop research diversity and academic performance, there is an increasing awareness of the need for collaboration between faculties to enable novel directions and advancements. This idea has been documented and discussed by several researchers; however, there is not a great deal of literature available from recent studies. Having a team based in the library that is adept at creating effective collaborative partnerships is valuable for any academic institution. This paper outlines the development of such a project, initiated within and around an identified library-specific need: the replication of fragile special collections for object-based learning. The research was developed as a multi-disciplinary project involving the faculties of engineering (digital twins lab), architecture, design, and education. Centred around methods for developing a fragile archive into a series of tactile objects furthers knowledge and understanding in both the role of the library as a facilitator of projects, chairing and supporting, alongside contributing to the research process and innovating ideas through the bank of knowledge found amongst the staff and their liaising capabilities. This paper shall present the method of project development from the initiation of ideas to the development of prototypes and dissemination of the objects to teaching departments for analysis. The exact replication of artefacts is also balanced with the adaptation and evolutionary speculations initiated by the design team when adapted as a teaching studio method. The dynamic response required from the library to generate and facilitate these multi-disciplinary projects highlights the information expertise and liaison skills that the librarian possesses. As academia embraces this evolution, the potential for groundbreaking discoveries and innovative solutions across disciplines becomes increasingly attainable.

Keywords: Liaison librarian, multi-disciplinary collaborations, library innovations, librarian stakeholders

Procedia PDF Downloads 61
6083 A Microwave and Millimeter-Wave Transmit/Receive Switch Subsystem for Communication Systems

Authors: Donghyun Lee, Cam Nguyen

Abstract:

Multi-band systems offer a great deal of benefit in modern communication and radar systems. In particular, multi-band antenna-array radar systems with their extended frequency diversity provide numerous advantages in detection, identification, locating and tracking a wide range of targets, including enhanced detection coverage, accurate target location, reduced survey time and cost, increased resolution, improved reliability and target information. An accurate calibration is a critical issue in antenna array systems. The amplitude and phase errors in multi-band and multi-polarization antenna array transceivers result in inaccurate target detection, deteriorated resolution and reduced reliability. Furthermore, the digital beam former without the RF domain phase-shifting is less immune to unfiltered interference signals, which can lead to receiver saturation in array systems. Therefore, implementing integrated front-end architecture, which can support calibration function with low insertion and filtering function from the farthest end of an array transceiver is of great interest. We report a dual K/Ka-band T/R/Calibration switch module with quasi-elliptic dual-bandpass filtering function implementing a Q-enhanced metamaterial transmission line. A unique dual-band frequency response is incorporated in the reception and calibration path of the proposed switch module utilizing the composite right/left-handed meta material transmission line coupled with a Colpitts-style negative generation circuit. The fabricated fully integrated T/R/Calibration switch module in 0.18-μm BiCMOS technology exhibits insertion loss of 4.9-12.3 dB and isolation of more than 45 dB in the reception, transmission and calibration mode of operation. In the reception and calibration mode, the dual-band frequency response centered at 24.5 and 35 GHz exhibits out-of-band rejection of more than 30 dB compared to the pass bands below 10.5 GHz and above 59.5 GHz. The rejection between the pass bands reaches more than 50 dB. In all modes of operation, the IP1-dB is between 4 and 11 dBm. Acknowledgement: This paper was made possible by NPRP grant # 6-241-2-102 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors.

Keywords: microwaves, millimeter waves, T/R switch, wireless communications, wireless communications

Procedia PDF Downloads 157
6082 Effect of Coronary Insulators in Increasing the Lifespan of Electrolytic Cells: Short-circuit and Heat Resistance

Authors: Robert P. Dufresne, Hamid Arabzadeh

Abstract:

The current study investigates the effectiveness of a new form of permanent baseboard insulators with an umbrella action, hereinafter referred to as Coronary Insulator, in supporting and protecting the assembly of electrodes immersed in an electrolytic cell and in increasing the lifespan of the lateral sides of the electrolytic cell, in both electro-winning and electro-refinery method. The advantages of using a coronary insulator in addition to the top capping board (equipotential insulator) were studied compared to the conventional assembly of an electrolytic cell. Then, a thermal imaging technique was utilized during high-temperature thermal (heat transfer) tests for sample cell walls with and without coronary insulators in their assembly to show the effectiveness of coronary insulators in protecting the cell wall under extreme conditions. It was shown that, unlike the conventional assembly, which is highly prone to damages to the cell wall under thermal shocks, the presence of coronary insulator can significantly increase the level of protection of the cell due to their ultra-high thermal and chemical resistance, as well as decreasing the replacement frequency of insulators to almost zero. Besides, the results of the study showed that the test assembly with the coronary insulator provides better consistency in positioning and, subsequently, better contact, compared to the conventional method, which reduces the chance of electric short-circuit in the system.

Keywords: capping board, coronary insulator, electrolytic cell, thermal shock.

Procedia PDF Downloads 185
6081 The Relationship between Vitamin D and Vitamin B12 Concentrations in Cataract Patients (Senile vs Diabetic)

Authors: Ali Showail Ali Alasmari

Abstract:

Introduction: Cataract is the loss of transparency of the lens inside the eye. It is the most common cause of visual loss and blindness worldwide. This study provides a systemic review of the recent findings on the association of vitamin D, and vitamin B12, and their possible role in preventing cataracts in senile (S) and diabetic mellitus (DM) patient groups. Objective: This study was intended to establish and investigate if there is any role between vitamin D and vitamin B12? Secondly, the connection between serum level of vitamin D and vitamin B12 in cataract incidence senile (s) vs. diabetic mellitus (DM) cataract patient groups. Furthermore, to evaluate and analyze cataract occurrence regarding vitamin D and vitamin B12 levels with other risk factors. Finally, to evaluate lens opacities pre and post treatment with vitamin D and vitaminB12 linked to age and visual acuity loss in both senile(S) and diabetic mellitus (DM) cataract patients’ groups. Methods: This study conducted at the ophthalmology clinic at Muhyail General Hospital. Select a prospective case-control to study the effect of vitamin D and Vit B12 on senile(S) cataracts that caused by age and diabetic mellitus (DM)cataract patients; then we compare these two groups. This study prospectively enrolled a total of 50 samples, 25 with senile cataract and 25 with diabetic cataract, from ophthalmology clinic at Muhyail General Hospital. Measuring 25-hydroxy vitamin D and vitamin B12 level concentrations in the assigned samples. Analyses were performed using SAS (statistical analysis software) program. Results: The most important finding in this study was that the senile(s) cataract patients’ group greatly benefited by the combination therapy of vitamin D, and Vitamin B12 reached (28.5±1.50 and 521.1±21.10) respectively; on the contrary, the diabetic cataract patient group hardly shows any significant improvement (21.5 ± 1.00 and 197.2 ± 7.20) respectively. This is because of the Metformin, the first line drug for treating diabetes, has been reported to potentially decrease vitamin B-12 status. This epigenetic modification was correlated with the diabetic mellitus (DM) cataract patients’ group not responding. Vitamin B12 deficiency also leads to an impairment of the conversion of methylmalonyl-CoA to succinyl-CoA, which has been associated with insulin resistance. There was no significant difference between the age, body mass index (BMI), the mean of Vit-D pre-treatments, and the mean values of Hemoglobin A1C of both senile (S) and diabetic mellitus (DM) cataract patient groups. On other hand, there was a highly significant difference between the mean values of glucose levels in both senile (S) and diabetic mellitus (DM) cataract patient groups. Conclusion: Here we conclude that diabetic mellitus (DM) cataract patient group hardly benefited from this combination therapy vitamin D and vitamin B12; on the other hand senile patient group (s) benefited a lot from the therapy.

Keywords: cataract patients, senile, diabetes mellitus, vitamin B12, vitamin D, Muhyail General Hospital, Saudi Arabia

Procedia PDF Downloads 98
6080 Between Ralph Waldo Emerson and the Dying Infidel

Authors: Michael Keller

Abstract:

Beyond the heterodoxy expressed in his now-famous 1838 address to the Harvard Divinity School, Emerson’s timing was particularly dangerous. Ideologically, New England faced a severe crisis of identity, as traditional categories of class and religion were growing increasingly unstable. Jones Very, influenced by Emerson, crossed the perceived border between acceptable religious zeal and insane enthusiasm. Abner Kneeland, on the other hand, crossed the uncomfortable border between post-Puritan Unitarian rationalism and blasphemous Enlightenment skepticism. More importantly, Kneeland oversaw a more overtly subversive brand of resistance (in the form of freethought periodicals) that not only threatened religious orthodoxy but also threatened to destabilize the class structure of New England. Very and Kneeland provide instructive case studies of how religious ideologies could run afoul of the social contract and the law itself. By looking closely at the social and religious forces that led to Kneeland’s prosecution for blasphemy, Jones Very’s forced committal to McLean Asylum, and Emerson’s escape from these fates, we gain a greater understanding of the shifting cultural landscape of 1830s New England. This paper will examine Emerson’s resistance to the traditional forces of class and ideology in Massachusetts by situating his early work in the context of the ideological battles of his time. More specifically, I will explore how Emerson was able to resist the conservative cultural forces of his time without experiencing the extremity of their wrath.

Keywords: American literature, cultural studies, emerson, religious studies

Procedia PDF Downloads 137
6079 Fuzzy Multi-Criteria Decision-Making Based on Ignatian Discernment Process

Authors: Pathinathan Theresanathan, Ajay Minj

Abstract:

Ignatian Discernment Process (IDP) is an intense decision-making tool to decide on life-issues. Decisions are influenced by various factors outside of the decision maker and inclination within. This paper develops IDP in the context of Fuzzy Multi-criteria Decision Making (FMCDM) process. Extended VIKOR method is a decision-making method which encompasses even conflict situations and accommodates weightage to various issues. Various aspects of IDP, namely three ways of decision making and tactics of inner desires, are observed, analyzed and articulated within the frame work of fuzzy rules. The decision-making situations are broadly categorized into two types. The issues outside of the decision maker influence the person. The inner feeling also plays vital role in coming to a conclusion. IDP integrates both the categories using Extended VIKOR method. Case studies are carried out and analyzed with FMCDM process. Finally, IDP is verified with an illustrative case study and results are interpreted. A confused person who could not come to a conclusion is able to take decision on a concrete way of life through IDP. The proposed IDP model recommends an integrated and committed approach to value-based decision making.

Keywords: AHP, FMCDM, IDP, ignatian discernment, MCDM, VIKOR

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6078 Mechanical, Physical and Durability Properties of Cement Mortars Added with Recycled PP/PE-Based Food Packaging Waste Material

Authors: Livia Guerini, Christian Paglia

Abstract:

In Switzerland, only a fraction of plastic waste from food packaging is collected and recycled for further use in the food industry. Therefore, reusing these waste plastics for building applications can be an attractive alternative to disposal in order to reduce the problem of waste management and to make up for the depletion of raw materials needed for construction. In this study, experiments were conducted on the mechanical properties (compressive and flexural strength, elastic modulus), physical properties (density, workability, porosity, and water permeability) and durability (freeze/thaw resistance) of cementitious mortars with additions of recycled low-/high-density polyethylene (LDPE/HDPE)/ polypropylene (PP) regrind (addition of 5% and 10% by weight) and LDPE sheets (addition of 0.5% and 1.5% by weight) coming from food packaging. The results show that as the addition of plastic material increases, the density and mechanical properties of the mortars decrease compared to conventional ones. Porosity is similar in all the mixtures made, while the workability and the permeability are affected not only by the amount added but also by the shape of the plastic aggregate. Freeze/thaw resistance, on the other hand, is significantly higher in mortars with plastic aggregates than in traditional mortar. This feature may be interesting for the realization of outdoor mortars in cold environments.

Keywords: food packaging waste, durability properties, mechanical properties, mortar, recycled PE, recycled PP

Procedia PDF Downloads 139
6077 Dynamic Simulation for Surface Wear Prognosis of the Main Bearings in the Internal Combustion Engine

Authors: Yanyan Zhang, Ziyu Diao, Zhentao Liu, Ruidong Yan

Abstract:

The wear character of the main bearing is one of the critical indicators for the overhaul of an internal combustion engine, and the aim of this paper is to reveal the dynamic wear mechanism of the main bearings. A numerical simulation model combined multi-body dynamic equations of the engine, the average Reynolds equations of the bearing lubricant, asperity contact and wear model of the joint surfaces were established under typical operating conditions. The wear results were verified by experimental data, and then the influence of operating conditions, bearing clearance and cylinder pressure on the wear character of selected main bearings were analyzed. The results show that the contribution degree of different working conditions on the wear profile and depth of each bearing is obviously different, and the increase of joint clearance or cylinder pressure will accelerate the wear. The numerical model presented can be used to wear prognosis for joints and provide guidance for optimization design of sliding bearings.

Keywords: dynamic simulation, multi-body dynamics, sliding bearing, surface wear

Procedia PDF Downloads 141
6076 Performance of Coded Multi-Line Copper Wire for G.fast Communications in the Presence of Impulsive Noise

Authors: Israa Al-Neami, Ali J. Al-Askery, Martin Johnston, Charalampos Tsimenidis

Abstract:

In this paper, we focus on the design of a multi-line copper wire (MLCW) communication system. First, we construct our proposed MLCW channel and verify its characteristics based on the Kolmogorov-Smirnov test. In addition, we apply Middleton class A impulsive noise (IN) to the copper channel for further investigation. Second, the MIMO G.fast system is adopted utilizing the proposed MLCW channel model and is compared to a single line G-fast system. Second, the performance of the coded system is obtained utilizing concatenated interleaved Reed-Solomon (RS) code with four-dimensional trellis-coded modulation (4D TCM), and compared to the single line G-fast system. Simulations are obtained for high quadrature amplitude modulation (QAM) constellations that are commonly used with G-fast communications, the results demonstrate that the bit error rate (BER) performance of the coded MLCW system shows an improvement compared to the single line G-fast systems.

Keywords: G.fast, Middleton Class A impulsive noise, mitigation techniques, Copper channel model

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6075 Optimization of SWL Algorithms Using Alternative Adder Module in FPGA

Authors: Tayab D. Memon, Shahji Farooque, Marvi Deshi, Imtiaz Hussain Kalwar, B. S. Chowdhry

Abstract:

Recently single-bit ternary FIR-like filter (SBTFF) hardware synthesize in FPGA is reported and compared with multi-bit FIR filter on similar spectral characteristics. Results shows that SBTFF dominates upon multi-bit filter overall. In this paper, an optimized adder module for ternary quantized sigma-delta modulated signal is presented. The adder is simulated using ModelSim for functional verification the area-performance of the proposed adder were obtained through synthesis in Xilinx and compared to conventional adder trees. The synthesis results show that the proposed adder tree achieves higher clock rates and lower chip area at higher inputs to the adder block; whereas conventional adder tree achieves better performance and lower chip area at lower number of inputs to the same adder block. These results enhance the usefulness of existing short word length DSP algorithms for fast and efficient mobile communication.

Keywords: short word length (SWL), DSP algorithms, FPGA, SBTFF, VHDL

Procedia PDF Downloads 341
6074 A Prospective Study on the Evaluation of Statins Usage on HbA1c Control among Type 2 Diabetes Mellitus in an Outpatients Setting

Authors: Mohamed A. Hammad, Dzul Azri Mohamed Noor, Syed Azhar Syed Sulaiman, Abeer Kharshid, Nor Azizah Aziz, Tarek M. Elsayed

Abstract:

Medication safety is always an issue. In 2015, the National Pharmaceutical Control Bureau released a statement requesting all statins manufacturers in Malaysia to include the risk of diabetes information in the drug information leaflet in response to United States Food and Drug Administration (U.S. FDA) report. However, the data regarding this warning label in Malaysia is limited, so there is still some uncertainty whether such risk can also be observed in the Malaysian population or not. The study aims to determine the effect of statins on HbA1c% in type 2 diabetic outpatients in endocrine clinics at Hospital Pulau Pinang between June 2015 and May 2016 in Malaysia. In a prospective cohort study, records of 400 type 2 diabetic patients (control group 104 patients not using statin and treatment group 296 patients using statin) were reviewed to identify demographic criteria and lab tests. The prevalence of glycemic control (Glycated hemoglobin, HbA1C ≤ 7% for patient < 65 years, and < 8% for patient ≥ 65 years) was estimated, according to American Diabetes Association guidelines 2015. The results were presented as descriptive statistics. From 296 patients with Type 2 diabetes using statins cohort with a mean age of 57.52 ± 12.2 years, only 81 (27.4%) cases had controlled glycemia, and 215 (72.6%) had uncontrolled glycemia, CI: 95% (6.3–11.1). While the control group 104 diabetic patients had a mean age 46.1 ± 18 years and distributed among 59 (56.7%) patients with controlled diabetes and 45 (43.3%) cases, had uncontrolled glycemia, CI: 95% (5.2–10.3). The relative risk (RR) of uncontrolled glycemia in diabetic patients used statins was 1.68, and the excessive relative risk (ERR) was 68%. The absolute risk (AR) was 29.3%, and the number needed to harm (NNH) was 4. Diabetic patients using statins have more risk of uncontrolled glycemia than the patients with Type 2 diabetes non-using statins.

Keywords: diabetes mellitus, HbA1c, Malaysia, outpatients, statin, type 2, uncontrolled glycemia

Procedia PDF Downloads 277
6073 Aspirin Loaded Poly-L-Lactic Acid Nanofibers and Their Potentials as Small Diameter Vascular Grafts

Authors: Mahboubeh Kabiri, Saba Aslani

Abstract:

Among various approaches used for the treatment of cardiovascular diseases, the occlusion of the small-diameter vascular graft (SDVG) is still an unresolved problem which seeks further research to address them. Though autografts are now the gold standards to be replaced for blocked coronary arteries, they suffer from inadequate quality and quantity. On the other hand, the major problems of the tissue engineered grafts are thrombosis and intimal hyperplasia. Provision of a suitable spatiotemporal release pattern of anticoagulant agents such as heparin and aspirin can be a step forward to overcome such issues . Herein, we fabricated electrospun scaffolds from FDA (Food and Drug Administration) approved poly-L-lactic acid (PLLA) with aspirin loaded into the nanofibers. Also, we surface coated the scaffolds with Amniotic Membrane lysate as a source for natural elastic polymers and a mimic of endothelial basement membrane. The scaffolds were characterized thoroughly structurally and mechanically for their morphology, fiber orientation, tensile strength, hydrophilicity, cytotoxicity, aspirin release and cell attachment support. According to the scanning electron microscopy (SEM) images, the size of fibers ranged from 250 to 500 nm. The scaffolds showed appropriate tensile strength expected for vascular grafts. Cellular attachment, growth, and infiltration were proved using SEM and MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. Drug-loaded scaffolds showed a sustained release profile of aspirin in 7 days. An enhanced cytocompatibility was observed in AM-coated electrospun PLLA fibers compared to uncoated scaffolds. Our results together indicated that AM lysate coated ASA releasing scaffolds have promising potentials for development of a biocompatible SDVG.

Keywords: vascular tissue engineering, vascular grafts, anticoagulant agent, aspirin, amniotic membrane

Procedia PDF Downloads 158
6072 Thermal Property of Multi-Walled-Carbon-Nanotube Reinforced Epoxy Composites

Authors: Min Ye Koo, Gyo Woo Lee

Abstract:

In this study, epoxy composite specimens reinforced with multi-walled carbon nanotube filler were fabricated using shear mixer and ultra-sonication processor. The mechanical and thermal properties of the fabricated specimens were measured and evaluated. From the electron microscope images and the results from the measurements of tensile strengths, the specimens having 0.6 wt% nanotube content show better dispersion and higher strength than those of the other specimens. The Young’s moduli of the specimens increased as the contents of the nanotube filler in the matrix were increased. The specimen having a 0.6 wt% nanotube filler content showed higher thermal conductivity than that of the other specimens. While, in the measurement of thermal expansion, specimens having 0.4 and 0.6 wt% filler contents showed a lower value of thermal expansion than that of the other specimens. On the basis of the measured and evaluated properties of the composites, we believe that the simple and time-saving fabrication process used in this study was sufficient to obtain improved properties of the specimens.

Keywords: carbon nanotube filler, epoxy composite, ultra-sonication, shear mixer, mechanical property, thermal property

Procedia PDF Downloads 363
6071 Ethics and Military Defections in Nonviolent Resistance Campaigns

Authors: Adi Levy

Abstract:

Military and security personnel defections during nonviolent resistance (NVR) campaigns are recognized as an effective way of undermining the regime’s power, but they also may generate moral dilemmas that contradict the moral standing of NVR tactics. NVR campaigns have been primarily praised for their adherence to moral and legal norms, yet some of NVR tactics raise serious ethical concerns. This paper focuses on NVR tactics that seek to promote defections and disobedience within military and security personnel to sustain their campaign. Academic literature regarding NVR tactics indicates that compared to violent forms of resistance, defections are more likely to occur when security forces confront nonviolent activists. Indeed, defections play a strategically fundamental role in nonviolent campaigns, particularly against authoritarian regimes, as it enables activists to undermine the regime’s central pillars of support. This study examines the events of the Arab Spring and discusses the ethical problems that arise in nonviolent activists’ promotion of defections and disobedience. The cases of Syria and Egypt suggest that the strategic promotion of defections and disobedience was significantly effective in sustaining the campaign. Yet, while such defections enhance nonviolent activists’ resilience, how they are promoted can be morally contentious and the consequences can be dire. Defections are encouraged by social, moral and emotional appeals that use the power disparities between unarmed civilians and powerful regimes to affect soldiers and security personnel’s process of decision-making. In what is commonly referred to as dilemma action, nonviolent activists deliberately entangle security forces in a moral dilemma that compels them to follow a moral code to protect unarmed civilians. In this way, activists sustain their struggle and even gain protection. Nonviolent activists are likely to be completely defeated when confronted with armed forces. Therefore they rely on the military and security personnel’s moral conscious of convincing them to refrain from using force against them. While this is effective, it also leaves soldiers and security forces exposed to the implications and punishments that might follow their disobedience or defection. As long as they remain nonviolent, activists enjoy civilian immunity despite using morally contentious tactics. But the severe implications brought upon defectors. As a result, demand a deep examination of this tactic’s moral permissibility and a discussion that assesses culpability for the moral implications of its application.

Keywords: culpability, defections, nonviolence, permissibility

Procedia PDF Downloads 108
6070 Micro-Arc Oxidation Titanium and Post Treatment by Cold Plasma and Graft Polymerization of Acrylic Acid for Biomedical Application

Authors: Shu-Chuan Liao, Chia-Ti Chang, Ko-Shao Chen

Abstract:

Titanium and its alloy are widely used in many fields such as dentistry or orthopaedics. Due to their high strength low elastic modulus that chemical inertness and bio inert. The micro-arc oxidation used to formation a micro porous ceramic oxide layer film on Titanium surface and also to improve the resistance corrosion. For improving the biocompatibility, micro-arc oxidation surfaces bio-inert need to introduce reactive group. We introduced boundary layer by used plasma enhanced chemical vapor deposition of hexamethyldisilazane (HMDS) and organic active layer by UV light graft reactive monomer acrylic acid (AAc) therefore we can immobilize Chondroitin sulphate on surface easily by crosslinking EDC/NHS. The surface properties and composition of the modified layer were measured by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) and water contact angle. Water contact angle of the plasma-treated Ti surface decreases from 60° to 38°, which is an indication of hydrophilicity. The results of electrochemical polarization analysis showed that the sample plasma treated at micro-arc oxidation after plasma treatment has the best corrosion resistance. The result showed that we can immobilize chondroitin sulfate successful by a series of modification and MTT assay indicated the biocompatibility has been improved in this study.

Keywords: MAO, plasma, graft polymerization, biomedical application

Procedia PDF Downloads 255
6069 Research on the Evaluation and Delineation of Value Units of New Industrial Parks Based on Implementation-Orientation

Authors: Chengfang Wang, Zichao Wu, Jianying Zhou

Abstract:

At present, much attention is paid to the development of new industrial parks in the era of inventory planning. Generally speaking, there are two types of development models: incremental development models and stock development models. The former relies on key projects to build a value innovation park, and the latter relies on the iterative update of the park to build a value innovation park. Take the Baiyun Western Digital Park as an example, considering the growth model of value units, determine the evaluation target. Based on a GIS platform, comprehensive land-use status, regulatory detailed planning, land use planning, blue-green ecological base, rail transit system, road network system, industrial park distribution, public service facilities, and other factors are used to carry out the land use within the planning multi-factor superimposed comprehensive evaluation, constructing a value unit evaluation system, and delineating value units based on implementation orientation and combining two different development models. The research hopes to provide a reference for the planning and construction of new domestic industrial parks.

Keywords: value units, GIS, multi-factor evaluation, implementation orientation

Procedia PDF Downloads 183
6068 Switching Studies on Ge15In5Te56Ag24 Thin Films

Authors: Diptoshi Roy, G. Sreevidya Varma, S. Asokan, Chandasree Das

Abstract:

Germanium Telluride based quaternary thin film switching devices with composition Ge15In5Te56Ag24, have been deposited in sandwich geometry on glass substrate with aluminum as top and bottom electrodes. The bulk glassy form of the said composition is prepared by melt quenching technique. In this technique, appropriate quantity of elements with high purity are taken in a quartz ampoule and sealed under a vacuum of 10-5 mbar. Then, it is allowed to rotate in a horizontal rotary furnace for 36 hours to ensure homogeneity of the melt. After that, the ampoule is quenched into a mixture of ice - water and NaOH to get the bulk ingot of the sample. The sample is then coated on a glass substrate using flash evaporation technique at a vacuum level of 10-6 mbar. The XRD report reveals the amorphous nature of the thin film sample and Energy - Dispersive X-ray Analysis (EDAX) confirms that the film retains the same chemical composition as that of the base sample. Electrical switching behavior of the device is studied with the help of Keithley (2410c) source-measure unit interfaced with Lab VIEW 7 (National Instruments). Switching studies, mainly SET (changing the state of the material from amorphous to crystalline) operation is conducted on the thin film form of the sample. This device is found to manifest memory switching as the device remains 'ON' even after the removal of the electric field. Also it is found that amorphous Ge15In5Te56Ag24 thin film unveils clean memory type of electrical switching behavior which can be justified by the absence of fluctuation in the I-V characteristics. The I-V characteristic also reveals that the switching is faster in this sample as no data points could be seen in the negative resistance region during the transition to on state and this leads to the conclusion of fast phase change during SET process. Scanning Electron Microscopy (SEM) studies are performed on the chosen sample to study the structural changes at the time of switching. SEM studies on the switched Ge15In5Te56Ag24 sample has shown some morphological changes at the place of switching wherein it can be explained that a conducting crystalline channel is formed in the device when the device switches from high resistance to low resistance state. From these studies it can be concluded that the material may find its application in fast switching Non-Volatile Phase Change Memory (PCM) Devices.

Keywords: Chalcogenides, Vapor deposition, Electrical switching, PCM.

Procedia PDF Downloads 373
6067 Relevance of Dosing Time for Everolimus Toxicity in Respect to the Circadian P-Glycoprotein Expression in Mdr1a::Luc Mice

Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

Abstract:

P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

Procedia PDF Downloads 339