Search results for: Irreversibility line
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2657

Search results for: Irreversibility line

2147 Apoptosis Pathway Targeted by Thymoquinone in MCF7 Breast Cancer Cell Line

Authors: M. Marjaneh, M. Y. Narazah, H. Shahrul

Abstract:

Array-based gene expression analysis is a powerful tool to profile expression of genes and to generate information on therapeutic effects of new anti-cancer compounds. Anti-apoptotic effect of thymoquinone was studied in MCF7 breast cancer cell line using gene expression profiling with cDNA micro array. The purity and yield of RNA samples were determined using RNeasyPlus Mini kit. The Agilent RNA 6000 Nano LabChip kit evaluated the quantity of the RNA samples. AffinityScript RT oligo-dT promoter primer was used to generate cDNA strands. T7 RNA polymerase was used to convert cDNA to cRNA. The cRNA samples and human universal reference RNA were labelled with Cy-3-CTP and Cy-5-CTP, respectively. Feature Extraction and GeneSpring software analysed the data. The single experiment analysis revealed involvement of 64 pathways with up-regulated genes and 78 pathways with down-regulated genes. The MAPK and p38-MAPK pathways were inhibited due to the up-regulation of PTPRR gene. The inhibition of p38-MAPK suggested up-regulation of TGF-ß pathway. Inhibition of p38 - MAPK caused up-regulation of TP53 and down-regulation of Bcl2 genes indicating involvement of intrinsic apoptotic pathway. Down-regulation of CARD16 gene as an adaptor molecule regulated CASP1 and suggested necrosis-like programmed cell death and involvement of caspase in apoptosis. Furthermore, down-regulation of GPCR, EGF-EGFR signalling pathways suggested reduction of ER. Involvement of AhR pathway which control cytochrome P450 and glucuronidation pathways showed metabolism of Thymoquinone. The findings showed differential expression of several genes in apoptosis pathways with thymoquinone treatment in estrogen receptor-positive breast cancer cells.

Keywords: cDNA microarray, thymoquinone, CARD16, PTPRR, CASP10

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2146 Secondary Charged Fragments Tracking for On-Line Beam Range Monitoring in Particle Therapy

Authors: G. Traini, G. Battistoni, F. Collamati, E. De Lucia, R. Faccini, C. Mancini-Terracciano, M. Marafini, I. Mattei, S. Muraro, A. Sarti, A. Sciubba, E. Solfaroli Camillocci, M. Toppi, S. M. Valle, C. Voena, V. Patera

Abstract:

In Particle Therapy (PT) treatments a large amount of secondary particles, whose emission point is correlated to the dose released in the crossed tissues, is produced. The measurement of the secondary charged fragments component could represent a valid technique to monitor the beam range during the PT treatments, that is a still missing item in the clinical practice. A sub-millimetrical precision on the beam range measurement is required to significantly optimise the technique and to improve the treatment quality. In this contribution, a detector, named Dose Profiler (DP), is presented. It is specifically planned to monitor on-line the beam range exploiting the secondary charged particles produced in PT Carbon ions treatment. In particular, the DP is designed to track the secondary fragments emitted at large angles with respect to the beam direction (mainly protons), with the aim to reconstruct the spatial coordinates of the fragment emission point extrapolating the measured track toward the beam axis. The DP is currently under development within of the INSIDE collaboration (Innovative Solutions for In-beam Dosimetry in hadrontherapy). The tracker is made by six layers (20 × 20 cm²) of BCF-12 square scintillating fibres (500 μm) coupled to Silicon Photo-Multipliers, followed by two plastic scintillator layers of 6 mm thickness. A system of front-end boards based on FPGAs arranged around the detector provides the data acquisition. The detector characterization with cosmic rays is currently undergoing, and a data taking campaign with protons will take place in May 2017. The DP design and the performances measured with using MIPs and protons beam will be reviewed.

Keywords: fragmentation, monitoring, particle therapy, tracking

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2145 Proposed Algorithms to Assess Concussion Potential in Rear-End Motor Vehicle Collisions: A Meta-Analysis

Authors: Rami Hashish, Manon Limousis-Gayda, Caitlin McCleery

Abstract:

Introduction: Mild traumatic brain injuries, also referred to as concussions, represent an increasing burden to society. Due to limited objective diagnostic measures, concussions are diagnosed by assessing subjective symptoms, often leading to disputes to their presence. Common biomechanical measures associated with concussion are high linear and/or angular acceleration to the head. With regards to linear acceleration, approximately 80g’s has previously been shown to equate with a 50% probability of concussion. Motor vehicle collisions (MVCs) are a leading cause of concussion, due to high head accelerations experienced. The change in velocity (delta-V) of a vehicle in an MVC is an established metric for impact severity. As acceleration is the rate of delta-V with respect to time, the purpose of this paper is to determine the relation between delta-V (and occupant parameters) with linear head acceleration. Methods: A meta-analysis was conducted for manuscripts collected using the following keywords: head acceleration, concussion, brain injury, head kinematics, delta-V, change in velocity, motor vehicle collision, and rear-end. Ultimately, 280 studies were surveyed, 14 of which fulfilled the inclusion criteria as studies investigating the human response to impacts, reporting head acceleration, and delta-V of the occupant’s vehicle. Statistical analysis was conducted with SPSS and R. The best fit line analysis allowed for an initial understanding of the relation between head acceleration and delta-V. To further investigate the effect of occupant parameters on head acceleration, a quadratic model and a full linear mixed model was developed. Results: From the 14 selected studies, 139 crashes were analyzed with head accelerations and delta-V values ranging from 0.6 to 17.2g and 1.3 to 11.1 km/h, respectively. Initial analysis indicated that the best line of fit (Model 1) was defined as Head Acceleration = 0.465

Keywords: acceleration, brain injury, change in velocity, Delta-V, TBI

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2144 On-Line Super Critical Fluid Extraction, Supercritical Fluid Chromatography, Mass Spectrometry, a Technique in Pharmaceutical Analysis

Authors: Narayana Murthy Akurathi, Vijaya Lakshmi Marella

Abstract:

The literature is reviewed with regard to online Super critical fluid extraction (SFE) coupled directly with supercritical fluid chromatography (SFC) -mass spectrometry that have typically more sensitive than conventional LC-MS/MS and GC-MS/MS. It is becoming increasingly interesting to use on-line techniques that combine sample preparation, separation and detection in one analytical set up. This provides less human intervention, uses small amount of sample and organic solvent and yields enhanced analyte enrichment in a shorter time. The sample extraction is performed under light shielding and anaerobic conditions, preventing the degradation of thermo labile analytes. It may be able to analyze compounds over a wide polarity range as SFC generally uses carbon dioxide which was collected as a by-product of other chemical reactions or is collected from the atmosphere as it contributes no new chemicals to the environment. The diffusion of solutes in supercritical fluids is about ten times greater than that in liquids and about three times less than in gases which results in a decrease in resistance to mass transfer in the column and allows for fast high resolution separations. The drawback of SFC when using carbon dioxide as mobile phase is that the direct introduction of water samples poses a series of problems, water must therefore be eliminated before it reaches the analytical column. Hundreds of compounds analysed simultaneously by simple enclosing in an extraction vessel. This is mainly applicable for pharmaceutical industry where it can analyse fatty acids and phospholipids that have many analogues as their UV spectrum is very similar, trace additives in polymers, cleaning validation can be conducted by putting swab sample in an extraction vessel, analysing hundreds of pesticides with good resolution.

Keywords: super critical fluid extraction (SFE), super critical fluid chromatography (SFC), LCMS/MS, GCMS/MS

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2143 Effects of Tenefovir Disiproxil Fumarate on the Renal Sufficiency of HIV Positive Patients

Authors: Londeka Ntuli, Frasia Oosthuizen

Abstract:

Background: Tenefovir disiproxil fumarate (TDF) is a nephrotoxic drug and has been proven to contribute to renal insufficiency necessitating intensive monitoring and management of adverse effects arising from prolonged exposure to the drug. TDF is one of the preferred first-line drugs used in combination therapy in most regions. There are estimated 300 000 patients being initiated on the Efavirenz/TDF/Emtricitabine first-line regimen annually in South Africa. It is against this background that this study aims to investigate the effects of TDF on renal sufficiency of HIV positive patients. Methodology: A retrospective quantitative study was conducted, analysing clinical charts of HIV positive patient’s older than 18 years of age and on a TDF-containing regimen for more than 1 year. Data were obtained from the analysis of patient files and was transcribed into Microsoft® Excel® spreadsheet. Extracted data were coded, categorised and analysed using STATA®. Results: A total of 275 patient files were included in this study. Renal function started decreasing after 3 months of treatment (with 93.5% patients having a normal EGFR), and kept on decreasing as time progressed with only 39.6% normal renal function at year 4. Additional risk factors for renal insufficiency included age below 25, female gender, and additional medication. Conclusion: It is clear from this study that the use of TDF necessitates intensive monitoring and management of adverse effects arising from prolonged exposure to the drug. The findings from this study generated pertinent information on the safety profile of the drug TDF in a resource-limited setting of a public health institution. The appropriate management is of tremendous importance in the South African context where the majority of HIV positive individuals are on the TDF containing regimen; thus it is beneficial to ascertain the possible level of toxicities these patients may be experiencing.

Keywords: renal insufficiency, tenefovir, HIV, risk factors

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2142 Hedgerow Detection and Characterization Using Very High Spatial Resolution SAR DATA

Authors: Saeid Gharechelou, Stuart Green, Fiona Cawkwell

Abstract:

Hedgerow has an important role for a wide range of ecological habitats, landscape, agriculture management, carbon sequestration, wood production. Hedgerow detection accurately using satellite imagery is a challenging problem in remote sensing techniques, because in the special approach it is very similar to line object like a road, from a spectral viewpoint, a hedge is very similar to a forest. Remote sensors with very high spatial resolution (VHR) recently enable the automatic detection of hedges by the acquisition of images with enough spectral and spatial resolution. Indeed, recently VHR remote sensing data provided the opportunity to detect the hedgerow as line feature but still remain difficulties in monitoring the characterization in landscape scale. In this research is used the TerraSAR-x Spotlight and Staring mode with 3-5 m resolution in wet and dry season in the test site of Fermoy County, Ireland to detect the hedgerow by acquisition time of 2014-2015. Both dual polarization of Spotlight data in HH/VV is using for detection of hedgerow. The varied method of SAR image technique with try and error way by integration of classification algorithm like texture analysis, support vector machine, k-means and random forest are using to detect hedgerow and its characterization. We are applying the Shannon entropy (ShE) and backscattering analysis in single and double bounce in polarimetric analysis for processing the object-oriented classification and finally extracting the hedgerow network. The result still is in progress and need to apply the other method as well to find the best method in study area. Finally, this research is under way to ahead to get the best result and here just present the preliminary work that polarimetric image of TSX potentially can detect the hedgerow.

Keywords: TerraSAR-X, hedgerow detection, high resolution SAR image, dual polarization, polarimetric analysis

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2141 Effects of Aerodynamic on Suspended Cables Using Non-Linear Finite Element Approach

Authors: Justin Nwabanne, Sam Omenyi, Jeremiah Chukwuneke

Abstract:

This work presents structural nonlinear static analysis of a horizontal taut cable using Finite Element Analysis (FEA) method. The FEA was performed analytically to determine the tensions at each nodal point and subsequently, performed based on finite element displacement method computationally using the FEA software, ANSYS 14.0 to determine their behaviour under the influence of aerodynamic forces imposed on the cable. The convergence procedure is adapted into the method to prevent excessive displacements through the computations. The work compared the two FEA cases by examining the effectiveness of the analytical model in describing the response with few degrees of freedom and the ability of the nonlinear finite element procedure adopted to capture the complex features of cable dynamics with reference to the aerodynamic external influence. Results obtained from this work explain that the analytic FEM results without aerodynamic influence show a parabolic response with an optimum deflection at nodal points 12 and 13 with the cable weight at nodes 12 and 13 having the value -1.002936N while for the cable tension shows an optimum deflection value for nodes 12 and 13 at -189396.97kg/km. The maximum displacement for the cable system was obtained from ANSYS 14.0 as 4483.83 mm for X, Y and Z components of displacements at node number 2 while the maximum displacement obtained is 4218.75mm for all the directional components. The dynamic behaviour of a taut cable investigated has application in a typical power transmission line. Aerodynamic influences on the cables were considered using FEA approach by employing ANSYS 14.0 showed a complex modal behaviour as expected.

Keywords: aerodynamics, cable tension and weight, finite element analysis, nodal, non-linear model, optimum deflection, suspended cable, transmission line

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2140 A High Amylose-Content and High-Yielding Elite Line Is Favorable to Cook 'Nanhan' (Semi-Soft Rice) for Nursing Care Food Particularly for Serving Aged Persons

Authors: M. Kamimukai, M. Bhattarai, B. B. Rana, K. Maeda, H. B. Kc, T. Kawano, M. Murai

Abstract:

Most of the aged people older than 70 have difficulty in chewing and swallowing more or less. According to magnitude of this difficulty, gruel, “nanhan” (semi-soft rice) and ordinary cooked rice are served in general, particularly in sanatoriums and homes for old people in Japan. Nanhan is the name of a cooked rice used in Japan, having softness intermediate between gruel and ordinary cooked rice, which is boiled with intermediate amount of water between those of the latter two kinds of cooked rice. In the present study, nanhan was made in the rate of 240g of water to 100g of milled rice with an electric rice cooker. Murai developed a high amylose-content and high-yielding elite line ‘Murai 79’. Sensory eating-quality test was performed for nanhan and ordinary cooked rice of Murai 79 and the standard variety ‘Hinohikari’ which is a high eating-quality variety representative in southern Japan. Panelists (6 to 14 persons) scored each cooked rice in six items viz. taste, stickiness, hardness, flavor, external appearance and overall evaluation. Grading (-3 ~ +3) in each trait was performed, regarding the value of the standard variety Hinohikari as 0. Paddy rice produced in a farmer’s field in 2013 and 2014 and in an experimental field of Kochi University in 2015 and 2016 were used for the sensory test. According to results of the sensory eating-quality test for nanhan, Murai 79 is higher in overall evaluation than Hinohikari in the four years. The former was less sticky than the latter in the four years, but the former was statistically significantly harder than the latter throughout the four years. In external appearance, the former was significantly higher than the latter in the four years. In the taste, the former was significantly higher than the latter in 2014, but significant difference was not noticed between them in the other three years. There were no significant differences throughout the four years in flavor. Regarding amylose content, Murai 79 is higher by 3.7 and 5.7% than Hinohikari in 2015 and 2016, respectively. As for protein content, Murai 79 was higher than Hinohikari in 2015, but the former was lower than the latter in 2016. Consequently, the nanhan of Murai 79 was harder and less sticky, keeping the shape of grains as compared with that of Hinohikari, which may be due to its higher amylose content. Hence, the nanhan of Murai 79 may be recognized as grains more easily in a human mouth, which could make easier the continuous performance of mastication and deglutition particularly in aged persons. Regarding ordinary cooked rice, Murai 79 was similar to or higher in both overall evaluation and external appearance as compared with Hinohikari, despite its higher hardness and lower stickiness. Additionally, Murai 79 had brown-rice yield of 1.55 times as compared with Hinohikari, suggesting that it would enable to supply inexpensive rice for making nanhan with high quality particularly for aged people in Japan.

Keywords: high-amylose content, high-yielding rice line, nanhan, nursing care food, sensory eating quality test

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2139 Bowing of a Pipeline from Longitudinal Compressive Stress Induced by Ground Movement

Authors: Gennaro Marino

Abstract:

This paper concerns a case of a 10.75 inch diameter buried gas transmission line which was exposed to mine subsidence ground movements. The pipeline was buried about 4ft. below the surface with maximum operating pressure of 1440 psi. The mine subsidence movement was the result of long walling ore at a depth of approximately 1600 ft. As ore extraction progressed, the stress in the monitored pipeline worsened and was approaching unacceptable levels. The excessive pipe compression resulted when it was exposed to the compression zone of subsidence basin created by mining. The pipe stress reached a significant compressive level due to the extensive length of the pipe exposed to frictional ground-pipe slip resistance. The backfill ground movement slip resistance depends on normal stress around the pipe, the rate of slip, and the backfill characteristics. Normal stress depends on the burial depth of the backfill density and the lateral subsidence induced stress. The backfill in this site has a soil dry density of approximately 90 PCF. A suite of direct shear tests was conducted a residual friction angle of 36 was determined for the ambient backfill. These tests showed that the residual shearing resistance was reached within a fraction of an inch. The pipe was coated with fusion-bonded epoxy, so friction reduce factory of 0.6 can be considered. To relieve ground movement induced compressive stress, the line was uncovered. As more of the pipeline was exposed, the pipe abruptly bowed in the excavation. An analysis of this pipe formation which was performed is provided in this paper. Also discussed in this paper are ways to mitigate this pipe deformation or upheaval buckling from occurring. Keywords: Pipe Upheaval, Pipe Buckling, Ground subsidence, Buried Pipeline, Pipe Stress Mitigation.

Keywords: pipe upheaval, pipe buckling, ground subsidence, buried pipeline, pipe stress mitigation

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2138 Prediction of Positive Cloud-to-Ground Lightning Striking Zones for Charged Thundercloud Based on Line Charge Model

Authors: Surajit Das Barman, Rakibuzzaman Shah, Apurv Kumar

Abstract:

Bushfire is known as one of the ascendant factors to create pyrocumulus thundercloud that causes the ignition of new fires by pyrocumulonimbus (pyroCb) lightning strikes and creates major losses of lives and property worldwide. A conceptual model-based risk planning would be beneficial to predict the lightning striking zones on the surface of the earth underneath the pyroCb thundercloud. PyroCb thundercloud can generate both positive cloud-to-ground (+CG) and negative cloud-to-ground (-CG) lightning in which +CG tends to ignite more bushfires and cause massive damage to nature and infrastructure. In this paper, a simple line charge structured thundercloud model is constructed in 2-D coordinates using the method of image charge to predict the probable +CG lightning striking zones on the earth’s surface for two conceptual thundercloud charge configurations: titled dipole and conventional tripole structure with excessive lower positive charge regions that lead to producing +CG lightning. The electric potential and surface charge density along the earth’s surface for both structures via continuously adjusting the position and the charge density of their charge regions is investigated. Simulation results for tilted dipole structure confirm the down-shear extension of the upper positive charge region in the direction of the cloud’s forward flank by 4 to 8 km, resulting in negative surface density, and would expect +CG lightning to strike within 7.8 km to 20 km around the earth periphery in the direction of the cloud’s forward flank. On the other hand, the conceptual tripole charge structure with enhanced lower positive charge region develops negative surface charge density on the earth’s surface in the range |x| < 6.5 km beneath the thundercloud and highly favors producing +CG lightning strikes.

Keywords: pyrocumulonimbus, cloud-to-ground lightning, charge structure, surface charge density, forward flank

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2137 Fabrication of Ligand Coated Lipid-Based Nanoparticles for Synergistic Treatment of Autoimmune Disease

Authors: Asiya Mahtab, Sushama Talegaonkar

Abstract:

The research is aimed at developing targeted lipid-based nanocarrier systems of chondroitin sulfate (CS) to deliver an antirheumatic drug to the inflammatory site in arthritic paw. Lipid-based nanoparticle (TEF-lipo) was prepared by using a thin-film hydration method. The coating of prepared drug-loaded nanoparticles was done by the ionic interaction mechanism. TEF-lipo and CS-coated lipid nanoparticle (CS-lipo) were characterized for mean droplet size, zeta potential, and surface morphology. TEF-lipo and CS-lipo were further subjected to in vitro cell line studies on RAW 264.7 murine macrophage, U937, and MG 63 cell lines. The pharmacodynamic study was performed to establish the effectiveness of the prepared lipid-based conventional and targeted nanoparticles in comparison to pure drugs. Droplet size and zeta potential of TEF-lipo were found to be 128. 92 ± 5.42 nm and +12.6 ± 1.2 mV. It was observed that after the coating of TEF-lipo with CS, particle size increased to 155.6± 2.12 nm and zeta potential changed to -10.2± 1.4mV. Transmission electron microscopic analysis revealed that the nanovesicles were uniformly dispersed and detached from each other. Formulations followed sustained release pattern up to 24 h. Results of cell line studies ind icated that CS-lipo formulation showed the highest cytotoxic potential, thereby proving its enhanced ability to kill the RAW 264.7 murine macrophage and U937 cells when compared with other formulations. It is clear from our in vivo pharmacodynamic results that targeted nanocarriers had a higher inhibitory effect on arthritis progression than nontargeted nanocarriers or free drugs. Results demonstrate that this approach will provide effective treatment for rheumatoid arthritis, and CS served as a potential prophylactic against the advancement of cartilage degeneration.

Keywords: adjuvant induced arthritis, chondroitin sulfate, rheumatoid arthritis, teriflunomide

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2136 Trajectory Generation Procedure for Unmanned Aerial Vehicles

Authors: Amor Jnifene, Cedric Cocaud

Abstract:

One of the most constraining problems facing the development of autonomous vehicles is the limitations of current technologies. Guidance and navigation controllers need to be faster and more robust. Communication data links need to be more reliable and secure. For an Unmanned Aerial Vehicles (UAV) to be useful, and fully autonomous, one important feature that needs to be an integral part of the navigation system is autonomous trajectory planning. The work discussed in this paper presents a method for on-line trajectory planning for UAV’s. This method takes into account various constraints of different types including specific vectors of approach close to target points, multiple objectives, and other constraints related to speed, altitude, and obstacle avoidance. The trajectory produced by the proposed method ensures a smooth transition between different segments, satisfies the minimum curvature imposed by the dynamics of the UAV, and finds the optimum velocity based on available atmospheric conditions. Given a set of objective points and waypoints a skeleton of the trajectory is constructed first by linking all waypoints with straight segments based on the order in which they are encountered in the path. Secondly, vectors of approach (VoA) are assigned to objective waypoints and their preceding transitional waypoint if any. Thirdly, the straight segments are replaced by 3D curvilinear trajectories taking into account the aircraft dynamics. In summary, this work presents a method for on-line 3D trajectory generation (TG) of Unmanned Aerial Vehicles (UAVs). The method takes as inputs a series of waypoints and an optional vector of approach for each of the waypoints. Using a dynamic model based on the performance equations of fixed wing aircrafts, the TG computes a set of 3D parametric curves establishing a course between every pair of waypoints, and assembling these sets of curves to construct a complete trajectory. The algorithm ensures geometric continuity at each connection point between two sets of curves. The geometry of the trajectory is optimized according to the dynamic characteristics of the aircraft such that the result translates into a series of dynamically feasible maneuvers. In summary, this work presents a method for on-line 3D trajectory generation (TG) of Unmanned Aerial Vehicles (UAVs). The method takes as inputs a series of waypoints and an optional vector of approach for each of the waypoints. Using a dynamic model based on the performance equations of fixed wing aircraft, the TG computes a set of 3D parametric curves establishing a course between every pair of waypoints, and assembling these sets of curves to construct a complete trajectory. The algorithm ensures geometric continuity at each connection point between two sets of curves. The geometry of the trajectory is optimized according to the dynamic characteristics of the aircraft such that the result translates into a series of dynamically feasible maneuvers.

Keywords: trajectory planning, unmanned autonomous air vehicle, vector of approach, waypoints

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2135 Proliferative Effect of Some Calcium Channel Blockers on the Human Embryonic Kidney Cell Line

Authors: Lukman Ahmad Jamil, Heather M. Wallace

Abstract:

Introduction: Numerous epidemiological studies have shown a positive as well as negative association and no association in some cases between chronic use of calcium channel blockers and the increased risk of developing cancer. However, these associations were enmeshed with controversies in the absence of laboratory based studies to back up those claims. Aim: The aim of this study was to determine in mechanistic terms the association between the long-term administration of nifedipine and diltiazem and increased risk of developing cancer using the human embryonic kidney (HEK293) cell line. Methods: Cell counting using the Trypan blue dye exclusion and 3-4, 5-Dimethylthiazol-2-yl-2, 5-diphenyl-tetrazolium bromide (MTT) assays were used to investigate the effect of nifedipine and diltiazem on the growth pattern of HEK293 cells. Protein assay using modified Lowry method and analysis of intracellular polyamines concentration using Liquid Chromatography – Tandem Mass Spectrometry (LC-MS) were performed to ascertain the mechanism through which chronic use of nifedipine increases the risk of developing cancer. Results: Both nifedipine and diltiazem significantly increased the proliferation of HEK293 cells dose and time dependently. This proliferative effect after 24, 48 and 72-hour incubation period was observed at 0.78, 1.56 and 25 µM for nifedipine and 0.39, 1.56 and 25 µM for diltiazem, respectively. The increased proliferation of the cells was found to be statistically significantly (p<0.05). Furthermore, the increased proliferation of the cells induced by nifedipine was associated with the increase in the protein content and elevated intracellular polyamines concentration level. Conclusion: The chronic use of nifedipine is associated with increased proliferation of cells with concomitant elevation of polyamines concentration and elevated polyamine levels have been implicated in many malignant transformations and hence, these provide a possible explanation on the link between long term use of nifedipine and development of some human cancers. Further studies are needed to evaluate the cause of this association.

Keywords: cancer, nifedipine, polyamine, proliferation

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2134 DNA Fragmentation and Apoptosis in Human Colorectal Cancer Cell Lines by Sesamum indicum Dried Seeds

Authors: Mohd Farooq Naqshbandi

Abstract:

The four fractions of aqueous extract of Sesame Seeds (Sesamum indicum L.) were studied for invitro DNA fragmentation, cell migration, and cellular apoptosis on SW480 and HTC116 human colorectal cancer cell lines. The seeds of Sesamum indicum were extracted with six solvents, including Methanol, Ethanol, Aqueous, Chloroform, Acetonitrile, and Hexane. The aqueous extract (IC₅₀ value 154 µg/ml) was found to be the most active in terms of cytotoxicity with SW480 human colorectal cancer cell lines. Further fractionation of this aqueous extract on flash chromatography gave four fractions. These four fractions were studied for anticancer and DNA binding studies. Cell viability was assessed by colorimetric assay (MTT). IC₅₀ values for all these four fractions ranged from 137 to 548 µg/mL for the HTC116 cancer cell line and 141 to 402 µg/mL for the SW480 cancer cell line. The four fractions showed good anticancer and DNA binding properties. The DNA binding constants ranged from 10.4 ×10⁴ 5 to 28.7 ×10⁴, showing good interactions with DNA. The DNA binding interactions were due to intercalative and π-π electron forces. The results indicate that aqueous extract fractions of sesame showed inhibition of cell migration of SW480 and HTC116 human colorectal cancer cell lines and induced DNA fragmentation and apoptosis. This was demonstrated by calculating the low wound closure percentage in cells treated with these fractions as compared to the control (80%). Morphological features of nuclei of cells treated with fractions revealed chromatin compression, nuclear shrinkage, and apoptotic body formation, which indicate cell death by apoptosis. The flow cytometer of fraction-treated cells of SW480 and HTC116 human colorectal cancer cell lines revealed death due to apoptosis. The results of the study indicate that aqueous extract of sesame seeds may be used to treat colorectal cancer.

Keywords: Sesamum indicum, cell migration inhibition, apoptosis induction, anticancer activity, colorectal cancer

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2133 Automation of Savitsky's Method for Power Calculation of High Speed Vessel and Generating Empirical Formula

Authors: M. Towhidur Rahman, Nasim Zaman Piyas, M. Sadiqul Baree, Shahnewaz Ahmed

Abstract:

The design of high-speed craft has recently become one of the most active areas of naval architecture. Speed increase makes these vehicles more efficient and useful for military, economic or leisure purpose. The planing hull is designed specifically to achieve relatively high speed on the surface of the water. Speed on the water surface is closely related to the size of the vessel and the installed power. The Savitsky method was first presented in 1964 for application to non-monohedric hulls and for application to stepped hulls. This method is well known as a reliable comparative to CFD analysis of hull resistance. A computer program based on Savitsky’s method has been developed using MATLAB. The power of high-speed vessels has been computed in this research. At first, the program reads some principal parameters such as displacement, LCG, Speed, Deadrise angle, inclination of thrust line with respect to keel line etc. and calculates the resistance of the hull using empirical planning equations of Savitsky. However, some functions used in the empirical equations are available only in the graphical form, which is not suitable for the automatic computation. We use digital plotting system to extract data from nomogram. As a result, value of wetted length-beam ratio and trim angle can be determined directly from the input of initial variables, which makes the power calculation automated without manually plotting of secondary variables such as p/b and other coefficients and the regression equations of those functions are derived by using data from different charts. Finally, the trim angle, mean wetted length-beam ratio, frictional coefficient, resistance, and power are computed and compared with the results of Savitsky and good agreement has been observed.

Keywords: nomogram, planing hull, principal parameters, regression

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2132 Toxicity of Bisphenol-A: Effects on Health and Regulations

Authors: Tuğba Özdal, Neşe Şahin Yeşilçubuk

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Bisphenol-A (BPA) is one of the highest volume chemicals produced worldwide in the plastic industry. This compound is mostly used in producing polycarbonate plastics that are often used for food and beverage storage, and BPA is also a component of epoxy resins that are used to line food and beverage containers. Studies performed in this area indicated that BPA could be extracted from such products while they are in contact with food. Therefore, BPA exposure is presumed. In this paper, the chemical structure of BPA, factors affecting BPA migration to food and beverages, effects on health, and recent regulations will be reviewed.

Keywords: BPA, health, regulations, toxicity

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2131 Satureja bachtiarica Bunge Induce Apoptosis via Mitochondrial Intrinsic Pathway and G1 Cell Cycle Arrest

Authors: Hamed Karimian, Noraziah Nordin, Mohamad Ibrahim Noordin, Syam Mohan, Mahboubeh Razavi, Najihah Mohd Hashim, Happipah Mohd Ali

Abstract:

Satureja bachtiarica Bunge is a perennial medicinal plant belonging to the Lamiaceae family and endemic species in Iran. Satureja bachtiarica Bunge with the local name of Marzeh koohi is edible vegetable use as flavoring agent, anti-bacterial and to relieve cough and indigestion. In this study, the anti-cancer effect of Satureja bachtiarica Bunge on the MDA-MB-231 cell line as an Breast cancer cell model has been analyzed for the first time. Satureja bachtiarica Bunge was extracted using different solvents in the order of increasing polarity. Cytotoxicity activity of hexane extract of Satureja bachtiarica Bunge (SBHE) was observed using MTT assay. Acridine orange/Propidium iodide staining was used to detect early apoptosis; Annexin-V-FITC assay was carried out to observe the detection of cell-surface Phosphatidylserine (PS), with Annexin-Vserving as a marker for apoptotic cells. Caspase 3/7, 8 and-9 assays showed significantly activation of caspase-9 where lead intrinsic mitochondrial pathway. Bcl-2/Bax expressions and cell cycle arrest were also investigated. SBHE had exhibited significantly higher cytotoxicity against MDA-MB-231 Cell line compare to other cell lines. A significant increase in chromatin condensation in the cell nucleus was observed by fluorescence analysis. Treatment of MDA-MB-231 cells with SBHE encouraged apoptosis, by down-regulating Bcl-2 and up-regulating Bax, which lead the activation of caspase 9. Moreover, SBHE treatment significantly arrested MDA-MB-231 cells in the G1 phase. Together, the results presented in this study demonstrated that SBHE inhibited the proliferation of MDA-MB-231 cells, leading cell cycle arrest and programmed cell death, which was confirmed to be through the mitochondrial pathway.

Keywords: Satureja bachtiarica Bunge, MDA-MB-231, apoptosis, annexin-V, cell cycle

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2130 Inverse Scattering for a Second-Order Discrete System via Transmission Eigenvalues

Authors: Abdon Choque-Rivero

Abstract:

The Jacobi system with the Dirichlet boundary condition is considered on a half-line lattice when the coefficients are real valued. The inverse problem of recovery of the coefficients from various data sets containing the so-called transmission eigenvalues is analyzed. The Marchenko method is utilized to solve the corresponding inverse problem.

Keywords: inverse scattering, discrete system, transmission eigenvalues, Marchenko method

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2129 Computation and Validation of the Stress Distribution around a Circular Hole in a Slab Undergoing Plastic Deformation

Authors: Sherif D. El Wakil, John Rice

Abstract:

The aim of the current work was to employ the finite element method to model a slab, with a small hole across its width, undergoing plastic plane strain deformation. The computational model had, however, to be validated by comparing its results with those obtained experimentally. Since they were in good agreement, the finite element method can therefore be considered a reliable tool that can help gain better understanding of the mechanism of ductile failure in structural members having stress raisers. The finite element software used was ANSYS, and the PLANE183 element was utilized. It is a higher order 2-D, 8-node or 6-node element with quadratic displacement behavior. A bilinear stress-strain relationship was used to define the material properties, with constants similar to those of the material used in the experimental study. The model was run for several tensile loads in order to observe the progression of the plastic deformation region, and the stress concentration factor was determined in each case. The experimental study involved employing the visioplasticity technique, where a circular mesh (each circle was 0.5 mm in diameter, with 0.05 mm line thickness) was initially printed on the side of an aluminum slab having a small hole across its width. Tensile loading was then applied to produce a small increment of plastic deformation. Circles in the plastic region became ellipses, where the directions of the principal strains and stresses coincided with the major and minor axes of the ellipses. Next, we were able to determine the directions of the maximum and minimum shear stresses at the center of each ellipse, and the slip-line field was then constructed. We were then able to determine the stress at any point in the plastic deformation zone, and hence the stress concentration factor. The experimental results were found to be in good agreement with the analytical ones.

Keywords: finite element method to model a slab, slab undergoing plastic deformation, stress distribution around a circular hole, visioplasticity

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2128 Housing First, Not Housing Only: The Life Skills Project

Authors: Sara Cumming, Julianne DiSanto, Leah Burton

Abstract:

Homelessness in Canada is a persistent problem. It has been widely argued that the best tactic for eradicating homelessness is to approach social issues from a Housing First perspective—an approach that centers on quickly moving people into permanent and independent housing and then providing them additional support and services as needed. It is recognized that life skills training is both necessary and an effective way to reduce cyclical homelessness; however, there is a scarcity of research on effective ways to teach life skills; this problem was exacerbated in a pandemic context, where in-person delivery was severely restricted or no longer possible. Very little attention has been paid to the diverse cultural needs of clients in a multicultural context and the need to foster cultural knowledge/awareness in individuals to successfully contribute to the cultural safety of communities. This research attempts to fill these gaps in the literature and in practice by employing a community-engaged research (CER) approach. Academic, government, funders, front-line staff, and clients at 15 not-for-profits from across the Greater Toronto Area in Ontario, Canada, collaborated to co-create a virtual, client-centric, equity, diversity, and inclusion (EDI) informed life skill learning management system. We employed a triangulation methodology for this research. An environmental scan was conducted for best practices. Two separate Creative Problem Solving Sessions were held with over 100 front-line workers, managers, and executive directors who work with homeless populations. Quantitative and open-ended surveys were completed by over 200 individuals with experience with homelessness. All sections of this research aimed to discover the areas of skills that individuals need to maintain housing and to ascertain what a more client-driven EDI approach to life skills training should include. This research will showcase which life skills are deemed essential for homeless and precariously housed individuals.

Keywords: homelessness, Housing First, life skills, community engaged research

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2127 Time Domain Dielectric Relaxation Microwave Spectroscopy

Authors: A. C. Kumbharkhane

Abstract:

Time domain dielectric relaxation microwave spectroscopy (TDRMS) is a term used to describe a technique of observing the time dependant response of a sample after application of time dependant electromagnetic field. A TDRMS probes the interaction of a macroscopic sample with a time dependent electrical field. The resulting complex permittivity spectrum, characterizes amplitude (voltage) and time scale of the charge-density fluctuations within the sample. These fluctuations may arise from the reorientation of the permanent dipole moments of individual molecules or from the rotation of dipolar moieties in flexible molecules, like polymers. The time scale of these fluctuations depends on the sample and its relative relaxation mechanism. Relaxation times range from some picoseconds in low viscosity liquids to hours in glasses, Therefore the TDRS technique covers an extensive dynamical process. The corresponding frequencies range from 10-4 Hz to 1012 Hz. This inherent ability to monitor the cooperative motion of molecular ensemble distinguishes dielectric relaxation from methods like NMR or Raman spectroscopy, which yield information on the motions of individual molecules. Recently, we have developed and established the TDR technique in laboratory that provides information regarding dielectric permittivity in the frequency range 10 MHz to 30 GHz. The TDR method involves the generation of step pulse with rise time of 20 pico-seconds in a coaxial line system and monitoring the change in pulse shape after reflection from the sample placed at the end of the coaxial line. There is a great interest to study the dielectric relaxation behaviour in liquid systems to understand the role of hydrogen bond in liquid system. The intermolecular interaction through hydrogen bonds in molecular liquids results in peculiar dynamical properties. The dynamics of hydrogen-bonded liquids have been studied. The theoretical model to explain the experimental results will be discussed.

Keywords: microwave, time domain reflectometry (TDR), dielectric measurement, relaxation time

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2126 User Experience Evaluation on the Usage of Commuter Line Train Ticket Vending Machine

Authors: Faishal Muhammad, Erlinda Muslim, Nadia Faradilla, Sayidul Fikri

Abstract:

To deal with the increase of mass transportation needs problem, PT. Kereta Commuter Jabodetabek (KCJ) implements Commuter Vending Machine (C-VIM) as the solution. For that background, C-VIM is implemented as a substitute to the conventional ticket windows with the purposes to make transaction process more efficient and to introduce self-service technology to the commuter line user. However, this implementation causing problems and long queues when the user is not accustomed to using the machine. The objective of this research is to evaluate user experience after using the commuter vending machine. The goal is to analyze the existing user experience problem and to achieve a better user experience design. The evaluation method is done by giving task scenario according to the features offered by the machine. The features are daily insured ticket sales, ticket refund, and multi-trip card top up. There 20 peoples that separated into two groups of respondents involved in this research, which consist of 5 males and 5 females each group. The experienced and inexperienced user to prove that there is a significant difference between both groups in the measurement. The user experience is measured by both quantitative and qualitative measurement. The quantitative measurement includes the user performance metrics such as task success, time on task, error, efficiency, and learnability. The qualitative measurement includes system usability scale questionnaire (SUS), questionnaire for user interface satisfaction (QUIS), and retrospective think aloud (RTA). Usability performance metrics shows that 4 out of 5 indicators are significantly different in both group. This shows that the inexperienced group is having a problem when using the C-VIM. Conventional ticket windows also show a better usability performance metrics compared to the C-VIM. From the data processing, the experienced group give the SUS score of 62 with the acceptability scale of 'marginal low', grade scale of “D”, and the adjective ratings of 'good' while the inexperienced group gives the SUS score of 51 with the acceptability scale of 'marginal low', grade scale of 'F', and the adjective ratings of 'ok'. This shows that both groups give a low score on the system usability scale. The QUIS score of the experienced group is 69,18 and the inexperienced group is 64,20. This shows the average QUIS score below 70 which indicate a problem with the user interface. RTA was done to obtain user experience issue when using C-VIM through interview protocols. The issue obtained then sorted using pareto concept and diagram. The solution of this research is interface redesign using activity relationship chart. This method resulted in a better interface with an average SUS score of 72,25, with the acceptable scale of 'acceptable', grade scale of 'B', and the adjective ratings of 'excellent'. From the time on task indicator of performance metrics also shows a significant better time by using the new interface design. Result in this study shows that C-VIM not yet have a good performance and user experience.

Keywords: activity relationship chart, commuter line vending machine, system usability scale, usability performance metrics, user experience evaluation

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2125 Technology in Commercial Law Enforcement: Tanzania, Canada, and Singapore Comparatively

Authors: Katarina Revocati Mteule

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The background of this research arises from global demands for fair business opportunities. As one of responses to these demands, nations embarked on reforms in commercial laws. In 1990s Tanzania resorted to economic transformation through liberalization to attract more investments included reform in commercial laws enforcement. This research scrutinizes the effectiveness of reforms in Tanzania in comparison with Canada and Singapore and the role of technology. The methodology to be used is doctrinal legal research mixed with international comparative legal research. It involves comparative analysis of library, online, and internet resources as well as Case Laws and Statutory Laws. Tanzania, Canada and Singapore are sampled comparators basing on their distinct level of economic development. The criteria of analysis includes the nature of reforms, type of technology, technological infrastructure and human resource technical competence in each country. As the world progresses towards reforms in commercial laws, improvements in law, policy, and regulatory frameworks are paramount. Specifically, commercial laws are essential in contract enforcement and dispute resolution and how it copes with modern technologies is a concern. Harnessing the best technology is necessary to cope with the modernity in world businesses. In line with this, Tanzania is improving its business environment, including law enforcement mechanisms that are supportive to investments. Reforms such as specialized commercial law enforcement coupled with alternative dispute resolutions such as arbitration, mediation, and reconciliation are emphasized. Court technology as one of the reform tools given high priority. This research evaluates the progress and the effectiveness of the reforms in Commercial Laws towards friendly business environment in Tanzania in comparison with Canada and Singapore. The experience of Tanzania is compared with Canada and Singapore to see what to improve for each country to enhance quick and fair enforcement of commercial law. The research proposes necessary global standards of procedures and in national laws to offer a business-friendly environment and the use of appropriate technology. Solutions are proposed in tackling the challenges of delays in enforcing Commercial Laws such as case management, funding, legal and procedural hindrances, laxity among staff, and abuse of Court process among litigants, all in line with modern technology. It is the finding of the research that proper use of technology has managed to reduce case backlogs and time taken to resolve a commercial dispute, to increase court integrity by minimizing human contacts in commercial law enforcement which may lead to solicitation of favors and saving of parties’ time due to online service. Among the three countries, each one is facing a distinct challenge due to the level of poverty and remoteness from online service. How solutions are found in one country is a lesson to another. To conclude, this paper is suggesting solutions for improving the commercial law enforcement mechanisms in line with modern technology. The call for technological transformation is essential for the enforcement of commercial laws.

Keywords: commercial law, enforcement, technology

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2124 Anticancer and Anti-Apoptotic Potential of Tridham and 1,2,3,4,6-Penta-O-Galloyl-β-D-Glucose in MCF-7 Breast Cancer Cell Line

Authors: R. Stalin, D. Karthick, H. Haseena Banu, T. P. Sachidanandam, P. Shanthi

Abstract:

Background: Breast cancer is emerging as one of the leading cause of cancer related deaths and hence there arises the need to look out for drugs which are more targets specific with minimal side effects. In recent times, there is a shift towards alternative medicine due to low cost and less side effects. Siddha system of medicine is one the oldest system of medicine practiced against various ailments. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio (TD) and its anticancer potential is evaluated in terms of induction of apoptosis. Objective: The present study was designed to investigate the anti proliferative effect of TD and 1,2,3,4,6-penta-O-galloyl-b-D-glucose (PGG), a pure compound isolated from TD on human mammary carcinoma cell line (MCF-7). Materials and Methods: Cell viability was studied using MTT analysis and trypan blue staining. Mitochondrial membrane potential was studied using DAPI staining. The protein and mRNA expressions of pro-apoptotic and anti- apoptotic markers namely Bax, Bad, Bcl-2 and caspases were also assessed by Western Blotting and RT PCR. Results: Viability studies of TD and PGG treated MCF-7 cells showed an inhibition in cell growth in time and dose dependent manner. The alteration in mitochondrial membrane potential was restored through treatment with TD and PGG which was confirmed by DAPI staining. The protein and mRNA expression of pro-apoptotic markers was found to be significantly increased in TD and PGG treated cells with a concomitant decrease in anti-apoptotic markers. Conclusion: The results of the study suggest that TD and PGG exhibit their anticancer effect through its membrane stabilizing property and activation of apoptotic cascade in MCF-7 cells.

Keywords: apoptosis, mammary carcinoma, MCF-7, penta galloyl glucose, Tridham

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2123 Effects of Different Thermal Processing Routes and Their Parameters on the Formation of Voids in PA6 Bonded Aluminum Joints

Authors: Muhammad Irfan, Guillermo Requena, Jan Haubrich

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Adhesively bonded aluminum joints are common in automotive and aircraft industries and are one of the enablers of lightweight construction to minimize the carbon emissions during transportation for a sustainable life. This study is focused on the effects of two thermal processing routes, i.e., by direct and induction heating, and their parameters on void formation in PA6 bonded aluminum EN-AW6082 joints. The joints were characterized microanalytically as well as by lap shear experiments. The aging resistance of the joints was studied by accelerated aging tests at 80°C hot water. It was found that the processing of single lap joints by direct heating in a convection oven causes the formation of a large number of voids in the bond line. The formation of voids in the convection oven was due to longer processing times and was independent of any surface pretreatments of the metal as well as the processing temperature. However, when processing at low temperatures, a large number of small-sized voids were observed under the optical microscope, and they were larger in size but reduced in numbers at higher temperatures. An induction heating process was developed, which not only successfully reduced or eliminated the voids in PA6 bonded joints but also reduced the processing times for joining significantly. Consistent with the trend in direct heating, longer processing times and higher temperatures in induction heating also led to an increased formation of voids in the bond line. Subsequent single lap shear tests revealed that the increasing void contents led to a 21% reduction in lap shear strengths (i.e., from ~47 MPa for induction heating to ~37 MPa for direct heating). Also, there was a 17% reduction in lap shear strengths when the consolidation temperature was raised from 220˚C to 300˚C during induction heating. However, below a certain threshold of void contents, there was no observable effect on the lap shear strengths as well as on hydrothermal aging resistance of the joints consolidated by the induction heating process.

Keywords: adhesive, aluminium, convection oven, induction heating, mechanical properties, nylon6 (PA6), pretreatment, void

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2122 Autonomy in Healthcare Organisations: A Comparative Case Study of Middle Managers in England and Iran

Authors: Maryam Zahmatkesh

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Middle managers form a significant occupational category in organisations. They undertake a vital role, as they sit between the operational and strategic roles. Traditionally they were acting as diplomat administrators, and were only in power to meet the demands of professionals. Following the introduction of internal market, in line with the principles of New Public Management, middle managers have been considered as change agents. More recently, in the debates of middle managers, there is emphasis on entrepreneurialism and enacting strategic role. It was assumed that granting autonomy to the local organisations and the inception of semi-autonomous hospitals (Foundation Trusts in England and Board of Trustees in Iran) would give managers more autonomy to act proactively and innovatively. This thesis explores the hospital middle managers’ perception of and responses to public management reforms (in particular, hospital autonomy) in England and Iran. In order to meet the aims of the thesis, research was undertaken within the interpretative paradigm, in line with social constructivism. Data were collected from interviews with forty-five middle managers, observational fieldwork and documentary analysis across four teaching university hospitals in England and Iran. The findings show the different ways middle managers’ autonomy is constrained in the two countries. In England, middle managers have financial and human recourses, but their autonomy is constrained by government policy and targets. In Iran, middle managers are less constrained by government policy and targets, but they do not have financial and human resources to exercise autonomy. Unbalanced autonomy causes tension and frustration for middle managers. According to neo-institutional theory, organisations are deeply embedded within social, political, economic and normative settings that exert isomorphic and internal population-level pressures to conform to existing and established modes of operation. Health systems which are seeking to devolve autonomy to middle managers must appreciate the multidimensional nature of the autonomy, as well as the wider environment that organisations are embedded, if they are about to improve the performance of managers and their organisations.

Keywords: autonomy, healthcare organisations, middle managers, new public management

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2121 Off-Line Text-Independent Arabic Writer Identification Using Optimum Codebooks

Authors: Ahmed Abdullah Ahmed

Abstract:

The task of recognizing the writer of a handwritten text has been an attractive research problem in the document analysis and recognition community with applications in handwriting forensics, paleography, document examination and handwriting recognition. This research presents an automatic method for writer recognition from digitized images of unconstrained writings. Although a great effort has been made by previous studies to come out with various methods, their performances, especially in terms of accuracy, are fallen short, and room for improvements is still wide open. The proposed technique employs optimal codebook based writer characterization where each writing sample is represented by a set of features computed from two codebooks, beginning and ending. Unlike most of the classical codebook based approaches which segment the writing into graphemes, this study is based on fragmenting a particular area of writing which are beginning and ending strokes. The proposed method starting with contour detection to extract significant information from the handwriting and the curve fragmentation is then employed to categorize the handwriting into Beginning and Ending zones into small fragments. The similar fragments of beginning strokes are grouped together to create Beginning cluster, and similarly, the ending strokes are grouped to create the ending cluster. These two clusters lead to the development of two codebooks (beginning and ending) by choosing the center of every similar fragments group. Writings under study are then represented by computing the probability of occurrence of codebook patterns. The probability distribution is used to characterize each writer. Two writings are then compared by computing distances between their respective probability distribution. The evaluations carried out on ICFHR standard dataset of 206 writers using Beginning and Ending codebooks separately. Finally, the Ending codebook achieved the highest identification rate of 98.23%, which is the best result so far on ICFHR dataset.

Keywords: off-line text-independent writer identification, feature extraction, codebook, fragments

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2120 Gene Expression Signature-Based Chemical Genomic to Identify Potential Therapeutic Compounds for Colorectal Cancer

Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

Abstract:

There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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2119 Ethical Issues around Online Marketing to Children

Authors: Chris Preston

Abstract:

As we devise ever more sophisticated methods of on-line marketing, devising systems that are able to reach into the everyday lives of consumers, we are confronted by a generation of children who face unprecedented intervention by commercial organisations into young minds, via electronic devices, and whether by computer, tablet or phone, such children have been somehow reduced to the status of their devices, with little regard for their well being as individuals. This discussion paper seeks to draw attention to such practice and questions the ethics of digital marketing methods.

Keywords: online marketing to children, online research of children, online targeting of children, consumer rights, ethics

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2118 Prevalence of Pretreatment Drug HIV-1 Mutations in Moscow, Russia

Authors: Daria Zabolotnaya, Svetlana Degtyareva, Veronika Kanestri, Danila Konnov

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An adequate choice of the initial antiretroviral treatment determines the treatment efficacy. In the clinical guidelines in Russia non-nucleoside reverse transcriptase inhibitors (NNRTIs) are still considered to be an option for first-line treatment while pretreatment drug resistance (PDR) testing is not routinely performed. We conducted a cohort retrospective study in HIV-positive treatment naïve patients of the H-clinic (Moscow, Russia) who performed PDR testing from July 2017 to November 2021. All the information was obtained from the medical records anonymously. We analyzed the mutations in reverse transcriptase and protease genes. RT-sequences were obtained by AmpliSens HIV-Resist-Seq kit. Drug resistance was defined using the HIVdb Program v. 8.9-1. PDR was estimated using the Stanford algorithm. Descriptive statistics were performed in Excel (Microsoft Office, 2019). A total of 261 HIV-1 infected patients were enrolled in the study including 197 (75.5%) male and 64 (24.5%) female. The mean age was 34.6±8.3 years. The median CD4 count – 521 cells/µl (IQR 367-687 cells/µl). Data on risk factors of HIV-infection were scarce. The total quantity of strains containing mutations in the reverse transcriptase gene was 75 (28.7%). From these 5 (1.9%) mutations were associated with PDR to nucleoside reverse transcriptase inhibitors (NRTIs) and 30 (11.5%) – with PDR to NNRTIs. The number of strains with mutations in protease gene was 43 (16.5%), from these only 3 (1.1%) mutations were associated with resistance to protease inhibitors. For NNRTIs the most prevalent PDR mutations were E138A, V106I. Most of the HIV variants exhibited a single PDR mutation, 2 were found in 3 samples. Most of HIV variants with PDR mutation displayed a single drug class resistance mutation. 2/37 (5.4%) strains had both NRTIs and NNRTIs mutations. There were no strains identified with PDR mutations to all three drug classes. Though earlier data demonstrated a lower level of PDR in HIV treatment naïve population in Russia and our cohort can be not fully representative as it is taken from the private clinic, it reflects the trend of increasing PDR especially to NNRTIs. Therefore, we consider either pretreatment testing or giving the priority to other drugs as first-line treatment necessary.

Keywords: HIV, resistance, mutations, treatment

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